U83836E reduces secondary brain injury in a rabbit model of cryogenic trauma.
Oxygen-derived free radicals have been implicated in secondary brain injury after head trauma. Although oxygen-free radicals may be derived from multiple sources, the activation and accumulation of neutrophils in areas of brain injury is a potential source of deleterious inflammatory mediators, including free radicals, which may exacerbate the primary insult. Neutrophils may also impede the cerebral microcirculation by congestion and occlusion of postcapillary venules. The lazaroid U83836E is a potent-free radical scavenger that inhibits lipid peroxidation. U83836E was studied in a cryogenic model of cerebral injury in pretreatment paradigm. Fifteen rabbits received a unilateral cryogenic brain lesion. Six animals received U83836E, and nine animals received vehicle only. Arterial blood gases, hematocrit, temperature, and mean arterial pressure were controlled in physiologic range throughout the experiment. Intracranial pressure was continuously monitored. Lesion size was determined by triphenyltertrazolium chloride staining and planimetric image analysis. Neutrophil aggregation and oxygen-free radical generation was assessed in whole blood by impedance aggregometry and simultaneous luminol-mediated chemiluminescence, respectively. Myeloperoxidase assay was used to determine neutrophil accumulation within the brain. Elevations in intracranial pressure from baseline values were significantly greater in the untreated (control) animals at all time points (p < 0.0001). Mean lesion size (% hemisphere +/- SEM) was significantly reduced in animals receiving U83836E (4.41 +/- 0.64, n = 6) when compared with controls (15.09 +/- 2.28, n = 9, p < 0.001). A reduction in both the release of oxygen-free radicals and in neutrophil aggregation following the cryogenic injury in the U83836E animals correlated with a smaller lesion volume.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002839:Chromans / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits
D002839:Chromans; D016166:Free Radical Scavengers; D010879:Piperazines; C066382:U 78517F; D010100:Oxygen