Summary:We developed a mouse model of embolic focal cerebral ischemia, in which a fibrin-rich clot was placed at the origin of the middle cerebral artery (MCA) in CS7BLl6J mice (n = 31) and B6C3 mice (n = 10). An additional three non emboli zed CS7BLl6J mice were used as a control. Embolus induction, cerebral vascular perfusion deficit, and consequent ischemic cell damage were confirmed by histopathology, im munohistochemistry, laser confocal microscopy, and regional cerebral blood flow (rCBF) measurements. Reduction in rCBF and cerebral infarct were not detected in the control animals. An embolus was found in all CS7BLl6J and B6C3 mice at 24 hours after injection of a clot. Regional CBF in the ipsilateral parietal cortex decreased to 23% (P < O.OS) and 17% (P < O.OS) of preembolizatioolevels immediately and persisted for at least Focal cerebral ischemia in mice has been induced ei ther by coagulating (Welsh et aI., 1987) or by mechani cally blocking (Yang et aI., 1994) the middle cerebral artery (MCA). These models are not accessible to fibri nolysis and do not mimic human stroke, as up to 80% of human strokes are caused by thrombosis or embolism (Sloan, 1987;Albers, 1995). In addition, these models show great variability in volume of cerebral infarction between strains (Barone et aI., 1993). With the develop ment of genetically altered mice with targeted mutations leading to gene deficiency in the plasminogen-plasmin system, such as the tissue plasminogen activator knock out mice (Carmeliet et aI., 1994;Carmeliet and Collen, 1995), and with the expected use of antithrombotic Received February 10, 1997; final revision received June 9, 1997; accepted June 10, 1997.This work was supported in part from National Institute of Neuro logical Disorders and Stroke grants PO NS23393, RO I NS33627, and ROI NS34l84.Address correspondence and reprint requests to Dr. Michael Chopp, Henry Ford Hospital, Neurology Department, 2799 West Grand Blvd., Detroit, MI 48202, U.S.A.Abbreviations used: CBF, cerebral blood flow; ECA, external ca rotid artery; H&E, hematoxylin and eosin; ICA, internal carotid artery; MAP2, microtubule-associated protein-2; MCA, middle cerebral ar tery; PTAH, phosphotungstic acid hematoxylin; rCBF, regional CBF; TTC, triphenyltetrazolium chloride.
1081I hour in CS7BLl6J mice (n = 6) and in B6C3 mice (n = 3), respectively. A significant decrease of rCBF was accompanied by a corresponding reduction of plasma perfusion in the ipsi lateral MCA territory. Neurons exhibited marked reduction in microtubule-associated protein-2 immunostaining coincident with the area of perfusion deficit. The percent infarct volume was 30.3% ± 13.4% for CS7BLl6J mice (n = 17), and 38.3% ± IS.3% for B6C3 mice (n = 7) at 24 hours after embolization. This model of embolic ischemia is relevant to thromboembolic stroke in humans and may be useful to investigate embolic cerebral ischemia in the genetically altered mouse and for evaluation of antiembolic therapies. Key Words: Cerebral blood flow-Laser scanning confocal microscopy-Middle...