4-Hydroxynonenal, a lipid peroxidation byproduct of spinal cord injury, is cytotoxic for oligodendrocyte progenitors and inhibits their responsiveness to PDGF

摘要: Oligodendroglial reactions to compression injury of spinal cord include apoptosis, secondary demyelination, and remyelination failure. Within hours after contusion, the membrane lipid peroxidation (MLP) byproduct, 4-hydroxynonenal (HNE), increases rapidly in gray matter thereafter white tracts beyond initial lesion level. Considering that HNE is a mediator marker neuronal MLP toxicity various neurodegenerative conditions, present study examined its effect on regeneration potential oligodendrocyte progenitors, as defined by their capacity survive, proliferate migrate primary culture. Treatment oligodendroblasts with evoked time- dose-dependent cytotoxicity resembling apoptosis at aldehyde concentrations known be produced neurons achieved tissue undergoing peroxidative injury. In addition, sublethal inhibited mitogenic chemotactic responses more immature progenitors platelet-derived growth factor. These effects appear mediated part formation adducts progenitor proteins located within plasma cytoplasmic compartments. Our data are first show can have direct, deleterious precursors. The also suggests mechanism which striking accumulation surrounding site other ischemic-hypoxic insults associated could suppress regenerative response endogenous cells. Microsc. Res. Tech. 52:709–718, 2001. © 2001 Wiley-Liss, Inc.