The lipid peroxidation by-product 4-hydroxynonenal is toxic to axons and oligodendrocytes.
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 micromol/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.
McCracken
E
E
Wellcome Surgical Institute and Hugh Fraser Laboratories. University of Glasgow, Scotland.
Valeriani
V
V
Simpson
C
C
Jover
T
T
McCulloch
J
J
Dewar
D
D
D000447:Aldehydes / Q000032:analysis / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis; D000818:Animals; D001369:Axons / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D009498:Neurotoxins / Q000378:metabolism*; D009836:Oligodendroglia / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; D016564:Amyloid beta-Protein Precursor; D005609:Free Radicals; D009498:Neurotoxins; C027576:4-hydroxy-2-nonenal