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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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General Review Article

The Role of Nrf2 in Relieving Cerebral Ischemia-Reperfusion Injury

Author(s): Yu Sun, Xu Yang, Lijun Xu, Mengxiao Jia, Limeng Zhang, Peng Li* and Pengfei Yang*

Volume 21, Issue 6, 2023

Published on: 03 January, 2023

Page: [1405 - 1420] Pages: 16

DOI: 10.2174/1570159X21666221129100308

Price: $65

Abstract

Ischemic stroke includes two related pathological damage processes: brain injury caused by primary ischemia and secondary ischemia reperfusion (I/R) injury. I/R injury has become a worldwide health problem. Unfortunately, there is still a lack of satisfactory drugs for ameliorating cerebral I/R damage. Nrf2 is a vital endogenous antioxidant protein, which combines with Keap1 to maintain a dormant state under physiological conditions. When pathological changes such as I/R occurs, Nrf2 dissociates from Keap1 and activates the expression of downstream antioxidant proteins to exert a protective effect. Recent research have shown that the activated Nrf2 not only effectively inhibits oxidative stress, but also performs the ability to repair the function of compromised mitochondria, alleviate endoplasmic reticulum stress, eliminate inflammatory response, reduce blood-brain barrier permeability, inhibit neuronal apoptosis, enhance the neural network remolding, thereby exerting significant protective effects in alleviating the injuries caused by cell oxygen-glucose deprivation, or animal cerebral I/R. However, no definite clinical application report demonstrated the efficacy of Nrf2 activators in the treatment of cerebral I/R. Therefore, further efforts are needed to elaborate the role of Nrf2 activators in the treatment of cerebral I/R. Here, we reviewed the possible mechanisms underlying its potential pharmacological benefits in alleviating cerebral I/R injury, so as to provide a theoretical basis for studying its mechanism and developing Nrf2 activators.

Keywords: Stroke, ischemic stroke, I/R, Nrf2, oxidative stress, hormesis.

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[1]
Barthels, D.; Das, H. Current advances in ischemic stroke research and therapies. Biochim. Biophys. Acta Mol. Basis Dis., 2020, 1866(4), 165260.
[http://dx.doi.org/10.1016/j.bbadis.2018.09.012] [PMID: 31699365]
[2]
Salim, S. Oxidative stress and the central nervous system. J. Pharmacol. Exp. Ther., 2017, 360(1), 201-205.
[http://dx.doi.org/10.1124/jpet.116.237503] [PMID: 27754930]
[3]
Jackman, K.; Iadecola, C. Neurovascular regulation in the ischemic brain. Antioxid. Redox Signal., 2015, 22(2), 149-160.
[http://dx.doi.org/10.1089/ars.2013.5669] [PMID: 24328757]
[4]
Bhaskar, S.; Stanwell, P.; Cordato, D.; Attia, J.; Levi, C. Reperfusion therapy in acute ischemic stroke: dawn of a new era? BMC Neurol., 2018, 18(1), 8.
[http://dx.doi.org/10.1186/s12883-017-1007-y] [PMID: 29338750]
[5]
Yuan, Q.; Yuan, Y.; Zheng, Y.; Sheng, R.; Liu, L.; Xie, F.; Tan, J. Anti-cerebral ischemia reperfusion injury of polysaccharides: A review of the mechanisms. Biomed. Pharmacother., 2021, 137, 111303.
[http://dx.doi.org/10.1016/j.biopha.2021.111303] [PMID: 33517189]
[6]
Zhang, W.; Song, J.; Yan, R.; Li, L.; Xiao, Z.; Zhou, W.; Wang, Z.; Xiao, W.; Du, G. Diterpene ginkgolides protect against cerebral ischemia/reperfusion damage in rats by activating Nrf2 and CREB through PI3K/Akt signaling. Acta Pharmacol. Sin., 2018, 39(8), 1259-1272.
[http://dx.doi.org/10.1038/aps.2017.149] [PMID: 29542683]
[7]
Chen, Q.M. Nrf2 for protection against oxidant generation and mitochondrial damage in cardiac injury. Free Radic. Biol. Med., 2022, 179, 133-143.
[http://dx.doi.org/10.1016/j.freeradbiomed.2021.12.001] [PMID: 34921930]
[8]
Nakano, Y.; Yamashita, T.; Li, Q.; Sato, K.; Ohta, Y.; Morihara, R.; Hishikawa, N.; Abe, K. Time-dependent change of in vivo optical imaging of oxidative stress in a mouse stroke model. J. Neurosci. Res., 2017, 95(10), 2030-2039.
[http://dx.doi.org/10.1002/jnr.24047] [PMID: 28276088]
[9]
Narayanan, S.V.; Dave, K.R.; Saul, I.; Perez-Pinzon, M.A. Resveratrol preconditioning protects against cerebral ischemic injury via nuclear erythroid 2-related factor 2. Stroke, 2015, 46(6), 1626-1632.
[http://dx.doi.org/10.1161/STROKEAHA.115.008921] [PMID: 25908459]
[10]
Dang, J; Brandenburg, L; Rosen, C Nrf2 expression by neurons, astroglia, and microglia in the cerebral cortical penumbra of ischemic rats. Journal of molecular neuroscience : MN, 2012, 46(3), 578-584.
[http://dx.doi.org/10.1007/s12031-011-9645-9]
[11]
Meng, X.; Wang, M.; Wang, X.; Sun, G.; Ye, J.; Xu, H.; Sun, X. Suppression of NADPH oxidase- and mitochondrion-derived superoxide by Notoginsenoside R1 protects against cerebral ischemia–reperfusion injury through estrogen receptor-dependent activation of Akt/Nrf2 pathways. Free Radic. Res., 2014, 48(7), 823-838.
[http://dx.doi.org/10.3109/10715762.2014.911853] [PMID: 24720662]
[12]
Wang, J.; Fields, J.; Zhao, C.; Langer, J.; Thimmulappa, R.K.; Kensler, T.W.; Yamamoto, M.; Biswal, S.; Doré, S. Role of Nrf2 in protection against intracerebral hemorrhage injury in mice. Free Radic. Biol. Med., 2007, 43(3), 408-414.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.04.020] [PMID: 17602956]
[13]
Zhao, X.; Sun, G.; Zhang, J.; Ting, S.M.; Gonzales, N.; Aronowski, J. Dimethyl fumarate protects brain from damage produced by intracerebral hemorrhage by mechanism involving Nrf2. Stroke, 2015, 46(7), 1923-1928.
[http://dx.doi.org/10.1161/STROKEAHA.115.009398] [PMID: 25977275]
[14]
Shah, Z.A.; Li, R.C.; Ahmad, A.S.; Kensler, T.W.; Yamamoto, M.; Biswal, S.; Doré, S. The flavanol (-)-epicatechin prevents stroke damage through the Nrf2/HO1 pathway. J. Cereb. Blood Flow Metab., 2010, 30(12), 1951-1961.
[http://dx.doi.org/10.1038/jcbfm.2010.53] [PMID: 20442725]
[15]
Li, Q.; Lou, J.; Yang, T.; Wei, Z.; Zhang, F. Ischemic preconditioning induces oligodendrogenesis in mouse brain: Effects of Nrf2 Deficiency. Cell. Mol. Neurobiol., 2022, 42(6), 59-73.
[PMID: 33666795]
[16]
Calabrese, V.; Cornelius, C.; Dinkova-Kostova, A.T.; Calabrese, E.J.; Mattson, M.P. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid. Redox Signal., 2010, 13(11), 1763-1811.
[http://dx.doi.org/10.1089/ars.2009.3074] [PMID: 20446769]
[17]
Calabrese, E.J.; Kozumbo, W.J. The phytoprotective agent sulforaphane prevents inflammatory degenerative diseases and age-related pathologies via Nrf2-mediated hormesis. Pharmacol. Res., 2021, 163, 105283.
[http://dx.doi.org/10.1016/j.phrs.2020.105283] [PMID: 33160067]
[18]
Calabrese, E.J.; Kozumbo, W.J. The hormetic dose-response mechanism: Nrf2 activation. Pharmacol. Res., 2021, 167, 105526.
[http://dx.doi.org/10.1016/j.phrs.2021.105526] [PMID: 33667690]
[19]
Calabrese, E.J.; Bachmann, K.A.; Bailer, A.J.; Bolger, P.M.; Borak, J.; Cai, L.; Cedergreen, N.; Cherian, M.G.; Chiueh, C.C.; Clarkson, T.W.; Cook, R.R.; Diamond, D.M.; Doolittle, D.J.; Dorato, M.A.; Duke, S.O.; Feinendegen, L.; Gardner, D.E.; Hart, R.W.; Hastings, K.L.; Hayes, A.W.; Hoffmann, G.R.; Ives, J.A.; Jaworowski, Z.; Johnson, T.E.; Jonas, W.B.; Kaminski, N.E.; Keller, J.G.; Klaunig, J.E.; Knudsen, T.B.; Kozumbo, W.J.; Lettieri, T.; Liu, S.Z.; Maisseu, A.; Maynard, K.I.; Masoro, E.J.; McClellan, R.O.; Mehendale, H.M.; Mothersill, C.; Newlin, D.B.; Nigg, H.N.; Oehme, F.W.; Phalen, R.F.; Philbert, M.A.; Rattan, S.I.S.; Riviere, J.E.; Rodricks, J.; Sapolsky, R.M.; Scott, B.R.; Seymour, C.; Sinclair, D.A.; Smith-Sonneborn, J.; Snow, E.T.; Spear, L.; Stevenson, D.E.; Thomas, Y.; Tubiana, M.; Williams, G.M.; Mattson, M.P. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose–response framework. Toxicol. Appl. Pharmacol., 2007, 222(1), 122-128.
[http://dx.doi.org/10.1016/j.taap.2007.02.015] [PMID: 17459441]
[20]
Calabrese, E.J. Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations. Pharmacol. Res., 2016, 110, 242-264.
[http://dx.doi.org/10.1016/j.phrs.2015.12.021] [PMID: 26757428]
[21]
Yang, T.; Sun, Y.; Li, Q.; Li, S.; Shi, Y.; Leak, R.K.; Chen, J.; Zhang, F. Ischemic preconditioning provides long-lasting neuroprotection against ischemic stroke: The role of Nrf2. Exp. Neurol., 2020, 325, 113142.
[http://dx.doi.org/10.1016/j.expneurol.2019.113142] [PMID: 31812555]
[22]
Cornelius, C.; Koverech, G.; Crupi, R.; Di Paola, R.; Koverech, A.; Lodato, F.; Scuto, M.; Salinaro, A.T.; Cuzzocrea, S.; Calabrese, E.J.; Calabrese, V. Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling. Front. Pharmacol., 2014, 5, 120.
[http://dx.doi.org/10.3389/fphar.2014.00120] [PMID: 24959146]
[23]
Glantz, L.; Avramovich, A.; Trembovler, V.; Gurvitz, V.; Kohen, R.; Eidelman, L.A.; Shohami, E. Ischemic preconditioning increases antioxidants in the brain and peripheral organs after cerebral ischemia. Exp. Neurol., 2005, 192(1), 117-124.
[http://dx.doi.org/10.1016/j.expneurol.2004.11.012] [PMID: 15698625]
[24]
He, J.T.; Li, H.; Yang, L.; Cheng, K.L. Involvement of endothelin-1, HS and Nrf2 in beneficial effects of remote ischemic preconditioning in global cerebral ischemia-induced vascular dementia in mice. Cell. Mol. Neurobiol., 2019, 39(5), 671-686.
[http://dx.doi.org/10.1007/s10571-019-00670-y] [PMID: 31025223]
[25]
Tuazon, J.P.; Castelli, V.; Lee, J.Y.; Desideri, G.B.; Stuppia, L.; Cimini, A.M.; Borlongan, C.V. Neural stem cells. Adv. Exp. Med. Biol., 2019, 1201, 79-91.
[http://dx.doi.org/10.1007/978-3-030-31206-0_4] [PMID: 31898782]
[26]
Narayanan, S.V.; Dave, K.R.; Perez-Pinzon, M.A. Ischemic preconditioning protects astrocytes against oxygen glucose deprivation via the nuclear erythroid 2-related factor 2 pathway. Transl. Stroke Res., 2018, 9(2), 99-109.
[http://dx.doi.org/10.1007/s12975-017-0574-y] [PMID: 29103101]
[27]
Ma, F.; Zhang, X.; Yin, K.J. MicroRNAs in central nervous system diseases: A prospective role in regulating blood-brain barrier integrity. Exp. Neurol., 2020, 323, 113094.
[http://dx.doi.org/10.1016/j.expneurol.2019.113094] [PMID: 31676317]
[28]
Yang, T.; Sun, Y.; Mao, L.; Zhang, M.; Li, Q.; Zhang, L.; Shi, Y.; Leak, R.K.; Chen, J.; Zhang, F. Brain ischemic preconditioning protects against ischemic injury and preserves the blood-brain barrier via oxidative signaling and Nrf2 activation. Redox Biol., 2018, 17, 323-337.
[http://dx.doi.org/10.1016/j.redox.2018.05.001] [PMID: 29775963]
[29]
Bell, K.F.S.; Fowler, J.H.; Al-Mubarak, B.; Horsburgh, K.; Hardingham, G.E. Activation of Nrf2-regulated glutathione pathway genes by ischemic preconditioning. Oxid. Med. Cell. Longev., 2011, 2011, 1-7.
[http://dx.doi.org/10.1155/2011/689524] [PMID: 21904646]
[30]
Bell, K.F.; Al-Mubarak, B.; Fowler, J.H.; Baxter, P.S.; Gupta, K.; Tsujita, T.; Chowdhry, S.; Patani, R.; Chandran, S.; Horsburgh, K.; Hayes, J.D.; Hardingham, G.E. Mild oxidative stress activates Nrf2 in astrocytes, which contributes to neuroprotective ischemic preconditioning. Proc. Natl. Acad. Sci. USA, 2011, 108(1), E1-E2.
[http://dx.doi.org/10.1073/pnas.1015229108] [PMID: 21177433]
[31]
Lee, J.C.; Kim, I.H.; Park, J.H.; Ahn, J.H.; Cho, J.H.; Cho, G.S.; Tae, H.J.; Chen, B.H.; Yan, B.C.; Yoo, K.Y.; Choi, J.H.; Lee, C.H.; Hwang, I.K.; Cho, J.H.; Kwon, Y.G.; Kim, Y.M.; Won, M.H. Ischemic preconditioning protects hippocampal pyramidal neurons from transient ischemic injury via the attenuation of oxidative damage through upregulating heme oxygenase-1. Free Radic. Biol. Med., 2015, 79, 78-90.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.11.022] [PMID: 25483558]
[32]
Jusic, A.; Devaux, Y. Mitochondrial noncoding RNA-regulatory network in cardiovascular disease. Basic Res. Cardiol., 2020, 115(3), 23.
[http://dx.doi.org/10.1007/s00395-020-0783-5] [PMID: 32140778]
[33]
van der Giezen, M.; Tovar, J. Degenerate mitochondria. EMBO Rep., 2005, 6(6), 525-530.
[http://dx.doi.org/10.1038/sj.embor.7400440] [PMID: 15940286]
[34]
Andrabi, S.S.; Parvez, S.; Tabassum, H. Ischemic stroke and mitochondria: mechanisms and targets. Protoplasma, 2020, 257(2), 335-343.
[http://dx.doi.org/10.1007/s00709-019-01439-2] [PMID: 31612315]
[35]
He, Z.; Ning, N.; Zhou, Q.; Khoshnam, S.E.; Farzaneh, M. Mitochondria as a therapeutic target for ischemic stroke. Free Radic. Biol. Med., 2020, 146, 45-58.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.11.005] [PMID: 31704373]
[36]
Turrens, J.F. Mitochondrial formation of reactive oxygen species. J. Physiol., 2003, 552(2), 335-344.
[http://dx.doi.org/10.1113/jphysiol.2003.049478] [PMID: 14561818]
[37]
Song, X.; Zhang, L.; Hui, X.; Sun, X.; Yang, J.; Wang, J.; Wu, H.; Wang, X.; Zheng, Z.; Che, F.; Wang, G. Selenium-containing protein from selenium-enriched Spirulina platensis antagonizes oxygen glucose deprivation-induced neurotoxicity by inhibiting ROS-mediated oxidative damage through regulating MPTP opening. Pharm. Biol., 2021, 59(1), 627-636.
[http://dx.doi.org/10.1080/13880209.2021.1928715] [PMID: 34062090]
[38]
Guo, J.D.; Zhao, X.; Li, Y.; Li, G.R.; Liu, X.L. Damage to dopaminergic neurons by oxidative stress in Parkinson’s disease (Review). Int. J. Mol. Med., 2018, 41(4), 1817-1825.
[http://dx.doi.org/10.3892/ijmm.2018.3406] [PMID: 29393357]
[39]
Anzell, A.R.; Maizy, R.; Przyklenk, K.; Sanderson, T.H. Mitochondrial quality control and disease: Insights into ischemia-reperfusion injury. Mol. Neurobiol., 2018, 55(3), 2547-2564.
[http://dx.doi.org/10.1007/s12035-017-0503-9] [PMID: 28401475]
[40]
Zhang, Y.; Cao, Y.; Liu, C. Autophagy and ischemic stroke. Adv. Exp. Med. Biol., 2020, 1207, 111-134.
[http://dx.doi.org/10.1007/978-981-15-4272-5_7] [PMID: 32671742]
[41]
Shen, Z.; Zheng, Y.; Wu, J.; Chen, Y.; Wu, X.; Zhou, Y.; Yuan, Y.; Lu, S.; Jiang, L.; Qin, Z.; Chen, Z.; Hu, W.; Zhang, X. PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window. Autophagy, 2017, 13(3), 473-485.
[http://dx.doi.org/10.1080/15548627.2016.1274596] [PMID: 28103118]
[42]
LX, A.; XX, A.; FZ, A. The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1. Redox Biol., 2017, 11, 297-311.
[43]
Kitagishi, Y.; Nakano, N.; Ogino, M.; Ichimura, M.; Minami, A.; Matsuda, S. PINK1 signaling in mitochondrial homeostasis and in aging (Review). Int. J. Mol. Med., 2017, 39(1), 3-8.
[http://dx.doi.org/10.3892/ijmm.2016.2827] [PMID: 27959386]
[44]
Xu, B.; Zhu, L.; Chu, J.; Ma, Z.; Fu, Q.; Wei, W.; Deng, X.; Ma, S. Esculetin improves cognitive impairments induced by transient cerebral ischaemia and reperfusion in mice via regulation of mitochondrial fragmentation and mitophagy. Behav. Brain Res., 2019, 372, 112007.
[http://dx.doi.org/10.1016/j.bbr.2019.112007] [PMID: 31238056]
[45]
Zhang, T.; Wu, P.; Budbazar, E.; Zhu, Q.; Sun, C.; Mo, J.; Peng, J.; Gospodarev, V.; Tang, J.; Shi, H.; Zhang, J.H. Mitophagy reduces oxidative stress via Keap1 (kelch-Like epichlorohydrin-associated protein 1)/Nrf2 (nuclear factor-E2-related factor 2)/PHB2 (prohibitin 2) pathway after subarachnoid hemorrhage in rats. Stroke, 2019, 50(4), 978-988.
[http://dx.doi.org/10.1161/STROKEAHA.118.021590] [PMID: 30890112]
[46]
Jiang, T.; Harder, B.; Rojo de la Vega, M.; Wong, P.K.; Chapman, E.; Zhang, D.D. p62 links autophagy and Nrf2 signaling. Free Radic. Biol. Med., 2015, 88(Pt B), 199-204.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.06.014] [PMID: 26117325]
[47]
Zhang, W.; Feng, C.; Jiang, H. Novel target for treating Alzheimer’s Diseases: Crosstalk between the Nrf2 pathway and autophagy. Ageing Res. Rev., 2021, 65(1), 101207.
[http://dx.doi.org/10.1016/j.arr.2020.101207] [PMID: 33144123]
[48]
Gu, C.; Yan, J.; Zhao, L.; Wu, G.; Wang, Y. Regulation of mitochondrial dynamics by aerobic exercise in cardiovascular diseases. Front. Cardiovasc. Med., 2022, 87, 88505.
[http://dx.doi.org/10.3389/fcvm.2021.788505] [PMID: 35097008]
[49]
Forte, M.; Schirone, L.; Ameri, P.; Basso, C.; Catalucci, D.; Modica, J.; Chimenti, C.; Crotti, L.; Frati, G.; Rubattu, S.; Schiattarella, G.G.; Torella, D.; Perrino, C.; Indolfi, C.; Sciarretta, S. The role of mitochondrial dynamics in cardiovascular diseases. Br. J. Pharmacol., 2021, 178(10), 2060-2076.
[http://dx.doi.org/10.1111/bph.15068] [PMID: 32294237]
[50]
Westrate, L.M.; Drocco, J.A.; Martin, K.R.; Hlavacek, W.S.; MacKeigan, J.P. Mitochondrial morphological features are associated with fission and fusion events. PLoS One, 2014, 9(4), e95265.
[http://dx.doi.org/10.1371/journal.pone.0095265] [PMID: 24733410]
[51]
Tian, H.; Chen, X.; Liao, J.; Yang, T.; Cheng, S.; Mei, Z.; Ge, J. Mitochondrial quality control in stroke: From the mechanisms to therapeutic potentials. J. Cell. Mol. Med., 2022, 26(4), 1000-1012.
[http://dx.doi.org/10.1111/jcmm.17189] [PMID: 35040556]
[52]
Kang, T. Nuclear factor-erythroid 2-related factor 2 (Nrf2) and mitochondrial dynamics/mitophagy in neurological diseases. Antioxidants (Basel, Switzerland), 2020, 9(7)
[53]
Shen, L.; Gan, Q.; Yang, Y.; Reis, C.; Zhang, Z.; Xu, S.; Zhang, T.; Sun, C. Mitophagy in cerebral ischemia and ischemia/reperfusion injury. Front. Aging Neurosci., 2021, 13, 687246.
[http://dx.doi.org/10.3389/fnagi.2021.687246] [PMID: 34168551]
[54]
Li, X.; Li, H.; Xu, Z.; Ma, C.; Wang, T.; You, W.; Yu, Z.; Shen, H.; Chen, G. Ischemia-induced cleavage of OPA1 at S1 site aggravates mitochondrial fragmentation and reperfusion injury in neurons. Cell Death Dis., 2022, 13(4), 321.
[http://dx.doi.org/10.1038/s41419-022-04782-0] [PMID: 35395832]
[55]
Chen, N.; Zhou, Z.; Li, J.; Li, B.; Feng, J.; He, D.; Luo, Y.; Zheng, X.; Luo, J.; Zhang, J. 3-n-butylphthalide exerts neuroprotective effects by enhancing anti-oxidation and attenuating mitochondrial dysfunction in an in vitro model of ischemic stroke. Drug Des. Devel. Ther., 2018, 12, 4261-4271.
[http://dx.doi.org/10.2147/DDDT.S189472] [PMID: 30587922]
[56]
Zhou, X.; Wang, H.Y.; Wu, B.; Cheng, C.Y.; Xiao, W.; Wang, Z.Z.; Yang, Y.Y.; Li, P.; Yang, H. Ginkgolide K attenuates neuronal injury after ischemic stroke by inhibiting mitochondrial fission and GSK-3β-dependent increases in mitochondrial membrane permeability. Oncotarget, 2017, 8(27), 44682-44693.
[http://dx.doi.org/10.18632/oncotarget.17967] [PMID: 28591721]
[57]
Chan, D.C. Mitochondrial dynamics and its involvement in disease. Annu. Rev. Pathol., 2020, 15(1), 235-259.
[http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032711] [PMID: 31585519]
[58]
Yuhuan Fu, G.J.; Xia, Q.; Bai, Y. The structure and function of mitochondria fusion protein mfn1 / 2 Chemistry of life. 2007, 27(6), 511-513.
[59]
Sabouny, R.; Fraunberger, E.; Geoffrion, M.; Ng, A.C.H.; Baird, S.D.; Screaton, R.A.; Milne, R.; McBride, H.M.; Shutt, T.E. The Keap1-Nrf2 stress response pathway promotes mitochondrial hyperfusion through degradation of the mitochondrial fission protein Drp1. Antioxid. Redox Signal., 2017, 27(18), 1447-1459.
[http://dx.doi.org/10.1089/ars.2016.6855] [PMID: 28494652]
[60]
Lee, K.H.; Cha, M.; Lee, B.H. Neuroprotective effect of antioxidants in the brain. Int. J. Mol. Sci., 2020, 21(19), 7152.
[http://dx.doi.org/10.3390/ijms21197152] [PMID: 32998277]
[61]
Meza, C.A.; La Favor, J.D.; Kim, D.H.; Hickner, R.C. Endothelial dysfunction: Is there a hyperglycemia-induced imbalance of NOX and NOS? Int. J. Mol. Sci., 2019, 20(15), 3775.
[http://dx.doi.org/10.3390/ijms20153775] [PMID: 31382355]
[62]
Su, X.T.; Wang, L.; Ma, S.M.; Cao, Y.; Yang, N.N.; Lin, L.L.; Fisher, M.; Yang, J.W.; Liu, C.Z. Mechanisms of acupuncture in the regulation of oxidative stress in treating ischemic stroke. Oxid. Med. Cell. Longev., 2020, 2020, 1-15.
[http://dx.doi.org/10.1155/2020/7875396] [PMID: 33178387]
[63]
Li, H.; Horke, S.; Förstermann, U. Oxidative stress in vascular disease and its pharmacological prevention. Trends Pharmacol. Sci., 2013, 34(6), 313-319.
[http://dx.doi.org/10.1016/j.tips.2013.03.007] [PMID: 23608227]
[64]
Orellana-Urzúa, S.; Rojas, I.; Líbano, L.; Rodrigo, R. Pathophysiology of ischemic stroke: role of oxidative stress. Curr. Pharm. Des., 2020, 26(34), 4246-4260.
[http://dx.doi.org/10.2174/1381612826666200708133912] [PMID: 32640953]
[65]
Ding, Y.; Chen, M.; Wang, M.; Li, Y.; Wen, A. Posttreatment with 11-Keto-β-Boswellic acid ameliorates cerebral ischemia-reperfusion injury: Nrf2/HO-1 pathway as a potential mechanism. Mol. Neurobiol., 2015, 52(3), 1430-1439.
[http://dx.doi.org/10.1007/s12035-014-8929-9] [PMID: 25452227]
[66]
Yang, M.Y.; Yu, Q.L.; Huang, Y.S.; Yang, G. Neuroprotective effects of andrographolide derivative CX-10 in transient focal ischemia in rat: Involvement of Nrf2/AE and TLR/NF-κB signaling. Pharmacol. Res., 2019, 144, 227-234.
[http://dx.doi.org/10.1016/j.phrs.2019.04.023] [PMID: 31028905]
[67]
Feng, L.; Gao, J.; Liu, Y.; Shi, J.; Gong, Q. Icariside II alleviates oxygen-glucose deprivation and reoxygenation-induced PC12 cell oxidative injury by activating Nrf2/SIRT3 signaling pathway. Biomed. Pharmacother., 2018, 103, 9-17.
[http://dx.doi.org/10.1016/j.biopha.2018.04.005] [PMID: 29635133]
[68]
Loboda, A.; Jozkowicz, A.; Dulak, J. HO-1/CO system in tumor growth, angiogenesis and metabolism — Targeting HO-1 as an anti-tumor therapy. Vascul. Pharmacol., 2015, 74, 11-22.
[http://dx.doi.org/10.1016/j.vph.2015.09.004] [PMID: 26392237]
[69]
Xie, J.; He, X.; Fang, H.; Liao, S.; Liu, Y.; Tian, L.; Niu, J. Identification of heme oxygenase-1 from golden pompano (Trachinotus ovatus) and response of Nrf2/HO-1 signaling pathway to copper-induced oxidative stress. Chemosphere, 2020, 253, 126654.
[http://dx.doi.org/10.1016/j.chemosphere.2020.126654] [PMID: 32464761]
[70]
Lan, X.; Han, X.; Li, Q.; Wang, J. ()-Epicatechin, a natural flavonoid compound, protects astrocytes against hemoglobin toxicity via Nrf2 and AP-1 signaling pathways. Mol. Neurobiol., 2017, 54(10), 7898-7907.
[http://dx.doi.org/10.1007/s12035-016-0271-y] [PMID: 27864733]
[71]
Spector, A.; Ma, W.; Wang, R.R.; Yang, Y.; Ho, Y.S. The contribution of GSH peroxidase-1, catalase and GSH to the degradation of H2O2 by the mouse lens. Exp. Eye Res., 1997, 64(3), 477-485.
[http://dx.doi.org/10.1006/exer.1996.0250] [PMID: 9196400]
[72]
Lin, X.; Bai, D.; Wei, Z.; Zhang, Y.; Huang, Y.; Deng, H.; Huang, X. Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway. PLoS One, 2019, 14(5), e0216711.
[http://dx.doi.org/10.1371/journal.pone.0216711] [PMID: 31112588]
[73]
Lu, J.; Holmgren, A. The thioredoxin antioxidant system. Free Radic. Biol. Med., 2014, 66, 75-87.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.036] [PMID: 23899494]
[74]
Napolitano, S.; Reber, R.J.; Rubini, M.; Glockshuber, R. Functional analyses of ancestral thioredoxins provide insights into their evolutionary history. J. Biol. Chem., 2019, 294(38), 14105-14118.
[http://dx.doi.org/10.1074/jbc.RA119.009718] [PMID: 31366732]
[75]
Nasoohi, S.; Ismael, S.; Ishrat, T. Thioredoxin-interacting protein (TXNIP) in cerebrovascular and neurodegenerative diseases: Regulation and implication. Mol. Neurobiol., 2018, 55(10), 7900-7920.
[http://dx.doi.org/10.1007/s12035-018-0917-z] [PMID: 29488135]
[76]
Tsubaki, H.; Tooyama, I.; Walker, D.G. Thioredoxin-interacting protein (TXNIP) with focus on brain and neurodegenerative diseases. Int. J. Mol. Sci., 2020, 21(24), 9357.
[http://dx.doi.org/10.3390/ijms21249357] [PMID: 33302545]
[77]
Xu, L.; Zhao, Y.; Pan, F.; Zhu, M.; Yao, L.; Liu, Y.; Feng, J.; Xiong, J.; Chen, X.; Ren, F.; Tan, Y.; Wang, H. Inhibition of the Nrf2-TrxR axis sensitizes the drug-resistant chronic myelogenous leukemia cell line K562/G01 to imatinib treatments. BioMed Res. Int., 2019, 2019, 1-12.
[http://dx.doi.org/10.1155/2019/6502793] [PMID: 31828114]
[78]
Oakes, S.A.; Papa, F.R. The role of endoplasmic reticulum stress in human pathology. Annu. Rev. Pathol., 2015, 10(1), 173-194.
[http://dx.doi.org/10.1146/annurev-pathol-012513-104649] [PMID: 25387057]
[79]
Hwang, J.; Qi, L. Quality control in the endoplasmic reticulum: Crosstalk between ERAD and UPR pathways. Trends Biochem. Sci., 2018, 43(8), 593-605.
[http://dx.doi.org/10.1016/j.tibs.2018.06.005] [PMID: 30056836]
[80]
Kopp, M.C.; Larburu, N.; Durairaj, V.; Adams, C.J.; Ali, M.M.U. UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor. Nat. Struct. Mol. Biol., 2019, 26(11), 1053-1062.
[http://dx.doi.org/10.1038/s41594-019-0324-9] [PMID: 31695187]
[81]
Yin, Y.; Sun, G.; Li, E.; Kiselyov, K.; Sun, D. ER stress and impaired autophagy flux in neuronal degeneration and brain injury. Ageing Res. Rev., 2017, 34, 3-14.
[http://dx.doi.org/10.1016/j.arr.2016.08.008] [PMID: 27594375]
[82]
Sen, T.; Saha, P.; Gupta, R.; Foley, L.M.; Jiang, T.; Abakumova, O.S.; Hitchens, T.K.; Sen, N. Aberrant ER stress induced neuronal-IFNβ elicits white matter injury due to microglial activation and T-Cell infiltration after TBI. J. Neurosci., 2020, 40(2), 424-446.
[http://dx.doi.org/10.1523/JNEUROSCI.0718-19.2019] [PMID: 31694961]
[83]
Li, M.T.; Ke, J.; Guo, S.F.; Wu, Y.; Bian, Y.F.; Shan, L.L.; Liu, Q.Y.; Huo, Y.J.; Guo, C.; Liu, M.Y.; Liu, Y.J.; Han, Y. The protective effect of Quercetin on endothelial cells injured by hypoxia and reoxygenation. Front. Pharmacol., 2021, 12732874.
[http://dx.doi.org/10.3389/fphar.2021.732874] [PMID: 34744717]
[84]
Ma, T.; Shi, Y.L.; Wang, Y.L. Forsythiaside A protects against focal cerebral ischemic injury by mediating the activation of the Nrf2 and endoplasmic reticulum stress pathways. Mol. Med. Rep., 2019, 20(2), 1313-1320.
[http://dx.doi.org/10.3892/mmr.2019.10312] [PMID: 31173213]
[85]
Lin, L.; Wang, X. Ischemia-reperfusion injury in the brain: Mechanisms and potential therapeutic strategies. Biochem. Pharmacol., 2016, 5(4)
[86]
Jurcau, A.; Simion, A. Neuroinflammation in cerebral ischemia and ischemia/reperfusion injuries: From pathophysiology to therapeutic strategies. Int. J. Mol. Sci., 2021, 23(1), 14.
[http://dx.doi.org/10.3390/ijms23010014] [PMID: 35008440]
[87]
Rayasam, A.; Hsu, M.; Kijak, J.A.; Kissel, L.; Hernandez, G.; Sandor, M.; Fabry, Z. Immune responses in stroke: how the immune system contributes to damage and healing after stroke and how this knowledge could be translated to better cures? Immunology, 2018, 154(3), 363-376.
[http://dx.doi.org/10.1111/imm.12918] [PMID: 29494762]
[88]
Sekerdag, E.; Solaroglu, I.; Gursoy-Ozdemir, Y. Cell death mechanisms in stroke and novel molecular and cellular treatment options. Curr. Neuropharmacol., 2018, 16(9), 1396-1415.
[http://dx.doi.org/10.2174/1570159X16666180302115544] [PMID: 29512465]
[89]
Alishahi, M.; Farzaneh, M.; Ghaedrahmati, F.; Nejabatdoust, A.; Sarkaki, A.; Khoshnam, S.E. NLRP3 inflammasome in ischemic stroke: As possible therapeutic target. Int. J. Stroke, 2019, 14(6), 574-591.
[http://dx.doi.org/10.1177/1747493019841242] [PMID: 30940045]
[90]
Wang, S.W.; Liu, Z.; Shi, Z.S. Non-Coding RNA in acute ischemic stroke: Mechanisms, biomarkers and therapeutic targets. Cell Transplant., 2018, 27(12), 1763-1777.
[http://dx.doi.org/10.1177/0963689718806818] [PMID: 30362372]
[91]
Franke, M.; Bieber, M.; Kraft, P.; Weber, A.N.R.; Stoll, G.; Schuhmann, M.K. The NLRP3 inflammasome drives inflammation in ischemia/reperfusion injury after transient middle cerebral artery occlusion in mice. Brain Behav. Immun., 2021, 92, 221-231.
[http://dx.doi.org/10.1016/j.bbi.2020.12.009] [PMID: 33307174]
[92]
Sivandzade, F.; Prasad, S.; Bhalerao, A.; Cucullo, L. NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: Molecular mechanisms and possible therapeutic approaches. Redox Biol., 2019, 21, 101059.
[http://dx.doi.org/10.1016/j.redox.2018.11.017] [PMID: 30576920]
[93]
Wang, L.; Ren, W.; Wu, Q.; Liu, T.; Wei, Y.; Ding, J.; Zhou, C.; Xu, H.; Yang, S. NLRP3 inflammasome activation: A therapeutic target for cerebral ischemia-reperfusion injury. Front. Mol. Neurosci., 2022, 15, 847440.
[http://dx.doi.org/10.3389/fnmol.2022.847440] [PMID: 35600078]
[94]
Zhen, L.; Peng, G.; Zhou, X.; Zhou, K. Efficacy of Shugan Jieyu Capsule on symptom alleviation and improvement of activities of daily living in post-stroke depression: A meta-analysis. Zhongguo Laonianxue Zazhi, 2018, 38(16), 3959-3963.
[95]
Wang, Y.; Huang, Y.; Xu, Y.; Ruan, W.; Wang, H.; Zhang, Y.; Saavedra, J.M.; Zhang, L.; Huang, Z.; Pang, T. A dual AMPK/Nrf2 activator reduces brain inflammation after stroke by enhancing microglia M2 polarization. Antioxid. Redox Signal., 2018, 28(2), 141-163.
[http://dx.doi.org/10.1089/ars.2017.7003] [PMID: 28747068]
[96]
Obermeier, B.; Verma, A.; Ransohoff, R.M. The blood-brain barrier. Handb. Clin. Neurol., 2016, 133, 39-59.
[http://dx.doi.org/10.1016/B978-0-444-63432-0.00003-7] [PMID: 27112670]
[97]
Daneman, R.; Prat, A. The blood-brain barrier. Cold Spring Harb. Perspect. Biol., 2015, 7(1), a020412.
[http://dx.doi.org/10.1101/cshperspect.a020412] [PMID: 25561720]
[98]
Ballabh, P.; Braun, A.; Nedergaard, M. The blood-brain barrier: an overview. Neurobiol. Dis., 2004, 16(1), 1-13.
[http://dx.doi.org/10.1016/j.nbd.2003.12.016] [PMID: 15207256]
[99]
Mayadas, T.N.; Cullere, X.; Lowell, C.A. The multifaceted functions of neutrophils. Annu. Rev. Pathol., 2014, 9(1), 181-218.
[http://dx.doi.org/10.1146/annurev-pathol-020712-164023] [PMID: 24050624]
[100]
Duris, K.; Splichal, Z.; Jurajda, M. The role of inflammatory response in stroke associated programmed cell death. Curr. Neuropharmacol., 2018, 16(9), 1365-1374.
[http://dx.doi.org/10.2174/1570159X16666180222155833] [PMID: 29473512]
[101]
Bauer, H.; Traweger, A. Tight junctions of the blood-brain barrier - A molecular gatekeeper. CNS Neurol. Disord. Drug Targets, 2016, 15(9), 1016-1029.
[http://dx.doi.org/10.2174/1871527315666160915142244] [PMID: 27633783]
[102]
Shi, Y.S.; Zhang, Y.; Liu, B.; Li, C.B.; Wu, J.; Li, Y. Nomilin protects against cerebral ischemia–reperfusion induced neurological deficits and blood–brain barrier disruption via the Nrf2 pathway. Food Funct., 2019, 10(9), 5323-5332.
[http://dx.doi.org/10.1039/C9FO01481K] [PMID: 31389456]
[103]
Cui, N.; Hu, M.; Khalil, R.A. Biochemical and biological attributes of matrix metalloproteinases. Prog. Mol. Biol. Transl. Sci., 2017, 147, 1-73.
[http://dx.doi.org/10.1016/bs.pmbts.2017.02.005] [PMID: 28413025]
[104]
Rempe, R.G.; Hartz, A.M.S.; Bauer, B. Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers. J. Cereb. Blood Flow Metab., 2016, 36(9), 1481-1507.
[http://dx.doi.org/10.1177/0271678X16655551] [PMID: 27323783]
[105]
Chen, Z.; Mao, X.; Liu, A.; Gao, X.; Chen, X.; Ye, M.; Ye, J.; Liu, P.; Xu, S.; Liu, J.; He, W.; Lian, Q.; Pi, R. Osthole, a natural coumarin improves cognitive impairments and BBB dysfunction after transient global brain ischemia in C57 BL/6J mice: involvement of Nrf2 pathway. Neurochem. Res., 2015, 40(1), 186-194.
[http://dx.doi.org/10.1007/s11064-014-1483-z] [PMID: 25424966]
[106]
Elmore, S. Apoptosis: a review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[107]
Obeng, E. Apoptosis (programmed cell death) and its signals - A review. Braz. J. Biol., 2021, 81(4), 1133-1143.
[http://dx.doi.org/10.1590/1519-6984.228437] [PMID: 33111928]
[108]
Uzdensky, A.B. Apoptosis regulation in the penumbra after ischemic stroke: expression of pro- and antiapoptotic proteins. Apoptosis, 2019, 24(9-10), 687-702.
[http://dx.doi.org/10.1007/s10495-019-01556-6] [PMID: 31256300]
[109]
Ding, Y.; Chen, M.; Wang, M.; Wang, M.; Zhang, T.; Park, J.; Zhu, Y.; Guo, C.; Jia, Y.; Li, Y.; Wen, A. Neuroprotection by acetyl-11-keto-β-Boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway. Sci. Rep., 2014, 4(1), 7002.
[http://dx.doi.org/10.1038/srep07002] [PMID: 25384416]
[110]
Idriss, H.T.; Naismith, J.H. TNF? and the TNF receptor superfamily: Structure-function relationship(s). Microsc. Res. Tech., 2000, 50(3), 184-195.
[http://dx.doi.org/10.1002/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO;2-H] [PMID: 10891884]
[111]
Tummers, B.; Green, D.R. Caspase-8: regulating life and death. Immunol. Rev., 2017, 277(1), 76-89.
[http://dx.doi.org/10.1111/imr.12541] [PMID: 28462525]
[112]
Boice, A.; Bouchier-Hayes, L. Targeting apoptotic caspases in cancer. Biochim. Biophys. Acta Mol. Cell Res., 2020, 1867(6), 118688.
[http://dx.doi.org/10.1016/j.bbamcr.2020.118688] [PMID: 32087180]
[113]
Wang, J.-J.; Cui, P. Neohesperidin attenuates cerebral ischemia-reperfusion injury via inhibiting the apoptotic pathway and activating the Akt/Nrf2/HO-1 pathway. J. Asian Nat. Prod. Res., 2013, 15(9), 1023-1037.
[http://dx.doi.org/10.1080/10286020.2013.827176] [PMID: 23952707]
[114]
El-Far, Y.; Khodir, A.; Noor, A. Selective cytotoxic activity and protective effects of sodium ascorbate against hepatocellular carcinoma through its effect on oxidative stress and apoptosis in vivo and in vitro. Redox report: Communicat. Free Radic. Res., 2020, 25(1), 17-25.
[115]
Webster, K.A.; Graham, R.M.; Thompson, J.W.; Spiga, M.G.; Frazier, D.P.; Wilson, A.; Bishopric, N.H. Redox stress and the contributions of BH3-only proteins to infarction. Antioxid. Redox Signal., 2006, 8(9-10), 1667-1676.
[http://dx.doi.org/10.1089/ars.2006.8.1667] [PMID: 16987020]
[116]
Lou, J.; Cao, G.; Li, R.; Liu, J.; Dong, Z.; Xu, L. β-caryophyllene attenuates focal cerebral ischemia-reperfusion injury by Nrf2/HO-1 pathway in rats. Neurochem. Res., 2016, 41(6), 1291-1304.
[http://dx.doi.org/10.1007/s11064-016-1826-z] [PMID: 26801169]
[117]
Huo, H.; Zhou, Z.; Qin, J.; Liu, W.; Wang, B.; Gu, Y. Erastin disrupts mitochondrial permeability transition pore (mPTP) and induces apoptotic death of colorectal cancer cells. PLoS One, 2016, 11(5), e0154605.
[http://dx.doi.org/10.1371/journal.pone.0154605] [PMID: 27171435]
[118]
Chen, J.; Venkat, P.; Zacharek, A.; Chopp, M. Neurorestorative therapy for stroke. Front. Hum. Neurosci., 2014, 8, 382.
[http://dx.doi.org/10.3389/fnhum.2014.00382] [PMID: 25018718]
[119]
Ziv, N.E.; Brenner, N. Synaptic tenacity or lack thereof: spontaneous remodeling of synapses. Trends Neurosci., 2018, 41(2), 89-99.
[http://dx.doi.org/10.1016/j.tins.2017.12.003] [PMID: 29275902]
[120]
Kanazawa, M.; Hatakeyama, M.; Ninomiya, I. Angiogenesis and neuronal remodeling after ischemic stroke. Neural Regen. Res., 2020, 15(1), 16-19.
[http://dx.doi.org/10.4103/1673-5374.264442] [PMID: 31535636]
[121]
Zhang, H.; Wang, W.; Feng, L.; Yang, Y.; Zheng, J.; Huang, L.; Chen, D. S-nitrosylation of cofilin-1 serves as a novel pathway for VEGF-stimulated endothelial cell migration. J. Cell. Physiol., 2015, 230(2), 406-417.
[http://dx.doi.org/10.1002/jcp.24724] [PMID: 25056928]
[122]
Huang, Y.; Mao, Y.; Li, H.; Shen, G.; Nan, G. Knockdown of Nrf2 inhibits angiogenesis by downregulating VEGF expression through PI3K/Akt signaling pathway in cerebral microvascular endothelial cells under hypoxic conditions. Biochem. Cell Biol., 2018, 96(4), 475-482.
[123]
Wang, F.; Li, R.; Tu, P.; Chen, J.; Zeng, K.; Jiang, Y. Total glycosides of Cistanche deserticola promote neurological function recovery by inducing neurovascular regeneration Nrf-2/Keap-1 pathway in MCAO/R rats. Front. Pharmacol., 2020, 11, 236.
[http://dx.doi.org/10.3389/fphar.2020.00236] [PMID: 32256351]
[124]
Berg, D.A.; Su, Y.; Jimenez-Cyrus, D.; Patel, A.; Huang, N.; Morizet, D.; Lee, S.; Shah, R.; Ringeling, F.R.; Jain, R.; Epstein, J.A.; Wu, Q.F.; Canzar, S.; Ming, G.L.; Song, H.; Bond, A.M. A common embryonic origin of stem cells drives developmental and adult neurogenesis. Cell, 2019, 177(3), 654-668.e15.
[http://dx.doi.org/10.1016/j.cell.2019.02.010] [PMID: 30929900]
[125]
Zhang, J.; Jiao, J. Molecular biomarkers for embryonic and adult neural stem cell and neurogenesis. BioMed. Res. Int., 2015, 2015, 1-14.
[http://dx.doi.org/10.1155/2015/727542] [PMID: 26421301]
[126]
Yu, J.; Yang, H.; Fang, B.; Zhang, Z.; Wang, Y.; Dai, Y. mfat-1 transgene protects cultured adult neural stem cells against cobalt chloride-mediated hypoxic injury by activating Nrf2/ARE pathways. J. Neurosci. Res., 2018, 96(1), 87-102.
[http://dx.doi.org/10.1002/jnr.24096] [PMID: 28639376]
[127]
Li, J.; Johnson, D.; Calkins, M. Stabilization of Nrf2 by tBHQ confers protection against oxidative stress-induced cell death in human neural stem cells. Toxicol. Sci., 2005, 83(2), 313-328.
[http://dx.doi.org/10.1093/toxsci/kfi027]
[128]
Shen, C.; Cheng, W.; Yu, P.; Wang, L.; Zhou, L.; Zeng, L.; Yang, Q. Resveratrol pretreatment attenuates injury and promotes proliferation of neural stem cells following oxygen-glucose deprivation/reoxygenation by upregulating the expression of Nrf2, HO-1 and NQO1 in vitro. Mol. Med. Rep., 2016, 14(4), 3646-3654.
[http://dx.doi.org/10.3892/mmr.2016.5670] [PMID: 27573874]
[129]
Sarkaki, A.; Farbood, Y.; Mansouri, S.M.T.; Badavi, M.; Khorsandi, L.; Dehcheshmeh, M.G.; Shooshtari, M.K. Chrysin prevents cognitive and hippocampal long-term potentiation deficits and inflammation in rat with cerebral hypoperfusion and reperfusion injury. Life Sci., 2019, 226, 202-209.
[http://dx.doi.org/10.1016/j.lfs.2019.04.027] [PMID: 30991061]
[130]
Yamagata, K. Astrocyte‐induced synapse formation and ischemic stroke. J. Neurosci. Res., 2021, 99(5), 1401-1413.
[http://dx.doi.org/10.1002/jnr.24807] [PMID: 33604930]
[131]
Goldshmit, Y.; Lythgo, N.; Galea, M.P.; Turnley, A.M. Treadmill training after spinal cord hemisection in mice promotes axonal sprouting and synapse formation and improves motor recovery. J. Neurotrauma, 2008, 25(5), 449-465.
[http://dx.doi.org/10.1089/neu.2007.0392] [PMID: 18352823]
[132]
Fu, H.Y.; Cui, Y.; Li, Q.; Wang, D.; Li, H.; Yang, L.; Wang, D.J.; Zhou, J.W. LAMP‐2A ablation in hippocampal CA1 astrocytes confers cerebroprotection and ameliorates neuronal injury after global brain ischemia. Brain Pathol., 2022, e13114.
[http://dx.doi.org/10.1111/bpa.13114] [PMID: 36059143]
[133]
Shi, A.; Xiang, J.; He, F.; Zhu, Y.; Zhu, G.; Lin, Y.; Zhou, N. The phenolic components of Gastrodia elat improve prognosis in rats after cerebral ischemia/reperfusion by enhancing the endogenous antioxidant mechanisms. Oxid. Med. Cell. Longev., 2018, 2018, 1-16.
[http://dx.doi.org/10.1155/2018/7642158] [PMID: 29765502]
[134]
Shi, Y.; Sun, L.; Ji, X.; Shi, R.; Xu, F.; Gu, J. Neuroprotective effects of oleanolic acid against cerebral ischemia-reperfusion injury in mice. Exp. Neurol., 2021, 343, 113785.
[http://dx.doi.org/10.1016/j.expneurol.2021.113785] [PMID: 34153323]
[135]
Pendlebury, S.T.; Rothwell, P.M. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol., 2009, 8(11), 1006-1018.
[http://dx.doi.org/10.1016/S1474-4422(09)70236-4] [PMID: 19782001]
[136]
Zhang, X.; Bi, X. Post-stroke cognitive impairment: A review focusing on molecular biomarkers. J. Mol. Neurosci., 2020, 70(8), 1244-1254.
[http://dx.doi.org/10.1007/s12031-020-01533-8] [PMID: 32219663]
[137]
Zhang, X.; Yuan, M.; Yang, S.; Chen, X.; Wu, J.; Wen, M.; Yan, K.; Bi, X. Enriched environment improves post-stroke cognitive impairment and inhibits neuroinflammation and oxidative stress by activating Nrf2-ARE pathway. Int. J. Neurosci., 2021, 131(7), 641-649.
[http://dx.doi.org/10.1080/00207454.2020.1797722] [PMID: 32677581]
[138]
Yagishita, Y.; Gatbonton-Schwager, T.N.; McCallum, M.L.; Kensler, T.W. Current landscape of NRF2 biomarkers in clinical trials. Antioxidants, 2020, 9(8), 716.
[http://dx.doi.org/10.3390/antiox9080716] [PMID: 32784785]
[139]
Wu, J.; Li, Q.; Wang, X.; Yu, S.; Li, L.; Wu, X.; Chen, Y.; Zhao, J.; Zhao, Y. Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway. PLoS One, 2013, 8(3), e59843.
[http://dx.doi.org/10.1371/journal.pone.0059843] [PMID: 23555802]
[140]
Li, Y.; Ding, Z.; Yuan, Y.; Li, P. Nrf2 in the treatment of cerebral ischemia using traditional chinese medicine. Jilin traditional. Chin. Med., 2021, 41(5), 689-693.
[141]
Zhang, D.D.; Chapman, E. The role of natural products in revealing NRF2 function. Nat. Prod. Rep., 2020, 37(6), 797-826.
[http://dx.doi.org/10.1039/C9NP00061E] [PMID: 32400766]
[142]
Yamamoto, M.; Kensler, T.W.; Motohashi, H. The KEAP1-NRF2 System: A thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol. Rev., 2018, 98(3), 1169-1203.
[http://dx.doi.org/10.1152/physrev.00023.2017] [PMID: 29717933]
[143]
Cuadrado, A.; Rojo, A.I.; Wells, G.; Hayes, J.D.; Cousin, S.P.; Rumsey, W.L.; Attucks, O.C.; Franklin, S.; Levonen, A.L.; Kensler, T.W.; Dinkova-Kostova, A.T. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat. Rev. Drug Discov., 2019, 18(4), 295-317.
[http://dx.doi.org/10.1038/s41573-018-0008-x] [PMID: 30610225]
[144]
Cuadrado, A.; Moreno-Murciano, P.; Pedraza-Chaverri, J. The transcription factor Nrf2 as a new therapeutic target in Parkinson’s disease. Expert Opin. Ther. Targets, 2009, 13(3), 319-329.
[http://dx.doi.org/10.1517/13543780802716501] [PMID: 19236154]
[145]
Perluigi, M.; Joshi, G.; Sultana, R.; Calabrese, V.; De Marco, C.; Coccia, R.; Cini, C.; Butterfield, D.A. In vivo protective effects of ferulic acid ethyl ester against amyloid-beta peptide 1–42-induced oxidative stress. J. Neurosci. Res., 2006, 84(2), 418-426.
[http://dx.doi.org/10.1002/jnr.20879] [PMID: 16634068]

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