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P85 Stroke is a vascular disease in which brain cell death is  initiated by a great reduction in blood flow. Only a few minutes of  markedly lowered local blood flow (focal ischemia) may injure neurons  and non-neuronal cells (e.g., endothelial cells and astrocytes) and  lead to their death. The size and type of lesion depend on the duration  and extent of flow reduction plus other local, mainly intrinsic  variables. To understand the interplay between flow reduction and  intrinsic factors in short-term, focal ischemic damage, blood flow and  cell injury were assessed in three strains of mice.Method: The middle cerebral artery (MCA) was unilaterally occluded for 15 min  in SV129, C57Bl/6, and Balb/C mice. Local cerebral blood flow (LCBF)  was measured at the end of MCA occlusion by quantitative  autoradiography (N=6 per strain). In other mice, cell damage and  infarct size were assayed after 1–7days of reperfusion.Results: LCBF in the ischemic core region during MCA  occlusion was greatly and similarly reduced in all three strains  (range=3–20 ml/100g/min); LCBF in the penumbra, however, differed  among the strains (LCBF in descending order: SV129&gt;C57Bl/6&gt;Balb/c  mice). In addition, the penumbral zone was strikingly narrow in Balb/C  mice. After 24 hr of reperfusion, the frequency of TUNEL positive cells  in the ischemic core was highest (and most widespread) in Balb/C mice,  much less in C57B1/6 mice, and nil in SV129 mice. Consistently,  infarcts were seen after 3-day reperfusion in Balb/C and C57B1/6 mice  but not in SV129 mice; increasing MCA occlusion to 30 min, however,  caused infarction in the cerebral cortex of SV129 mice.Conclusion: These results indicate considerable dependence  of brain cell damage on LCBF reduction with transient focal ischemia  and suggest that there are intrinsic differences in cerebrovascular  structure and/or function among these three mouse strains. Other  differences in genetic background may, however, contribute to this  interstrain variation in vulnerability to transient focal ischemic.  Supported by NIH grants NS37372 and NS25545.

Intrinsic differences in local cerebral blood flow yield higher vulnerability to transient focal ischemia in Balb/C than C57B1/6 or SV129J mice.