Temporary and permanent focal cerebral ischemia in the mouse: assessment of cerebral blood flow, brain damage and blood-brain barrier permeability

Objective To establish a mouse model of middle cerebral artery occlusion, which mimics focal ischemia in humans and to demonstrate the advantages and disadvantages of the model. Methods CD-1 mice (n = 126) had permanent middle cerebral artery occlusion for 24 h, or temporary occlusion for either one hour followed by 23 h of reperfusion or 2 h of occlusion with 22 h of reperfusion. The middle cerebral artery was occluded by insertion of suture through the internal carotid artery. Reperfusion was established by suture withdrawal. The degree of occlusion and the extent of reperfusion were determined using laser Doppler. Infarct volume was measured with 2, 3, 5-triphenyl tetrazolium chloride staining, and the blood-brain barrier disruption was demonstrated using albumin immunohistochemistry. Results Blood flow decreased to 14% - 19% of baseline in both the permanent and temporary occlusion groups and was restored to 51% - 75% of baseline after reperfusion. The infarct volume was smaller in the 1 h/23 h temporary occlusion group (P < 0.05) than in either the 24 h permanent occlusion group or the 2 h/22 h temporary occlusion group. Blood-brain barrier disruption was also smaller in the 1 h/23 h temporary occlusion group than in either the 24 h permanent occlusion or the 2 h/22 h temporary occlusion group (P<0.05). Conclusion Permanent or temporary middle cerebral artery occlusion causes reproducible brain injury in the mouse. Blood-brain barrier disruption and infarct volume remain important markers of focal cerebral ischemia.