Reduction of tyrosine nitration after N(omega)-nitro-L-arginine-methylester treatment of mice with traumatic brain injury.
Oxygen free radicals and nitric oxide (NO) have been proposed to be involved in the cascade of injury elicited by traumatic brain injury. However, the mechanism(s) of injury remain to be explored. Since superoxide generation is triggered by traumatic brain injury, the cytotoxic peroxynitrite could be formed, but it is not known if this actually occurs. Dot blot and immunohistochemistry studies were performed to quantify tyrosine nitration and identify cell types in which such reactions occur in the brain of mice submitted to traumatic brain injury. Nitrotyrosine formation increased from 4 to 24 h after traumatic brain injury and was primarily observed in degenerating neurons, in areas corresponding to the sites of direct impact (frontal cortex) and diffuse impact (frontoparietal cortex and ventromedial hypothalamic nucleus). Furthermore, N omega-nitro-L-arginine-methylester (L-NAME), a NO-synthase inhibitor which has previously been shown to promote neurological recovery in traumatic brain injury, reduced nitrotyrosine formation and the number of nitrotyrosine-positive neurons. These results indicate that traumatic brain injury induces peroxynitrite formation which may contribute to cell damage.
Laboratoire de Pharmacologie, Université René Descartes, Paris, France.
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Mésenge
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Charriaut-Marlangue
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Verrecchia
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Allix
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Boulu
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D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D014443:Tyrosine / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009566:Nitrates; C039642:peroxynitric acid; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester