Extension of cerebral hypoperfusion and ischaemic pathology beyond MCA territory after intraluminal filament occlusion.in C57B1/6J mice

Rodent models of focal cerebral ischaemia are critical for understanding pathophysiological concepts in human stroke. The availability of genetically modified mice has prompted the adaptation of the intraluminal filament occlusion model of focal ischaemia for use in mice. In the present study, we investigated the effects of increasing duration of intraluminal occlusion on the extent and distribution of ischaemic pathology and local cerebral blood flow (LCBF) in C57B1/6J mice, the most common background mouse strain. Volumetric assessment of ischaemic damage was performed after 15, 30 or 60 min occlusion followed by 24 h reperfusion. LCBF was measured after 15 and 60 min occlusion using quantitative C-14-iodoantipyrine autoradiography. The extent and distribution of ischaemic damage was highly sensitive to increasing occlusion duration. Recruitment of tissue outside MCA territory produced a steep increase in the volume of damage with increasing occlusion duration: 15 min (9 +/- 2 mm(3)); 30 min (56 +/- 6 mm(3)); 60 min (69 +/- 2 mm(3)). Significant increases in the severity of cerebral hypoperfusion were observed after 60 min compared to 15 min occlusion within and outside MCA territory, e.g. caudate nucleus (9 +/- 6 ml per 100 g per min at 60 min vs. 33 ml per 100 g per min at 15 min) and hippocampus (16 +/- 14 ml per 100 g per min at 60 min vs. 61 16 ml per 100 g per min at 15 min). MABP remained stable for 25 min after occlusion onset and declined thereafter. The integrity of the circle of Willis was examined by carbon black perfusion of the vasculature. A complete circle of Willis was present in only one of 10 mice. These results demonstrate that intraluminal filament occlusion in C57B1/6J mice leads to an occlusion duration-dependent increase in severity of cerebral hypoperfusion and extension of ischaemic pathology beyond MCA territory. (C) 2003 Elsevier B.V. All rights reserved.