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Apolipoprotein E deficiency worsens outcome from global cerebral ischemia in the mouse
被引:109
作者:
Sheng, HX
Laskowitz, DT
Mackensen, GB
Kudo, M
Pearlstein, RD
Warner, DS
机构:
[1] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Med Neurol, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[4] Tech Univ Munich, Klinikum Rechts Isar, Dept Anesthesiol, D-8000 Munich, Germany
[5] Yamagata Univ, Dept Anesthesiol & Resuscitat, Yamagata, Japan
来源:
关键词:
apolipoproteins;
cerebral blood flow;
ischemia;
histology;
mice;
D O I:
10.1161/01.STR.30.5.1118
中图分类号:
R74 [神经病学与精神病学];
学科分类号:
摘要:
Background and Purpose-Apolipoprotein E (apoE) has been found relevant in a variety of central nervous system disorders. This experiment examined the effect of endogenous murine apoE on selective neuronal necrosis resulting from a transient forebrain ischemia insult. Methods-ApoE deficient (n = 16) and wild type (n = 17) halothane-anesthetized mice were subjected to severe forebrain ischemia (10 minutes of bilateral carotid occlusion and systemic hypotension). After 3 days' recovery, brain injury was determined histologically. In other apoE-deficient and wild-type mice, regional cerebral blood flow (CBF) was determined by C-14-iodoantipyrine autoradiography 10 minutes before, 5 minutes after onset of, and 30 minutes after reperfusion from 10 minutes of forebrain ischemia. Results-The percentage of dead hippocampal CA1 neurons (mean+/-SD) was greater in the apoE-deficient group (apoE deficient = 67+/-30%; wild type = 37+/-33%; P=0.011). A similar pattern was observed in the caudoputamen (P = 0.002) and neocortex (P = 0.014). Cerebral blood flow was similar between groups at each measurement interval. Marked hypoperfusion persisted in both groups at 30 minutes after ischemia. Conclusions-ApoE deficiency worsens ischemic outcome. This is not attributable to effects on CBF. A role of apoE in the cerebral response to global ischemia is consistent with prior reports that murine apoE deficiency increases infarct size resulting from focal cerebral ischemia.
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页码:1118 / 1123
页数:6
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