Time-Related Neuronal Changes following Middle Cerebral Artery Occlusion: Implications for Therapeutic Intervention and the Role of Calpain
Open Access
- 1 November 1995
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 15 (6), 969-979
- https://doi.org/10.1038/jcbfm.1995.123
Abstract
Changes in neocortex and striatum were characterized over time following focal ischemia to the brain. Rats were subjected to permanent middle cerebral artery occlusion (MCA-O) and sacrificed 1, 3, 6, 12, or 24 h later. The affected tissue was processed for tetrazolium chloride (TTC) and cresyl violet staining, as well as for Western blots to detect calpain-induced spectrin proteolysis. Significant changes in cell size and spectrin breakdown occurred within the first hour of occlusion, with further, dramatic changes in these two early markers continuing over time. Initial evidence of cell loss was noted at 1 h postocclusion in the striatum and at 3 h in the neocortex. However, even in the center of the most affected portion of the neocortex, the majority of cells appeared to be intact through 6 h. By this time, a significant TTC-defined infarct also emerged. These quantitative data indicate that calpain-induced proteolysis occurs very soon after the ischemic insult, is correlated with earliest changes in cell hypotrophy, and precedes or occurs in tandem with evidence of significant cell loss. They also demonstrate that, while some cell loss occurs earlier than previously believed, the majority of cells remains morphologically intact well beyond what is typically thought to be the window of opportunity for intervention. The results thus raise the question of how long after the ischemic event pharmaceutic intervention might be employed to salvage substantial numbers of neurons.Keywords
This publication has 50 references indexed in Scilit:
- Calpain inhibitor AK295 protects neurons from focal brain ischemia. Effects of postocclusion intra-arterial administration.Stroke, 1994
- Postischemic Administration of AK275, a Calpain Inhibitor, Provides Substantial Protection against Focal Ischemic Brain DamageJournal of Cerebral Blood Flow & Metabolism, 1994
- Qualitative and quantitative analysis of the progressive cerebral damage after middle cerebral artery occlusion in miceBrain Research, 1993
- Development of tissue damage, inflammation and resolution following stroke: An immunohistochemical and quantitative planimetric studyBrain Research Bulletin, 1993
- A new model of temporary focal neocortical ischemia in the rat.Stroke, 1992
- Neuronal fodrin proteolysis occurs independently of excitatory amino acid-induced neurotoxicityNeuron, 1991
- Drugs to Treat Age-Related Neurodegenerative Problems The Final Frontier of Medical Science?Journal of the American Geriatrics Society, 1990
- Glutamate neurotoxicity and diseases of the nervous systemNeuron, 1988
- Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats.Stroke, 1986
- Dorsal cerebral arterial collaterals of the ratThe Anatomical Record, 1982