Bradykinin B2 receptor antagonism with LF 18-1505T reduces brain edema and improves neurological outcome after closed head trauma in rats

BACKGROUND: We evaluated the effect of LF 18-1505T, a novel nonpeptide bradykinin type-2 receptor antagonist, on brain edema and neurologic severity score (NSS) after closed head trauma (CHT). METHODS: There were 132 rats anesthetized and assigned for sham or CHT; infusion of saline or LF 18-1505T (0.3, 1, 3, 10, or 30 μg • kg • min); and determination of neurologic outcome (brain water content and NSS) or physiologic variables (blood pressure, glucose concentration, etc.). RESULTS: Post-CHT brain water content was less with LF 18-1505T doses of 3 and 10 μg • kg • min (80.1 ± 3.8 through 81.6 ± 2.6%, mean ± SD) than in the untreated group (84.6 ± 1.9%, p < 0.01). Post-CHT NSS improved with doses of 3, 10, and 30 μg • kg • min (median, 7; range, 0-12 through median, 10; range, 8-18) as compared with that in the untreated group (median, 17; range, 14-23; p < 0.05). LF 18-1505T with or without CHT did not significantly alter physiologic variables. CONCLUSIONS: LF 18-1505T decreased brain edema and improved neurologic status after CTH in rats without significantly altering physiologic values.