Neuroprotective Effect of Hydrogen Sulfide Subchronic Treatment Against TBI-Induced Ferroptosis and Cognitive Deficits Mediated Through Wnt Signaling Pathway

Bao WD, Pang P, Zhou XT, Hu F, Xiong W, Chen K, Wang J, Wang F, Xie D, Hu YZ, Han ZT, Zhang HH, Wang WX, Nelson PT, Chen JG, Lu Y, Man HY, Liu D, Zhu LQ (2021) Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease. Cell Death Differ 28:1548–1562. https://doi.org/10.1038/s41418-020-00685-9 Bhattacherjee D, Raina K, Mandal TK, Thummer RP, Bhabak KP (2022) Targeting Wnt/beta-catenin signaling pathway in triple-negative breast cancer by benzylic organotrisulfides: contribution of the released hydrogen sulfide towards potent anti-cancer activity. Free Radic Biol Med 191:82–96. https://doi.org/10.1016/j.freeradbiomed.2022.08.029 Birle C, Slavoaca D, Balea M, Livint Popa L, Muresanu I, Stefanescu E, Vacaras V, Dina C, Strilciuc S, Popescu BO, Muresanu DF (2021) Cognitive function: holarchy or holacracy? Neurol Sci 42:89–99. https://doi.org/10.1007/s10072-020-04737-3 Chen X, Wu S, Tang L, Ma L, Wang F, Feng H, Meng J, Han Z (2019) Mesenchymal stem cells overexpressing heme oxygenase-1 ameliorate lipopolysaccharide-induced acute lung injury in rats. J Cell Physiol 234:7301–7319. https://doi.org/10.1002/jcp.27488 Chen G, Gao C, Yan Y, Wang T, Luo C, Zhang M, Chen X, Tao L (2020) Inhibiting ER stress weakens neuronal pyroptosis in a mouse acute hemorrhagic stroke model. Mol Neurobiol 57:5324–5335. https://doi.org/10.1007/s12035-020-02097-9 Chen X, Gao C, Yan Y, Cheng Z, Chen G, Rui T, Luo C, Gao Y, Wang T, Chen X, Tao L (2021) Ruxolitinib exerts neuroprotection via repressing ferroptosis in a mouse model of traumatic brain injury. Exp Neurol 342:113762. https://doi.org/10.1016/j.expneurol.2021.113762 Chen X, Li J, Kang R, Klionsky DJ, Tang D (2021b) Ferroptosis: machinery and regulation. Autophagy 17:2054–2081. https://doi.org/10.1080/15548627.2020.1810918 Chen X, Huang X, Liu C, Li S, Yang Z, Zhang F, Chen X, Shan H, Tao L, Zhang M (2022) Surface-fill H(2)S-releasing silk fibroin hydrogel for brain repair through the repression of neuronal pyroptosis. Acta Biomater 154:259–274. https://doi.org/10.1016/j.actbio.2022.11.021 Conrad M, Pratt DA (2019) The chemical basis of ferroptosis. Nat Chem Biol 15:1137–1147. https://doi.org/10.1038/s41589-019-0408-1 D’Amico R, Trovato Salinaro A, Fusco R, Cordaro M, Impellizzeri D, Scuto M, Ontario ML, Lo Dico G, Cuzzocrea S, Di Paola R, Siracusa R, Calabrese V (2021) Hericium erinaceus and coriolus versicolor modulate molecular and biochemical changes after traumatic brain injury. Antioxidants. https://doi.org/10.3390/antiox10060898 Fang X, Cai Z, Wang H, Han D, Cheng Q, Zhang P, Gao F, Yu Y, Song Z, Wu Q, An P, Huang S, Pan J, Chen HZ, Chen J, Linkermann A, Min J, Wang F (2020) Loss of cardiac ferritin H facilitates cardiomyopathy via Slc7a11-mediated ferroptosis. Circ Res 127:486–501. https://doi.org/10.1161/CIRCRESAHA.120.316509 Fei YX, Zhu JP, Zhao B, Yin QY, Fang WR, Li YM (2020) XQ-1H regulates Wnt/GSK3beta/beta-catenin pathway and ameliorates the integrity of blood brain barrier in mice with acute ischemic stroke. Brain Res Bull 164:269–288. https://doi.org/10.1016/j.brainresbull.2020.08.032 Feng Z, Hua S, Li W, Han J, Li F, Chen H, Zhang Z, Xie Y, Ouyang Q, Zou X, Liu Z, Li C, Huang S, Lai Z, Cai X, Cai Y, Zou Y, Tang Y, Jiang X (2022) Mesenchymal stem cells protect against TBI-induced pyroptosis in vivo and in vitro through TSG-6. Cell Commun Signal 20:125. https://doi.org/10.1186/s12964-022-00931-2 Gao M, Monian P, Quadri N, Ramasamy R, Jiang X (2015) Glutaminolysis and transferrin regulate ferroptosis. Mol Cell 59:298–308. https://doi.org/10.1016/j.molcel.2015.06.011 Gao J, Li Y, Song R (2021) SIRT2 inhibition exacerbates p53-mediated ferroptosis in mice following experimental traumatic brain injury. NeuroReport 32:1001–1008. https://doi.org/10.1097/WNR.0000000000001679 Gao Y, Wang T, Cheng Y, Wu Y, Zhu L, Gu Z, Wu Y, Cai L, Wu Y, Zhang Y, Gao C, Li L, Li J, Li Q, Wang Z, Wang Y, Wang F, Luo C, Tao L (2023) Melatonin ameliorates neurological deficits through MT2/IL-33/ferritin H signaling-mediated inhibition of neuroinflammation and ferroptosis after traumatic brain injury. Free Radic Biol Med 199:97–112. https://doi.org/10.1016/j.freeradbiomed.2023.02.014 Geng Z, Guo Z, Guo R, Ye R, Zhu W, Yan B (2021) Ferroptosis and traumatic brain injury. Brain Res Bull 172:212–219. https://doi.org/10.1016/j.brainresbull.2021.04.023 Guo R, Wang X, Fang Y, Chen X, Chen K, Huang W, Chen J, Hu J, Liang F, Du J, Dordoe C, Tian X, Lin L (2021) rhFGF20 promotes angiogenesis and vascular repair following traumatic brain injury by regulating Wnt/beta-catenin pathway. Biomed Pharmacother 143:112200. https://doi.org/10.1016/j.biopha.2021.112200 Guo T, Chen M, Liu J, Wei Z, Yuan J, Wu W, Wu Z, Lai Y, Zhao Z, Chen H, Liu N (2023) Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia. J Transl Med 21:297. https://doi.org/10.1186/s12967-023-04125-3 Hambright WS, Fonseca RS, Chen L, Na R, Ran Q (2017) Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox Biol 12:8–17. https://doi.org/10.1016/j.redox.2017.01.021 Hu T, Han Z, Xiong X, Li M, Guo M, Yin Z, Wang D, Cheng L, Li D, Zhang S, Wang L, Zhao J, Liu Q, Chen F, Lei P (2022) Inhibition of exosome release alleviates cognitive impairment after repetitive mild traumatic brain injury. Front Cell Neurosci 16:832140. https://doi.org/10.3389/fncel.2022.832140 Hu X, Zhang H, Zhang Q, Yao X, Ni W, Zhou K (2022b) Emerging role of STING signalling in CNS injury: inflammation, autophagy, necroptosis, ferroptosis and pyroptosis. J Neuroinflammation 19:242. https://doi.org/10.1186/s12974-022-02602-y Huerta de la Cruz S, Rocha L, Santiago-Castaneda C, Sanchez-Lopez A, Pinedo-Rodriguez AD, Medina-Terol GJ, Centurion D (2022) Hydrogen sulfide subchronic treatment improves hypertension induced by traumatic brain injury in rats through vasopressor sympathetic outflow inhibition. J Neurotrauma 39:181–195. https://doi.org/10.1089/neu.2020.7552 Jang J, Jung Y, Chae S, Bae T, Kim SM, Shim YJ, Chung SI, Yoon Y (2019) XAV939, a Wnt/beta-catenin pathway modulator, has inhibitory effects on LPS-induced inflammatory response. Immunopharmacol Immunotoxicol 41:394–402. https://doi.org/10.1080/08923973.2018.1536984 Jassam YN, Izzy S, Whalen M, McGavern DB, El Khoury J (2017) Neuroimmunology of traumatic brain injury: time for a paradigm shift. Neuron 95:1246–1265. https://doi.org/10.1016/j.neuron.2017.07.010 Jiang X, Stockwell BR, Conrad M (2021) Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 22:266–282. https://doi.org/10.1038/s41580-020-00324-8 Katoh M (2018) Multi-layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/beta-catenin signaling activation (Review). Int J Mol Med 42:713–725. https://doi.org/10.3892/ijmm.2018.3689 Khellaf A, Khan DZ, Helmy A (2019) Recent advances in traumatic brain injury. J Neurol 266:2878–2889. https://doi.org/10.1007/s00415-019-09541-4 Kimura Y, Dargusch R, Schubert D, Kimura H (2006) Hydrogen sulfide protects HT22 neuronal cells from oxidative stress. Antioxid Redox Signal 8:661–670. https://doi.org/10.1089/ars.2006.8.661 Kumar M, Arora P, Sandhir R (2021) Hydrogen sulfide reverses LPS-induced behavioral deficits by suppressing microglial activation and promoting M2 polarization. J Neuroimmune Pharmacol 16:483–499. https://doi.org/10.1007/s11481-020-09920-z Li M, Gao W, Ji L, Li J, Jiang W, Ji W (2020) Methane Saline ameliorates traumatic brain injury through anti-inflammatory, antiapoptotic, and antioxidative effects by activating the wnt signalling pathway. Biomed Res Int 2020:3852450. https://doi.org/10.1155/2020/3852450 Li J, Li M, Li L, Ma J, Yao C, Yao S (2022) Hydrogen sulfide attenuates ferroptosis and stimulates autophagy by blocking mTOR signaling in sepsis-induced acute lung injury. Mol Immunol 141:318–327. https://doi.org/10.1016/j.molimm.2021.12.003 Lin L, Zheng S, Lai J, Ye D, Huang Q, Wu Z, Chen X, Wang S (2023) Omega-3 polyunsaturated fatty acids protect neurological function after traumatic brain injury by suppressing microglial transformation to the proinflammatory phenotype and activating exosomal NGF/TrkA signaling. Mol Neurobiol. https://doi.org/10.1007/s12035-023-03419-3 Liu J, Xiao Q, Xiao J, Niu C, Li Y, Zhang X, Zhou Z, Shu G, Yin G (2022) Wnt/beta-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther 7:3. https://doi.org/10.1038/s41392-021-00762-6 Luo L, Langley C, Moreno-Lopez L, Kendrick K, Menon DK, Stamatakis EA, Sahakian BJ (2023) Depressive symptoms following traumatic brain injury are associated with resting-state functional connectivity. Psychol Med 53:2698–2705. https://doi.org/10.1017/S0033291721004724 Mahoney-Sanchez L, Bouchaoui H, Ayton S, Devos D, Duce JA, Devedjian JC (2021) Ferroptosis and its potential role in the physiopathology of Parkinson’s Disease. Prog Neurobiol 196:101890. https://doi.org/10.1016/j.pneurobio.2020.101890 Maiorino M, Conrad M, Ursini F (2018) GPx4, lipid peroxidation, and cell death: discoveries, rediscoveries, and open issues. Antioxid Redox Signal 29:61–74. https://doi.org/10.1089/ars.2017.7115 Matei N, Camara J, McBride D, Camara R, Xu N, Tang J, Zhang JH (2018) Intranasal wnt3a attenuates neuronal apoptosis through Frz1/PIWIL1a/FOXM1 pathway in MCAO Rats. J Neurosci 38:6787–6801. https://doi.org/10.1523/JNEUROSCI.2352-17.2018 Meyfroidt G, Bouzat P, Casaer MP, Chesnut R, Hamada SR, Helbok R, Hutchinson P, Maas AIR, Manley G, Menon DK, Newcombe VFJ, Oddo M, Robba C, Shutter L, Smith M, Steyerberg EW, Stocchetti N, Taccone FS, Wilson L, Zanier ER, Citerio G (2022) Management of moderate to severe traumatic brain injury: an update for the intensivist. Intensive Care Med 48:649–666. https://doi.org/10.1007/s00134-022-06702-4 Miess H, Dankworth B, Gouw AM, Rosenfeldt M, Schmitz W, Jiang M, Saunders B, Howell M, Downward J, Felsher DW, Peck B, Schulze A (2018) The glutathione redox system is essential to prevent ferroptosis caused by impaired lipid metabolism in clear cell renal cell carcinoma. Oncogene 37:5435–5450. https://doi.org/10.1038/s41388-018-0315-z Mohammad KUA, Warsi MH, Alkreathy HM, Karim S, Jain GK, Ali A (2023) Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats. Front Pharmacol 14:1188470. https://doi.org/10.3389/fphar.2023.1188470 Robert S (2020) Traumatic brain injury and mood disorders. Ment Health Clin 10:335–345. https://doi.org/10.9740/mhc.2020.11.335 Rui T, Wang H, Li Q, Cheng Y, Gao Y, Fang X, Ma X, Chen G, Gao C, Gu Z, Song S, Zhang J, Wang C, Wang Z, Wang T, Zhang M, Min J, Chen X, Tao L, Wang F, Luo C (2021) Deletion of ferritin H in neurons counteracts the protective effect of melatonin against traumatic brain injury-induced ferroptosis. J Pineal Res 70:e12704. https://doi.org/10.1111/jpi.12704 Song S, Huang H, Guan X, Fiesler V, Bhuiyan MIH, Liu R, Jalali S, Hasan MN, Tai AK, Chattopadhyay A, Chaparala S, Sun M, Stolz DB, He P, Agalliu D, Sun D, Begum G (2021) Activation of endothelial Wnt/beta-catenin signaling by protective astrocytes repairs BBB damage in ischemic stroke. Prog Neurobiol 199:101963. https://doi.org/10.1016/j.pneurobio.2020.101963 Sun J, Li X, Gu X, Du H, Zhang G, Wu J, Wang F (2021) Neuroprotective effect of hydrogen sulfide against glutamate-induced oxidative stress is mediated via the p53/glutaminase 2 pathway after traumatic brain injury. Aging 13:7180–7189. https://doi.org/10.18632/aging.202575 Tang D, Chen X, Kang R, Kroemer G (2021) Ferroptosis: molecular mechanisms and health implications. Cell Res 31:107–125. https://doi.org/10.1038/s41422-020-00441-1 Wang Y, Wang S, Xin Y, Zhang J, Wang S, Yang Z, Liu C (2021) Hydrogen sulfide alleviates the anxiety-like and depressive-like behaviors of type 1 diabetic mice via inhibiting inflammation and ferroptosis. Life Sci 278:119551. https://doi.org/10.1016/j.lfs.2021.119551 Wang D, Zhang S, Ge X, Yin Z, Li M, Guo M, Hu T, Han Z, Kong X, Li D, Zhao J, Wang L, Liu Q, Chen F, Lei P (2022a) Mesenchymal stromal cell treatment attenuates repetitive mild traumatic brain injury-induced persistent cognitive deficits via suppressing ferroptosis. J Neuroinflammation 19:185. https://doi.org/10.1186/s12974-022-02550-7 Wang H, Zhang H, Chen Y, Wang H, Tian Y, Yi X, Shi Q, Zhao T, Zhang B, Gao T, Guo S, Li C, Guo W (2022) Targeting Wnt/beta-catenin signaling exacerbates ferroptosis and increases the efficacy of melanoma immunotherapy via the regulation of MITF. Cells. https://doi.org/10.3390/cells11223580 Wang Y, Liao S, Pan Z, Jiang S, Fan J, Yu S, Xue L, Yang J, Ma S, Liu T, Zhang J, Chen Y (2022c) Hydrogen sulfide alleviates particulate matter-induced emphysema and airway inflammation by suppressing ferroptosis. Free Radic Biol Med 186:1–16. https://doi.org/10.1016/j.freeradbiomed.2022.04.014 Wang Y, Zheng L, Shang W, Yang Z, Li T, Liu F, Shao W, Lv L, Chai L, Qu L, Xu Q, Du J, Liang X, Zeng J, Jia J (2022d) Wnt/beta-catenin signaling confers ferroptosis resistance by targeting GPX4 in gastric cancer. Cell Death Differ 29:2190–2202. https://doi.org/10.1038/s41418-022-01008-w Wei ZZ, Zhang JY, Taylor TM, Gu X, Zhao Y, Wei L (2018) Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice. J Cereb Blood Flow Metab 38:404–421. https://doi.org/10.1177/0271678X17702669 Wu H, Yu W, Meng F, Mi J, Peng J, Liu J, Zhang X, Hai C, Wang X (2017) Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-kappaB signaling via downregulation of HNF1b. Redox Biol 12:300–310. https://doi.org/10.1016/j.redox.2017.02.026 Xie BS, Wang YQ, Lin Y, Mao Q, Feng JF, Gao GY, Jiang JY (2019) Inhibition of ferroptosis attenuates tissue damage and improves long-term outcomes after traumatic brain injury in mice. CNS Neurosci Ther 25:465–475. https://doi.org/10.1111/cns.13069 Xu X, Yin D, Ren H, Gao W, Li F, Sun D, Wu Y, Zhou S, Lyu L, Yang M, Xiong J, Han L, Jiang R, Zhang J (2018) Selective NLRP3 inflammasome inhibitor reduces neuroinflammation and improves long-term neurological outcomes in a murine model of traumatic brain injury. Neurobiol Dis 117:15–27. https://doi.org/10.1016/j.nbd.2018.05.016 Zhang M, Ye M (2019) Hydrogen sulfide attenuates high glucose-induced myocardial injury in rat cardiomyocytes by suppressing wnt/beta-catenin pathway. Curr Med Sci 39:938–946. https://doi.org/10.1007/s11596-019-2120-5 Zhang M, Shan H, Chang P, Wang T, Dong W, Chen X, Tao L (2014) Hydrogen sulfide offers neuroprotection on traumatic brain injury in parallel with reduced apoptosis and autophagy in mice. PLoS One 9:e87241. https://doi.org/10.1371/journal.pone.0087241 Zhang JY, Lee JH, Gu X, Wei ZZ, Harris MJ, Yu SP, Wei L (2018) Intranasally delivered wnt3a improves functional recovery after traumatic brain injury by modulating autophagic, apoptotic, and regenerative pathways in the mouse brain. J Neurotrauma 35:802–813. https://doi.org/10.1089/neu.2016.4871 Zhang J, Zhang S, Shan H, Zhang M (2020a) Biologic effect of hydrogen sulfide and its role in traumatic brain injury. Oxid Med Cell Longev 2020:7301615. https://doi.org/10.1155/2020/7301615 Zhang Y, Yang J, Yang X, Wu Y, Liu J, Wang Y, Huo F, Yan C (2020b) The 5-HT(6) receptors in the ventrolateral orbital cortex attenuate allodynia in a rodent model of neuropathic pain. Front Neurosci 14:884. https://doi.org/10.3389/fnins.2020.00884 Zhang R, Lei J, Chen L, Wang Y, Yang G, Yin Z, Luo L (2022) Gamma-glutamylcysteine exerts neuroprotection effects against cerebral ischemia/reperfusion injury through inhibiting lipid peroxidation and ferroptosis. Antioxidants (Basel). https://doi.org/10.3390/antiox11091653 Zhao B, Zhu J, Fei Y, Yin Q, Shen W, Liang B, Zhu X, Li Y (2020) JLX001 attenuates blood-brain barrier dysfunction in MCAO/R rats via activating the Wnt/beta-catenin signaling pathway. Life Sci 260:118221. https://doi.org/10.1016/j.lfs.2020.118221 Zhou MY, Zhang YJ, Ding HM, Wu WF, Cai WW, Wang YQ, Geng DQ (2022) Diprotin A TFA exerts neurovascular protection in ischemic cerebral stroke. Front Neurosci 16:861059. https://doi.org/10.3389/fnins.2022.861059