Differential regional vulnerability in transient focal cerebral ischemia.

339 The Framingham study and the epidemiology of stroke.iate analysis of risk factors for stroke: Eight-year follow-up study of farming villages in Akita, Japan.WHEN A MAJOR CEREBRAL ARTERY is abruptly occluded, many factors play a role in determining whether damage to the brain will occur. The adequacy of collateral circulation governs the severity and extent of ischemia.' The duration of ischemia is critical for A prospective study of cerebrovascular disease in Japanese rural communities, Akabane and Asahi. Part 1: Evaluation of risk factors in the occurrence of cerebral hemorrhage and thrombosis. recovery of function. 2,3-4 Blood flow thresholds of is-chemia have been defined for paralysis and infarction. 5 For cerebral ischemia of a given degree, some areas may be especially vulnerable. Zones of greater metabolic activity may require more substrate to maintain structural integrity. 6 ' 7 Thus gray matter, with its greater metabolic activity, might be expected to be particularly sensitive to ischemia. Some histopathologic studies have supported this notion, 8 but correlated blood flow data have been lacking. We have investigated regional cerebral vulnerability SUMMARY An unanesthetized monkey model for transient focal cerebral ischemia was used to determine differential regional vulnerability, as denned by histologic criteria for injury. Awake Macaque monkeys underwent unilateral, temporary middle cerebral artery (MCA) occlusion for a period ranging from 15 minutes to 3 hours. Hydrogen clearance was used to monitor local cerebral blood flow (LCBF) from affected cortical and subcortical sites before, during, and after occlusion. Two to four weeks following MCA occlusion, animals were sacrificed and neuropathologic evaluation identified cerebral tissue damage and its precise relation to blood flow recording sites. MCA occlusion led to decreased ipsilateral flow and neurological impairment in all animals. Decreases in LCBF were largest in putamen. MCA de-occlusion led to recovery of neurological function in some, but not all, animals and return of LCBF to near control in all surviving animals. Neuropathologic evaluation revealed areas of incomplete, selective tissue necrosis in the gray matter and areas of total necrosis in both gray and white matter. Selective necrosis was associated with brief, moderate ischemia, while total necrosis was associated with longer, more severe ischemia. Tissue damage was observed both earlier and at higher levels of LCBF in the gray matter than in the white matter. Post-ischemic flow levels during the weeks following occlusion did not correlate with either the degree of residual neurological impairment or the extent or …