alpha-Phenyl-tert-butyl-nitrone inhibits free radical release in brain concussion.
Traumatic brain injury (TBI) is one of the important causes of mortality and morbidity. The pathogenesis of the underlying brain dysfunction is poorly understood. Recent data have suggested that oxygen free radicals play a key role in the primary and secondary processes of acute TBI. We report direct electron spin resonance (ESR) evidence of hydroxyl (.OH) radical generation in closed-head injury of rats. Moderate brain concussion was produced by controlled and reproducible mechanical, fixed, closed-head injury. A cortical cup was placed over one cerebral hemisphere within 20 min of the concussion, perfused with artificial cerebrospinal fluid (aCSF) containing the spin trap agent pyridyl-N-oxide-tert-butyl nitrone (POBN, 100 mM), and superfusate samples collected at 10 min intervals for a duration up to 130 min post brain trauma. In addition, POBN was administered systemically (50 mg/kg body wt.) 10 min pretrauma and 20 min posttrauma to improve our ability to detect free radicals. ESR analysis of the superfusate samples revealed six line spectra (alpha N = 15.4 G and alpha beta H = 2.5 G) characteristic of POBN-OH radical adducts, the intensity of which peaked 40 min posttrauma. The signal was undetectable after 120 min. Administration of alpha-phenyl-tert-butyl-nitrone (PBN), a spin adduct forming agent systemically (100 mg/kg body wt. IP 10 min prior to concussion) alone or along with topical PBN (100 mM PBN in aCSF), significantly (p < 0.001) attenuated the ESR signal, suggesting its possible role in the treatment of TBI.
Sen
S
S
Department of Physiology, Wayne State University, School of Medicine, Detroit, MI.
Goldman
H
H
Morehead
M
M
Murphy
S
S
Phillis
J W
JW
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D011725:Pyridines; D051381:Rats; D013113:Spin Labels; D013997:Time Factors
D003497:Cyclic N-Oxides; D005609:Free Radicals; D009589:Nitrogen Oxides; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; D017665:Hydroxyl Radical; C029217:phenyl-N-tert-butylnitrone; C000820:semidehydroascorbic acid; D003683:Dehydroascorbic Acid