MOUSE STRAIN DIFFERENCES IN SUSCEPTIBILITY TO CEREBRAL-ISCHEMIA ARE RELATED TO CEREBRAL VASCULAR ANATOMY

The consequences of cerebral ischemia were studied in three different strains (BDF, CFW, and BALB/C) of mice. The different strains exhibite d significant differences in susceptibility to 24-h focal ischemia. Fo llowing middle cerebral artery occlusion (MCAO), infarct volumes (mm3) were 5 +/- 3 in BDF, 15 +/- 5 in CFW, and 23 +/- 3 in BALB/C mice (p < 0.05). MCAO plus ipsilateral common carotid artery occlusion (CCAO) resulted in infarct volumes of 15 +/- 9 in BDF, 38 +/- 10 in CFW, and 72 +/- 12 in BALB/C mice (p < 0.05). In addition, MCAO plus CCAO produ ced death by 24 h in 42% of CFW and 67% of BALB/C mice, but not in any BDF mice (p < 0.05). CCAO alone produced multifocal hemispheric infar ctions in 36% of BALB/C mice but not in the other two strains. Brains of all mouse strains subjected to sham surgery were free of any ischem ic injury. Arterial blood pressures, blood gases, and blood cell profi les were relatively similar for the three mouse strains. However, carb on black studies of the cerebrovascular anatomy revealed an incomplete circle of Willis (i.e., a significant decrease in the frequency of pa tent posterior communicating arteries) for BALB/C compared with BDF mi ce (p < 0.05), with CFW mice being intermediary. Based on these anatom ical data, BALB/C mice also were evaluated following transient global brain ischemia produced by bilateral CCAO. BALB/C mice exhibited a >85 % reduction in cortical microvascular perfusion and EEG power within 1 min of bilateral CCAO. Also, hippocampal neuronal CA1 damage and mort ality over 7 days were related to the duration of global brain ischemi a (p < 0.05). These data demonstrate a significant difference between mouse strains in their sensitivity to cerebral ischemia that appears t o be related, at least in part, to the functional vascular anatomy at the level of the posterior communicating arteries. In particular, we p oint out the potential usefulness of BALB/C mice as a sensitive and re producible model of focal and global ischemia.