Adenosine A(2A) receptors in early ischemic vascular injury after subarachnoid hemorrhage. Laboratory investigation.
OBJECTIVE
The role of adenosine A(2A) receptors in the early vascular response after subarachnoid hemorrhage (SAH) is unknown. In other forms of cerebral ischemia both activation and inhibition of A(2A) receptors is reported to be beneficial. However, these studies mainly used pharmacological receptor modulation, and most of the agents available exhibit low specificity. The authors used adenosine A(2A) receptor knockout mice to study the role of A(2A) receptors in the early vascular response to SAH.


METHODS
Subarachnoid hemorrhage was induced in wild-type mice (C57BL/6) and A(2A) receptor knockout mice by endovascular puncture. Cerebral blood flow, intracranial pressure, and blood pressure were recorded, and cerebral perfusion pressure was deduced. Animals were sacrificed at 1, 3, or 6 hours after SAH or sham surgery. Coronal brain sections were immunostained for Type IV collagen, the major protein of the basal lamina. The internal diameter of major cerebral arteries and the area fraction of Type IV collagen-positive microvessels (< 100 μm) were determined.


RESULTS
The initial increase in intracranial pressure and decrease in cerebral perfusion pressure at SAH induction was similar in both types of mice, but cerebral blood flow decline was significantly smaller in A(2A) receptor knockout mice as compared with wild-type cohorts. The internal diameter of major cerebral vessels decreased progressively after SAH. The extent of diameter reduction was significantly less in A(2A) receptor knockout mice than in wild-type mice. Type IV collagen immunostaining decreased progressively after SAH. This decrease was significantly less in A(2A) receptor knockout mice than in wild-type mice.


CONCLUSIONS
These results demonstrate that global inactivation of A(2A) receptors decreases the intensity of the early vascular response to SAH. Early inhibition of A(2A) receptors after SAH might reduce cerebral injury.
Sehba
Fatima A
FA
Department of Neurosurgery, Mount Sinai School of Medicine, New York, New York 10029, USA. fatima.sehba@mssm.edu
Flores
Rowena
R
Muller
Artur
A
Friedrich
Victor
V
Chen
Jiang-Fan
JF
Britz
Gavin W
GW
Winn
H Richard
HR
Bederson
Joshua B
JB
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D024141:Collagen Type IV / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007427:Intracranial Pressure / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology
D024141:Collagen Type IV; D043705:Receptor, Adenosine A2A