Influence of the bradykinin B1/B2-receptor-antagonist B 9430 on the cerebral microcirculation and outcome of gerbils from global cerebral ischemia.
The influence of the bradykinin B1/B2 antagonist B 9430 on the cerebral microcirculation following global cerebral ischemia was investigated in a closed cranial window preparation in Mongolian gerbils by intravital fluorescence microscopy. Global cerebral ischemia (GCI) was induced by occlusion of both common carotid arteries for 15 min. Leukocyte-endothelium interactions, vessel diameters, and the segmental microvascular blood flow were observed by intravital microscopy before and up to three hours after global cerebral ischemia. Following the early reperfusion period the animals survived up to 4 days after ischemia. The neurological deficit and the body weight were assessed daily. On day 4 animals were subjected to perfusion fixation and the brain was removed. Nerve cell damage from ischemia was quantified histologically in cortex, hippocampus, and striatum. Animals with treatment received the bradykinin B1/B2 receptor antagonist B 9430 before (i.v.), during, and after ischemia (s.c.) until the end of the experiment. The frequency of leukocytes (cells/100 microns x min) rolling along the venular endothelium post ischemia was significantly decreased (p < 0.05) in treated animals as compared to untreated controls (33.0 +/- 6.2 vs. 8.5 +/- 2.3) as well as the number of leukocytes attached to the endothelial surface (7.2 +/- 3.0 vs. 2.0 +/- 1.0, n.s.). The neuroscore on day 4 (pre-ischemic control: 22 points) was reduced to 13.4 +/- 3.2 in untreated animals, while to 4.7 +/- 3.2 points in the treatment group. No differences between animals with and without treatment were found as to the number of viable neurons. Although bradykinin is released in the brain during global cerebral ischemia, its antagonisation does not improve outcome despite the effective inhibition of leukocyte-endothelium interactions.
Lehmberg
J
J
Institute for Surgical Research, Klinikum of Ludwig-Maximilians-University Standort Grosshadern, Munich, Germany.
Beck
J
J
Baethmann
A
A
Uhl
E
E
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D001921:Brain / Q000098:blood supply*; D001929:Brain Edema / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005849:Gerbillinae; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D018002:Receptors, Bradykinin / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*
C121351:B 9430; D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin; D001920:Bradykinin