Mouse Strain Differences in Susceptibility to Cerebral Ischemia are Related to Cerebral Vascular Anatomy

Abstract

The consequences of cerebral ischemia were studied in three different strains (BDF, CFW, and BALB/C) of mice. The different strains exhibited significant differences in susceptibility to 24-h focal ischemia. Following 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 produced 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 infarctions 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 ischemic injury. Arterial blood pressures, blood gases, and blood cell profiles were relatively similar for the three mouse strains. However, carbon black studies of the cerebrovascular anatomy revealed an incomplete circle of Willis (i.e., a significant decrease in the frequency of patent posterior communicating arteries) for BALB/C compared with BDF mice (p < 0.05), with CFW mice being intermediary. Based on these anatomical 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 mortality over 7 days were related to the duration of global brain ischemia (p < 0.05). These data demonstrate a significant difference between mouse strains in their sensitivity to cerebral ischemia that appears to be related, at least in part, to the functional vascular anatomy at the level of the posterior communicating arteries. In particular, we point out the potential usefulness of BALB/C mice as a sensitive and reproducible model of focal and global ischemia.

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

“…In keeping with previous findings (Barone et al, 1993), significant (~50%) pyramidal cell death occurred in the CA1 region of dorsal hippocampus in mice subjected to 6 min of BCCAO. Dead and dying pyramidal cells in the injured hippocampi displayed features of cellular necrosis, characterized in Nissl-stained coronal sections by pyknotic nuclei, irregular cell contours, and loss of nuclear dye retention.…”

CD18-Mediated Neutrophil Recruitment Contributes to the Pathogenesis of Reperfused but Not Nonreperfused Stroke

“…Because there can be variations in cerebrovascular anatomy between strains of mice which can affect the severity of cerebral ischemic tissue damage, 23 initial experiments were performed to ascertain that the CD18 Ϫ/Ϫ mice did not have grossly detectable variations in cerebrovascular anatomy. For these experiments, an antemortem intravascular injection of India Ink was used to define the Circle of Willis and its principal branches.…”

Reduction of CuZn-Superoxide Dismutase Activity Exacerbates Neuronal Cell Injury and Edema Formation after Transient Focal Cerebral Ischemia

“…The present study also confirms that a decreased level of CuZn-SOD in mutant mice does not affect the residual CBF during ischemia. Recently, Barone et al (1993) reported a significant difference between mouse strains in their sensitivity to focal ischemia that was related to the structural and functional differences in the potency of the circle of Willis. Although the functional vascular anatomy was not examined in the present study, a similar level of CBF decreases during ischemia in Wt and mutant animals clearly suggests that functional vascular anatomy does not play a role in the outcomes after focal cerebral ischemia.…”