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The role of bradykinin B(1) and B(2) receptors for secondary brain damage after traumatic brain injury in mice

Item Type:Article
Title:The role of bradykinin B(1) and B(2) receptors for secondary brain damage after traumatic brain injury in mice
Creators Name:Trabold, R. and Eroes, C. and Zweckberger, K. and Relton, J. and Beck, H. and Nussberger, J. and Mueller-Esterl, W. and Bader, M. and Whalley, E. and Plesnila, N.
Abstract:Inflammatory mechanisms are known to contribute to the pathophysiology of traumatic brain injury (TBI). Since bradykinin is one of the first mediators activated during inflammation, we investigated the role of bradykinin and its receptors in posttraumatic secondary brain damage. We subjected wild-type (WT), B(1)-, and B(2)-receptor-knockout mice to controlled cortical impact (CCI) and analyzed tissue bradykinin as well as kinin receptor mRNA and protein expression up to 48 h thereafter. Brain edema, contusion volume, and functional outcome were assessed 24 h and 7 days after CCI. Tissue bradykinin was maximally increased 2 h after trauma (P<0.01 versus sham). Kinin B(1) receptor mRNA was upregulated up to four-fold 24 h after CCI. Immunohistochemistry showed that B(1) and B(2) receptors were expressed in the brain and were significantly upregulated in the traumatic penumbra 1 to 24 h after CCI. B(2)R(-/-) mice had significantly less brain edema (-51% versus WT, 24 h; P<0.001), smaller contusion volumes ( approximately 50% versus WT 24 h and 7 d after CCI; P<0.05), and better functional outcome 7 days after TBI as compared with WT mice (P<0.05). The present results show that bradykinin and its B(2) receptors play a causal role for brain edema formation and cell death after TBI.
Keywords:Traumatic Brain Injury, Brain Edema, Inflammation, Bradykinin, Kallikerin-Kinin System, Neuroptotection, Animals, Mice
Source:Journal of Cerebral Blood Flow and Metabolism
ISSN:0271-678X
Publisher:Nature Publishing Group (U.S.A.)
Volume:30
Number:1
Page Range:130-139
Date:January 2010
Official Publication:https://doi.org/10.1038/jcbfm.2009.196
PubMed:View item in PubMed

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