Therapeutic time window and dose response of the beneficial effects of ketamine in experimental head injury.

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Abstract
The aim of this study was to determine the time and dose response of the therapeutic effects of the N-methyl-D-aspartate receptor antagonist ketamine in experimental head injury.Sixty-six male Sprague-Dawley rats were divided into eight groups. Groups A, B, and C were surgically prepared but received no trauma. Groups D through H received a nonpenetrating impact to the left cranium. Group A (n = 7) received no treatment. Groups B (n = 4) and C (n = 5) received 60 and 120 mg/kg IP ketamine, respectively. Group D (n = 8) received no treatment. Groups E (n = 8) and F (n = 7) received 120 and 180 mg/kg IP ketamine, respectively, 1 hour after head trauma. Groups G (n = 7) and H (n = 9) were treated with 180 mg/kg IP ketamine 2 and 4 hours after head trauma, respectively. Neurological severity score (NSS, 0 through 25 from no injury to severe injury) was determined at 1, 24, and 48 hours after head trauma. After death at 48 hours, cortical slices were taken adjacent to the lesion on the traumatized hemisphere a...