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

Yulia Ivashkova, Albert Svetnitsky, Olga Mayzler, Didier Pruneau, Mony Benifla, Yulia Fuxman, Avi Cohen, Alan A. Artru, Yoram Shapira

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)879-885
Number of pages7
JournalJournal of Trauma and Acute Care Surgery
Volume61
Issue number4
DOIs
StatePublished - 1 Oct 2006

Keywords

  • Bradykinin antagonist
  • Brain edema
  • Head injury
  • Neurologic outcome
  • Rat

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