title: Apolipoprotein E-deficient mice have increased susceptibility to focal cerebral ischemia.
abstract: Recent evidence suggests that apolipoprotein E (ApoE) plays a role in neurologic disease. This experiment compared the neurologic and histologic outcome of ApoE-deficient mutant and wild-type mice subjected to a 60- or 90-minute episode of middle cerebral artery filament occlusion and a recovery interval of 24 hours. With 60 minutes of ischemia, there was no mortality. Apolipoprotein E-deficient mice had larger infarcts (cortex: ApoE deficient = 20 mm3 +/- 12, wild-type = 9 +/- 7 mm3, P = 0.03; subcortex: ApoE deficient = 22 +/- 7 mm3, wild-type = 16 +/- 7 mm3, P = 0.07). Hemiparesis was less severe in wild-type animals (P = 0.02). After 90 minutes of ischemia, mortality in ApoE-deficient 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 mm3; wild-type = 31 +/- 18 mm3; P = 0.49) or subcortical (ApoE deficient = 30 +/- 11 mm3; wild-type = 32 +/- 18 mm3; P = 0.78) infarct volumes was present among survivors. ApoE-deficient mice had a prolonged activated partial thromboplastin time and increased fibrinogen concentration. This data supports the hypothesis that apolipoprotein E plays a role in the pathophysiology of ischemic brain damage.
authors.affiliation: Department of Medicine Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Laskowitz
authors.forename: H
authors.initials: H
authors.lastname: Sheng
authors.forename: R D
authors.initials: RD
authors.lastname: Bart
authors.forename: K A
authors.initials: KA
authors.lastname: Joyner
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: D S
authors.initials: DS
authors.lastname: Warner
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001760:Bleeding Time; D002545:Brain Ischemia / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000401:mortality; D002544:Cerebral Infarction / Q000473:pathology; D004198:Disease Susceptibility; D008297:Male; D051379:Mice; D012016:Reference Values; D015424:Reperfusion; D016019:Survival Analysis
chemical_list: D001057:Apolipoproteins E