Regulated necrosis pathways: a potential target for ischemic stroke

Kaidi Ren; Jinyan Pei; Yuanyuan Guo; Yuxue Jiao; Han Xing; Yi Xie; Yang Yang; Qi Feng; Jing Yang

doi:10.1093/burnst/tkad016

您当前的位置：

首页 >

文章列表页 >

Regulated necrosis pathways: a potential target for ischemic stroke

更新时间：2024-02-04

- Regulated necrosis pathways: a potential target for ischemic stroke
- Burns & Trauma Vol. 11, Issue 1, (2023)
- 作者机构：
  
  1. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University
  2. Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University
  3. Henan Engineering Research Center for Application & Translation of Precision Clinical Pharmacy
  4. Zhengzhou University
  5. Quality Management Department, Henan No. 3 Provincial People’s Hospital
  6. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Dong Road, ErQi District, Zhengzhou University
  7. Research Center for Clinical System Biology
  8. The First Affiliated Hospital of Zhengzhou University
  9. Research Institute of Nephrology, The First Affiliated Hospital of Zhengzhou University
  10. Department of Integrated Traditional and Western Nephrology, The First Affiliated Hospital of Zhengzhou University
  11. Henan Province Research Center for Kidney Disease, The First Affiliated Hospital of Zhengzhou University
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkad016
  CLC：
- Published：2023，
  
  Published Online：18 November 2023，
扫描看全文
Kaidi Ren, Jinyan Pei, Yuanyuan Guo, Yuxue Jiao, Han Xing, Yi Xie, Yang Yang, Qi Feng, Jing Yang, Regulated necrosis pathways: a potential target for ischemic stroke, Burns & Trauma, Volume 11, 2023, tkad016, https://doi.org/10.1093/burnst/tkad016
DOI：

Kaidi Ren, Jinyan Pei, Yuanyuan Guo, Yuxue Jiao, Han Xing, Yi Xie, Yang Yang, Qi Feng, Jing Yang, Regulated necrosis pathways: a potential target for ischemic stroke, Burns & Trauma, Volume 11, 2023, tkad016, https://doi.org/10.1093/burnst/tkad016 DOI：

摘要

Abstract

Globally

ischemic stroke causes millions of deaths per year. The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and reperfusion-related neuronal death in the infarct region. In the infarct region

cell injuries follow either the regulated pathway involving precise signaling cascades

such as apoptosis and autophagy

or the nonregulated pathway

which is uncontrolled by any molecularly defined effector mechanisms such as necrosis. However

numerous studies have recently found that a certain type of necrosis can be regulated and potentially modified by drugs and is nonapoptotic; this type of necrosis is referred to as regulated necrosis. Depending on the signaling pathway

various elements of regulated necrosis contribute to the development of ischemic stroke

such as necroptosis

pyroptosis

ferroptosis

pathanatos

mitochondrial permeability transition pore-mediated necrosis and oncosis. In this review

we aim to summarize the underlying molecular mechanisms of regulated necrosis in ischemic stroke and explore the crosstalk and interplay among the diverse types of regulated necrosis. We believe that targeting these regulated necrosis pathways both pharmacologically and genetically in ischemia-induced neuronal death and protection could be an efficient strategy to increase neuronal survival and regeneration in ischemic stroke.

关键词

Keywords

Ischemic strokeNecroptosisPyroptosisFerroptosisPathanatosmPTP-mediated necrosisOncosis

references

1.Collaborators GBDS. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol. 2019;18:439–58.

2.Catanese L, Tarsia J, Fisher M. Acute ischemic stroke therapy overview. Circ Res. 2017;120:541–58.

3.Cheon SY, Kim EJ, Kim JM, Koo BN. Cell type-specific mechanisms in the pathogenesis of ischemic stroke: the role of apoptosis signal-regulating kinase 1. Oxidative Med Cell Longev. 2018;2018:1–9.

4.Jayaraj RL, Azimullah S, Beiram R, Jalal FY, Rosenberg GA. Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammation. 2019;16:142.

5.O'Collins VE, Macleod MR, Cox SF, Van Raay L, Aleksoska E, Donnan GA, et al. Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing. J Cereb Blood Flow Metab. 2011;31:962–75.

6.Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al. Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ. 2009;16:3–11.

7.Sun J, Ren DD, Wan JY, Chen C, Chen D, Yang H, et al. Desensitizing mitochondrial permeability transition by ERK-Cyclophilin D Axis contributes to the neuroprotective effect of Gallic acid against cerebral ischemia/reperfusion injury. Front Pharmacol. 2017;8:184.

8.Deng XX, Li SS, Sun FY. Necrostatin-1 prevents necroptosis in brains after ischemic stroke via inhibition of RIPK1-mediated RIPK3/MLKL Signaling. Aging Dis. 2019;10:807–17.

9.Yan W, Sun W, Fan J, Wang H, Han S, Li J, et al. Sirt1-ROS-TRAF6 Signaling-induced Pyroptosis contributes to early injury in ischemic mice. Neurosci Bull. 2020;36:845–59.

10.Li Y, Feng D, Wang Z, Zhao Y, Sun R, Tian D, et al. Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion. Cell Death Differ. 2019;26:2284–99.

11.Sairanen T, Szepesi R, Karjalainen-Lindsberg ML, Saksi J, Paetau A, Lindsberg PJ. Neuronal caspase-3 and PARP-1 correlate differentially with apoptosis and necrosis in ischemic human stroke. Acta Neuropathol. 2009;118:541–52.

12.Yuan J, Amin P, Ofengeim D. Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases. Nat Rev Neurosci. 2019;20:19–33.

13.Mandal P, Berger SB, Pillay S, Moriwaki K, Huang C, Guo H, et al. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol Cell. 2014;56:481–95.

14.Vercammen D, Brouckaert G, Denecker G, Van de Craen M, Declercq W, Fiers W, et al. Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways. J Exp Med. 1998;188:919–30.

15.Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005;1:112–9.

16.Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, Xavier RJ, et al. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell. 2008;135:1311–23.

17.Chan FK, Shisler J, Bixby JG, Felices M, Zheng L, Appel M, et al. A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J Biol Chem. 2003;278:51613–21.

18.Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2000;1:489–95.

19.Weinlich R, Oberst A, Beere HM, Green DR. Necroptosis in development, inflammation and disease. Nat Rev Mol Cell Biol. 2017;18:127–36.

20.Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137:1112–23.

21.Dondelinger Y, Declercq W, Montessuit S, Roelandt R, Goncalves A, Bruggeman I, et al. MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphates. Cell Rep. 2014;7:971–81.

22.Siegmund D, Ehrenschwender M, Wajant H. TNFR2 unlocks a RIPK1 kinase activity-dependent mode of proinflammatory TNFR1 signaling. Cell Death Dis. 2018;9:921.

23.Wang L, Chang X, Feng J, Yu J, Chen G. TRADD mediates RIPK1-independent necroptosis induced by tumor necrosis factor. Front Cell Dev Biol. 2019;7:393.

24.Moujalled DM, Cook WD, Okamoto T, Murphy J, Lawlor KE, Vince JE, et al. TNF can activate RIPK3 and cause programmed necrosis in the absence of RIPK1. Cell Death Dis. 2013;4:e465.

25.Lule S, Wu L, McAllister LM, Edmiston WJ, 3rd, Chung JY, Levy E, et al. Genetic inhibition of receptor interacting protein Kinase-1 reduces cell death and improves functional outcome after intracerebral Hemorrhage in mice. Stroke. 2017;48:2549–56.

26.Jiao Y, Wang J, Zhang H, Cao Y, Qu Y, Huang S, et al. Inhibition of microglial receptor-interacting protein kinase 1 ameliorates neuroinflammation following cerebral ischaemic stroke. J Cell Mol Med. 2020;24:12585–98.

27.Li W, Liu J, Chen JR, Zhu YM, Gao X, Ni Y, et al. Neuroprotective effects of DTIO, a novel Analog of Nec-1, in acute and chronic stages after ischemic stroke. Neuroscience. 2018;390:12–29.

28.Liu ZM, Chen QX, Chen ZB, Tian DF, Li MC, Wang JM, et al. RIP3 deficiency protects against traumatic brain injury (TBI) through suppressing oxidative stress, inflammation and apoptosis: dependent on AMPK pathway. Biochem Biophys Res Commun. 2018;499:112–9.

29.Han F, Guan X, Guo W, Lu B. Therapeutic potential of a TrkB agonistic antibody for ischemic brain injury. Neurobiol Dis. 2019;127:570–81.

30.Zhang YY, Liu WN, Li YQ, Zhang XJ, Yang J, Luo XJ, et al. Ligustroflavone reduces necroptosis in rat brain after ischemic stroke through targeting RIPK1/RIPK3/MLKL pathway. Naunyn Schmiedeberg's Arch Pharmacol. 2019;392:1085–95.

31.Zhang S, Hu ZW, Mao CY, Shi CH, Xu YM. CHIP as a therapeutic target for neurological diseases. Cell Death Dis. 2020;11:727.

32.Ganjam GK, Terpolilli NA, Diemert S, Eisenbach I, Hoffmann L, Reuther C, et al. Cylindromatosis mediates neuronal cell death in vitro and in vivo. Cell Death Differ. 2018;25:1394–407.

33.Yuan Z, Yi-Yun S, Hai-Yan Y. Triad3A displays a critical role in suppression of cerebral ischemic/reperfusion (I/R) injury by regulating necroptosis. Biomed Pharmacother. 2020;128:110045.

34.Wang M, Wan H, Wang S, Liao L, Huang Y, Guo L, et al. RSK3 mediates necroptosis by regulating phosphorylation of RIP3 in rat retinal ganglion cells. J Anat. 2020;237:29–47.

35.Lipton P. Ischemic cell death in brain neurons. Physiol Rev. 1999;79:1431–568.

36.Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011;17:796–808.

37.Xiong XY, Liu L, Yang QW. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke. Prog Neurobiol. 2016;142:23–44.

38.Dojo Soeandy C, Elia AJ, Cao Y, Rodgers C, Huang S, Elia AC, et al. Necroptotic-apoptotic regulation in an Endothelin-1 model of cerebral ischemia. Cell Mol Neurobiol. 2021;41:1727–42.

39.Naito MG, Xu D, Amin P, Lee J, Wang H, Li W, et al. Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke. Proc Natl Acad Sci U S A. 2020;117:4959–70.

40.Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O'Keeffe S, et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014;34:11929–47.

41.Legler DF, Micheau O, Doucey MA, Tschopp J, Bron C. Recruitment of TNF receptor 1 to lipid rafts is essential for TNFalpha-mediated NF-kappaB activation. Immunity. 2003;18:655–64.

42.Park SM, Yoon JB, Lee TH. Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) in vitro. FEBS Lett. 2004;566:151–6.

43.Petersen SL, Chen TT, Lawrence DA, Marsters SA, Gonzalvez F, Ashkenazi A. TRAF2 is a biologically important necroptosis suppressor. Cell Death Differ. 2015;22:1846–57.

44.Li J, Zhang J, Zhang Y, Wang Z, Song Y, Wei S, et al. TRAF2 protects against cerebral ischemia-induced brain injury by suppressing necroptosis. Cell Death Dis. 2019;10:328.

45.Alturki NA, McComb S, Ariana A, Rijal D, Korneluk RG, Sun SC, et al. Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis. Cell Death Dis. 2018;9:592.

46.Geng J, Ito Y, Shi L, Amin P, Chu J, Ouchida AT, et al. Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis. Nat Commun. 2017;8:359.

47.White BJ, Tarabishy S, Venna VR, Manwani B, Benashski S, McCullough LD, et al. Protection from cerebral ischemia by inhibition of TGFbeta-activated kinase. Exp Neurol. 2012;237:238–45.

48.Zeyen T, Noristani R, Habib S, Heinisch O, Slowik A, Huber M, et al. Microglial-specific depletion of TAK1 is neuroprotective in the acute phase after ischemic stroke. J Mol Med (Berl). 2020;98:833–47.

49.Neubert M, Ridder DA, Bargiotas P, Akira S, Schwaninger M. Acute inhibition of TAK1 protects against neuronal death in cerebral ischemia. Cell Death Differ. 2011;18:1521–30.

50.Wang YZ, Wang JJ, Huang Y, Liu F, Zeng WZ, Li Y, et al. Tissue acidosis induces neuronal necroptosis via ASIC1a channel independent of its ionic conduction. elife. 2015;4:e05682.

51.Wang JJ, Liu F, Yang F, Wang YZ, Qi X, Li Y, et al. Disruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis. Nat Commun. 2020;11:475.

52.Liu Z, Chopp M. Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke. Prog Neurobiol. 2016;144:103–20.

53.Linnerbauer M, Rothhammer V. Protective functions of reactive astrocytes following central nervous system insult. Front Immunol. 2020;11:573256.

54.Kim JH, Min KJ, Seol W, Jou I, Joe EH. Astrocytes in injury states rapidly produce anti-inflammatory factors and attenuate microglial inflammatory responses. J Neurochem. 2010;115:1161–71.

55.Li L, Lundkvist A, Andersson D, Wilhelmsson U, Nagai N, Pardo AC, et al. Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab. 2008;28:468–81.

56.Zhu YM, Lin L, Wei C, Guo Y, Qin Y, Li ZS, et al. The key regulator of necroptosis, RIP1 kinase, contributes to the formation of Astrogliosis and glial scar in ischemic stroke. Transl Stroke Res. 2021;12:991–1017.

57.Liu J, Zhu YM, Guo Y, Lin L, Wang ZX, Gu F, et al. Inhibition of GSK3beta and RIP1K attenuates glial scar formation induced by ischemic stroke via reduction of inflammatory cytokine production. Front Pharmacol. 2020;11:812.

58.Holinstat M. Normal platelet function. Cancer Metastasis Rev. 2017;36:195–8.

59.Zhang Y, Zhang J, Yan R, Tian J, Zhang Y, Zhang J, et al. Receptor-interacting protein kinase 3 promotes platelet activation and thrombosis. Proc Natl Acad Sci U S A. 2017;114:2964–9.

60.Schuhmann MK, Stoll G, Bieber M, Vogtle T, Hofmann S, Klaus V, et al. CD84 links T cell and platelet activity in cerebral Thrombo-inflammation in acute stroke. Circ Res. 2020;127:1023–35.

61.Nakazawa D, Desai J, Steiger S, Muller S, Devarapu SK, Mulay SR, et al. Activated platelets induce MLKL-driven neutrophil necroptosis and release of neutrophil extracellular traps in venous thrombosis. Cell Death Dis. 2018;4:6.

62.Cognasse F, Hamzeh H, Chavarin P, Acquart S, Genin C, Garraud O. Evidence of toll-like receptor molecules on human platelets. Immunol Cell Biol. 2005;83:196–8.

63.Nian K, Harding IC, Herman IM, Ebong EE. Blood-brain barrier damage in ischemic stroke and its regulation by endothelial Mechanotransduction. Front Physiol. 2020;11:605398.

64.Abdullahi W, Tripathi D, Ronaldson PT. Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection. Am J Physiol Cell Physiol. 2018;315:C343–56.

65.Chen AQ, Fang Z, Chen XL, Yang S, Zhou YF, Mao L, et al. Microglia-derived TNF-alpha mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke. Cell Death Dis. 2019;10:487.

66.Kovacs SB, Miao EA. Gasdermins: effectors of Pyroptosis. Trends Cell Biol. 2017;27:673–84.

67.Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010;87:779–89.

68.Barrington J, Lemarchand E, Allan SM. A brain in flame; do inflammasomes and pyroptosis influence stroke pathology? Brain Pathol. 2017;27:205–12.

69.Martinon F, Tschopp J. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell. 2004;117:561–74.

70.Boucher D, Monteleone M, Coll RC, Chen KW, Ross CM, Teo JL, et al. Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity. J Exp Med. 2018;215:827–40.

71.Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016;535:111–6.

72.Man SM, Karki R, Kanneganti TD. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev. 2017;277:61–75.

73.Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, et al. Non-canonical inflammasome activation targets caspase-11. Nature. 2011;479:117–21.

74.Wang Y, Gao W, Shi X, Ding J, Liu W, He H, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017;547:99–103.

75.Masuda Y, Futamura M, Kamino H, Nakamura Y, Kitamura N, Ohnishi S, et al. The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage. J Hum Genet. 2006;51:652–64.

76.Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol. 2001;9:113–4.

77.Mamik MK, Power C. Inflammasomes in neurological diseases: emerging pathogenic and therapeutic concepts. Brain. 2017;140:2273–85.

78.Fann DY, Lim YA, Cheng YL, Lok KZ, Chunduri P, Baik SH, et al. Evidence that NF-kappaB and MAPK Signaling promotes NLRP Inflammasome activation in neurons following ischemic stroke. Mol Neurobiol. 2018;55:1082–96.

79.Kaushal V, Dye R, Pakavathkumar P, Foveau B, Flores J, Hyman B, et al. Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death Differ. 2015;22:1676–86.

80.Heinisch O, Zeyen T, Goldmann T, Prinz M, Huber M, Jung J, et al. Erythropoietin abrogates post-ischemic activation of the NLRP3, NLRC4, and AIM2 Inflammasomes in microglia/macrophages in a TAK1-dependent manner. Transl Stroke Res. 2022;13:462–82.

81.Zhang D, Qian J, Zhang P, Li H, Shen H, Li X, et al. Gasdermin D serves as a key executioner of pyroptosis in experimental cerebral ischemia and reperfusion model both in vivo and in vitro. J Neurosci Res. 2019;97:645–60.

82.Wang K, Sun Z, Ru J, Wang S, Huang L, Ruan L, et al. Ablation of GSDMD improves outcome of ischemic stroke through blocking canonical and non-canonical Inflammasomes dependent Pyroptosis in microglia. Front Neurol. 2020;11:577927.

83.Li J, Hao JH, Yao D, Li R, Li XF, Yu ZY, et al. Caspase-1 inhibition prevents neuronal death by targeting the canonical inflammasome pathway of pyroptosis in a murine model of cerebral ischemia. CNS Neurosci Ther. 2020;26:925–39.

84.Lv Y, Sun B, Lu XX, Liu YL, Li M, Xu LX, et al. The role of microglia mediated pyroptosis in neonatal hypoxic-ischemic brain damage. Biochem Biophys Res Commun. 2020;521:933–8.

85.Poh L, Kang SW, Baik SH, Ng GYQ, She DT, Balaganapathy P, et al. Evidence that NLRC4 inflammasome mediates apoptotic and pyroptotic microglial death following ischemic stroke. Brain Behav Immun. 2019;75:34–47.

86.Nakagawa Y, Chiba K. Diversity and plasticity of microglial cells in psychiatric and neurological disorders. Pharmacol Ther. 2015;154:21–35.

87.Tammaro A, Derive M, Gibot S, Leemans JC, Florquin S, Dessing MC. TREM-1 and its potential ligands in non-infectious diseases: from biology to clinical perspectives. Pharmacol Ther. 2017;177:81–95.

88.Xu P, Zhang X, Liu Q, Xie Y, Shi X, Chen J, et al. Microglial TREM-1 receptor mediates neuroinflammatory injury via interaction with SYK in experimental ischemic stroke. Cell Death Dis. 2019;10:555.

89.Liang YB, Song PP, Zhu YH, Xu JM, Zhu PZ, Liu RR, et al. TREM-1-targeting LP17 attenuates cerebral ischemia-induced neuronal injury by inhibiting oxidative stress and pyroptosis. Biochem Biophys Res Commun. 2020;529:554–61.

90.Wang J, Li J, Wang Q, Kong Y, Zhou F, Li Q, et al. Dcf1 deficiency attenuates the role of activated microglia during Neuroinflammation. Front Mol Neurosci. 2018;11:256.

91.Liu Z, Ning J, Zheng X, Meng J, Han L, Zheng H, et al. TMEM59 interacts with TREM2 and modulates TREM2-dependent microglial activities. Cell Death Dis. 2020;11:678.

92.Zhang L, Wang T, Chen XF, Xu ZX, Cao JB, Sun H. TMEM59 protects against cerebral ischemic stroke by suppressing pyroptosis and microglial activation. Biochem Biophys Res Commun. 2021;543:72–9.

93.Li Q, Cao Y, Dang C, Han B, Han R, Ma H, et al. Inhibition of double-strand DNA-sensing cGAS ameliorates brain injury after ischemic stroke. EMBO Mol Med. 2020;12:e11002.

94.Liu X, Zhang M, Liu H, Zhu R, He H, Zhou Y, et al. Bone marrow mesenchymal stem cell-derived exosomes attenuate cerebral ischemia-reperfusion injury-induced neuroinflammation and pyroptosis by modulating microglia M1/M2 phenotypes. Exp Neurol. 2021;341:113700.

95.Wang K, Ru J, Zhang H, Chen J, Lin X, Lin Z, et al. Melatonin enhances the therapeutic effect of plasma exosomes against cerebral ischemia-induced Pyroptosis through the TLR4/NF-kappaB pathway. Front Neurosci. 2020;14:848.

96.Fricker M, Tolkovsky AM, Borutaite V, Coleman M, Brown GC. Neuronal cell death. Physiol Rev. 2018;98:813–80.

97.Zhu S, Zhang Z, Jia LQ, Zhan KX, Wang LJ, Song N, et al. Valproic acid attenuates global cerebral ischemia/reperfusion injury in gerbils via anti-pyroptosis pathways. Neurochem Int. 2019;124:141–51.

98.Sun R, Peng M, Xu P, Huang F, Xie Y, Li J, et al. Low-density lipoprotein receptor (LDLR) regulates NLRP3-mediated neuronal pyroptosis following cerebral ischemia/reperfusion injury. J Neuroinflammation. 2020;17:330.

99.Liang J, Wang Q, Li JQ, Guo T, Yu D. Long non-coding RNA MEG3 promotes cerebral ischemia-reperfusion injury through increasing pyroptosis by targeting miR-485/AIM2 axis. Exp Neurol. 2020;325:113139.

100.Zhao B, Fei Y, Zhu J, Yin Q, Fang W, Li Y. PAF receptor inhibition attenuates neuronal Pyroptosis in cerebral ischemia/reperfusion injury. Mol Neurobiol. 2021;58:6520–39.

101.Liang Y, Song P, Chen W, Xie X, Luo R, Su J, et al. Inhibition of Caspase-1 ameliorates ischemia-associated blood-brain barrier dysfunction and integrity by suppressing Pyroptosis activation. Front Cell Neurosci. 2020;14:540669.

102.Wang Y, Guan X, Gao CL, Ruan W, Zhao S, Kai G, et al. Medioresinol as a novel PGC-1alpha activator prevents pyroptosis of endothelial cells in ischemic stroke through PPARalpha-GOT1 axis. Pharmacol Res. 2021;169:105640.

103.Lyu Z, Chan Y, Li Q, Zhang Q, Liu K, Xiang J, et al. Destructive effects of Pyroptosis on homeostasis of neuron survival associated with the dysfunctional BBB-Glymphatic system and amyloid-Beta accumulation after cerebral ischemia/reperfusion in rats. Neural Plast. 2021;2021:4504363.

104.Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171:273–85.

105.Liu J, Guo ZN, Yan XL, Huang S, Ren JX, Luo Y, et al. Crosstalk between autophagy and Ferroptosis and its putative role in ischemic stroke. Front Cell Neurosci. 2020;14:577403.

106.Pratt DA, Tallman KA, Porter NA. Free radical oxidation of polyunsaturated lipids: new mechanistic insights and the development of peroxyl radical clocks. Acc Chem Res. 2011;44:458–67.

107.Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060–72.

108.Cao JY, Dixon SJ. Mechanisms of ferroptosis. Cell Mol Life Sci. 2016;73:2195–209.

109.Ursini F, Maiorino M, Gregolin C. The selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Biochim Biophys Acta. 1985;839:62–70.

110.Seiler A, Schneider M, Forster H, Roth S, Wirth EK, Culmsee C, et al. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab. 2008;8:237–48.

111.Bannai S, Kitamura E. Transport interaction of L-cystine and L-glutamate in human diploid fibroblasts in culture. J Biol Chem. 1980;255:2372–6.

112.Yang WS, Stockwell BR. Ferroptosis: death by lipid peroxidation. Trends Cell Biol. 2016;26:165–76.

113.Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, et al. Ferroptosis: process and function. Cell Death Differ. 2016;23:369–79.

114.Dixon SJ. Ferroptosis: bug or feature? Immunol Rev. 2017;277:150–7.

115.Lane DJR, Ayton S, Bush AI. Iron and Alzheimer's disease: an update on emerging mechanisms. J Alzheimers Dis. 2018;64:S379–95.

116.Roskams AJ, Connor JR. Iron, transferrin, and ferritin in the rat brain during development and aging. J Neurochem. 1994;63:709–16.

117.Patt A, Horesh IR, Berger EM, Harken AH, Repine JE. Iron depletion or chelation reduces ischemia/reperfusion-induced edema in gerbil brains. J Pediatr Surg. 1990;25:224–8 discussion 227-8.

118.Tuo QZ, Lei P, Jackman KA, Li XL, Xiong H, Li XL, et al. Tau-mediated iron export prevents ferroptotic damage after ischemic stroke. Mol Psychiatry. 2017;22:1520–30.

119.Cui Y, Zhang Y, Zhao X, Shao L, Liu G, Sun C, et al. ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation. Brain Behav Immun. 2021;93:312–21.

120.Chen J, Yang L, Geng L, He J, Chen L, Sun Q, et al. Inhibition of acyl-CoA Synthetase long-chain family member 4 facilitates neurological recovery after stroke by regulation Ferroptosis. Front Cell Neurosci. 2021;15:632354.

121.Yuan Y, Zhai Y, Chen J, Xu X, Wang H. Kaempferol ameliorates oxygen-glucose deprivation/Reoxygenation-induced neuronal Ferroptosis by activating Nrf2/SLC7A11/GPX4 Axis. Biomol Ther. 2021;11:923.

122.Lu J, Xu F, Lu H. LncRNA PVT1 regulates ferroptosis through miR-214-mediated TFR1 and p53. Life Sci. 2020;260:118305.

123.Li C, Sun G, Chen B, Xu L, Ye Y, He J, et al. Nuclear receptor coactivator 4-mediated ferritinophagy contributes to cerebral ischemia-induced ferroptosis in ischemic stroke. Pharmacol Res. 2021;174:105933.

124.Zhao Y, Rempe DA. Prophylactic neuroprotection against stroke: low-dose, prolonged treatment with deferoxamine or deferasirox establishes prolonged neuroprotection independent of HIF-1 function. J Cereb Blood Flow Metab. 2011;31:1412–23.

125.Selim M. Treatment with the iron chelator, deferoxamine mesylate, alters serum markers of oxidative stress in stroke patients. Transl Stroke Res. 2010;1:35–9.

126.Chow EJ, Aplenc R, Vrooman LM, Doody DR, Huang YV, Aggarwal S, et al. Late health outcomes after dexrazoxane treatment: a report from the Children's oncology group. Cancer. 2022;128:788–96.

127.Guan X, Li X, Yang X, Yan J, Shi P, Ba L, et al. The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation. Life Sci. 2019;235:116795.

128.Li G, Li X, Dong J, Han Y. Electroacupuncture ameliorates cerebral ischemic injury by inhibiting Ferroptosis. Front Neurol. 2021;12:619043.

129.Andrabi SA, Dawson TM, Dawson VL. Mitochondrial and nuclear cross talk in cell death: parthanatos. Ann N Y Acad Sci. 2008;1147:233–41.

130.Houl JH, Ye Z, Brosey CA, Balapiti-Modarage LPF, Namjoshi S, Bacolla A, et al. Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death. Nat Commun. 2019;10:5654.

131.Yu SW, Andrabi SA, Wang H, Kim NS, Poirier GG, Dawson TM, et al. Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death. Proc Natl Acad Sci U S A. 2006;103:18314–9.

132.Zhang J, Dawson VL, Dawson TM, Snyder SH. Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science. 1994;263:687–9.

133.Eliasson MJ, Sampei K, Mandir AS, Hurn PD, Traystman RJ, Bao J, et al. Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med. 1997;3:1089–95.

134.Joly LM, Benjelloun N, Plotkine M, Charriaut-Marlangue C. Distribution of poly(ADP-ribosyl)ation and cell death after cerebral ischemia in the neonatal rat. Pediatr Res. 2003;53:776–82.

135.Love S, Barber R, Wilcock GK. Neuronal death in brain infarcts in man. Neuropathol Appl Neurobiol. 2000;26:55–66.

136.Chiarugi A, Meli E, Calvani M, Picca R, Baronti R, Camaioni E, et al. Novel isoquinolinone-derived inhibitors of poly(ADP-ribose) polymerase-1: pharmacological characterization and neuroprotective effects in an in vitro model of cerebral ischemia. J Pharmacol Exp Ther. 2003;305:943–9.

137.Lo EH, Bosque-Hamilton P, Meng W. Inhibition of poly(ADP-ribose) polymerase: reduction of ischemic injury and attenuation of N-methyl-D-aspartate-induced neurotransmitter dysregulation. Stroke. 1998;29:830–6.

138.Chiarugi A. Poly(ADP-ribosyl)ation and stroke. Pharmacol Res. 2005;52:15–24.

139.Kim Y, Kim YS, Kim HY, Noh MY, Kim JY, Lee YJ, et al. Early treatment with poly(ADP-ribose) Polymerase-1 inhibitor (JPI-289) reduces infarct volume and improves long-term behavior in an animal model of ischemic stroke. Mol Neurobiol. 2018;55:7153–63.

140.Han S, Kim YH, Choi HY, Soh DJ, Kim J, Nam J, et al. First-in-human evaluation of the safety, tolerability, and pharmacokinetics of a neuroprotective poly (ADP-ribose) Polymerase-1 inhibitor, JPI-289, in healthy volunteers. Drug Des Devel Ther. 2020;14:3189–99.

141.Ying W, Sevigny MB, Chen Y, Swanson RA. Poly(ADP-ribose) glycohydrolase mediates oxidative and excitotoxic neuronal death. Proc Natl Acad Sci U S A. 2001;98:12227–32.

142.Lu XC, Massuda E, Lin Q, Li W, Li JH, Zhang J. Post-treatment with a novel PARG inhibitor reduces infarct in cerebral ischemia in the rat. Brain Res. 2003;978:99–103.

143.Burkle A, Virag L. Poly(ADP-ribose): PARadigms and PARadoxes. Mol Asp Med. 2013;34:1046–65.

144.Mashimo M, Kato J, Moss J. ADP-ribosyl-acceptor hydrolase 3 regulates poly (ADP-ribose) degradation and cell death during oxidative stress. Proc Natl Acad Sci U S A. 2013;110:18964–9.

145.Mashimo M, Bu X, Aoyama K, Kato J, Ishiwata-Endo H, Stevens LA, et al. PARP1 inhibition alleviates injury in ARH3-deficient mice and human cells. JCI Insight. 2019;4:e124519.

146.Kang HC, Lee YI, Shin JH, Andrabi SA, Chi Z, Gagne JP, et al. Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage. Proc Natl Acad Sci U S A. 2011;108:14103–8.

147.Andrabi SA, Kang HC, Haince JF, Lee YI, Zhang J, Chi Z, et al. Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death. Nat Med. 2011;17:692–9.

148.Zeng M, Zhou H, He Y, Wang Z, Shao C, Yin J, et al. Danhong injection alleviates cerebral ischemia/reperfusion injury by improving intracellular energy metabolism coupling in the ischemic penumbra. Biomed Pharmacother. 2021;140:111771.

149.Li Y, Yang Y, Zhao Y, Zhang J, Liu B, Jiao S, et al. Astragaloside IV reduces neuronal apoptosis and parthanatos in ischemic injury by preserving mitochondrial hexokinase-II. Free Radic Biol Med. 2019;131:251–63.

150.Li WH, Yang YL, Cheng X, Liu M, Zhang SS, Wang YH, et al. Baicalein attenuates caspase-independent cells death via inhibiting PARP-1 activation and AIF nuclear translocation in cerebral ischemia/reperfusion rats. Apoptosis. 2020;25:354–69.

151.Kong D, Zhu J, Liu Q, Jiang Y, Xu L, Luo N, et al. Mesenchymal stem cells protect neurons against hypoxic-ischemic injury via inhibiting parthanatos, necroptosis, and apoptosis, but not autophagy. Cell Mol Neurobiol. 2017;37:303–13.

152.Chiu LY, Ho FM, Shiah SG, Chang Y, Lin WW. Oxidative stress initiates DNA damager MNNG-induced poly(ADP-ribose)polymerase-1-dependent parthanatos cell death. Biochem Pharmacol. 2011;81:459–70.

153.Gerace E, Masi A, Resta F, Felici R, Landucci E, Mello T, et al. PARP-1 activation causes neuronal death in the hippocampal CA1 region by increasing the expression of CA(2+)-permeable AMPA receptors. Neurobiol Dis. 2014;70:43–52.

154.Zhao H, Tang J, Chen H, Gu W, Geng H, Wang L, et al. 14,15-EET reduced brain injury from cerebral ischemia and reperfusion via suppressing neuronal Parthanatos. Int J Mol Sci. 2021;22:9660.

155.Zhong H, Song R, Pang Q, Liu Y, Zhuang J, Chen Y, et al. Propofol inhibits parthanatos via ROS-ER-calcium-mitochondria signal pathway in vivo and vitro. Cell Death Dis. 2018;9:932.

156.Basso E, Fante L, Fowlkes J, Petronilli V, Forte MA, Bernardi P. Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D. J Biol Chem. 2005;280:18558–61.

157.Bernardi P. The mitochondrial permeability transition pore: a mystery solved? Front Physiol. 2013;4:95.

158.Denorme F, Manne BK, Portier I, Eustes AS, Kosaka Y, Kile BT, et al. Platelet necrosis mediates ischemic stroke outcome in mice. Blood. 2020;135:429–40.

159.Kim SY, Shim MS, Kim KY, Weinreb RN, Wheeler LA, Ju WK. Inhibition of cyclophilin D by cyclosporin a promotes retinal ganglion cell survival by preventing mitochondrial alteration in ischemic injury. Cell Death Dis. 2014;5:e1105.

160.Zhao LP, Ji C, Lu PH, Li C, Xu B, Gao H. Oxygen glucose deprivation (OGD)/re-oxygenation-induced in vitro neuronal cell death involves mitochondrial cyclophilin-D/P53 signaling axis. Neurochem Res. 2013;38:705–13.

161.Ye F, Li X, Li F, Li J, Chang W, Yuan J, et al. Cyclosporin a protects against lead neurotoxicity through inhibiting mitochondrial permeability transition pore opening in nerve cells. Neurotoxicology. 2016;57:203–13.

162.Xi J, Wang H, Mueller RA, Norfleet EA, Xu Z. Mechanism for resveratrol-induced cardioprotection against reperfusion injury involves glycogen synthase kinase 3beta and mitochondrial permeability transition pore. Eur J Pharmacol. 2009;604:111–6.

163.Zhou X, Wang HY, Wu B, Cheng CY, Xiao W, Wang ZZ, et al. Ginkgolide K attenuates neuronal injury after ischemic stroke by inhibiting mitochondrial fission and GSK-3beta-dependent increases in mitochondrial membrane permeability. Oncotarget. 2017;8:44682–93.

164.Cheng A, Yang Y, Zhou Y, Maharana C, Lu D, Peng W, et al. Mitochondrial SIRT3 mediates adaptive responses of neurons to exercise and metabolic and excitatory challenges. Cell Metab. 2016;23:128–42.

165.Yang Y, Tian Y, Guo X, Li S, Wang W, Shi J. Ischemia injury induces mPTP opening by reducing Sirt3. Neuroscience. 2021;468:68–74.

166.Yang X, Zhang Y, Geng K, Yang K, Shao J, Xia W. Sirt3 protects against ischemic stroke injury by regulating HIF-1alpha/VEGF Signaling and blood-brain barrier integrity. Cell Mol Neurobiol. 2021;41:1203–15.

167.Yang X, Geng KY, Zhang YS, Zhang JF, Yang K, Shao JX, et al. Sirt3 deficiency impairs neurovascular recovery in ischemic stroke. CNS Neurosci Ther. 2018;24:775–83.

168.Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell. 2012;149:1536–48.

169.Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 1995;146:3–15.

170.Loh KY, Wang Z, Liao P. Oncotic cell death in stroke. Rev Physiol Biochem Pharmacol. 2019;176:37–64.

171.Huang Q, Zhang R, Zou L, Cao X, Chu X. Cell death pathways in astrocytes with a modified model of oxygen-glucose deprivation. PLoS One. 2013;8:e61345.

172.Cao X, Zhang Y, Zou L, Xiao H, Chu Y, Chu X. Persistent oxygen-glucose deprivation induces astrocytic death through two different pathways and calpain-mediated proteolysis of cytoskeletal proteins during astrocytic oncosis. Neurosci Lett. 2010;479:118–22.

173.Nilius B, Prenen J, Tang J, Wang C, Owsianik G, Janssens A, et al. Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4. J Biol Chem. 2005;280:6423–33.

174.Chen B, Ng G, Gao Y, Low SW, Sandanaraj E, Ramasamy B, et al. Non-invasive multimodality imaging directly shows TRPM4 inhibition ameliorates stroke reperfusion injury. Transl Stroke Res. 2019;10:91–103.

175.Schattling B, Steinbach K, Thies E, Kruse M, Menigoz A, Ufer F, et al. TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med. 2012;18:1805–11.

176.Wei S, Low SW, Poore CP, Chen B, Gao Y, Nilius B, et al. Comparison of anti-oncotic effect of TRPM4 blocking antibody in neuron, astrocyte and vascular endothelial cell under hypoxia. Front Cell Dev Biol. 2020;8:562584.

177.Ren KD, Liu WN, Tian J, Zhang YY, Peng JJ, Zhang D, et al. Mitochondrial E3 ubiquitin ligase 1 promotes brain injury by disturbing mitochondrial dynamics in a rat model of ischemic stroke. Eur J Pharmacol. 2019;861:172617.

178.Li Y, Sun J, Wu R, Bai J, Hou Y, Zeng Y, et al. Mitochondrial MPTP: a novel target of Ethnomedicine for stroke treatment by apoptosis inhibition. Front Pharmacol. 2020;11:352.

179.Fakharnia F, Khodagholi F, Dargahi L, Ahmadiani A. Prevention of Cyclophilin D-mediated mPTP opening using cyclosporine-a alleviates the elevation of necroptosis, autophagy and apoptosis-related markers following global cerebral ischemia-reperfusion. J Mol Neurosci. 2017;61:52–60.

180.Linkermann A, Brasen JH, Darding M, Jin MK, Sanz AB, Heller JO, et al. Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2013;110:12024–9.

181.Zhou Y, Liao J, Mei Z, Liu X, Ge J. Insight into crosstalk between Ferroptosis and necroptosis: novel therapeutics in ischemic stroke. Oxidative Med Cell Longev. 2021;2021:9991001.

182.Huang Y, Liu J, He J, Hu Z, Tan F, Zhu X, et al. UBIAD1 alleviates ferroptotic neuronal death by enhancing antioxidative capacity by cooperatively restoring impaired mitochondria and Golgi apparatus upon cerebral ischemic/reperfusion insult. Cell Biosci. 2022;12:42.

183.DeGregorio-Rocasolano N, Marti-Sistac O, Gasull T. Deciphering the iron side of stroke: neurodegeneration at the crossroads between iron Dyshomeostasis, Excitotoxicity, and Ferroptosis. Front Neurosci. 2019;13:85.

184.Nakamura T, Naguro I, Ichijo H. Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases. Biochim Biophys Acta Gen Subj. 2019;1863:1398–409.

185.LaRocca TJ, Seeger T, Prado M, Perea-Gil I, Neofytou E, Mecham BH, et al. Pharmacological silencing of MicroRNA-152 prevents pressure overload-induced heart failure. Circ Heart Fail. 2020;13:e006298.

186.Xu Y, Wu X, Hu W, Yu D, Shao Z, Li W, et al. RIP3 facilitates necroptosis through CaMKII and AIF after intracerebral hemorrhage in mice. Neurosci Lett. 2021;749:135699.

187.Schriewer JM, Peek CB, Bass J, Schumacker PT. ROS-mediated PARP activity undermines mitochondrial function after permeability transition pore opening during myocardial ischemia-reperfusion. J Am Heart Assoc. 2013;2:e000159.

188.Song X, Gong Z, Liu K, Kou J, Liu B, Liu K. Baicalin combats glutamate excitotoxicity via protecting glutamine synthetase from ROS-induced 20S proteasomal degradation. Redox Biol. 2020;34:101559.

189.Navarro-Yepes J, Zavala-Flores L, Anandhan A, Wang F, Skotak M, Chandra N, et al. Antioxidant gene therapy against neuronal cell death. Pharmacol Ther. 2014;142:206–30.

190.He Y, Xu Y, Chen Z, He B, Quan Z, Zhang R, et al. Protective effect of Mitochondrially targeted peptide against oxidant injury of cone photoreceptors through preventing necroptosis pathway. J Biomed Nanotechnol. 2021;17:279–90.

191.Lu B, Gong X, Wang ZQ, Ding Y, Wang C, Luo TF, et al. Shikonin induces glioma cell necroptosis in vitro by ROS overproduction and promoting RIP1/RIP3 necrosome formation. Acta Pharmacol Sin. 2017;38:1543–53.

192.Sun Y, Yu J, Liu X, Zhang C, Cao J, Li G, et al. Oncosis-like cell death is induced by berberine through ERK1/2-mediated impairment of mitochondrial aerobic respiration in gliomas. Biomed Pharmacother. 2018;102:699–710.

193.Tian Q, Qin B, Gu Y, Zhou L, Chen S, Zhang S, et al. ROS-mediated necroptosis is involved in iron overload-induced osteoblastic cell death. Oxidative Med Cell Longev. 2020;2020:1295382.

194.Gao L, Qin JX, Shi JQ, Jiang T, Wang F, Xie C, et al. Fine particulate matter exposure aggravates ischemic injury via NLRP3 inflammasome activation and pyroptosis. CNS Neurosci Ther. 2022;28:1045–58.

195.Zhu P, Hu S, Jin Q, Li D, Tian F, Toan S, et al. Ripk3 promotes ER stress-induced necroptosis in cardiac IR injury: a mechanism involving calcium overload/XO/ROS/mPTP pathway. Redox Biol. 2018;16:157–68.

196.Chen Y, Mi Y, Zhang X, Ma Q, Song Y, Zhang L, et al. Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells. J Exp Clin Cancer Res. 2019;38:402.

197.Jacobson J, Duchen MR. Mitochondrial oxidative stress and cell death in astrocytes--requirement for stored Ca2+ and sustained opening of the permeability transition pore. J Cell Sci. 2002;115:1175–88.

198.Tian J, Guo S, Chen H, Peng JJ, Jia MM, Li NS, et al. Combination of Emricasan with Ponatinib synergistically reduces ischemia/reperfusion injury in rat brain through simultaneous prevention of apoptosis and necroptosis. Transl Stroke Res. 2018;9:382–92.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Broadening horizons: ferroptosis as a new target for traumatic brain injury

Related Author

Ziqing Wei

Haihan Yu

Huijuan Zhao

Mingze Wei

Han Xing

Jinyan Pei

Yang Yang

Kaidi Ren

Related Institution

Department of Neurology, The First Affiliated Hospital of Zhengzhou University

Henan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University

Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University

Henan International Joint Laboratory of Thrombosis and Hemostasis

Henan University of Science and Technology

⁰