Neuronal subclass-selective loss of pyruvate dehydrogenase immunoreactivity following canine cardiac arrest and resuscitation

被引:43
作者
Bogaert, YE
Sheu, KFR
Hof, PR
Brown, AM
Blass, JP
Rosenthal, RE
Fiskum, G
机构
[1] George Washington Univ, Dept Biochem & Mol Biol, Sch Med, Washington, DC 20031 USA
[2] George Washington Univ, Dept Emergency Med, Sch Med, Washington, DC 20031 USA
[3] Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA
[4] CUNY Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, New York, NY 10029 USA
[5] CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA
[6] CUNY Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA
[7] CUNY Mt Sinai Sch Med, Dept Adult Dev & Ophthalmol, New York, NY 10029 USA
关键词
cardiac arrest; cerebral ischemia; laser scanning microscopy; mitochondria; neocortex; reperfusion;
D O I
10.1006/exnr.1999.7250
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Chronic impairment of aerobic energy metabolism accompanies global cerebral ischemia and reperfusion and likely contributes to delayed neuronal cell death. Reperfusion-dependent inhibition of pyruvate dehydrogenase complex (PDHC) enzyme activity has been described and proposed to be at least partially responsible for this metabolic abnormality. This study tested the hypothesis that global cerebral ischemia and reperfusion results in the loss of pyruvate dehydrogenase immunoreactivity and that such loss is associated with selective neuronal vulnerability to transient ischemia. Following 10 min canine cardiac arrest, resuscitation, and 2 or 24 h of restoration of spontaneous circulation, brains were either perfusion fixed for immunohistochemical analyses or biopsy samples were removed for Western immunoblot analyses of PDHC immunoreactivity, A significant decrease in immunoreactivity was observed in frontal cortex homogenates from both 2 and 24 h reperfused animals compared to samples from nonischemic control animals. These results were supported by confocal microscopic immunohistochemical determinations of pyruvate dehydrogenase immunoreactivity in the neuronal cell bodies located within different layers of the frontal cortex. Loss of immunoreactivity was greatest for pyramidal neurons located in layer V compared to neurons in layers IIIc/IV, which correlates with a greater vulnerability of layer V neurons to delayed death caused by transient global cerebral ischemia. (C) 2000 Academic Press.
引用
收藏
页码:115 / 126
页数:12
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