The Role of Bradykinin B1 and B2 Receptors for Secondary Brain Damage after Traumatic Brain Injury in Mice

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), B₁-, and B₂-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 ( P1 receptor mRNA was upregulated up to four-fold 24 h after CCI. Immunohistochemistry showed that B₁ and B₂ receptors were expressed in the brain and were significantly upregulated in the traumatic penumbra 1 to 24 h after CCI. B₂R^−/− mice had significantly less brain edema (−51% versus WT, 24 h; P2 receptors play a causal role for brain edema formation and cell death after TBI.