APOLIPOPROTEIN E-DEFICIENT MICE HAVE INCREASED SUSCEPTIBILITY TO FOCAL CEREBRAL-ISCHEMIA

Recent evidence suggests that apolipoprotein E (ApoE) plays a role in neurologic disease. This experiment compared the neurologic and histol ogic outcome of ApoE-deficient mutant and wild-type mice subjected to a 60- or 90-minute episode of middle cerebral artery filament occlusio n and a recovery interval of 24 hours. With 60 minutes of ischemia, th ere was no mortality. Apolipoprotein E-deficient mice had larger infar cts (cortex: ApoE deficient = 20 mm(3) +/- 12, wild-type = 9 +/- 7 mm( 3), P = 0.03; subcortex: ApoE deficient = 22 +/- 7 mm(3), wild-type = 16 +/- 7 mm(3), P = 0.07). Hemiparesis was less severe in wild-type an imals (P = 0.02). After 90 minutes of ischemia, mortality in ApoE-defi cient mice (n = 10) was 40% versus 0% in wild-type mice(n = 10; P = 0. 09). Intraparenchymal hemorrhage was found in 3 of the 4 dead mice. No difference in cortical (ApoE deficient = 37 +/- 8 mm(3); wild-type = 31 +/- 18 mm(3); P = 0.49) or subcortical (ApoE deficient = 30 +/- 11 mm(3); wild-type = 32 +/- 18 mm(3); P = 0.78) infarct volumes was pres ent among survivors. ApoE deficient mice had a prolonged activated par tial thromboplastin time and increased fibrinogen concentration. This data supports the hypothesis that apolipoprotein E plays a role in the pathophysiology of ischemic brain damage.