Delayed neuropathology after carbon monoxide poisoning is immune-mediated

Abstract

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 autoreactive 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. myelin basic protein ͉ malonylaldehyde ͉ lymphocyte activation ͉ CD-40 ͉ microglia

Actin S-Nitrosylation Inhibits Neutrophil β2 Integrin Function

“…Protein bands identified as containing biotin on Western blots were cut from nitrocellulose paper, trypsin-digested, and analyzed with a nano-liquid chromatography/nanospray/LTQ mass spectrometer following our published methods (36). The raw data files were searched using Mascot against the NCBI data base with a cutoff protein score of 70.…”

“…The supernatants were discarded and pellets resuspended in SDS buffer for Western blots that were probed with anti-biotin following published methods (36). Band densities were quantified using an Odyssey Infrared Imager (Li-Cor, Inc., Lincoln, NE).…”

Single Versus Multiple Hyperbaric Sessions for Carbon Monoxide Poisoning in a Murine Model

“…Thom et al showed a decrease in inflammatory markers in the brain after HBO therapy with improved performance on maze testing [9][10][11][12][13]. Meanwhile, Gilmer et al showed no benefit from one treatment in terms of cognitive outcome [14], but this study was subsequently criticized for excessive hypoxic insult to the animals, which may have inadvertently obscured a potential benefit to HBO therapy [15].…”

“…Meanwhile, Gilmer et al showed no benefit from one treatment in terms of cognitive outcome [14], but this study was subsequently criticized for excessive hypoxic insult to the animals, which may have inadvertently obscured a potential benefit to HBO therapy [15]. We sought to investigate whether three sessions of HBO would provide any benefit over a single treatment with HBO in preventing cognitive impairment in a murine model, using a previously established protocol [9,10,12,13].…”

In Reply: “Single Versus Multiple Hyperbaric Sessions for Carbon Monoxide Poisoning in a Murine Model”

“…Our poisoning protocol was based upon a previously published protocol demonstrated to induce delayed neurologic sequelae in mice [1]. This has been validated in additional studies [2][3][4], so we believe that our model was appropriate.…”