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Ischemic cell death in brain neurons.
1Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin, USA.
Physiological Reviews
|October 3, 1999
Summary
Neuronal death from ischemia involves necrotic and apoptotic pathways, driven by damaging events like free radicals and calpain activation. Further research is needed to understand the exact mechanisms and triggers of these cell death processes.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Ischemic insults, including global and focal ischemia, are primary models for human neurological diseases.
- Neuronal death can occur through necrosis, apoptosis, or autophagocytosis, each with distinct characteristics.
Purpose of the Study:
- To review the mechanisms of neuronal death in global and focal ischemia.
- To elucidate the stages and key events leading to cell death following ischemic injury.
Main Methods:
- Review of existing literature on rodent models of global and focal ischemia.
- Analysis of cellular changes, signaling pathways, and molecular events involved in neuronal death.
Main Results:
- Cell death pathways include necrosis (ischemic/homogenizing or edematous changes) and apoptosis (DNA laddering, caspase activity).
- The induction stage involves ischemia/reperfusion effects like altered ATP, pH, calcium influx, glutamate release, and gene activation.
- Five key damaging events (perpetrators) are identified: free radicals/peroxynitrite, calpain, phospholipases, PARP, and apoptosis.
- Later stages involve damage to cellular macromolecules, functions (plasmalemma, mitochondria, cytoskeleton), and protein synthesis.
Conclusions:
- Activation of perpetrators, particularly free radical and peroxynitrite generation, appears to be a major driver of ischemic cell death.
- Understanding the precise triggers for apoptosis and autophagocytosis, and the specific functional/structural targets of perpetrators, requires further investigation.