LF 16‐0687 Ms, a bradykinin B 2 receptor antagonist, reduces ischemic brain injury in a murine model of transient focal cerebral ischemia

LF 16‐0687 Ms, a bradykinin B 2 receptor antagonist, reduces ischemic brain injury in a murine... Bradykinin promotes neuronal damage and brain edema through the activation of the B2 receptor. The neuroprotective effect of LF 16‐0687 Ms, a B2 receptor antagonist, has been described when given prior to induction of transient focal cerebral ischemia in rat, but there are no data regarding the consequence of a treatment when given after injury. Therefore, in a murine model of transient middle cerebral artery occlusion (MCAO), we evaluated the effect of LF 16‐0687 Ms given prior to and/or after the onset of ischemia on neurological deficit, infarct volume and inflammatory responses including cerebral edema, blood–brain barrier (BBB) disruption and neutrophil accumulation. LF 16‐0687 Ms (1, 2 and 4 mg kg−1) administered 0.5 h before and, 1.25 and 6 h after MCAO, decreased the infarct volume by a maximum of 33% and significantly improved the neurological recovery. When given at 0.25 and 6.25 h after MCAO, LF 16‐0687 Ms (1.5, 3 and 6 mg kg−1) decreased the infarct volume by a maximum of 25% and improved the neurological score. Post‐treatment with LF 16‐0687 Ms (1.5 mg kg−1) significantly decreased brain edema (−28%), BBB disruption (−60%) and neutrophil accumulation (−65%) induced by ischemia. Physiological parameters were not modified by LF 16‐0687 Ms. These data emphasize the role of bradykinin B2 receptor in the development of infarct lesion, neurological deficit and inflammatory responses resulting from transient focal cerebral ischemia. Therefore, B2 receptor antagonist might represent a new therapeutic approach in the pharmacological treatment of stroke. British Journal of Pharmacology (2003) 139, 1539–1547. doi:10.1038/sj.bjp.0705385 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

LF 16‐0687 Ms, a bradykinin B 2 receptor antagonist, reduces ischemic brain injury in a murine model of transient focal cerebral ischemia

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Publisher
Wiley
Copyright
2003 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0705385
pmid
12922942
Publisher site
See Article on Publisher Site

Abstract

Bradykinin promotes neuronal damage and brain edema through the activation of the B2 receptor. The neuroprotective effect of LF 16‐0687 Ms, a B2 receptor antagonist, has been described when given prior to induction of transient focal cerebral ischemia in rat, but there are no data regarding the consequence of a treatment when given after injury. Therefore, in a murine model of transient middle cerebral artery occlusion (MCAO), we evaluated the effect of LF 16‐0687 Ms given prior to and/or after the onset of ischemia on neurological deficit, infarct volume and inflammatory responses including cerebral edema, blood–brain barrier (BBB) disruption and neutrophil accumulation. LF 16‐0687 Ms (1, 2 and 4 mg kg−1) administered 0.5 h before and, 1.25 and 6 h after MCAO, decreased the infarct volume by a maximum of 33% and significantly improved the neurological recovery. When given at 0.25 and 6.25 h after MCAO, LF 16‐0687 Ms (1.5, 3 and 6 mg kg−1) decreased the infarct volume by a maximum of 25% and improved the neurological score. Post‐treatment with LF 16‐0687 Ms (1.5 mg kg−1) significantly decreased brain edema (−28%), BBB disruption (−60%) and neutrophil accumulation (−65%) induced by ischemia. Physiological parameters were not modified by LF 16‐0687 Ms. These data emphasize the role of bradykinin B2 receptor in the development of infarct lesion, neurological deficit and inflammatory responses resulting from transient focal cerebral ischemia. Therefore, B2 receptor antagonist might represent a new therapeutic approach in the pharmacological treatment of stroke. British Journal of Pharmacology (2003) 139, 1539–1547. doi:10.1038/sj.bjp.0705385

Journal

British Journal of PharmacologyWiley

Published: Aug 1, 2003

References

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