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


OBJECTIVE
To investigate the role of proinflammatory bradykinin B(1) and B(2) receptors for the pathophysiology of SAH.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Neurosurgery, University of Munich Medical Center-Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Karsten
K
Schöller
Sergej
S
Feiler
Stephanie
S
Anetsberger
Seong-Woong
SW
Kim
Nikolaus
N
Plesnila
D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043783:Receptor, Bradykinin B1 / Q000172:deficiency*; D043782:Receptor, Bradykinin B2 / Q000172:deficiency*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism*
D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2