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

• Published in: British journal of pharmacology Vol. 139; no. 8; pp. 1539 - 1547
• Main Authors: Ding‐Zhou, Li, Margaill, Isabelle, Palmier, Bruno, Pruneau, Didier, Plotkine, Michel, Marchand‐Verrecchia, Catherine
• Format: Journal Article
• Language: English
• Published: 30-01-2009
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705385

Bradykinin promotes neuronal damage and brain edema through the activation of the B
2
receptor. The neuroprotective effect of LF 16‐0687 Ms, a B
2
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 B
2
receptor in the development of infarct lesion, neurological deficit and inflammatory responses resulting from transient focal cerebral ischemia. Therefore, B
2
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