Blockade of Bradykinin Receptor B1 but Not Bradykinin Receptor B2 Provides Protection From Cerebral Infarction and Brain Edema
- 1 January 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 40 (1), 285-293
- https://doi.org/10.1161/strokeaha.108.526673
Abstract
Background and Purpose— Brain edema is detrimental in ischemic stroke and its treatment options are limited. Kinins are proinflammatory peptides that are released during tissue injury. The effects of kinins are mediated by 2 different receptors (B1 and B2 receptor [B1R and B2R]) and comprise induction of edema formation and release of proinflammatory mediators. Methods— Focal cerebral ischemia was induced in B1R knockout, B2R knockout, and wild-type mice by transient middle cerebral artery occlusion. Infarct volumes were measured by planimetry. Evan’s blue tracer was applied to determine the extent of brain edema. Postischemic inflammation was assessed by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. To analyze the effect of a pharmacological kinin receptor blockade, B1R and B2R inhibitors were injected. Results— B1R knockout mice developed significantly smaller brain infarctions and less neurological deficits compared to wild-type controls (16.8±4.7 mm 3 vs 50.1±9.1 mm 3 , respectively; P 3 vs 50.1±9.1 mm 3 , respectively; P Conclusions— These data demonstrate that blocking of B1R can diminish brain infarction and edema formation in mice and may open new avenues for acute stroke treatment in humans.Keywords
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