Delayed neuropathology after carbon monoxide poisoning is immune-mediated.
The neuropathological sequelae of carbon monoxide (CO) poisoning cannot be explained by hypoxic stress alone. CO poisoning also causes adduct formation between myelin basic protein (MBP) and malonylaldehyde, a reactive product of lipid peroxidation, resulting in an immunological cascade. MBP loses its normal cationic characteristics, and antibody recognition of MBP is altered. Immunohistochemical evidence of degraded MBP occurs in brain over days, along with influx of macrophages and CD-4 lymphocytes. Lymphocytes from CO-poisoned rats subsequently exhibit an auto-reactive proliferative response to MBP, and there is a significant increase in the number of activated microglia in brain. Rats rendered immunologically tolerant to MBP before CO poisoning exhibit acute biochemical changes in MBP but no lymphocyte proliferative response or brain microglial activation. CO poisoning causes a decrement in learning that is not observed in immunologically tolerant rats. These results demonstrate that delayed CO-mediated neuropathology is linked to an adaptive immunological response to chemically modified MBP.
Thom
Stephen R
SR
Institute for Environmental Medicine, Department of Emergency Medicine, University of Pennsylvania Medical Center, 3620 Hamilton Walk, Philadelphia, PA 19104-6068, USA. sthom@mail.med.upenn.edu
Bhopale
Veena M
VM
Fisher
Donald
D
Zhang
Jie
J
Gimotty
Phyllis
P
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002248:Carbon Monoxide / Q000494:pharmacology; D002249:Carbon Monoxide Poisoning / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004676:Myelin Basic Protein / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004676:Myelin Basic Protein; D020033:Protein Isoforms; D008315:Malondialdehyde; D002248:Carbon Monoxide