Therapeutical efficacy of a novel non-peptide bradykinin B2 receptor antagonist on brain edema formation and ischemic tissue damage in focal cerebral ischemia.
OBJECTIVE
Bradykinin has been identified as a mediator of secondary brain damage in acute insults. We currently studied neuroprotective properties of a bradykinin B2 receptor antagonist (LF16-0687 Ms) in transitory focal cerebral ischemia to assess infarct formation and the development of brain edema.


METHODS
55 Rats were subjected to 90 min of MCA-occlusion. The receptor antagonist was administered at two dose levels, given from 30 min prior to ischemia over two days after ischemia. Ischemic tissue damage was quantified at day 7 after MCA-occlusion together with assessment of brain edema in separate experiments. Neurological recovery was studied daily.


RESULTS
Animals receiving treatment (low dose) had a better functional recovery, particularly at days 3 and 4 (P < 0.05). Infarct formation was significantly attenuated in these animals in both total and cortical brain tissue by 50, or 80%, respectively. Postischemic brain swelling was significantly lowered, i.e. by 62%.


CONCLUSIONS
Our findings provide further support for a mediator role of bradykinin in ischemic brain damage including edema formation, obviously by ligand binding to the bradykinin B2 receptor. The availability of a receptor antagonist may afford opportunity for translation of this experimental treatment into stroke patients.
Zausinger
S
S
Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany. Stefan.Zausinger@nc.med.uni-muenchen.de
Lumenta
D B
DB
Pruneau
D
D
Schmid-Elsaesser
R
R
Plesnila
N
N
Baethmann
A
A
D000818:Animals; D065094:Bradykinin B2 Receptor Antagonists; D001921:Brain / Q000473:pathology*; D001929:Brain Edema / Q000209:etiology*; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009420:Nervous System / Q000187:drug effects / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D065094:Bradykinin B2 Receptor Antagonists; C403051:LF 16-0687; D011804:Quinolines