Cell and Tissue Research

, Volume 301, Issue 1, pp 173–187

Apoptotic and antiapoptotic mechanisms in stroke

  • Mark P. Mattson
  • Carsten Culmsee
  • Zai Fang Yu
Review

DOI: 10.1007/s004419900154

Cite this article as:
Mattson, M., Culmsee, C. & Yu, Z. Cell Tissue Res (2000) 301: 173. doi:10.1007/s004419900154

Abstract

Apoptosis is a form of programmed cell death that occurs in neurons during development of the nervous system and may also be a prominent form of neuronal death in chronic neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Recent findings also implicate apoptosis in neuronal degeneration after ischemic brain injury in animal models of stroke. Activation of both apoptotic and antiapoptotic signaling cascades occurs in neurons in animal and cell culture models of stroke. Apoptotic cascades involve: increased levels of intracellular oxyradicals and calcium; induction of expression of proteins such as Par-4 (prostate apoptosis response-4), which act by promoting mitochondrial dysfunction and suppressing antiapoptotic mechanisms; mitochondrial membrane depolarization, calcium uptake, and release of factors (e.g., cytochrome c) that ultimately induce nuclear DNA condensation and fragmentation; activation of cysteine proteases of the caspase family; activation of transcription factors such as AP-1 that may induce expression of "killer genes." Antiapoptotic signaling pathways are activated by neurotrophic factors, certain cytokines, and increases in oxidative and metabolic stress. Such protective pathways include: activation of the transcription factors (e.g., nuclear factor-κB, NF-κB) that induce expression of stress proteins, antioxidant enzymes, and calcium-regulating proteins; phosphorylation-mediated modulation of ion channels and membrane transporters; cytoskeletal alterations that modulate calcium homeostasis; and modulation of proteins that stabilize mitochondrial function (e.g., Bcl-2). Intervention studies in experimental stroke models have identified a battery of approaches of potential benefit in reducing neuronal death in stroke patients, including administration of antioxidants, calcium-stabilizing agents, caspase inhibitors, and agents that activate NF-κB. Interestingly, recent studies suggest novel dietary approaches (e.g., food restriction and supplementation with antioxidants) that may reduce brain damage following stroke.

Calcium Free radicals Ischemia Neurotrophic factor NF-κB Par-4 

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Mark P. Mattson
    • 1
  • Carsten Culmsee
    • 1
  • Zai Fang Yu
    • 1
  1. 1.National Institute on Aging, GRC4F01Laboratory of NeurosciencesBaltimoreUSA
  2. 2.Sanders-Brown Research Center on AgingUniversity of KentuckyLexingtonUSA

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