LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats

Abstract

Objective: Bradykinin (B) contributes to secondary brain injury. This injury is mediated in part by prostaglandin (PG). Antagonism of B(2) receptors improves neurological status after brain injury, but the effect of B(2) antagonism on brain tissue PG is unknown. This study examined the effect of LF 16-0687 Ms, a new B(2) receptor antagonist, on brain tissue PGE(2) after closed head trauma (CHT).

Methods: Rats were anesthetized and received sham+saline, sham+LF 16-0687 Ms, CHT+saline, or CHT+LF 16-0687 Ms. Brain tissue samples were obtained at 24 h for determination of PGE(2) (after 2 h of ex vivo incubation) and water content. Neurological severity score (NSS) was assessed at 1 and 24 h.

Results: In the group receiving CHT+LF 16-0687 Ms, brain tissue PGE(2) (77.7+/-65.9 pg/mg tissue, mean+/-SD) was less than in the group receiving CHT+saline (368.1+/-186.2 pg/mg tissue) and not different than sham+saline (78.7+/-30.7 pg/mg tissue). LF 16-0687 Ms also improved NSS and decreased brain water content by 51%.

Conclusion: We conclude that the beneficial effect of LF 16-0687 Ms on outcome after CHT is accompanied by blockade of PGE(2) increase in injured brain tissue.