Invited Symposium: Stroke/Cerebral Vasospasm
Elisa Beres, MD (Dept. of Neuroscience & Neurosurgery, University of Virginia Health Sciences Center, USA)
Robert Replogle, MD (Dept of Neuroscience & Neurosurgery, University of Virginia Health Sciences Center, USA)
A biphasic shift in cerebral blood flow can occur during the reperfusion phase that succeeds a transient ischemic event. An initial period of post-ischemic hyperemia is followed by a delayed, and more prolonged, period of hypoperfusion. Delayed hypoperfusion can be quite detrimental because it represents a secondary ischemic insult to cells that have already been compromised. Cerebral microvessels positioned downstream from a reperfused vessel can contribute significantly to delayed hypoperfusion. It is therefore, reasonable to evaluate the therapeutic value of targeting delayed hypoperfusion at the level of the cerebral microvasculature. In the present study, cerebral microvessels were visualized in the parenchyma of the hippocampus by utilizing videomicroscopy of an in vitro brain slice preparation. Microvessels became dilated during hypoxia, and remained dilated for approximately twenty minutes after reoxygenation. The vessels then constricted beyond their baseline levels and maintained a constricted state for several hours. The biphasic changes in cerebral microvessels induced by hypoxia in vitro thus mimic the vascular changes observed in response to ischemia-reperfusion in vivo. Delayed post-hypoxic constriction of cerebral microvessels was blocked by treating the slices with an inhibitor of the calcium-activated protease calpain. These findings indicate that calpain-mediated proteolysis contributes to delayed constriction of cerebral microvessels after hypoxic challenge. Calpain inhibitors have previously been shown to provide a protective effect against ischemic neuronal injury invivo. It is possible that this neuroprotective effect derives in part from the ability of calpain inhibitors to limit secondary ischemia at the level of the cerebral microvasculature.
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|Kevin Lee, MD; Elisa Beres, MD; Robert Replogle, MD; (1998). Cerebral Microvasculature as a Target for Stroke Therapeutics. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/zhang/kevin_lee0598/index.html|
|© 1998 Author(s) Hold Copyright|