Ischemic insult exacerbates acrolein-induced conduction loss and axonal membrane disruption in guinea pig spinal cord white matter.
Cellular destruction following ischemic insult may be due to secondary injury mechanisms, not the oxygen-glucose deprivation itself. We have examined the effect of acrolein, an aldehyde product of lipid peroxidation (LPO) and oxidative stress, on the axons in isolated guinea pig spinal cord white matter following ischemic insult. We have found that acrolein at 50 microM, which is unharmful to spinal cord when applied alone, causes action potential conduction failure and membrane disruption following 1 to 2 h of exposure when applied during the reperfusion period. Ischemic insult also exacerbates the effect of acrolein at 200 microM, which does inflict functional and anatomical damage when applied alone. Unlike metabolic poisoning, acrolein-mediated damage is not a function of axonal size and does not affect the refractoriness in response to dual and multiple stimuli. These results indicate that spinal cord axons, in addition to experiencing elevated free radicals, are more vulnerable to acrolein attack when the level of oxygen and glucose is low. We conclude that free radicals and lipid peroxidation in general, and acrolein in specific, may play a critical role in cellular destruction and functional loss in such injury.
Peasley
Melissa A
MA
Department of Basic Medical Sciences, Center for Paralysis Research, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Shi
Riyi
R
D000171:Acrolein / Q000378:metabolism / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D005609:Free Radicals; D000171:Acrolein; D005947:Glucose