Contribution of bradykinin receptors to the development of secondary brain damage after experimental subarachnoid hemorrhage.

Abstract

Subarachnoid hemorrhage (SAH) is the stroke subtype with the highest mortality and morbidity. Which molecular events mediate brain damage after SAH is not well understood. To investigate the role of proinflammatory bradykinin B(1) and B(2) receptors for the pathophysiology of SAH. B(1) and B(2) receptor knockout or wild-type mice were subjected to SAH by endovascular puncture. Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure were continuously monitored up to 60 minutes after SAH. Brain water content was quantified 24 hours after SAH; mortality, neurological function, and body weight were assessed daily for 7 days after hemorrhage. Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure did not differ between groups. Mortality was 60% in wild-type mice and 82% in B(1)R mice but only 20% in B(2)R animals (P < .05). B(2)R mice also exhibited less severe neurological deficits (P < .05), a less pronounced loss of body weight (P < .05), and significantly less brain edema formation (P < .05) compared with wild-type mice. Signaling mediated by bradykinin B(2) receptors contributes to mortality and secondary brain damage after SAH in mice. Thus, B(2) receptors may represent novel targets for the treatment of SAH.