Bradykinin 2 receptor antagonist LF 16-0687Ms reduces posttraumatic brain edema.
Activation of the kallikrein-kinin system contributes to traumatic brain edema formation. Inhibition of bradykinin 2 (B2) receptors has been shown to successfully reduce brain edema formation. The purpose of this study was to investigate the protective effect of the novel nonpeptide B2 receptor antagonist LF 16-0687Ms in brain-injured rats. Contusion was produced in forty rats by controlled cortical impact injury. Five minutes after trauma rats received a single dose of 0, 3, or 30 mg/kg of LF 16-0687Ms. After 24 hours brain swelling and hemispheric water content were determined. Brain swelling was significantly decreased by 25% in the low and 27% in the high dose group compared to controls (p < 0.03). Water content of the traumatized hemisphere tended to be decreased (80.2 +/- 0.1 vs. 80.4 +/- 0.1%) while water content of the non-traumatized hemispheres tended to be increased after administering LF 16.0687Ms (79.3 +/- 0.1 vs. 79.0 +/- 0.1%). Single administration of the novel nonpeptide B2 receptor antagonist LF 16-0687Ms significantly reduces brain swelling. The missing significant reduction in water content of the traumatized hemisphere, however, could be related to an unspecific increase in water content due to LF 16.0687Ms as suggested by increased water content in the non-traumatized hemisphere.
Stover
J F
JF
Department of Neurosurgery, Charité- Virchow Medical Center, Augstenburger Platz 01, D-13353 Berlin.
Dohse
N K
NK
Unterberg
A W
AW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D065168:Bradykinin Receptor Antagonists; D001924:Brain Concussion / Q000473:pathology*; D001929:Brain Edema / Q000473:pathology*; D002540:Cerebral Cortex / Q000293:injuries* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2
D065168:Bradykinin Receptor Antagonists; C403051:LF 16-0687; D018696:Neuroprotective Agents; D011804:Quinolines; D043782:Receptor, Bradykinin B2