Therapeutical efficacy of a novel non-peptide bradykinin B2 receptor antagonist on brain edema formation and ischemic tissue damage in focal cerebral ischemia.
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| Abstract | 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. MATERIAL AND 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.
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| Authors | S Zausinger, D B Lumenta, D Pruneau, R Schmid-Elsaesser, N Plesnila, A Baethmann |
| Journal | Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 86 Pg. 205-7 ( 2003) ISSN: 0065-1419 [Print] Austria |
| PMID | 14753436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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