Mining the topography and dynamics of the 4D Nucleome to identify novel CNS drug pathways

Azevedo, 2009, Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain, J. Comp. Neurol., 513, 532, 10.1002/cne.21974 Mann, 1973, Polyploidy in the human nervous systemPart 1. The DNA content of neurones and glia of the cerebellum, J. Neurol. Sci., 18, 183, 10.1016/0022-510X(73)90005-1 Rehen, 2005, Constitutional aneuploidy in the normal human brain, J. Neurosci., 25, 2176, 10.1523/JNEUROSCI.4560-04.2005 Ernst, 2014, Neurogenesis in the striatum of the adult human brain, Cell, 156, 1072, 10.1016/j.cell.2014.01.044 Eriksson, 1998, In the adult human hippocampus, Nat. Med., 4, 1313, 10.1038/3305 Prabhakar, 2006, Accelerated evolution of conserved noncoding sequences in humans, Science, 314, 10.1126/science.1130738 Kang, 2011, Spatio-temporal transcriptome of the human brain, Nature, 478, 483, 10.1038/nature10523 Hawrylycz, 2012, An anatomically comprehensive atlas of the adult human brain transcriptome, Nature, 489, 391, 10.1038/nature11405 Nestler, 2010, Animal models of neuropsychiatric disorders, Nat. Neurosci., 13, 1161, 10.1038/nn.2647 Parker, 2005, Lateralization of ventral and dorsal auditory-language pathways in the human brain, NeuroImage, 24, 656, 10.1016/j.neuroimage.2004.08.047 Odorico, 2001, Multilineage differentiation from human embryonic stem cell lines, Stem Cells, 19, 193, 10.1634/stemcells.19-3-193 K. Hill, M. Barton., A.M. Hurtado. The emergence of human uniquenesscharacters underlying behavioral modernity. Evol. Anthropol. 18(5), (2009), 187–200. Sapolsky, 1994 Seyfarth, 2013, Affiliation, empathy, and the origins of theory of mind, Proc. Nat. Acad. Sci., 110, 10349, 10.1073/pnas.1301223110 Seeley, 2009, Neurodegenerative diseases target large-scale human brain networks, Neuron, 62, 42, 10.1016/j.neuron.2009.03.024 Hyman, 2014, Revitalizing psychiatric therapeutics, Neuropsychopharmacology, 39, 220, 10.1038/npp.2013.181 W.W. Sneader, Drug Discovery (the history), John Wiley and Sons, Inc., 2005 Jun 23. Scott, 1993 Anderson, 1994, The efficacy of selective serotonin re-uptake inhibitors in depressiona meta-analysis of studies against tricyclic antidepressants, J. Psychopharmacol., 8, 238, 10.1177/026988119400800407 Hampton, 2014, Emergency department visits by adults for psychiatric medication adverse events, JAMA Psychiatry, 71, 1006, 10.1001/jamapsychiatry.2014.436 Higgins, 2015, The epigenome, 4D nucleome and next-generation neuropsychiatric pharmacogenomics, Pharmacogenomics, 16, 1649, 10.2217/pgs.15.111 Oldham, 2008, Functional organization of the transcriptome in human brain, Nat. Neurosci., 11, 1271, 10.1038/nn.2207 Hawrylycz, 2015, Canonical genetic signatures of the adult human brain, Nat. Neurosci., 18, 1832, 10.1038/nn.4171 César-Razquin, 2015, A call for systematic research on solute carriers, Cell, 162, 478, 10.1016/j.cell.2015.07.022 Welter, 2014, The NHGRI GWAS Catalog, a curated resource of SNP-trait associations, Nucleic Acids Res., 42, D1001, 10.1093/nar/gkt1229 Wang, 2011, Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs, Pharmacogenomics, 11, 274, 10.1038/tpj.2010.28 Higgins, 2015, Epigenomic mapping and effect sizes of noncoding variants associated with psychotropic drug response, Pharmacogenomics, 16, 1565, 10.2217/pgs.15.105 Hu, 2016, Network biology concepts in complex disease comorbidities, Nat. Rev. Genet., 17, 615, 10.1038/nrg.2016.87 Arrowsmith, 2012, Epigenetic protein familiesa new frontier for drug discovery, Nat. Rev. Drug Discovery, 11, 384, 10.1038/nrd3674 Gonzalez-Sandoval, 2016, On TADs and LADsspatial control over gene expression, Trends Genet., 32, 485, 10.1016/j.tig.2016.05.004 Lupiáñez, 2015, Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions, Cell, 161, 1012, 10.1016/j.cell.2015.04.004 Lee, 2015, A method to predict the impact of regulatory variants from DNA sequence, Nat. Genet., 47, 955, 10.1038/ng.3331 Fukaya, 2016, Enhancer control of transcriptional bursting, Cell, 166, 358, 10.1016/j.cell.2016.05.025 Zhang, 2014, A circadian gene expression atlas in mammalsimplications for biology and medicine, Proc. Natl. Acad. Sci., 11, 16219, 10.1073/pnas.1408886111 Bunney, 2015, Circadian dysregulation of clock genesclues to rapid treatments in major depressive disorder, Mol. Psychiatry, 20, 48, 10.1038/mp.2014.138 Wang, 2016, Spatial organization of chromatin domains and compartments in single chromosomes, Science, 353, 598, 10.1126/science.aaf8084 Dixon, 2016, Chromatin domainsthe unit of chromosome organization, Mol. Cell, 62, 668, 10.1016/j.molcel.2016.05.018 Dixon, 2012, Topological domains in mammalian genomes identified by analysis of chromatin interactions, Nature, 485, 376, 10.1038/nature11082 Zullo, 2012, DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina, Cell, 149, 1474, 10.1016/j.cell.2012.04.035 Lieberman-Aiden, 2009, Comprehensive mapping of long-range interactions reveals folding principles of the human genome, Science, 326, 289, 10.1126/science.1181369 Rao, 2014, A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping, Cell, 159, 1665, 10.1016/j.cell.2014.11.021 Halverson, 2014, From a melt of rings to chromosome territoriesthe role of topological constraints in genome folding, Rep. Prog. Phys., 77, 022601, 10.1088/0034-4885/77/2/022601 Mateos-Langerak, 2009, Spatially confined folding of chromatin in the interphase nucleus, Proc. Natl. Acad. Sci., 106, 3812, 10.1073/pnas.0809501106 Fudenberg, 2016, Formation of chromosomal domains by loop extrusion, Cell Rep.., 15, 2038, 10.1016/j.celrep.2016.04.085 Maurano, 2012, Systematic localization of common disease-associated variation in regulatory DNA, Science, 337, 1190, 10.1126/science.1222794 Guenther, 2014, A molecular basis for classic blond hair color in Europeans, Nat. Genet., 46, 748, 10.1038/ng.2991 Parker, 2013, Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants, Proc. Natl. Acad. Sci., 110, 17921, 10.1073/pnas.1317023110 Matharu, 2015, Minor loops in major foldsenhancer–promoter looping, chromatin restructuring, and their association with transcriptional regulation and disease, PLoS Genet., 11, e1005640, 10.1371/journal.pgen.1005640 Gómez-Díaz, 2014, Architectural proteinsregulators of 3D genome organization in cell fate, Trends Cell Biol., 24, 703, 10.1016/j.tcb.2014.08.003 Van Bortle, 2014, Insulator function and topological domain border strength scale with architectural protein occupancy, Genome Biol., 15, 1, 10.1186/gb-2014-15-5-r82 Pope, 2014, Topologically associating domains are stable units of replication-timing regulation, Nature, 515, 402, 10.1038/nature13986 E. Giorgio, D. Robyr, M. Spielmann, E. Ferrero, E. Di Gregorio, D. Imperiale, G. Vaula et al., A large genomic deletion leads to enhancer adoption by the lamin B1 genea second path to autosomal dominant leukodystrophy (ADLD), Human Mol. Genet. (2015), ddv065. Kasowski, 2013, Extensive variation in chromatin states across humans, Science, 342, 750, 10.1126/science.1242510 Waszak, 2015, Population variation and genetic control of modular chromatin architecture in humans, Cell, 162, 1039, 10.1016/j.cell.2015.08.001 Zhu, 2013, Genome-wide chromatin state transitions associated with developmental and environmental cues, Cell, 152, 642, 10.1016/j.cell.2012.12.033 Dekker, 2013, Exploring the three-dimensional organization of genomesinterpreting chromatin interaction data, Nat. Rev. Genet., 14, 390, 10.1038/nrg3454 Bonev, 2016, Organization and function of the 3D genome, Nat. Rev. Genet., 17, 661, 10.1038/nrg.2016.112 Higgins, 2017, Network reconstruction reveals that valproic acid activates neurogenic transcriptional programs in adult brain following traumatic injury, Pharm. Res., 10.1007/s11095-017-2130-6 Zlotorynski, 2015, DevelopmentUbiquitylation determines cell fate, Nat. Rev. Mol. Cell Biol., 16, 640, 10.1038/nrm4071 N.E. Sanjana, J. Wright, K. Zheng, O. Shalem, P. Fontanillas, J. Joung, C. Cheng, A. Regev, F. Zhang, High-resolution interrogation of functional elements in the noncoding genome, bioRxiv. (2016), 049130. Shalem, 2014, Genome-scale CRISPR-Cas9 knockout screening in human cells, Science, 343, 84, 10.1126/science.1247005 Cremer, 2015, The 4D nucleomeEvidence for a dynamic nuclear landscape based on co-aligned active and inactive nuclear compartments, FEBS Lett., 589, 2931, 10.1016/j.febslet.2015.05.037 Bickmore, 2013, The spatial organization of the human genome, Annu. Rev. Genomics Hum. Genet., 14, 67, 10.1146/annurev-genom-091212-153515 Fanucchi, 2013, Chromosomal contact permits transcription between coregulated genes, Cell, 155, 606, 10.1016/j.cell.2013.09.051 Zhang, 2014, A circadian gene expression atlas in mammalsimplications for biology and medicine, Proc. Natl. Acad. Sci., 111, 16219, 10.1073/pnas.1408886111 Raj Arjun, 2008, Nature, nurture, or chancestochastic gene expression and its consequences, Cell, 135, 216, 10.1016/j.cell.2008.09.050 R. Cloney, Gene expressiondynamic enhancer-promoter interactions for transcriptional bursting, Nat. Rev. Genet. 17 (437), (2016). doi:10.1038/nrg.2016.81. McCarthy, 2012, A survey of genomic studies supports association of circadian clock genes with bipolar disorder spectrum illnesses and lithium response, PLoS One, 7, e32091, 10.1371/journal.pone.0032091 Q. Yan, Circadian Rhythms and Cellular Networks in Cancer. InCellular Rhythms and Networks, Springer International Publishing, 2015, pp. 61–70. T. Kino, G.P. Chrousos. Circadian CLOCK-mediated regulation of target-tissue sensitivity to glucocorticoidsimplications for cardiometabolic diseases. InPediatric Adrenal Diseases, vol. 20, Karger Publishers, 2010, pp. 116–126. Goel, 2009, Circadian rhythm profiles in women with night eating syndrome, J. Biol. Rhythms, 24, 85, 10.1177/0748730408328914 Chrousos, 1995, The hypothalamic–pituitary–adrenal axis and immune-mediated inflammation, NEJM, 332, 1351, 10.1056/NEJM199505183322008 Konturek, 2011, Gut clockimplication of circadian rhythms in the gastrointestinal tract, J. Physiol. Pharmacol., 62, 139 Chen, 2015, Functional organization of the human 4D Nucleome, Proc. Natl. Acad. Sci., 112, 8002, 10.1073/pnas.1505822112 C. Dai, W. Li, H. Tjong, S. Hao, Y. Zhou, Q. Li, L. Chen, B. Zhu, F. Alber, X.J. Zhou, Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities, Nat. Commun. 7 (11549), (2016). doi:10.1038/ncomms11549. Tjong, 2016, Population-based 3D genome structure analysis reveals driving forces in spatial genome organization, Proc. Natl. Acad. Sci., E1663, 10.1073/pnas.1512577113 Bharadwaj, 2014, Conserved higher-order chromatin regulates NMDA receptor gene expression and cognition, Neuron, 84, 997, 10.1016/j.neuron.2014.10.032 Thakurela, 2015, Dynamics and function of distal regulatory elements during neurogenesis and neuroplasticity, Genome Res., 25, 1309, 10.1101/gr.190926.115 Hung, 2011, Association of genetic variants in six candidate genes with valproic acid therapy optimization, Pharmacogenomics, 12, 1107, 10.2217/pgs.11.64 Zhang, 2014, A study of N-methyl-d-aspartate receptor gene (GRIN2B) variants as predictors of treatment-resistant major depression, Psychopharmacology, 231, 685, 10.1007/s00213-013-3297-0 Bush, 2016, Unravelling the human genome-phenome relationship using phenome-wide association studies, Nat. Rev. Genet., 17, 129, 10.1038/nrg.2015.36 Denny, 2010, PheWASdemonstrating the feasibility of a phenome-wide scan to discover gene–disease associations, Bioinformatics, 26, 1205, 10.1093/bioinformatics/btq126 Hebbring, 2015, Application of clinical text data for phenome-wide association studies (PheWASs), Bioinformatics, 31, 1981, 10.1093/bioinformatics/btv076 Yates, 2016, Ensembl 2016, Nucleic Acids Res., 44, D710, 10.1093/nar/gkv1157 Koike, 2012, Transcriptional architecture and chromatin landscape of the core circadian clock in mammals, Science, 338, 349, 10.1126/science.1226339 J.W. Wiley, G.A. Higgins, B.D. Athey, Stress and glucocorticoid receptor transcriptional programming in time and spaceImplications for the brain–gut axis, Neurogastroenterology ∗∗ Motility. 28(1), (2016), 12–25. Krämer, 2014, Causal analysis approaches in ingenuity pathway analysis (ipa), Bioinformatics, 30, 523, 10.1093/bioinformatics/btt703 Bai, 2013, Systems pharmacology to predict drug toxicityintegration across levels of biological organization, Ann. Rev. Pharmacol. Toxicol., 53, 451, 10.1146/annurev-pharmtox-011112-140248 Le, 2016, Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment, Nat. Cell Biol., 18, 864, 10.1038/ncb3387 Y. Wang, E. Makhija, K. Damodaran, G.V. Shivashankar, Role of cell geometry on nuclear mechanics, chromosome reorganization, and gene expression, inMolecular and Cellular Mechanobiology, Springer, New York, 2016, pp. 197–216. Jain, 2013, Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility, Proc. Natl. Acad. Sci., 110, 11349, 10.1073/pnas.1300801110 Uhler, 2016, Geometric control and modeling of genome reprogramming, Bioarchitecture, 6, 76, 10.1080/19490992.2016.1201620 K. Haase, J.K.L. Macadangdang, C.H. Edrington, C.M. Cuerrier, S. Hadjiantoniou, J.L. Harden, I.S. Skerjanc, A.E. Pelling, Extracellular forces cause the nucleus to deform in a highly controlled anisotropic manner, Scientific Reports. 6 (21300), (2016), doi:10.1038/srep21300. E. Banigan, A. Stephens, J. Marko. A simple polymeric model describes cell nuclear mechanical response, APS Meeting Abstracts. 2016. Felisbino, 2014, Changes in chromatin structure in NIH 3T3 cells induced by valproic acid and trichostatin A, J. Cell. Biochem., 115, 1937 Yi, 2015, Fractal characterization of chromatin decompaction in live cells, Biophys. J., 109, 2218, 10.1016/j.bpj.2015.10.014 Halsall, 2015, Cells adapt to the epigenomic disruption caused by histone deacetylase inhibitors through a coordinated, chromatin-mediated transcriptional response, Epigenet. Chromatin., 8, 1, 10.1186/s13072-015-0021-9 Chiang, 2009, Systematic evaluation of drug-disease relationships to identify leads for novel drug uses, Clin. Pharmacol. Therap., 86, 507, 10.1038/clpt.2009.103 ENCODE Project Consortium, 2012, An integrated encyclopedia of DNA elements in the human genome, Nature, 489, 57, 10.1038/nature11247 Bernstein, 2010, The NIH roadmap epigenomics mapping consortium, Nat. Biotechol., 28, 1045, 10.1038/nbt1010-1045 Vivien, 2016, Genomics in 3D and 4D, Nat. Methods, 13, 829, 10.1038/nmeth.4001 GTEx Consortium, The Genotype-Tissue Expression (GTEx) pilot analysisMultitissue gene regulation in humans, Science 348(6235), (2015) 648–660. J. Monlong, C. Miquel, P.G. Ferreira, R. Guigó, Identification of genetic variants associated with alternative splicing using sQTLseekeR, Nat. Commun. 5 (4698), (2014). doi:10.1038/ncomms5698. del Rosario, 2015, Sensitive detection of chromatin-altering polymorphisms reveals autoimmune disease mechanisms, Nat. Methods, 12, 458, 10.1038/nmeth.3326 Son, 2014, The role of BAF (mSWI/SNF) complexes in mammalian neural development, Am. J. Med. Genet. Part C, 166, 333, 10.1002/ajmg.c.31416 Narayanan, 2014, Roles of chromatin remodeling BAF complex in neural differentiation and reprogramming, Cell Tissue Res., 356, 575, 10.1007/s00441-013-1791-7 Wadi, 2016, Impact of outdated gene annotations on pathway enrichment analysis, Nat. Methods, 13, 705, 10.1038/nmeth.3963 W.S. Bush, M.T. Oetjens D.C., Crawford, Unravelling the human genome-phenome relationship using phenome-wide association studies, Nat. Rev. Gen. 17(3), (2016) 1. Tsushihashi, 2014, Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration, Clin. Ophthalmol., 8, 2471, 10.2147/OPTH.S71305 M. Fagny, J.N. Marieke, L. Kuijjer, R. Abhijeet, C. Sonawane, C.-Y.. Chen, C.M. Lopes-Ramos, K. Glass, J. Quackenbush, J. Platig, A network-based approach to eQTL interpretation and SNP functional characterization, bioRxiv (2016) 086587. Higgins, 2015, A glutamatergic network mediates lithium response in bipolar disorder as defined by epigenome pathway analysis, Pharmacogenomics, 16, 1547, 10.2217/pgs.15.106 J. Song, S.E. Bergen, A. Di Florio, R. Karlsson, A. Charney, D.M. Ruderfer, E.A. Stahl et al. Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder, Mol. Psychiatry (21), (2015) 1290–1297. doi:10.1038/mp.2015.165. Crisafulli, 2012, Case–control association study of 14 variants of CREB1, CREBBP and CREM on diagnosis and treatment outcome in major depressive disorder and bipolar disorder, Psychiatry Res., 198, 39, 10.1016/j.psychres.2011.08.022 Calati, 2013, Evaluation of the role of MAPK1 and CREB1 polymorphisms on treatment resistance, response and remission in mood disorder patients, Prog. Neuropsychopharmacol. Biol. Psychiatry, 1, 271, 10.1016/j.pnpbp.2013.03.005 Kishi, 2013, The serotonin 1A receptor gene confer susceptibility to mood disordersresults from an extended meta-analysis of patients with major depression and bipolar disorder, Eur. Arch. Psychiatry Clin. Neurosci., 263, 105, 10.1007/s00406-012-0337-4 Nowrouzi, 2013, Finite mixture regression model analysis on antipsychotics induced weight gainInvestigation of the role of the serotonergic genes, Eur. Neuropsychopharmacol., 23, 224, 10.1016/j.euroneuro.2012.05.008 Severino, 2009, Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBα gene, a critical component of the circadian clock system, Bipolar Disord., 11, 215, 10.1111/j.1399-5618.2009.00667.x McCarthy, 2011, Functional genetic variation in the Rev-Erbα pathway and lithium response in the treatment of bipolar disorder, Genes Brain Behav, 10, 852, 10.1111/j.1601-183X.2011.00725.x Elks, 2010, Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies, Nat. Genet., 42, 1077, 10.1038/ng.714 Perry, 2014, Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche, Nature, 514, 92, 10.1038/nature13545 Croteau-Chonka, 2015, Genetic studies of body mass index yield new insights for obesity biology, Nature, 518, 197, 10.1038/nature14177 Børglum, 2014, Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci, Mol. Psychiatry, 19, 325, 10.1038/mp.2013.2 Lin, 2013, Glycogen synthase kinase 3β gene polymorphisms may be associated with bipolar I disorder and the therapeutic response to lithium, J. Affect. Disord., 147, 401, 10.1016/j.jad.2012.08.025 Benedetti, 2013, Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder, Neuropsychopharmacology, 38, 313, 10.1038/npp.2012.172 Dallaspezia, 2012, Influence of an interaction between lithium salts and a functional polymorphism in SLC1A2 on the history of illness in bipolar disorder, Mol. Diagn. Therapy, 16, 303, 10.1007/s40291-012-0004-5 Thier, 2012, Polymorphisms in the glial glutamate transporter SLC1A2 are associated with essential tremor, Neurology, 79, 243, 10.1212/WNL.0b013e31825fdeed Jin, 2012, Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo, Nat. Genet., 44, 676, 10.1038/ng.2272 Silberberg, 2008, Stargazin involvement with bipolar disorder and response to lithium treatment, Pharmacogenet. Genomics, 18, 403, 10.1097/FPC.0b013e3282f974ca R. Weideman, The genetics of lithium-induced adverse drug reactions in bipolar disorder patientsa pilot study (Doctoral dissertation, University of Cape Town). Perlis, 2009, A genomewide association study of response to lithium for prevention of recurrence in bipolar disorder, Am. J. Psychiatry, 166, 718, 10.1176/appi.ajp.2009.08111633 Ferreira, 2008, Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder, Nat. Genet., 40, 1056, 10.1038/ng.209 Dage, 2014, Pharmacological characterisation of ligand-and voltage-gated ion channels expressed in human iPSC-derived forebrain neurons, Psychopharmacology, 231, 1105, 10.1007/s00213-013-3384-2 Athanasiu, 2010, Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort, J. Psychiatr. Res., 44, 748, 10.1016/j.jpsychires.2010.02.002 Hayashi, 2015, Calcium-dependent intracellular signal pathways in primary cultured adipocytes and ANK3 gene variation in patients with bipolar disorder and healthy controls, Mol. Psychiatry, 20, 931, 10.1038/mp.2014.104 Ruderfer, 2014, Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia, Mol. Psychiatry, 19, 1017, 10.1038/mp.2013.138 Ripke, 2013, Genome-wide association analysis identifies 13 new risk loci for schizophrenia, Nat. Genet., 45, 1150, 10.1038/ng.2742 Crawford, 2015, Multiple lithium-dependent Brugada syndrome unmasking events in a bipolar patient, Clin. Case Rep., 3, 14, 10.1002/ccr3.136 McCarthy, 2016, Calcium channel genes associated with bipolar disorder modulate lithium's amplification of circadian rhythms, Neuropharmacology, 29, 439, 10.1016/j.neuropharm.2015.10.017 Byrne, 2013, A genome-wide association study of sleep habits and insomnia, Am. J. Med. Genet. Part B, 162, 439, 10.1002/ajmg.b.32168 Halaweish, 2015, Addition of low-dose valproic acid to saline resuscitation provides neuroprotection and improves long-term outcomes in a large animal model of combined traumatic brain injury and hemorrhagic shock, J. Trauma Acute Care Surg., 79, 911, 10.1097/TA.0000000000000789 Sillesen, 2014, Assessment of coagulopathy, endothelial injury, and inflammation after traumatic brain injury and hemorrhage in a porcine model, J. Trauma Acute Care Surg., 76, 12, 10.1097/TA.0b013e3182aaa675 Lv, 2011, Valproic acid improves outcome after rodent spinal cord injurypotential roles of histone deacetylase inhibition, Brain Res., 17, 60, 10.1016/j.brainres.2011.03.040 Kim, 2009, The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain, J. Neurochem., 110, 1226, 10.1111/j.1471-4159.2009.06212.x Gibson, 2010, Benefits of histone deacetylase inhibitors for acute brain injurya systematic review of animal studies, J. Neurochem., 115, 806, 10.1111/j.1471-4159.2010.06993.x Liu, 2012, Valproic acid increases white matter repair and neurogenesis after stroke, Neuroscience, 220, 313, 10.1016/j.neuroscience.2012.06.012