Brain hydroxyl radical generation in acute experimental head injury.
The time course and intensity of brain hydroxyl radical (.OH) generation were examined in male CF-1 mice during the first hour after moderate or severe concussive head injury. Hydroxyl radical production was measured using the salicylate trapping method in which the production of 2,3- and/or 2,5-dihydroxybenzoic acid (DHBA) in brain 15 min after salicylate administration was used as an index of .OH formation. In mice injured with a concussion of moderate severity as defined by the 1-h posttraumatic neurologic recovery (grip score), a 60% increase in 2,5-DHBA formation was observed by 1 min after injury compared with that observed in uninjured mice. The peak in DHBA formation occurred at 15 min after injury (+67.5%; p < 0.02, compared with uninjured). At 30 min, the increase in DHBA lost significance, indicating that the posttraumatic increase in brain .OH formation is a transient phenomenon. In severely injured mice, the peak increase in DHBA (both 2,3- and 2,5-) was observed at 30 min after injury, but also fell off thereafter as with the moderate injury severity. Preinjury dosing of the mice with SKF-525A (50 mg/kg i.p.), an inhibitor of microsomal drug oxidations, did not blunt the posttraumatic increase in salicylate-derived 2,5-DHBA, thus showing that it is not due to increased metabolic hydroxylation. Neither injury nor SKF-525A administration affected the DHBA plasma levels. However, saline perfusion of the injured mice to remove the intravascular blood before brain removal eliminated the injury-induced increase in 2,5-DHBA, but did not affect the baseline levels seen in uninjured mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Hall
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Central Nervous System Diseases Research, Upjohn Company, Kalamazoo, Michigan.
Andrus
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Yonkers
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PA
D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006259:Craniocerebral Trauma / Q000378:metabolism* / Q000503:physiopathology; D005609:Free Radicals / Q000378:metabolism; D005841:Gentisates; D006878:Hydroxides / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011281:Pregnatrienes / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D000975:Antioxidants; D005609:Free Radicals; D005841:Gentisates; D006878:Hydroxides; D062385:Hydroxybenzoates; D011281:Pregnatrienes; D017665:Hydroxyl Radical; C010925:2,5-dihydroxybenzoic acid; C053355:tirilazad