The lipid peroxidation by-product 4-hydroxynonenal is toxic to axons and oligodendrocytes

被引:108
作者
McCracken, E
Valeriani, V
Simpson, C
Jover, T
McCulloch, J
Dewar, D
机构
[1] Univ Glasgow, Wellcome Surg Inst, Glasgow G61 1QH, Lanark, Scotland
[2] Univ Glasgow, Hugh Fraser Labs, Glasgow G61 1QH, Lanark, Scotland
关键词
ischemia; oxidative damage; free radicals; white matter;
D O I
10.1097/00004647-200011000-00002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Lipid peroxidation and the cytotoxic by-product 4-hydroxynonenal (4-HNE) have been implicated in neuronal perikaryal damage. This study sought to determine whether 4-HNE was involved in white matter damage in vivo and in vitro. Immunohistochemical studies detected an increase in cellular and axonal 4-HNE within the ischemic region in the rat after a 24-hour period of permanent middle cerebral artery occlusion. Exogenous 4-HNE (3.2 nmol) was stereotaxically injected into the subcortical white matter of rats that were killed 24 hours later. Damaged axons detected by accumulation of beta -amyloid precursor protein (beta -APP) were observed transversing medially and laterally away from the injection site after intracerebral injection of 4-HNE. In contrast, in the vehicle-treated animals, axonal damage was restricted to an area immediately surrounding the injection site. Exogenous 4-HNE produced oligodendrocyte cell death in culture in a time-dependent and a concentration-dependent manner. After 4 hours, the highest concentration of 4-HNE (50 mu mol/L) produced 100% oligodendrocyte cell death. Data indicate that lipid peroxidation and production of 4-HNE occurs in white matter after cerebral ischemia and the lipid peroxidation by-product 4-HNE is toxic to axons and oligodendrocytes.
引用
收藏
页码:1529 / 1536
页数:8
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