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.
机构:Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA
Zhang, DQ
;
Dhillon, HS
论文数: 0引用数: 0
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机构:Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA
Dhillon, HS
;
Mattson, MP
论文数: 0引用数: 0
h-index: 0
机构:Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA
Mattson, MP
;
Yurek, DM
论文数: 0引用数: 0
h-index: 0
机构:Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA
Yurek, DM
;
Prasad, RM
论文数: 0引用数: 0
h-index: 0
机构:
Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USAUniv Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA
机构:Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA
Zhang, DQ
;
Dhillon, HS
论文数: 0引用数: 0
h-index: 0
机构:Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA
Dhillon, HS
;
Mattson, MP
论文数: 0引用数: 0
h-index: 0
机构:Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA
Mattson, MP
;
Yurek, DM
论文数: 0引用数: 0
h-index: 0
机构:Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA
Yurek, DM
;
Prasad, RM
论文数: 0引用数: 0
h-index: 0
机构:
Univ Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USAUniv Kentucky, Albert B Chandler Med Ctr, Dept Surg, Lexington, KY 40536 USA