Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis

Hesdorffer, 2010, Estimating risk for developing epilepsy, Neurology., 76, 23, 10.1212/WNL.0b013e318204a36a

Baulac, 2015, Epilepsy priorities in Europe: a report of the ILAE-IBE epilepsy advocacy Europe task force, Epilepsia., 56, 1687, 10.1111/epi.13201

Kimelberg, 2010, Functions of astrocytes and their potential as therapeutic targets, Am Soc Exp Neurother., 7, 338, 10.1016/j.nurt.2010.07.006

Boldog, 2018, Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type, Nat Neurosci., 21, 1185, 10.1038/s41593-018-0205-2

Jäkel, 2017, Glial cells and their function in the adult brain : a journey through the history of their ablation, Front Cell Neurosci., 11, 24, 10.3389/fncel.2017.00024

Bahney, 2017, The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting, J Comp Neurol., 524, 3865, 10.1002/cne.24040

Herculano-Houzel, 2016, How to count cells: the advantages and disadvantages of the isotropic fractionator compared with stereology, Cell Tissue Res., 360, 29, 10.1007/s00441-015-2127-6

Herculano-Houzel, 2014, The glia/neuron ratio : how it varies uniformly across brain structures and species and what that means for brain physiology and evolution, Glia., 62, 1377, 10.1002/glia.22683

Oberheim, 2009, Uniquely hominid features of adult human astrocytes, J Neurosci., 29, 3276, 10.1523/JNEUROSCI.4707-08.2009

Robel, 2016, Glia as drivers of abnormal neuronal activity, Nat Neurosci., 19, 28, 10.1038/nn.4184

Zeisel, 2018, Molecular architecture of the mouse nervous system, Cell., 174, 999, 10.1016/j.cell.2018.06.021

Batiuk, 2020, Identification of region-specific astrocyte subtypes at single cell resolution, Nat Commun., 11, 1220, 10.1038/s41467-019-14198-8

John Lin, 2017, Identification of diverse astrocyte populations and their malignant analogs, Nat Neurosci., 20, 396, 10.1038/nn.4493

Lanjakornsiripan, 2018, Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers, Nat Commun., 9, 1623, 10.1038/s41467-018-03940-3

Duran, 2019, Brain region-specific gene signatures revealed by distinct astrocyte subpopulations unveil links to glioma and neurodegenerative diseases, eNeuro., 6, 1, 10.1523/ENEURO.0288-18.2019

Vezzani, 2011, The role of inflammation in epilepsy, Nat Rev Neurol., 7, 31, 10.1038/nrneurol.2010.178

Devinsky, 2013, Glia and epilepsy: excitability and inflammation, Trends Neurosci., 36, 174, 10.1016/j.tins.2012.11.008

Chen, 2020, The role of astrocytes in oxidative stress of central nervous system: a mixed blessing, Cell Prolif., 53, 1, 10.1111/cpr.12781

Pellerin, 2007, Activity-dependent regulation of energy metabolism by astrocytes an update, Glia., 55, 1251, 10.1002/glia.20528

Falkowska, 2015, Energy metabolism of the brain, including the cooperation between astrocytes and neurons, especially in the context of glycogen metabolism, Int J Mol Sci., 16, 25959, 10.3390/ijms161125939

Boison, 2018, Epilepsy and astrocyte energy metabolism, Glia., 66, 1235, 10.1016/j.physbeh.2017.03.040

Brunel, 2016, Astrocytes: orchestrating synaptic plasticity?, Neuroscience., 323, 43, 10.1016/j.neuroscience.2015.04.001

Hussaini, 2018, New roles for old glue : astrocyte function in synaptic plasticity and neurological disorders, Int Neurourol J., 22, 106, 10.5213/inj.1836214.107

Volterra, 2005, Astrocytes, from brain glue to communication elements: the revolution continues, Nat Rev Neurosci., 6, 626, 10.1038/nrn1722

Bak, 2006, The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer, J Neurochem., 98, 641, 10.1111/j.1471-4159.2006.03913.x

Haj-Yasein, 2012, Aquaporin-4 regulates extracellular space volume dynamics during high-frequency synaptic stimulation A gene deletion study in mouse hippocampus, Glia., 60, 867, 10.1002/glia.22319

Vasile, 2017, Human astrocytes : structure and functions in the healthy brain, Brain Struct Funct., 222, 2017, 10.1007/s00429-017-1383-5

Abbott, 2006, Astrocyte-endothelial interactions at the blood-brain barrier, Nat Rev Neurosci., 7, 41, 10.1038/nrn1824

Serlin, 2015, Anatomy and physiology of the blood-brain barrier yonatan, Semin Cell Dev Biol., 38, 2, 10.1016/j.semcdb.2015.01.002

Gordon, 2007, Astrocyte control of the cerebrovasculature, Glia., 1221, 1214, 10.1002/glia.20543

Iadecola, 2007, Glial regulation of the cerebral microvasculature, Nat Neurosci., 10, 1369, 10.1038/nn2003

Sofroniew, 2015, Astrogliosis, Cold Spring Harb Perspect Biol., 7, 1, 10.1101/cshperspect.a020420

Escartin, 2019, Questions and (some) answers on reactive astrocytes, Glia., 67, 2221, 10.1002/glia.23687

Sofroniew, 2010, Astrocytes: biology and pathology, Acta Neuropathol., 119, 7, 10.1007/s00401-009-0619-8

Kettenmann, 2013, Neuroglia, 10.1093/med/9780199794591.001.0001

Robel, 2017, Astroglial scarring and seizures : a cell biological perspective on epilepsy, Neurosci, 23, 152, 10.1177/1073858416645498

Brambilla, 2005, Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury, J Exp Med., 202, 145, 10.1084/jem.20041918

Lian, 2015, NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with alzheimer's disease, Neuron, 85, 101, 10.1016/j.neuron.2014.11.018

Takano, 2005, Receptor-mediated glutamate release from volume sensitive channels in astrocytes, Proc Natl Acad Sci USA., 102, 16466, 10.1073/pnas.0506382102

Jo, 2014, GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease, Nat Med., 20, 886, 10.1038/nm.3639

Wu, 2014, Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer's disease model, Nat Commun., 5, 4159, 10.1038/ncomms5159

Hamby, 2006, TGF-β1 potentiates astrocytic nitric oxide production by expanding the population of astrocytes that express NOS-2, Glia., 54, 566, 10.1002/glia.20411

Chou, 2008, Expanded-polyglutamine huntingtin protein suppresses the secretion and production of a chemokine (CCL5/RANTES) by astrocytes, J Neurosci., 28, 3277, 10.1523/JNEUROSCI.0116-08.2008

Tadesse, 2009, VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown, Proc Natl Acad Sci USA., 106, 1977, 10.1073/pnas.0808698106

Galic, 2012, Cytokines and brain excitability, Front Neuroendocr., 33, 116, 10.1016/j.yfrne.2011.12.002

Vezzani, 2015, Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability, Neuropharmacology., 96, 70, 10.1016/j.neuropharm.2014.10.027

Sofroniew, 2014, Multiple roles for astrocytes as effectors of cytokines and inflammatory mediators, Neuroscientist., 20, 160, 10.1177/1073858413504466

Vezzani, 2019, Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy, Nat Rev Neurol., 15, 459, 10.1038/s41582-019-0217-x

Lau, 2001, Astrocytes produce and release interleukin-1, interleukin-6, tumor necrosis factor alpha and interferon-gamma following traumatic and metabolic injury, J Neurotrauma., 18, 351, 10.1089/08977150151071035

Hyvärinen, 2019, Co-stimulation with IL-1β and TNF-α induces an inflammatory reactive astrocyte phenotype with neurosupportive characteristics in a human pluripotent stem cell model system, Sci Rep., 9, 16944, 10.1038/s41598-019-53414-9

Bianco, 2005, Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia, J Immunol., 174, 7268, 10.4049/jimmunol.174.11.7268

Terrone, 2019, Inflammation and reactive oxygen species as disease modifiers in epilepsy, Neuropharmacology., 167, 107742, 10.1016/j.neuropharm.2019.107742

Minami, 1991, Effects of kainic acid on messenger RNA levels of IL-1b, IL-6, TNFa and LIFE in the rat brain, Biochem Biophys Res Commun., 176, 593, 10.1016/s0006-291x(05)80225-6

Vezzani, 1999, Interleukin-1β immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application: functional evidence for enhancement of electrographic seizures, J Neurosci., 19, 5054, 10.1523/jneurosci.19-12-05054.1999

Simoni, 2000, Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus, Eur J Neurosci., 12, 2623, 10.1046/j.1460-9568.2000.00140.x

Merbl, 2014, Tumor necrosis factor- a and interleukin-6 concentrations in cerebrospinal fluid of dogs after seizures, J Vet Intern Med., 28, 1775, 10.1111/jvim.12462

Patel, 2017, Hippocampal TNFα signaling contributes to seizure generation in an infection-induced mouse model of limbic epilepsy, Disord Nerv Syst Hippocampal., 4, 1, 10.1523/ENEURO.0105-17.20171

Semple, 2017, Interleukin-1 receptor in seizure susceptibility after traumatic injury to the pediatric brain, J Neurosci., 37, 7864, 10.1523/JNEUROSCI.0982-17.2017

Kostic, 2019, Evaluation of IL-1β levels in epilepsy and traumatic brain injury in dogs, BMC Neurosci., 20, 29, 10.1186/s12868-019-0509-5

Ichiyama, 1998, Tumor necrosis factor-alfa, interleukin-1beta, and interleukin-6 in cerebrospinal fluid from children with prolonged febrile seizures comparison with acute encephalitis/encephalopathy, Neurology., 50, 407, 10.1212/WNL.50.2.407

Peltola, 2000, Interleukin-6 and interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic-clonic seizures, Epilepsy Res., 41, 205, 10.1016/S0920-1211(00)00140-6

Uludag, 2015, IL-1β, IL-6 and IL1Ra levels in temporal lobe epilepsy, Seizure Eur J Epilepsy., 26, 22, 10.1016/j.seizure.2015.01.009

Alapirtti, 2017, The production of IL-6 in acute epileptic seizure: a video-EEG study, J Neuroimmunol., 316, 50, 10.1016/j.jneuroim.2017.12.008

Wang, 2000, Interleukin-1beta Inhibits gamma-aminobutyric acid type A (GABA A) receptor current in cultured hippocampal neurons, J Pharmacol Exp Ther., 292, 497

Yang, 2005, Interleukin-1beta enhances NMDA receptor-mediated current but inhibits excitatory synaptic transmission, Brain Res., 1034, 172, 10.1016/j.brainres.2004.11.018

Viviani, 2003, Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases, J Neurosci., 23, 8692, 10.1523/jneurosci.23-25-08692.2003

Balosso, 2008, A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1β, Brain., 131, 3256, 10.1093/brain/awn271

Scheppingen, 2016, Expression of MicroRNAs miR21, miR146a, and miR155 in tuberous sclerosis complex cortical tubers and their regulation in human astrocytes and SEGA-derived cell cultures, Glia., 64, 1066, 10.1002/glia.22983

Scheppingen, 2018, miR147b: a novel key regulator of interleukin 1 beta-mediated inflammation in human astrocytes, Glia., 66, 1082, 10.1002/glia.23302

Korotkov, 2020, microRNA-132 is overexpressed in glia in temporal lobe epilepsy and reduces the expression of pro-epileptogenic factors in human cultured astrocytes, Glia., 68, 60, 10.1002/glia.23700

Zurolo, 2012, Regulation of Kir4.1 expression in astrocytes and astrocytic tumors: a role for interleukin-1 β, J Neuroinflamm., 9, 1, 10.1186/1742-2094-9-280

Korotkov, 2018, Increased expression of matrix metalloproteinase 3 can be attenuated by inhibition of microRNA-155 in cultured human astrocytes, J Neuroinflam., 15, 1, 10.1186/s12974-018-1245-y

Ye, 1996, Cytokine modulation of glial glutamate uptake: a possible involvement of nitric oxide, Neuroreport., 7, 2181, 10.1097/00001756-199609020-00025

Hu, 2000, Cytokine effects on glutamate uptake by human astrocytes, Neuroimmunomodulation., 7, 153, 10.1159/000026433

Pita, 1999, IL-1β increases intracellular calcium through an IL-1 type 1 receptor mediated mechanism in C6 astrocytic cells, Int J Devl Neurosci., 17, 813, 10.1016/S0736-5748(99)00063-5

Sanz, 2020, Reactive glia inflammatory signaling pathways and epilepsy, Int J Mol Sci., 21, 1, 10.3390/ijms21114096

Zhang, 2015, Anti-IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus, FASEB J., 29, 1739, 10.1096/fj.14-258822

Fine, 1996, Tumor necrosis factor α inhibits glutamate uptake by primary human astrocytes, J Biol Chem., 271, 15303, 10.1074/jbc.271.26.15303

Clark, 2016, Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents, J Neuroinflamm., 13, 1, 10.1186/s12974-016-0708-2

Bedner, 2019, TNFα-driven astrocyte purinergic signaling during epileptogenesis, Trends Mol Med., 25, 70, 10.1016/j.molmed.2018.12.001

Stellwagen, 2005, Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-α, J Neurosci., 25, 3219, 10.1523/JNEUROSCI.4486-04.2005

Aronica, 2011, Inflammation in epilepsy: clinical observations, Epilepsia., 52, 26, 10.1111/j.1528-1167.2011.03033.x

Das, 2012, Hippocampal tissue of patients with refractory temporal lobe epilepsy is associated with astrocyte activation, inflammation, and altered expression of channels and receptors, Neuroscience., 220, 237, 10.1016/j.neuroscience.2012.06.002

Ravizza, 2006, Inactivation of Caspase-1 in rodent brain : a novel anticonvulsive strategy, Epilepsia., 47, 1160, 10.1111/j.1528-1167.2006.00590.x

Maroso, 2011, Interleukin-1β biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice, J Am Soc Exp Neurother., 8, 304, 10.1007/s13311-011-0039-z

Bialer, 2013, Progress report on new antiepileptic drugs: a summary of the eleventh eilat conference (EILAT XI), Epilepsy Res., 103, 2, 10.1016/j.eplepsyres.2012.10.001

Lafrance-Corey, 2016, Super-refractory status epilepticus and febrile infection-related epilepsy syndrome treated with anakinra, Ann Neurol., 80, 939, 10.1002/ana.24806.Super-refractory

Kenney-Jung, 2016, FIRES induced status epilepticus treated with anakinra, Ann Neurol., 80, 939, 10.1002/ana.24806

Dilena, 2019, Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection – related epilepsy syndrome, Epilepsia Open., 4, 344, 10.1002/epi4.12317

Westbrook, 2019, Febrile infection-related epilepsy syndrome (FIRES) treated successfully with anakinra in A 21-year-old woman, WMJ., 118, 135, 10.1111/j.1528-1167.2011.03250.x

Jyonouchi, 2016, Intractable epilepsy (IE) and responses to anakinra, a human recombinant IL-1 receptor agonist (IL-1ra): case reports, J Clin Cell Immunol., 7, 1, 10.4172/2155-9899.1000456

Desena, 2018, Systemic autoinflammation with intractable epilepsy managed with interleukin-1 blockade, J Neuroinflamm., 15, 1, 10.1186/s12974-018-1063-2

Steinborn, 2014, Concentration of Il-1β, Il-2, Il-6, TNFα in the blood serum in children with generalized epilepsy treated by valproate, Pharmacol Rep., 66, 972, 10.1016/j.pharep.2014.06.005

Lagarde, 2016, Anti – tumor necrosis factor alpha therapy (adalimumab) in rasmussen's encephalitis: an open pilot study, Epilepsia., 57, 956, 10.1111/epi.13387

Frigerio, 2018, n-3 Docosapentaenoic acid-derived protectin D1 promotes resolution of neuroinflammation and arrests epileptogenesis, Brain., 141, 3130, 10.1093/brain/awy247

Puttachary, 2016, 1400W, a highly selective inducible nitric oxide synthase inhibitor is a potential disease modifier in the rat kainate model of temporal lobe epilepsy, Neurobiol Dis., 93, 184, 10.1016/j.nbd.2016.05.013

Boison, 2015, Comorbidities in neurology: is adenosine the common link?, Neuropharmacology., 97, 18, 10.1016/j.gde.2016.03.011

Pekny, 2016, Astrocytes: a central element in neurological diseases, Acta Neuropathol., 131, 323, 10.1007/s00401-015-1513-1

Binder, 2018, Astrocytes: stars of the sacred disease, Epilepsy Curr., 18, 172, 10.5698/1535-7597.18.3.172

Eid, 2004, Loss of glutamine synthetase in the human epileptogenic hippocampus : possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy, Lancet., 363, 28, 10.1016/s0140-6736(03)15166-5

Gouder, 2004, Overexpression of adenosine kinase in epileptic hippocampus contributes to epileptogenesis, J Neurosci., 24, 692, 10.1523/JNEUROSCI.4781-03.2004

Aronica, 2012, Upregulation of adenosine kinase in astrocytes in experimental and human temporal lobe epilepsy, Epilepsia., 52, 1645, 10.1111/j.1528-1167.2011.03115.x

Amiry-Moghaddam, 2003, Delayed K+ clearance associated with aquaporin-4 mislocalization : phenotypic defects in brains of alfa-syntrophin-null mice, Proc Natl Acad Sci USA., 100, 13615, 10.1073/pnas.2336064100

Binder, 2012, Aquaporin-4 and epilepsy, Glia., 1214, 1203, 10.1002/glia.22317

Bordey, 1998, Properties of human glial cells associated with epileptic seizure foci, Epilepsy Res, 32, 286, 10.1016/S0920-1211(98)00059-X

Heuser, 2012, Loss of perivascular kir4.1 potassium channels in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy, J Neuropathol Exp Neurol., 71, 814, 10.1097/NEN.0b013e318267b5af

Lauritzen, 2012, Redistribution of monocarboxylate transporter 2 on the surface of astrocytes in the human epileptogenic hippocampus, Gila, 1181, 1172, 10.1002/glia.22344

Lauritzen, 2012, Neurobiology of disease altered expression of brain monocarboxylate transporter 1 in models of temporal lobe epilepsy, Neurobiol Dis., 45, 165, 10.1016/j.nbd.2011.08.001

Escartin, 2007, Activation of astrocytes by CNTF induces metabolic plasticity and increases resistance to metabolic insults, J Neurosci., 27, 7094, 10.1523/JNEUROSCI.0174-07.2007

Gavillet, 2008, Modulation of astrocytic metabolic phenotype by proinflammatory cytokines, Glia., 56, 975, 10.1002/glia.20671

Valenza, 2010, Cholesterol defect is marked across multiple rodent models of huntington's disease and is manifest in astrocytes, J Neurosci., 30, 10844, 10.1523/JNEUROSCI.0917-10.2010

Rossi, 2009, Astrocytic dysfunction: Insights on the role in neurodegeneration, Brain Res Bull., 80, 224, 10.1016/j.brainresbull.2009.07.012

Escartin, 2013, Astroglial networking contributes to neurometabolic coupling, Front Neuroenergetics., 5, 4, 10.3389/fnene.2013.00004

Pannasch, 2013, Emerging role for astroglial networks in information processing: from synapse to behavior, Trends Neurosci., 36, 405, 10.1016/j.tins.2013.04.004

Escartin, 2006, Ciliary neurotrophic factor activates astrocytes, redistributes their glutamate transporters GLAST and GLT-1 to raft microdomains, and improves glutamate handling in vivo, J Neurosci, 26, 5978, 10.1523/JNEUROSCI.0302-06.2006

Sheldon, 2007, The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention, Neurochem Int., 51, 333, 10.1016/j.neuint.2007.03.012

Tian, 2005, An astrocytic basis of epilepsy, Nat Med., 11, 973, 10.1038/nm1277

Sofroniew, 2010, Molecular dissection of reactive astrogliosis and glial scar formation, Trends Neurosci., 32, 638, 10.1016/j.tins.2009.08.002.Molecular

Liddelow, 2017, Reactive astrocytes: production, function, and therapeutic potential, Immunity., 46, 957, 10.1016/j.immuni.2017.06.006

Jha, 2019, Microglia-astrocyte crosstalk: an intimate molecular conversation, Neuroscientist., 25, 227, 10.1177/1073858418783959

Domingues, 2016, Oligodendrocyte, astrocyte, and microglia crosstalk in myelin development, damage, and repair, Front Cell Dev Biol., 4, 71, 10.3389/fcell.2016.00071

Vainchtein, 2020, Astrocytes and microglia: in sickness and in health, Trends Neurosci., 43, 144, 10.1016/j.tins.2020.01.003

Burda, 2017, Seducing astrocytes to the dark side, Cell Res., 27, 726, 10.1038/cr.2017.37

Liddelow, 2017, Neurotoxic reactive astrocytes are induced by activated microglia, Nature., 541, 481, 10.1038/nature21029

Heiss, 2019, The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system, J Neuroendocrinol., 31, 1, 10.1111/jne.12684

Ma, 2019, Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis, J Neuroinflamm., 16, 1, 10.1186/s12974-019-1434-3

Wikoff, 2009, Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites, Proc Natl Acad Sci USA., 106, 3698, 10.1073/pnas.0812874106

Zhang, 2018, Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice, J Neuroinflamm., 15, 1, 10.1186/s12974-017-1052-x

Bélanger, 2011, Brain energy metabolism : focus on astrocyte-neuron metabolic cooperation, Cell Metab., 14, 724, 10.1016/j.cmet.2011.08.016

Brown, 2007, Astrocyte glycogen and brain energy metabolism, Glia., 1271, 1263, 10.1002/glia.20557

Suh, 2007, Astrocyte glycogen sustains neuronal activity during hypoglycemia: studies with the glycogen phosphorylase inhibitor CP-316,819 ([R-R*,S*]-5-Chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmethyl)propyl]-1H-indole-2-carboxamide), J Pharmacol Exp Ther., 321, 45, 10.1124/jpet.106.115550

Pellerin, 2005, Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain, J Neurosci Res., 64, 55, 10.1002/jnr.20307

Phelps, 1972, Barbiturate-induced glycogen accumulation in brain, an electron microscopic study. Brain Res., 39, 225, 10.1016/0006-8993(72)90797-4

Pfeiffer-Guglielmi, 2003, Immunocytochemical localization of glycogen phosphorylase isozymes in rat nervous tissues by using isozyme-specific antibodies, J Neurochem., 85, 73, 10.1046/j.1471-4159.2003.01644.x

Schwartz, 2007, Neurovascular coupling and epilepsy: hemodynamic markers for localizing and predicting seizure onset, Epilepsy Curr., 7, 91, 10.1111/j.1535-7511.2007.00183.x

Wong, 2009, Astrocyte networks and epilepsy: when stars collide, Curr Lit Basic Sci., 9, 113, 10.1111/j.1535-7511.2009.01310.x

Greene, 2003, Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies, J Neurochem., 86, 529, 10.1046/j.1471-4159.2003.01862.x

Henderson, 2006, Efficacy of the ketogenic diet as a treatment option for epilepsy : meta-analysis, J Child Neurol., 21, 193, 10.2310/7010.2006.00044

Kossoff, 2009, Ketogenic diets : evidence for short- and long-term efficacy, Am Soc Exp Neurother., 6, 406, 10.1016/j.nurt.2009.01.005

Rho, 2017, How does the ketogenic diet induce anti-seizure effects?, Neurosci Lett., 637, 4, 10.1016/j.neulet.2015.07.034

Kossoff, 2008, The modified atkins diet, Epilepsia., 49, 37, 10.1111/j.1528-1167.2008.01831.x

Pfeifer, 2008, Low glycemic index treatment : implementation and new insights into efficacy, Epilepsia., 49, 42, 10.1111/j.1528-1167.2008.01832.x

Guzel, 2019, Efficacy and tolerability of olive oil-based ketogenic diet in children with drug-resistant epilepsy: a single center experience from Turkey, Eur J Paediatr Neurol., 23, 143, 10.1016/j.ejpn.2018.11.007

Masino, 2019, Metabolism and epilepsy: ketogenic diets as a homeostatic link, Brain Res., 1703, 26, 10.1016/j.brainres.2018.05.049

Liu, 2018, Ketogenic diet for treatment of intractable epilepsy in adults: a meta-analysis of observational studies, Epilepsia Open., 3, 9, 10.1002/epi4.12098

Garriga-Canut, 2006, 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP–dependent metabolic regulation of chromatin structure, Nat Neurosci., 9, 1382, 10.1038/nn1791

Stafstrom, 2009, Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models, Ann Neurol., 65, 435, 10.1002/ana.21603

Ockuly, 2012, Behavioral, cognitive, and safety profile of 2-deoxy-2-glucose (2DG) in adult rats, Epilepsy Res., 101, 246, 10.1016/j.eplepsyres.2012.04.012

Sada, 2015, Targeting LDH enzymes with a stiripentol analog to treat epilepsy, Science., 347, 1362, 10.1126/science.aaa1299

Rouach, 2008, Astroglial metabolic networks sustain hippocampal synaptic transmission, Science., 322, 1551, 10.1126/science.1164022

Dermietzel, 1993, Gap jundions in the brain: where, what type, how many and why?, TINS, 16, 186

Dermietzel, 2000, Connexin43 null mice reveal that astrocytes express multiple connexins, Brain Res Rev., 32, 45, 10.1016/s0165-0173(99)00067-3

Parpura, 2012, Homeostatic function of astrocytes: Ca2+ and Na+ signalling, Transl Neurosci., 3, 334, 10.2478/s13380-012-0040-y

Stout, 2002, Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels, J Biol Chem., 277, 10482, 10.1074/jbc.M109902200

Strohschein, 2011, Impact of aquaporin-4 channels on K+ buffering and gap junction coupling in the hippocampus, Glia., 980, 973, 10.1002/glia.21169

Wallraff, 2006, The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus, J Neurosci., 26, 5438, 10.1523/JNEUROSCI.0037-06.2006

Huguet, 2016, Neuroprotective role of gap junctions in a neuron astrocyte network model, Biophys J., 111, 452, 10.1016/j.bpj.2016.05.051

Mu, 2015, Astrocyte uncoupling as a cause of human temporal lobe epilepsy, Brain., 138, 1208, 10.1093/brain/awv067

Crunelli, 2015, Novel astrocyte targets : new avenues for the therapeutic treatment of epilepsy, Neurosci., 21, 62, 10.1177/1073858414523320

Li, 2019, Targeting gap junction in epilepsy: perspectives and challenges, Biomed Pharmacother., 109, 57, 10.1016/j.biopha.2018.10.068

Deshpande, 2017, Subcellular reorganization and altered phosphorylation of the astrocytic gap junction protein connexin43 in human and experimental temporal lobe epilepsy, Glia., 65, 1809, 10.1002/glia.23196

Losi, 2010, An excitatory loop with astrocytes contributes to drive neurons to seizure threshold, PLoS Biol., 8, e1000352, 10.1371/journal.pbio.1000352

Jacobson, 2010, Connexin36 knockout mice display increased sensitivity to pentylenetetrazol-induced seizure-like behaviors, Brain Res., 1360, 198, 10.1016/j.brainres.2010.09.006

Curti, 2012, Synergy between electrical coupling and membrane properties promotes strong synchronization of neurons of the mesencephalic trigeminal nucleus, J Neurosci., 32, 4341, 10.1523/JNEUROSCI.6216-11.2012

Hosseinzadeh, 2003, Anticonvulsant, sedative and muscle relaxant effects of carbenoxolone in mice, BMC Pharmacol., 3, 3, 10.1186/1471-2210-3-3

Ventura-Mejía, 2014, Decreased fast ripples in the hippocampus of rats with spontaneous recurrent seizures treated with carbenoxolone and quinine, Biomed Res Int., 2014, 282490, 10.1155/2014/282490

Ran, 2018, Effects of gap junctions blockers on fast ripples and connexin in rat hippocampi after status epilepticus, Epilepsy Res., 146, 28, 10.1016/j.eplepsyres.2018.07.010

Franco-Pérez, 2015, Anticonvulsant effects of mefloquine on generalized tonic-clonic seizures induced by two acute models in rats, BMC Neurosci., 16, 7, 10.1186/s12868-015-0145-7

Nassiri-Asl, 2009, Antiepileptic effects of quinine in the pentylenetetrazole model of seizure, Seizure., 18, 129, 10.1016/j.seizure.2008.08.002

Manjarrez-Marmolejo, 2016, Gap Junction blockers : an overview of their effects on induced seizures in animal models, Curr Neuropharmacol., 14, 759, 10.2174/1570159X14666160603115

Venance, 1995, Inhibition by anandamide of gap junctions and intercellular calcium signalling in striatal astrocytes, Nature., 376, 590, 10.1038/376590a0

Guan, 1997, The sleep-inducing lipid oleamide deconvolutes gap junction communication and calcium wave transmission in glial cells, J Cell Biol., 139, 1785, 10.1083/jcb.139.7.1785

Lambert, 2001, Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice, Epilepsia., 42, 321, 10.1046/j.1528-1157.2001.41499.x

Wallace, 2002, Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity, Eur J Pharmacol., 452, 295, 10.1016/S0014-2999(02)02331-2

Wu, 2003, Selective effect of oleamide, an endogenous sleepinducing lipid amide, on pentylenetetrazole-induced seizures in mice, J Pharm Pharmacol., 55, 1159, 10.1211/0022357021431

Solomonia, 2008, Effect of oleamide on pentylenetetrazole-induced seizures in rats, Bull Exp Biol Med., 145, 225, 10.1007/s10517-008-0056-z

Parpura, 1994, Glutamate-mediated astrocyte-neuron signalling, Nature., 369, 744, 10.1038/369744a0

Angulo, 2004, Glutamate released from glial cells synchronizes neuronal activity in the hippocampus, J Neurosci., 24, 6920, 10.1523/JNEUROSCI.0473-04.2004

Fellin, 2004, Neurone-to-astrocyte signalling in the brain represents a distinct multifunctional unit, J Physiol., 559, 3, 10.1113/jphysiol.2004.063214

Schell, 1997, D-serine as a neuromodulator: regional and developmental localizations in rat brain glia resemble NMDA receptors, J Neurosci., 17, 1604, 10.1523/jneurosci.17-05-01604.1997

Beltrán-Castillo, 2017, D-serine released by astrocytes in brainstem regulates breathing response to CO2 levels, Nat Commun., 8, 838, 10.1038/s41467-017-00960-3

Barakat, 2002, GAT-1 and reversible GABA transport in bergmann glia in slices, J Neurophysiol., 88, 1407, 10.1152/jn.2002.88.3.1407

Jiménez-González, 2011, Non-neuronal, slow GABA signalling in the ventrobasal thalamus targets δ-subunit-containing GABAA receptors, Eur J Neurosci., 33, 1471, 10.1111/j.1460-9568.2011.07645.x

Yoon, 2014, GABA as a rising gliotransmitter, Front Neural Circuits., 8, 141, 10.3389/fncir.2014.00141

Eulenburg, 2010, Neurotransmitter transporters expressed in glial cells as regulators of synapse function, Brain Res Rev., 63, 103, 10.1016/j.brainresrev.2010.01.003

Bardóczi, 2017, Glycinergic input to the mouse basal forebrain cholinergic neurons, J Neurosci., 37, 9534, 10.1523/JNEUROSCI.3348-16.2017

Shibasaki, 2017, Glycine release from astrocytes via functional reversal of GlyT1, J Neurochem., 140, 395, 10.1111/jnc.13741

Newman, 2003, Glial cell inhibition of neurons by release of ATP, J Neurosci., 23, 1659, 10.1523/jneurosci.23-05-01659.2003

Zhang, 2003, ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression, Neuron., 40, 971, 10.1016/S0896-6273(03)00717-7

Gordon, 2005, Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy, Nat Neurosci., 8, 1078, 10.1038/nn1498

Pellerin, 1994, Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization, Proc Natl Acad Sci USA., 91, 10625, 10.1073/pnas.91.22.10625

Tang, 2014, Lactate-mediated glia-neuronal signalling in the mammalian brain, Nat Commun., 5, 3284, 10.1038/ncomms4284

DiNuzzo, 2016, Astrocyte-neuron interactions during learning may occur by lactate signaling rather than metabolism, Front Integr Neurosci., 10, 2, 10.3389/fnint.2016.00002

Kimelberg, 1990, Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures, J Neurosci., 10, 1583, 10.1523/jneurosci.10-05-01583.1990

Choe, 2012, Taurine release by astrocytes modulates osmosensitive glycine receptor tone and excitability in the adult supraoptic nucleus, J Neurosci., 32, 12518, 10.1523/JNEUROSCI.1380-12.2012

Do, 1997, β-Adrenergic stimulation promotes homocysteic acid release from astrocyte cultures: evidence for a role of astrocytes in the modulation of synaptic transmission, J Neurochem., 68, 2386, 10.1046/j.1471-4159.1997.68062386.x

Benz, 2004, Glutamate-induced homocysteic acid release from astrocytes: Possible implication in glia-neuron signaling, Neuroscience., 124, 377, 10.1016/j.neuroscience.2003.08.067

Krzan, 2003, Calcium-dependent exocytosis of atrial natriuretic peptide from astrocytes, J Neurosci., 23, 1580, 10.1523/jneurosci.23-05-01580.2003

Desai, 1999, BDNF regulates the intrinsic excitability of cortical neurons, Learn Mem., 6, 284, 10.1101/lm.6.3.284

Jean, 2008, Glutamate elicits release of BDNF from basal forebrain astrocytes in a process dependent on metabotropic receptors and the PLC pathway, Neuron Glia Biol., 4, 35, 10.1017/S1740925X09000052

Dani, 1992, Neuronal activity triggers calcium waves in hippocampal astrocyte networks, Neuron., 8, 429, 10.1016/0896-6273(92)90271-e

Porter, 1996, Hippocampal astrocytes in situ respond to glutamate released from synaptic terminals, J Neurosci., 16, 5073, 10.1523/JNEUROSCI.16-16-05073.1996

Pasti, 1997, Intracellular calcium oscillations in astrocytes: A highly plastic, bidirectional form of communication between neurons and astrocytes in situ, J Neurosci, 17, 7817, 10.1523/jneurosci.17-20-07817.1997

Wang, 2006, Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo, Nat Neurosci, 9, 816, 10.1038/nn1703

Takata, 2008, Cortical layer 1 and layer 2/3 astrocytes exhibit distinct calcium dynamics in vivo, PLoS ONE, 3, e2525, 10.1371/journal.pone.0002525

Perea, 2009, Tripartite synapses: astrocytes process and control synaptic information, Trends Neurosci., 32, 421, 10.1016/j.tins.2009.05.001

Nimmerjahn, 2004, Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo, Nat Methods, 1, 31, 10.1038/nmeth706

Hoogland, 2009, Radially expanding transglial calcium waves in the intact cerebellum, Proc Natl Acad Sci USA., 106, 3496, 10.1073/pnas.0809269106

Kuga, 2011, Large-scale calcium waves traveling through astrocytic networks in vivo, J Neurosci, 31, 2607, 10.1523/JNEUROSCI.5319-10.2011

Savtchouk, 2018, Gliotransmission: beyond black and white, J Neurosci., 38, 14, 10.1523/JNEUROSCI.0017-17.2017

Fiacco, 2018, Multiple lines of evidence indicate that gliotransmission does not occur under physiological conditions, J Neurosci., 38, 3, 10.1523/JNEUROSCI.0016-17.2017

Hubbard, 2010, Astrocytes and epilepsy, Neurotherapeutics, 7, 424, 10.1016/j.nurt.2010.08.002

Volterra, 2014, Astrocyte Ca2+ signalling: an unexpected complexity, Nat Neurosci., 15, 327, 10.1038/nrn3725

Araque, 1999, Tripartite synapses: glia, the unacknowledged partner, Trends Neurosci., 22, 208, 10.1016/S0166-2236(98)01349-6

Santello, 2012, Synaptic plasticity: dynamics, development and disease, Advances in Experimental Medicine and Biology., p. 945

Arizono, 2020, Structural basis of astrocytic Ca2+ signals at tripartite synapses, Nat Commun., 11, 1906, 10.1038/s41467-020-15648-4

Lorenzo, 2020, Spatiotemporal model of tripartite synapse with perinodal astrocytic process, J Comput Neurosci., 48, 1, 10.1007/s10827-019-00734-4

Halassa, 2007, The tripartite synapse: roles for gliotransmission in health and disease, Trends Mol Med., 13, 54, 10.1016/j.molmed.2006.12.005

Jourdain, 2007, Glutamate exocytosis from astrocytes controls synaptic strength, Nat Neurosci., 10, 331, 10.1038/nn1849

Woo, 2012, TREK-1 and best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation, Cell., 151, 25, 10.1016/j.cell.2012.09.005

Park, 2013, High glutamate permeability and distal localization of Best1 channel in CA1 hippocampal astrocyte, Mol Brain., 6, 1, 10.1186/1756-6606-6-54

Yang, 2003, Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine, Proc Natl Acad Sci USA., 100, 15194, 10.1073/pnas.2431073100

Mothet, 2005, Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine, Proc Natl Acad Sci USA., 102, 5606, 10.1073/pnas.0408483102

Martineau, 2013, Storage and uptake of D-serine into astrocytic synaptic-like vesicles specify gliotransmission, J Neurosci., 33, 3413, 10.1523/JNEUROSCI.3497-12.2013

Pascual, 2005, Astrocytic purinergic signaling coordinates synaptic networks, Science., 310, 113, 10.1126/science.1116916

Lalo, 2014, Exocytosis of ATP from astrocytes modulates phasic and tonic inhibition in the neocortex, PLoS Biol., 12, e1001747, 10.1371/journal.pbio.1001747

Bazargani, 2016, Astrocyte calcium signaling : the third wave, Nat Neurosci, 19, 182, 10.1038/nn.4201

Xiong, 2018, Ca2+-Dependent and Ca2+-independent ATP release in astrocytes, Front Mol Neurosci., 11, 224, 10.3389/fnmol.2018.00224

Heinrich, 2012, K+ depolarization evokes ATP, adenosine and glutamate release from glia in rat hippocampus: a microelectrode biosensor study, Br J Pharmacol., 167, 1003, 10.1111/j.1476-5381.2012.01932.x

Orellana, 2011, ATP and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels, J Neurochem., 118, 826, 10.1111/j.1471-4159.2011.07210.x

Stehberg, 2012, Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala, FASEB J., 26, 3649, 10.1096/fj.11-198416

Szatkowski, 1990, Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake, Nature., 348, 443, 10.1038/348443a0

Rossi, 2000, Glutamate release in severe brain ischaemia is mainly by reversed uptake, Nature., 403, 316, 10.1038/35002090

Abudara, 2018, Synaptic functions of hemichannels and pannexons: A double-edged sword, Front Mol Neurosci., 11, 435, 10.3389/fnmol.2018.00435

Warr, 1999, Modulation of extracellular glutamate concentration in rat brain slices by cystine-glutamate exchange, J Physiol., 514, 783, 10.1111/j.1469-7793.1999.783ad.x

Bridges, 2012, System x c- cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS, Br J Pharmacol., 165, 20, 10.1111/j.1476-5381.2011.01480.x

Duan, 2003, P2X 7 receptor-mediated release of excitatory amino acids from astrocytes, J Neurosci., 23, 1320, 10.1523/JNEUROSCI.23-04-01320.2003

Iglesias, 2009, Pannexin 1: the molecular substrate of astrocyte “hemichannels.”, J Neurosci, 29, 7092, 10.1523/JNEUROSCI.6062-08.2009

Kang, 2008, Connexin 43 hemichannels are permeable to ATP, J Neurosci., 28, 4702, 10.1523/JNEUROSCI.5048-07.2008

Suadicani, 2006, P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling, J Neurosci., 26, 1378, 10.1523/JNEUROSCI.3902-05.2006

Xiong, 2018, Stretch-induced Ca2+ independent ATP release in hippocampal astrocytes, J Physiol., 596, 1931, 10.1113/JP275805

Mylvaganam, 2010, Hippocampal seizures alter the expression of the pannexin and connexin transcriptome, J Neurochem., 112, 92, 10.1111/j.1471-4159.2009.06431.x

Jiang, 2013, Altered expression of pannexin proteins in patients with temporal lobe epilepsy, Mol Med Rep., 8, 1801, 10.3892/mmr.2013.1739

Jimenez-Pacheco, 2013, Increased neocortical expression of the P2X7 receptor after status epilepticus and anticonvulsant effect of P2X7 receptor antagonist A-438079, Epilepsia., 54, 1551, 10.1111/epi.12257

Grygorowicz, 2016, Early P2X7R-related astrogliosis in autoimmune encephalomyelitis, Mol Cell Neurosci., 74, 1, 10.1016/j.mcn.2016.02.003

Evanko, 2004, Defining pathways of loss and secretion of chemical messengers from astrocytes, Glia., 47, 233, 10.1002/glia.20050

Retamal, 2007, Cx43 hemichannels and gap junction channels in astrocytes are regulated oppositely by proinflammatory cytokines released from activated microglia, J Neurosci., 27, 13781, 10.1523/JNEUROSCI.2042-07.2007

Bennet, 2012, Connexin and pannexin hemichannels in inflammatory responses of glia and neurons, Brain Res., 3, 3, 10.1161/CIRCULATIONAHA.110.956839

Orellana, 2012, Glial hemichannels and their involvement in aging and neurodegenerative diseases, Rev Neurosci., 23, 163, 10.1515/revneuro-2011-0065

Medina-Ceja, 2019, Connexins-based hemichannels/channels and their relationship with inflammation, seizures and epilepsy, Int J Mol Sci., 20, 1, 10.3390/ijms20235976

Santiago, 2011, Targeting pannexin1 improves seizure outcome, PLoS ONE., 6, e25178, 10.1371/journal.pone.0025178

Dossi, 2018, Pannexin-1 channels contribute to seizure generation in human epileptic brain tissue and in a mouse model of epilepsy, Sci Transl Med., 10, 1, 10.1126/scitranslmed.aar3796

Engel, 2012, Seizure suppression and neuroprotection by targeting the purinergic P2X7 receptor during status epilepticus in mice, FASEB J., 26, 1616, 10.1096/fj.11-196089

Amhaoul, 2016, P2X7 receptor antagonism reduces the severity of spontaneous seizures in a chronic model of temporal lobe epilepsy, Neuropharmacology., 105, 175, 10.1016/j.neuropharm.2016.01.018

Lord, 2014, Pharmacology of a novel central nervous system-penetrant P2X7 antagonist JNJ-42253432, J Pharmacol Exp Ther., 351, 628, 10.1124/jpet.114.218487

Engel, 2016, ATPergic signalling during seizures and epilepsy, Neuropharmacology., 104, 140, 10.1016/j.neuropharm.2015.11.001

Fischer, 2016, Critical evaluation of P2X7 receptor antagonists in selected seizure models, PLoS ONE., 11, e0156468, 10.1371/journal.pone.0156468

Riquelme, 2020, Gliotransmission: a novel target for the development of antiseizure drugs, Neuroscientist., 26, 293, 10.1177/1073858420901474

Choi, 1994, Glutamate receptors and the induction of excitotoxic neuronal death, Prog Brain Res., 100, 47, 10.1016/S0079-6123(08)60767-0

Perez, 2012, Evidence for astrocytes as a potential source of the glutamate excess in temporal lobe epilepsy, Neurobiol Dis., 47, 331, 10.1016/j.nbd.2012.05.010

Syková, 2008, Diffusion in brain extracellular space, Physiol Rev., 88, 1277, 10.1152/physrev.00027.2007

Sosunov, 2014, Phenotypic heterogeneity and plasticity of isocortical and hippocampal astrocytes in the human brain, J Neurosci., 34, 2285, 10.1523/JNEUROSCI.4037-13.2014

Zielinska, 2016, System N transporters are critical for glutamine release and modulate metabolic fluxes of glucose and acetate in cultured cortical astrocytes: changes induced by ammonia, J Neurochem., 136, 329, 10.1111/jnc.13376

Parpura, 2014, Glutamate and ATP at the interface of metabolism and signaling in the brain, Adv Neurobiol., 11, 11, 10.1007/978-3-319-08894-5

Cavus, 2005, Extracellular metabolites in the cortex and hippocampus of epileptic patients, Ann Neurol., 57, 226, 10.1002/ana.20380

Cavus, 2008, Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients, Epilepsia., 49, 1358, 10.1111/j.1528-1167.2008.01603.x

Ueda, 2001, Collapse of extracellular glutamate regulation during epileptogenesis: down-regulation and functional failure of glutamate transporter function in rats with chronic seizures induced by kainic acid, J Neurochem., 76, 892, 10.1046/j.1471-4159.2001.00087.x

Gorter, 2002, Glutamate transporters alterations in the reorganizing dentate gyrus are associated with progressive seizure activity in chronic epileptic rats, J Comp Neurol., 442, 365, 10.1002/cne.10101

Lopes, 2013, Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy, Exp Brain Res., 226, 153, 10.1007/s00221-013-3421-8

Samuelsson, 2000, Decreased cortical levels of astrocytic glutamate transport protein GLT- 1 in a rat model of posttraumatic epilepsy, Neurosci Lett., 289, 185, 10.1016/S0304-3940(00)01284-2

Watanabe, 1999, Amygdala-kindled and pentylenetetrazole-induced seizures in glutamate transporter GLAST-deficient mice, Brain Res., 845, 92, 10.1016/S0006-8993(99)01945-9

Tanaka, 1997, Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1, Science., 276, 1699, 10.1126/science.276.5319.1699

Sepkuty, 2002, A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy, J Neurosci., 22, 6372, 10.1523/JNEUROSCI.22-15-06372.2002

Sarac, 2009, Excitatory amino acid transporters EAAT-1 and EAAT-2 in temporal lobe and hippocampus in intractable temporal lobe epilepsy, APMIS., 291, 10.1111/j.1600-0463.2009.02443.x

Zeng, 2010, Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of tuberous sclerosis complex, Neurobiol Dis., 37, 764, 10.1016/j.nbd.2009.12.020

Susarla, 2008, Internalization and degradation of the glutamate transporter GLT-1 in response to phorbol ester, Neurochem Int., 52, 709, 10.1016/j.neuint.2007.08.020

Sha, 2017, Pharmacologic inhibition of Hsp90 to prevent GLT-1 degradation as an effective therapy for epilepsy, J Exp Med., 214, 547, 10.1084/jem.20160667

Eid, 2004, Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy, Lancet., 363, 28, 10.1016/S0140-6736(03)15166-5

Van Der Hel, 2005, Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy, Neurology., 64, 326, 10.1212/01.WNL.0000149636.44660.99

Ortinski, 2010, Selective induction of astrocytic gliosis generates deficits in neuronal inhibition, Nat Publ Gr., 13, 584, 10.1038/nn.2535

Zou, 2010, Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons, Neurochem Int., 56, 577, 10.1016/j.neuint.2009.12.021

Eid, 2019, Astrocytes and glutamine synthetase in epileptogenesis, J Neurosci Res., 97, 1345, 10.1002/jnr.24267

Khazipov, 2016, GABAergic synchronization in epilepsy, Cold Spring Harb Perspect Med., 6, 1, 10.1101/cshperspect.a022764

Navazio, 1961, Relationship of ammonia intoxication to convulsions and coma in rats, J Neurochem., 8, 146, 10.1111/j.1471-4159.1961.tb13536.x

Papageorgiou, 2018, Astrocytic glutamine synthetase is expressed in the neuronal somatic layers and down-regulated proportionally to neuronal loss in the human epileptic hippocampus, Glia., 66, 920, 10.1002/glia.23292

Kritis, 2015, Researching glutamate – induced cytotoxicity in different cell lines: a comparative/collective analysis/study, Front Cell Neurosci., 9, 91, 10.3389/fncel.2015.00091

Robel, 2015, Reactive astrogliosis causes the development of spontaneous seizures, J Neurosci., 35, 3330, 10.1523/JNEUROSCI.1574-14.2015

Martineau, 2014, Cell-type specific mechanisms of D-serine uptake and release in the brain, Front Synaptic Neurosci., 6, 12, 10.3389/fnsyn.2014.00012

Scianni, 2013, Fractalkine (CX3CL1) enhances hippocampal N-methyl-d-aspartate receptor (NMDAR) function via d-serine and adenosine receptor type A2 (A2AR) activity, J Neuroinflamm., 10, 1, 10.1186/1742-2094-10-108

Martineau, 2008, Confocal imaging and tracking of the exocytotic routes for D-serine-mediated gliotransmission, Glia, 56, 1271, 10.1002/glia.20696

Zhuang, 2010, EphrinBs regulate D-serine synthesis and release in astrocytes, J Neurosci., 30, 16015, 10.1523/JNEUROSCI.0481-10.2010

Schell, 1995, D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release, Proc Natl Acad Sci USA., 92, 3948, 10.1073/pnas.92.9.3948

Diniz, 2012, Astrocyte-induced synaptogenesis is mediated by transforming growth factor β signaling through modulation of d-serine levels in cerebral cortex neurons, J Biol Chem., 287, 41432, 10.1074/jbc.M112.380824

Takata, 2011, Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo, J Neurosci, 31, 18155, 10.1523/JNEUROSCI.5289-11.2011

López-Hidalgo, 2012, Nicotine uses neuron-glia communication to enhance hippocampal synaptic transmission and long-term memory, PLoS ONE., 7, e49998, 10.1371/journal.pone.0049998

Wolosker, 2016, The rise and fall of the D-serine-mediated gliotransmission hypothesis, Trends Neurosci., 39, 712, 10.1016/j.tins.2016.09.007

Ehmsen, 2013, D-serine in glia and neurons derives from 3-phosphoglycerate dehydrogenase, J Neurosci., 33, 12464, 10.1523/JNEUROSCI.4914-12.2013

Wolosker, 2013, The serine shuttle between glia and neurons: implications for neurotransmission and neurodegeneration, Biochem Soc Trans., 41, 1546, 10.1042/BST20130220

Perez, 2017, Enhanced astrocytic d-serine underlies synaptic damage after traumatic brain injury, J Clin Invest., 127, 3114, 10.1172/JCI92300

Ma, 2019, D-Serine contributes to seizure development via ERK signaling, Front Neurosci., 13, 254, 10.3389/fnins.2019.00254

Losi, 2012, The role of astroglia in the epileptic brain, Front Pharmacol., 3, 132, 10.3389/fphar.2012.00132

Wang, 2002, Activation of P2x7 receptors induced [3H]GABA release from the RBA-2 type-2 astrocyte cell line through a Cl-/HCO3- - dependent mechanism, Glia., 37, 8, 10.1002/glia.10004

Torres, 2012, Extracellular Ca2+ acts as a mediator of communication from neurons to glia, Sci Signal., 5, ra28, 10.1126/scisignal.2002160

Kumaria, 2008, ATP signalling in epilepsy, Purinergic Signal., 4, 339, 10.1007/s11302-008-9115-1

Gordon, 2009, Astrocyte-mediated distributed plasticity at hypothalamic glutamate synapses, Neuron., 64, 391, 10.1016/j.neuron.2009.10.021

Scemes, 2019, Astrocyte and neuronal pannexin1 contribute distinctly to seizures, ASN Neuro., 11, 1, 10.1177/1759091419833502

Aquilino, 2019, Pannexin-1 channels in epilepsy, Neurosci Lett., 695, 71, 10.1016/j.neulet.2017.09.004

Rudolphi, 1997, Modulation of neuronal and glial cell function by adenosine and neuroprotection in vascular dementia, Behav Brain Res., 83, 123, 10.1016/s0166-4328(97)86055-x

Calker, 2005, The role of glial adenosine receptors in neural resilience and the neurobiology of mood disorders, Neurochem Res., 30, 1205, 10.1007/s11064-005-8792-1

Boison, 2008, Astrogliosis and adenosine kinase: a glial basis of epilepsy, Futur Neurol., 3, 221, 10.2217/14796708.3.3.221

Boison, 2016, Adenosinergic signaling in epilepsy, Neuropharmacology., 104, 131, 10.1016/j.neuropharm.2015.08.046

Lopes, 1999, Cross talk between A 1 and A 2A adenosine receptors in the hippocampus and cortex of young adult and old rats, J Neurophysiol., 82, 3196, 10.1152/jn.1999.82.6.3196

Ciruela, 2006, Presynaptic control of striatal glutamatergic neurotransmission by adenosine A 1 – A 2A receptor heteromers, J Neurosci., 26, 2080, 10.1523/JNEUROSCI.3574-05.2006

Glass, 1996, Loss of A1 adenosine receptors in human temporal lobe epilepsy, Brain Res., 710, 56, 10.1016/0006-8993(95)01313-x

Ekonomou, 2000, Reduction of A1 adenosine receptors in rat hippocampus after kainic acid-induced limbic seizures, Neurosci Lett., 284, 49, 10.1016/s0304-3940(00)00954-x

Barros-Barbosa, 2016, Adenosine A2A receptor and ecto-5′-nucleotidase-CD73 are upregulated in hippocampal astrocytes of human MTLE, Purinergic Signal., 12, 719, 10.1007/s11302-016-9535-2

Hindley, 1994, Stimulation of reactive astrogliosis in vivo by extracellular adenosine diphosphate or an adenosine A2 receptor agonist, J Neurosci Res., 38, 399, 10.1002/jnr.490380405

Popoli, 2007, Functions, dysfunctions and possible therapeutic relevance of adenosine A 2A receptors in Huntington' s disease, Prog Neurobiol., 81, 331, 10.1016/j.pneurobio.2006.12.005

Ribeiro, 2007, Influence of age on BDNF modulation of hippocampal synaptic transmission : interplay with adenosine A 2A receptors, Hippocampus., 17, 577, 10.1002/hipo

Ke, 2009, Adenosine A2a receptor induced gliosis via Akt/NF-kB pathway in vitro, Neurosci Res., 65, 280, 10.1016/j.neures.2009.08.002

Erion, 1998, Design, synthesis and anticonvulsant activity of the potent adenosine kinase inhibitor GP3269, Nucleic Acids., 16, 1013, 10.1080/07328319708006124

Ugarkar, 2000, Adenosine kinase inhibitors. 1. Synthesis, enzyme inhibition, and antiseizure activity of 5-iodotubercidin analogues, J Med Chem., 43, 2883, 10.1021/jm000024g

Ugarkar, 2000, Adenosine kinase inhibitors. 2. Synthesis, enzyme inhibition, and antiseizure activity of diaryltubercidin analogues, J Med Chem., 43, 2894, 10.1021/jm0000259

Zhang, 1993, Manipulation of endogenous adenosine in the rat prepiriform cortex modulates seizure susceptibility, J Pharmacol Exp Ther., 264, 1415

McGaraughty, 2005, Anticonvulsant and antinociceptive actions of novel adenosine kinase inhibitors, Curr Top Med Chem., 5, 43, 10.2174/1568026053386845

Köse, 2016, Focused screening to identify new adenosine kinase inhibitors, Bioorganic Med Chem., 24, 5127, 10.1016/j.bmc.2016.08.026

Arciénega, 2010, Cell locations for AQP1, AQP4 and 9 in the non-human primate brain, Neuroscience., 167, 1103, 10.1016/j.neuroscience.2010.02.059

Eid, 2005, Loss of perivascular aquaporin 4 may underlie deficient water and K+ homeostasis in the human epileptogenic hippocampus, Proc Natl Acad Sci USA., 102, 1193, 10.1073/pnas.0409308102

Sheilabi, 2017, Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy, Eur J Neurosci., 46, 2121, 10.1111/ejn.13652

Lee, 2004, Aquaporin-4 is increased in the sclerotic hippocampus in human temporal lobe epilepsy, Acta Neuropathol., 108, 493, 10.1007/s00401-004-0910-7

Binder, 2006, Functional changes in astroglial cells in epilepsy, Glia., 368, 358, 10.1002/glia.20394

Coulter, 2015, Role of astrocytes in epilepsy, Cold Spring Harb Perspect Med., 5, 649, 10.1101/cshperspect.a022434

Li, 2008, Long-term expressional changes of Na+-K+-Cl− co-transporter NKCC1 and KCC2 in CA1 region of hippo following pilo epilepsy, Brain Res., 141, 10.1016/j.brainres.2008.04.047

Brandt, 2010, Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy, J Neurosci., 30, 8602, 10.1523/JNEUROSCI.0633-10.2010

Otalora, 2009, Downregulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy, Brain Res., 1200, 116, 10.1016/j.brainres.2008.01.017

Yeo, 2011, Changes in TWIK-related acid sensitive K+−1 and−3 channel expressions from neurons to glia in the hippocampus of temporal lobe epilepsy patients and experimental animal model, Neurochem Res., 36, 2155, 10.1007/s11064-011-0540-0

Nagao, 2013, Expressional analysis of the astrocytic Kir4. 1 channel in a pilocarpine-induced temporal lobe epilepsy model, Front Cell Neurosci., 7, 104, 10.3389/fncel.2013.00104

Kang, 2008, Expression of Kir2. 1 channels in astrocytes under pathophysiological conditions, Mol Cells., 25, 124, 10.1016/S1016-8478(23)17560-1

Kim, 2007, Seizure activity affects neuroglial Kv1 channel immunoreactivities in the gerbil hippocampus, Brain Res., 1151, 172, 10.1016/j.brainres.2007.03.017

Grisar, 1992, Contribution of Na+, K+-ATPase to focal epilepsy: a brief review, Epilepsy Res., 12, 141, 10.1016/0920-1211(92)90034-q

Palma, 2006, Anomalous levels of Cl- transporters in the hippocampal subiculum from temporal lobe epilepsy patients make GABA excitatory, Proc Natl Acad Sci USA., 103, 8465, 10.1073/pnas.0602979103

Ketelaars, 2004, Calcium extrusion protein expression in the hippocampal formation of chronic epileptic rats after kainate-induced status epilepticus, Epilepsia., 45, 1189, 10.1111/j.0013-9580.2004.03304.x

Lin, 2014, Auricular electroacupuncture reduced inflammation-related epilepsy accompanied by altered trpa1, ppkc ppkc ε, and perk1/2 signaling pathways in kainic acid-treated rats, Mediators Inflamm., 2014, 1, 10.1155/2014/493480

Tai, 2011, Plasma membrane insertion of TRPC5 channels contributes to the cholinergic plateau potential in hippocampal CA1 pyramidal neurons, Hippocampus., 21, 958, 10.1002/hipo.20807

Xu, 2014, Increased expression of TRPC5 in cortical lesions of the focal cortical dysplasia, J Mol Neurosci., 55, 561, 10.1007/s12031-014-0390-8

Zeng, 2015, Upregulation and diverse roles of TRPC3 and TRPC6 in synaptic reorganization of the mossy fiber pathway in temporal lobe epilepsy, Mol Neurobiol., 52, 562, 10.1007/s12035-014-8871-x

Sun, 2013, Increased expression of TRPV1 in the cortex and hippocampus from patients with mesial temporal lobe epilepsy, J Mol Neurosci., 1, 182, 10.1007/s12031-012-9878-2

Seifert, 2002, Changes in flip/flop splicing of astroglial AMPA receptors in human temporal lobe epilepsy, Epilepsia., 43, 162, 10.1046/j.1528-1157.43.s.5.10.x

Seifert, 2004, Enhanced relative expression of glutamate receptor 1 flip AMPA receptor subunits in hippocampal astrocytes of epilepsy patients with ammon' s horn sclerosis, J Neurosci., 24, 1996, 10.1523/JNEUROSCI.3904-03.2004

Naylor, 2013, Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus, Neurobiol Dis., 54, 225, 10.1016/j.nbd.2012.12.015

Simard, 2004, The neurobiology of glia in the context of water and ion homeostasis, Neuroscience., 129, 877, 10.1016/j.neuroscience.2004.09.053

Ke, 2002, Impact of experimental acute hyponatremia on severe traumatic brain injury in rats : influences on injuries, permeability of blood – brain, Exp Neurol., 206, 194, 10.1006/exnr.2002.8037

Pasantes-Morales, 2002, Mechanisms counteracting swelling in brain cells during hyponatremia, Arch Med Res., 33, 237, 10.1016/s0188-4409(02)00353-3

Murphy, 2017, Turning down the volume: astrocyte volume change in the generation and termination of epileptic seizures, Neurobiol Dis., 104, 24, 10.1016/j.nbd.2017.04.016

Wang, 2020, Astrocytic modulation of potassium under seizures, Neural Regen Res., 15, 980, 10.4103/1673-5374.270295

Abdullaev, 2006, Pharmacological comparison of swelling-activated excitatory amino acid release and Cl- currents in cultured rat astrocytes, J Physiol., 572, 677, 10.1113/jphysiol.2005.103820

Haskew-Layton, 2008, Two distinct modes of hypoosmotic medium-induced release of excitatory amino acids and taurine in the rat brain in vivo, PLoS ONE, 3, e3543, 10.1371/journal.pone.0003543

Seifert, 2018, Diversity of astrocyte potassium channels : an update, Brain Res Bull., 136, 26, 10.1016/j.brainresbull.2016.12.002

Day, 2014, Human aquaporins : regulators of transcellular water flow, BBA Gen Subj., 1840, 1492, 10.1016/j.bbagen.2013.09.033

Macaulay, 2004, Water transport in the brain: role of cotransporters, Neuroscience., 129, 1031, 10.1016/j.neuroscience.2004.06.045

Papadopoulos, 2014, Aquaporin water channels in the nervous system, Nat Rev Neurosci., 14, 265, 10.1038/nrn3468

Wetherington, 2008, Astrocytes in the epileptic brain, Neuron., 58, 168, 10.1016/j.neuron.2008.04.002

Frigeri, 2001, Aquaporin-4 deficiency in skeletal muscle and brain of dystrophic mdx mice, FASEB J., 15, 90, 10.1096/fj.00-0260com

Wertz, 2002, Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice, Proc Natl Acad Sci USA., 99, 13131, 10.1073/pnas.192457099

Marchi, 2012, Blood–brain barrier dysfunction and epilepsy: pathophysiologic role and therapeutic approaches, Epilepsia., 53, 1877, 10.1111/j.1528-1167.2012.03637.x

Lee, 2013, Decreased expression of the glial water channel aquaporin-4 in the intrahippocampal kainic acid model of epileptogenesis, Exp Neurol., 235, 246, 10.1016/j.expneurol.2012.02.002

Alvestad, 2013, Mislocalization of AQP4 precedes chronic seizures in the kainate model of temporal lobe epilepsy, Epilepsy Res., 105, 30, 10.1016/j.eplepsyres.2013.01.006

Han, 2018, Changes in the expression of AQP4 and AQP9 in the hippocampus following eclampsia-like seizure, Int J Mol Sci., 19, 1, 10.3390/ijms19010300

Kim, 2009, Differential expressions of aquaporin subtypes in astroglia in the hippocampus of chronic epileptic rats, Neuroscience., 163, 781, 10.1016/j.neuroscience.2009.07.028

Liu, 2012, Aquaporin 9 in rat brain after severe traumatic brain injury, Arq Neuropsiquiatr., 70, 214, 10.1590/s0004-282x2012000300012

Shenaq, 2012, Neuronal damage and functional deficits are ameliorated by inhibition of aquaporin and HIF1α after traumatic brain injury (TBI), J Neurol Sci., 323, 134, 10.1016/j.jns.2012.08.036

Saadoun, 2005, Involvement of aquaporin-4 in astroglial cell migration and glial scar formation, J Cell Sci., 118, 5691, 10.1242/jcs.02680

Hibino, 2004, Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes, J Biol Chem., 279, 44065, 10.1074/jbc.M405985200

Kucheryavykh, 2007, Downregulation of Kir4.1 inward rectifying potassium channel subunits by RNAi impairs potassium transfer and glutamate uptake by cultured cortical astrocytes, Glia., 281, 274, 10.1002/glia.20455

Li, 2000, Inward rectifier K+ channel Kir2.3 (IRK3) in reactive astrocytes from adult rat brain, Glia, 192, 181, 10.1002/1098-1136(200008)31:2<181::aid-glia90>3.0.co;2-8

Thomzig, 2001, Kir6.1 is the principal pore-forming subunit of astrocyte but not neuronal plasma membrane K-ATP channels, Mol Cell Neurosci., 690, 671, 10.1006/mcne.2001.1048

Connors, 2004, The potassium channel Kir4. 1 associates with the dystrophin- glycoprotein complex via alfa-syntrophin in glia, J Biol Chem., 279, 28387, 10.1074/jbc.M402604200

Bragg, 2006, Assembly of a perivascular astrocyte protein scaffold at the mammalian blood – brain barrier is dependent on a -syntrophin, Glia., 890, 879, 10.1002/glia.20347

Hubbard, 2015, Expression of the astrocyte water channel aquaporin-4 in the mouse brain, ASN Neuro., 7, 1759091415605486, 10.1177/1759091415605486

Jin, 2013, Aquaporin-4 – dependent K+ and water transport modeled in brain extracellular space following neuroexcitation, J Gen Physiol., 141, 119, 10.1085/jgp.201210883

Soe, 2009, Modulation of Kir4. 1 and Kir4. 1 – Kir5. 1 channels by small changes in cell volume, Neurosci Lett., 457, 80, 10.1016/j.neulet.2009.04.010

Bringmann, 2000, Role of Glial K+ channels in ontogeny and gliosis: a hypothesis based upon studies on müller cells, Glia, 44, 35, 10.1002/(sici)1098-1136(20000101)29:1<35::aid-glia4>3.0.co;2-a

Olsen, 2010, Spinal cord injury causes a wide-spread, persis- tent loss of Kir4.1 and glutamate transporter 1: benefit of 17 beta-oestradiol treatment, Brain., 133, 1013, 10.1093/brain/awq049

Frigerio, 2012, Long-lasting pro-ictogenic effects induced in vivo by rat brain exposure to serum albumin in the absence of concomitant pathology, Epilepsia., 53, 1887, 10.1111/j.1528-1167.2012.03666.x

Stewart, 2010, Chronic dysfunction of astrocytic inwardly rectifying K+ channels specific to the neocortical epileptic focus after fluid percussion injury in the rat, J Neurophysiol., 104, 3345, 10.1152/jn.00398.2010

Kinboshi, 2017, Inhibition of inwardly rectifying potassium (Kir) 4.1 channels facilitates brain-derived neurotrophic factor (BDNF) expression in astrocytes, Front Mol Neurosci., 10, 408, 10.3389/fnmol.2017.00408

Murray, 2000, Altered mRNA expression for brain- derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy, J Comp Neurol., 422, 411, 10.1002/(sici)1096-9861(20000320)418:4<411::aid-cne4>3.0.co;2-f

Heinrich, 2011, Neurobiology of disease increase in BDNF-mediated TrkB signaling promotes epileptogenesis in a mouse model of mesial temporal lobe epilepsy, Neurobiol Dis., 42, 35, 10.1016/j.nbd.2011.01.001

Tanaka, 1997, Inhibition of GABA A synaptic responses by brain-derived neurotrophic factor (BDNF) in rat hippocampus, J Neurosci., 17, 2959, 10.1523/JNEUROSCI.17-09-02959.1997

Rivera, 2002, BDNF-induced TrkB activation down-regulates the K+-Cl− cotransporter KCC2 and impairs neuronal Cl– extrusion, J Cell Biol., 159, 747, 10.1083/jcb.200209011

Kahle, 2015, Modulation of neuronal activity by phosphorylation of the K-Cl cotransporter KCC2, Trends Neurosci., 36, 726, 10.1016/j.tins.2013.08.006

Woo, 2002, Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K–Cl cotransporter gene, Hippocampus., 268, 258, 10.1002/hipo.10014

Girouard, 2009, Astrocytic endfoot Ca2+and BK channels determine both arteriolar dilation and constriction, Proc Natl Acad Sci USA., 107, 1, 10.1073/pnas.0914722107

N'Gouemo, 2012, Targeting BK (big potassium) channels in epilepsy, Expert Opin Ther Targets., 15, 1283, 10.1517/14728222.2011.620607

Brenner, 2005, BK channel β4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures, Nat Neurosci., 8, 1752, 10.1038/nn1573

Shruti, 2008, A seizure-induced gain-of-function in BK channels is associated with elevated firing activity in neocortical pyramidal neurons, Neurobiol Dis., 30, 323, 10.1016/j.nbd.2008.02.002

Liu, 2020, Selective blockade of neuronal BK (α + β4) channels preventing epileptic seizure, J Med Chem., 63, 216, 10.1021/acs.jmedchem.9b01241

Whitmire, 2017, Downregulation of KCNMB4 expression and changes in BK channel subtype in hippocampal granule neurons following seizure activity, PLoS ONE., 12, e0188064, 10.1371/journal.pone.0188064

Mehranfard, 2015, Long-term increases in BK potassium channel underlie increased action potential firing in dentate granule neurons following pilocarpine-induced status epilepticus in rats, Neurosci Lett., 585, 88, 10.1016/j.neulet.2014.11.041

Shirazi-Zand, 2013, The role of potassium BK channels in anticonvulsant effect of cannabidiol in pentylenetetrazole and maximal electroshock models of seizure in mice, Epilepsy Behav., 28, 1, 10.1016/j.yebeh.2013.03.009

Wickenden, 2002, Potassium channels as anti-epileptic drug targets, Neuropharmacology., 43, 1055, 10.1016/S0028-3908(02)00237-X

Dvorzhak, 2016, Functional indicators of glutamate transport in single striatal astrocytes and the influence of Kir4. 1 in normal and huntington mice, J Neurosci., 36, 4959, 10.1523/JNEUROSCI.0316-16.2016

Pappalardo, 2015, Voltage-gated sodium channel Nav 1.5 contributes to astrogliosis in an in vitro model of glial injury via reverse Na+/Ca2+ exchange, Glia., 62, 1162, 10.1002/glia.22671

Black, 2010, Astrocytes within multiple sclerosis lesions upregulate sodium channel Nav1.5., Brain., 133, 835, 10.1093/brain/awq003

Pappalardo, 2014, Dynamics of sodium channel Nav 1.5 expression in astrocytes in mouse models of multiple sclerosis, Neuroreport., 25, 1208, 10.1097/WNR.0000000000000249

Pappalardo, 2016, Sodium channels in astroglia and microglia, Glia., 64, 1628, 10.1002/glia.22967

Vaillend, 2002, Mechanisms of neuronal hyperexcitability caused by partial inhibition of Na+-K+-ATPases in the rat CA1 hippocampal region, J Neurophysiol., 88, 2963, 10.1152/jn.00244.2002

Clapcote, 2009, Mutation I810N in the α3 isoform of Na+, K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS, Proc Natl Acad Sci USA., 106, 14085, 10.1073/pnas.0904817106

Gallanti, 2008, A novel de novo nonsense mutation in ATP1A2 associated with sporadic hemiplegic migraine and epileptic seizures, J Neurol Sci., 273, 123, 10.1016/j.jns.2008.06.006

Su, 2000, Regulation of Na+-K+-Cl− cotransporter in primary astrocytes by dibutyryl cAMP and high [K+] o, Am J Physiol Cell Physiol., 297, 1710, 10.1152/ajpcell.2000.279.6.C1710

Su, 2001, Astrocytes from Na+ -K+ -Cl - cotransporter-null mice exhibit absence of swelling and decrease in EAA release, Am J Physiol Cell Physiol., 53792, 1147, 10.1152/ajpcell.00538.2001

Østby, 2009, Astrocytic mechanisms explaining neural-activity-induced shrinkage of extraneuronal space, PLoS Comput Biol., 5, e1000272, 10.1371/journal.pcbi.1000272

Malarkey, 2008, Ca2+ entry through TRPC1 channels contributes to intracellular Ca2+ dynamics and consequent glutamate release from rat astrocytes, Glia., 835, 821, 10.1002/glia.20656

Verkhratsky, 2013, TRP channels coordinate ion signalling in astroglia, Rev Physiol Biochem Pharmacol., 166, 1, 10.1007/112

Anderson, 2000, Astrocyte glutamate transport : review of properties, regulation, and physiological functions, Glia., 14, 1, 10.1002/1098-1136(200010)32:1<1::AID-GLIA10>3.0.CO;2-W

Uwechue, 2012, Activation of glutamate transport evokes rapid glutamine release from perisynaptic astrocytes, J Physiol., 10, 2317, 10.1113/jphysiol.2011.226605

Kleene, 2007, Prion protein regulates glutamate-dependent lactate transport of astrocytes, J Neurosci., 27, 12331, 10.1523/JNEUROSCI.1358-07.2007

Minelli, 2007, Cellular and subcellular localization of Na+- Ca2+ exchanger protein isoforms, NCX1, NCX2, and NCX3 in cerebral cortex and hippocampus of adult rat, Cell Calcium., 41, 221, 10.1016/j.ceca.2006.06.004

Shigetomi, 2012, TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3, Nat Neurosci., 15, 70, 10.1038/nn.3000.TRPA1

Shigetomi, 2013, TRPA1 channels are regulators of astrocyte basal calcium levels and long-term potentiation via constitutive d-serine release, J Neurosci., 33, 10143, 10.1523/JNEUROSCI.5779-12.2013

Lee, 2010, Characterisation of the expression of NMDA receptors in human astrocytes, PLoS ONE., 5, e14123, 10.1371/journal.pone.0014123

Palygin, 2010, Ionotropic NMDA and P2X 1/5 receptors mediate synaptically induced Ca 2 + signalling in cortical astrocytes, Cell Calcium., 48, 225, 10.1016/j.ceca.2010.09.004

Mikawa, 2002, Developmental changes in KCC1, KCC2 and NKCC1 mRNAs in the rat cerebellum, Dev Brain Res., 136, 93, 10.1016/s0165-3806(02)00345-0

Gagnon, 2007, Characterization of glial cell K-Cl cotransport, Cell Physiol Biochem., 20, 121, 10.1159/000104160

Ringel, 2008, Expression and functional role of potassium-chloride cotransporters (KCC) in astrocytes and C6 glioma cells, Neurosci Lett., 442, 219, 10.1016/j.neulet.2008.07.017

Kaila, 2015, Cation-chloride cotransporters in neuronal development, plasticity and disease, Nat Rev Neurosci., 15, 637, 10.1038/nrn3819

Mu, 2007, Cation-chloride cotransporters and GABA-ergic innervation in the human epileptic hippocampus, Epilepsia., 48, 663, 10.1111/j.1528-1167.2007.00986.x

Chen, 2017, KCC2 downregulation facilitates epileptic seizures, Sci Rep., 7, 156, 10.1038/s41598-017-00196-7

Eftekhari, 2013, Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy, Epilepsia, 54, 10, 10.1111/j.1528-1167.2012.03654.x

Larsen, 2014, Contributions of the Na+/K+-ATPase, NKCC1, and Kir4.1 to hippocampal K+ clearance and volume responses, Glia., 62, 608, 10.1002/glia.22629

Gharaylou, 2019, Longitudinal effects of bumetanide on neuro-cognitive functioning in drug-resistant epilepsy, Front Neurol., 10, 1, 10.3389/fneur.2019.00483

Kim, 2012, Blood–brain barrier dysfunction–induced inflammatory signaling in brain pathology and epileptogenesis, Epilepsia., 53, 37, 10.1111/j.1528-1167.2012.03701.x

Abbott, 2010, Structure and function of the blood-brain barrier, Neurobiol Dis., 37, 13, 10.1016/j.nbd.2009.07.030

Sobue, 1999, Induction of blood-brain barrier properties in immortalized bovine brain endothelial cells by astrocytic factors, Neurosci Res., 35, 155, 10.1016/S0168-0102(99)00079-6

Régina, 2001, Factor(s) released by glucose-deprived astrocytes enhance glucose transporter expression and activity in rat brain endothelial cells, Biochim Biophys Acta Mol Cell Res., 1540, 233, 10.1016/S0167-4889(01)00133-1

Schinkel, 1999, P-Glycoprotein, a gatekeeper in the blood-brain barrier, Adv Drug Deliv Rev., 36, 179, 10.1016/S0169-409X(98)00085-4

Gaillard, 2000, Astrocytes increase the functional expression of P-glycoprotein in an in vitro model of the blood-brain barrier, Pharm Res., 17, 1198, 10.1023/A:1026406528530

Dehouck, 1990, An easier, reproducible, and mass-production method to study the blood–brain barrier in vitro, J Neurochem., 54, 1798, 10.1111/j.1471-4159.1990.tb01236.x

Haseloff, 2005, In search of the astrocytic factor(s) modulating blood-brain barrier functions in brain capillary endothelial cells in vitro, Cell Mol Neurobiol., 25, 25, 10.1007/s10571-004-1375-x

Abbott, 2005, Dynamics of CNS Barriers: Evolution, Differentiation, and Modulation, Cell Mol Neurobiol., 25, 5, 10.1007/s10571-004-1374-y

Alvarez, 2013, Glial influence on the blood brain barrier, Glia., 61, 1939, 10.1002/glia.22575

Abbott, 2000, Inflammatory mediators and modulation of blood-brain barrier permeability, Cell Mol Neurobiol., 20, 131, 10.1023/A:1007074420772

Schwaninger, 1999, Bradykinin induces interleukin-6 expression in astrocytes through activation of nuclear factor-κB, J Neurochem., 73, 1461, 10.1046/j.1471-4159.1999.0731461.x

Smith, 2018, Inflammation and blood-brain barrier breach remote from the primary injury following neurotrauma, J Neuroinflamm., 15, 1, 10.1186/s12974-018-1227-0

Vliet, 2007, Blood – brain barrier leakage may lead to progression of temporal lobe epilepsy, Brain., 130, 521, 10.1093/brain/awl318

Tomkins, 2011, Blood-brain barrier breakdown following traumatic brain injury : a possible role in posttraumatic epilepsy, Cardiovasc Psychiatry Neurol., 2011, 1, 10.1155/2011/765923

Marchi, 2014, Seizure-promoting effect of blood–brain barrier disruption, Epilepsia, 48, 732, 10.1111/j.1528-1167.2007.00988.x

van Vliet, 2014, Role of blood-brain barrier in temporal lobe epilepsy and pharmacoresistance, Neuroscience., 277, 455, 10.1016/j.neuroscience.2014.07.030

Rigau, 2007, Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy, Brain., 130, 1942, 10.1093/brain/awm118

Lebrun, 2011, Epileptiform activity induces vascular remodeling and zonula occludens 1 downregulation in organotypic hippocampal cultures : role of VEGF signaling pathways me, J Neurosci., 31, 10677, 10.1523/JNEUROSCI.5692-10.2011

Castañeda-Cabral, 2019, Increased protein expression of VEGF-A, VEGF-B, VEGF-C and their receptors in the temporal neocortex of pharmacoresistant temporal lobe epilepsy patients, J Neuroimmunol., 328, 68, 10.1016/j.jneuroim.2018.12.007

Montpellier, 2013, Cerebrovascular remodeling and epilepsy, Neuroscientist., 19, 304, 10.1177/1073858412462747

Ivens, 2007, TGF- b receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis, Brain., 130, 535, 10.1093/brain/awl317

Aronica, 2000, Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in a rat model of mesial temporal lobe epilepsy, Eur J Neurosci., 12, 2333, 10.1046/j.1460-9568.2000.00131.x

Perillan, 2002, Transforming growth factor-beta 1 regulates Kir2.3 inward rectifier K+ channels via phospholipase C and protein kinase c-delta in reactive astrocytes from adult rat brain, J Biol Chem., 277, 1974, 10.1074/jbc.M107984200

Braganza, 2013, Albumin is taken up by hippocampal NG2 cells and astrocytes and decreases gap junction coupling, Epilepsia., 53, 1898, 10.1111/j.1528-1167.2012.03665.x

Seiffert, 2004, Lasting blood – brain barrier disruption induces epileptic focus in the rat somatosensory cortex, J Neurosci., 24, 7829, 10.1523/JNEUROSCI.1751-04.2004

Levy, 2015, Differential TGF- β signaling in glial subsets underlies IL-6 – mediated epileptogenesis in mice, J Immunol., 195, 1713, 10.4049/jimmunol.1401446

Kimple, 2009, A high-throughput fluorescence polarization assay for inhibitors of the goloco motif/G-alpha interaction, Comb Chem High Throughput Screen., 11, 396, 10.2174/138620708784534770

Weissberg, 2015, Neurobiology of disease albumin induces excitatory synaptogenesis through astrocytic TGF- β/ALK5 signaling in a model of acquired epilepsy following blood – brain barrier dysfunction, Neurobiol Dis., 78, 115, 10.1016/j.nbd.2015.02.029

Vliet, 2010, COX-2 inhibition controls P-glycoprotein expression and promotes brain delivery of phenytoin in chronic epileptic rats, Neuropharmacology., 58, 404, 10.1016/j.neuropharm.2009.09.012

Dombrowski, 2001, Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory, Epilepsy, 42, 1501, 10.1046/j.1528-1157.2001.12301.x

Löscher, 2002, Role of multidrug transporters in pharmacoresistance to antiepileptic drugs, J Pharmacol Exp Ther., 301, 7, 10.1124/jpet.301.1.7

Sisodiya, 2002, Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy, Brain., 125, 22, 10.1093/brain/awf002

Aronica, 2012, Cerebral expression of drug transporters in epilepsy, Adv Drug Deliv Rev., 64, 919, 10.1016/j.addr.2011.11.008

Schinkel, 2003, Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview, Adv Drug Deliv Rev., 55, 3, 10.1016/s0169-409x(02)00169-2

Sun, 2003, Drug efflux transporters in the CNS, Adv Drug Deliv Rev., 55, 83, 10.1016/s0169-409x(02)00172-2

Löscher, 2007, Drug transporters in the epileptic brain, Epilepsia., 48, 8, 10.1111/j.1528-1167.2007.00993.x

Brandt, 2006, The multidrug transporter hypothesis of drug resistance in epilepsy: proof-of-principle in a rat model of temporal lobe epilepsy, Neurobiol Dis., 24, 202, 10.1016/j.nbd.2006.06.014

Van Vliet, 2006, Inhibition of the multidrug transporter P-glycoprotein improves seizure control in phenytoin-treated chronic epileptic rats, Epilepsia., 47, 672, 10.1111/j.1528-1167.2006.00496.x

Vliet, 2007, Region-specific overexpression of P-glycoprotein at the blood-brain barrier affects brain uptake of phenytoin in epileptic rats, J Pharmacol Exp Ther, 322, 141, 10.1124/jpet.107.121178

Lange, 2018, P-glycoprotein protein expression versus functionality at the blood-brain barrier using immunohistochemistry, microdialysis and mathematical modeling, Eur J Pharm Sci., 124, 61, 10.1016/j.ejps.2018.08.022

Borlot, 2014, A pilot double-blind trial using verapamil as adjuvant therapy for refractory seizures, Epilepsy Res., 108, 1642, 10.1016/j.eplepsyres.2014.08.009

Nicita, 2014, Efficacy of verapamil as an adjunctive treatment in children with drug-resistant epilepsy : a pilot study, Seizure Eur J Epilepsy., 23, 36, 10.1016/j.seizure.2013.09.009

Summers, 2004, Use of verapamil as a potential P-glycoprotein inhibitor in a patient with refractory epilepsy, Ann Pharmacother., 38, 1631, 10.1345/aph.1E068

Pirker, 2011, Termination of refractory focal status epilepticus by the P-glycoprotein inhibitor verapamil, Eur J Neurol., 18, e151, 10.1111/j.1468-1331.2011.03513.x

Asadi-Pooya, 2013, Epilepsy and behavior adjunctive use of verapamil in patients with refractory temporal lobe epilepsy : a pilot study, Epilepsy Behav., 29, 150, 10.1016/j.yebeh.2013.07.006

Narayanan, 2016, Low dose verapamil as an adjunct therapy for medically refractory epilepsy – an open label pilot study, Epilepsy Res., 126, 197, 10.1016/j.eplepsyres.2016.07.004

Metea, 2006, Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling, J Neurosci., 26, 2862, 10.1523/JNEUROSCI.4048-05.2006

Fabene, 2003, Magnetic resonance imaging of changes elicited by status epilepticus in the rat brain : diffusion-weighted and T2-weighted images, regional blood volume maps, and direct correlation with tissue and cell damage, Neuroimage., 18, 375, 10.1016/s1053-8119(02)00025-3

Winkler, 2013, Impaired neurovascular coupling to ictal epileptic activity and spreading depolarization in a patient with subarachnoid hemorrhage: possible link to blood–brain barrier dysfunction, Epilepsia., 53, 22, 10.1111/j.1528-1167.2012.03699.x

Zhao, 2007, Focal increases in perfusion and decreases in hemoglobin oxygenation precede seizure onset in spontaneous human epilepsy, Epilepsia., 48, 2059, 10.1111/j.1528-1167.2007.01229.x

Gómez-Gonzalo, 2011, Ictal but not interictal epileptic discharges activate astrocyte endfeet and elicit cerebral arteriole responses, Front Cell Neurosci., 5, 8, 10.3389/fncel.2011.00008

Vezzani, 2017, Biomarkers of epileptogenesis: the focus on glia and cognitive dysfunctions, Neurochem Res., 42, 2089, 10.1007/s11064-017-2271-3

van Vliet, 2018, Review: neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies, Neuropathol Appl Neurobiol., 44, 91, 10.1111/nan.12444