Apolipoprotein E Isoform-Specific Differences in Outcome from Focal Ischemia in Transgenic Mice

Journal of Cerebral Blood Flow and Metabolism - Tập 18 Số 4 - Trang 361-366 - 1998
Huaxin Sheng1, Daniel T. Laskowitz2, Ellen Bennett2, Donald E. Schmechel2, Robert D. Bart3, Ann M. Saunders2, Robert D. Pearlstein4, Tommy Martinsson2,5, David S. Warner1,5,4
1Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, U.S.A.
2Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina, U.S.A.
3Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, U.S.A.
4Department of Surgery, Duke University Medical Center, Durham, North Carolina, U.S.A.
5Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, U.S.A.

Tóm tắt

Apolipoprotein E (apoE), a 34-kD glycosylated lipid-binding protein, is expressed as three common isoforms in humans (E2, E3, or E4). Clinical evidence suggests that the apoE genotype (APOE) may be a risk factor for poor outcome after acute central nervous system injury. This was examined further in transgenic mice constructed with the human APOE3 or APOE4 gene under the control of human promoter and tissue expression elements. Presence of human apoE3 and apoE4 proteins in brains of human APOE homozygous transgenic mice was confirmed by Western blotting. APOE3 (n = 12) and APOE4 (n = 10) mice underwent 60 minutes of middle cerebral artery occlusion. After 24-hour recovery, infarct size was measured. Infarct volumes (mean ± standard deviation) were smaller in the APOE3 group (cortex: APOE3 = 18 ± 4 mm3; APOE4 = 30 ± 11 mm3, P = 0.04; subcortex: APOE3 = 12 ± 4 mm3; APOE4 = 18 ± 4 mm3, P = 0.003). Hemiparesis was less severe in APOE3 mice ( P = 0.02). These data indicate that human isoform-specific effects of apoE are relevant to acute pathomechanisms of focal ischemic brain damage when examined in the mouse. APOE transgenic mice may provide an appropriate model to examine the mechanistic basis for the differential effects of human apoE isoforms in acute central nervous system injury.

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Journal of Cerebral Blood Flow and Metabolism

Tập 18 Số 4

361-366

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