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Cell Death Mechanisms in Cerebral Ischemia–Reperfusion Injury

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Abstract

Ischemic stroke is one of the major causes of morbidity and mortality, affecting millions of people worldwide. Inevitably, the interruption of cerebral blood supply after ischemia may promote a cascade of pathophysiological processes. Moreover, the subsequent restoration of blood flow and reoxygenation may further aggravate brain tissue injury. Although recombinant tissue plasminogen activator (rt-PA) is the only approved therapy for restoring blood perfusion, the reperfusion injury and the narrow therapeutic time window restrict its application for most stroke patients. Increasing evidence indicates that multiple cell death mechanisms are relevant to cerebral ischemia–reperfusion injury, including apoptosis, necrosis, necroptosis, autophagy, pyroptosis, ferroptosis, and so on. Therefore, it is crucial to comprehend various cell death mechanisms and their interactions. In this review, we summarize the various signaling pathways underlying cerebral ischemia–reperfusion injury and elaborate on the crosstalk between the different mechanisms.

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Abbreviations

AIF:

Apoptosis-inducing factor

AMPK:

AMP-activated protein kinase

Bcl-2:

B-cell lymphoma 2

CMA:

Chaperone-mediated autophagy

CypD:

Cyclophilin D

DISC:

Death-inducing signaling complex

ER:

Endoplasmic reticulum

FADD:

Fas-associated death domain

FasL:

Fas ligand

GPX4:

Glutathione peroxidase 4

GSH:

Glutathione

HMGB1:

High mobility group box-1

HSP90:

Heat shock protein 90

IL-1β:

Interleukin-1β

I/R:

Ischemia–reperfusion

JNK1:

C-Jun N-termin

3-MA:

3-Methyladenine

MAPK:

Mitogen-activated protein kinase

MCAO/R:

Middle cerebral artery occlusion/reperfusion

MLKL:

Mixed lineage kinase domain-like protein

MPT:

Mitochondrial permeability transition

MPTP:

Mitochondrial permeability transition pore

mTORC1:

Mammalian targets of rapamycin complex 1

NLRP3:

NOD-like receptor thermal protein domain associated protein

OGD/R:

Oxygen–glucose deprivation and reperfusion

PARP-1:

Poly(ADP-ribose) polymerase-1

PCD:

Programmed cell death

PI3K:

Phosphatidylinositol 3-kinase

RIPK1:

Receptor-interacting protein kinase-1

RIPK3:

Receptor-interacting protein kinase-3

ROS:

Reactive oxygen species

rt-PA:

Recombinant tissue plasminogen activator

SD:

Sprague–Dawley

TNF:

Tumor necrosis

TNFR1:

TNF-α receptor 1

TRADD:

TNF-α receptor-associated death domain

TRAIL:

TNF-related apoptosis-inducing ligand

ULK:

Unc-51-like kinase

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Acknowledgements

The authors would like to thank Dr. Zahra Aqeela in Wuhan University of Technology for her helpful suggestions and improvements to this manuscript English editing.

Funding

This work was supported by grants from the National Natural Science Foundation of China (81870935, JW), the Natural Science Foundation of Beijing (7214224, MJ), the Beijing Natural Science Foundation (Z200024, QW), and the Capital Health Research and Development of Special grants (2020-1-2013, QW).

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Authors and Affiliations

  1. School of Chemistry, Chemical Engineering, and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China

    Qian Zhang & Jianping Wu

  2. Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China

    Qian Zhang, Meng Jia, Qun Wang & Jianping Wu

  3. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100070, China

    Qian Zhang, Meng Jia & Jianping Wu

  4. National Clinical Research Center for Neurological Disease, Beijing, 100070, China

    Qian Zhang, Meng Jia, Qun Wang & Jianping Wu

  5. Taihe Hospital, Hubei University of Medicine, Shiyan, 440070, China

    YunFu Wang

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QZ conducted the literature review and wrote the initial draft of the manuscript. MJ, YW and QW made preliminary revisions to the manuscript. JW made critical revisions and approved the final version of the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Jianping Wu.

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Zhang, Q., Jia, M., Wang, Y. et al. Cell Death Mechanisms in Cerebral Ischemia–Reperfusion Injury. Neurochem Res 47, 3525–3542 (2022). https://doi.org/10.1007/s11064-022-03697-8

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  • DOI: https://doi.org/10.1007/s11064-022-03697-8

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