Inhibition of bradykinin B2 receptors before, not after onset of experimental subarachnoid hemorrhage prevents brain edema formation and improves functional outcome.
OBJECTIVE
Brain edema following subarachnoid hemorrhage (SAH) is a result of impairment of cerebral autoregulation and breakdown of the blood-brain barrier. We investigated the role of bradykinin B2 receptors (BrdB2Rs) on brain edema formation after SAH.


METHODS
In vivo and ex vivo animal study.


METHODS
University research laboratory.


METHODS
Male Sprague-Dawley rats.


METHODS
Rats were subjected to an endovascular perforation of the circle of Willis and were randomly assigned to a) vehicle, b) immediate treatment (30 minutes before and 300 minutes post-SAH) or c) delayed treatment (30 and 300 minutes post-SAH) with the B2 receptor antagonist Anatibant (LF 16-0687 Ms), and d) sham surgery. BrdB2R, kininogen (Kng1), and kallikrein mRNA expression was determined 6 hours after SAH or sham surgery.


RESULTS
SAH resulted in a significant increase in brain water content (vehicle: 80.3% +/- 1.2% vs. sham: 79.1% +/- 0.2%, p < 0.01) after 24 hours. Blockade of BrdB2Rs before SAH significantly prevented brain edema formation (79.0% +/- 0.3%, p < 0.05) and significantly improved neurologic recovery. BrdB2Rs and Kng1 mRNA were significantly increased 6 hours post-SAH (BrdB2R: 216%; Kng1: 2729%; p < 0.02 vs. sham). Delayed treatment regimen failed to reduce brain water content and neurologic impairment.


CONCLUSIONS
Our results indicate that BrdB2Rs play a key role in the initial phase after SAH contributing to brain edema formation. Inhibition of B2 receptors in a posttreatment regimen did not influence brain edema formation. Delayed pathophysiologic processes after SAH seem to be independent of B2 receptors.
Thal
Serge C
SC
Institute for Surgical Research, University of Munich Medical Center-Grosshadern, Munich, Germany. thal@uni-mainz.de
Sporer
Sonja
S
Schmid-Elsaesser
Robert
R
Plesnila
Nikolaus
N
Zausinger
Stefan
S
D000818:Animals; D065094:Bradykinin B2 Receptor Antagonists; D001929:Brain Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007427:Intracranial Pressure; D017078:Laser-Doppler Flowmetry; D008297:Male; D011804:Quinolines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology
D065094:Bradykinin B2 Receptor Antagonists; C403051:LF 16-0687; D011804:Quinolines