Adenosine A(2A) receptors in early ischemic vascular injury after subarachnoid hemorrhage. Laboratory investigation.
Adenosine A(2A) receptors in early ischemic vascular injury after subarachnoid hemorrhage. Laboratory investigation.
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DOI：
10.3171/2009.9.jns09802
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发表时间：
2010-10
影响因子：
4.1
通讯作者：
Bederson JB
中科院分区：
文献类型：
--
作者：
Sehba FA;Flores R;Muller A;Friedrich V;Chen JF;Britz GW;Winn HR;Bederson JB
The role of adenosine A2A receptors (A2AR) in the early vascular response after subarachnoid hemorrhage (SAH) is not known. In other forms of cerebral ischemia both activation and inhibition of A2AR is reported to be beneficial. However, these studies mainly used pharmacological receptor modulation and most of the agents available exhibit low specificity. We used adenosine A2A receptor knockout mice to study the role of A2AR in the early vascular response to SAH. SAH was induced in the wild type (WT; C57BL/6) and A2AR knockout mice (A2AR-KO) by endovascular puncture. Cerebral blood flow (CBF), intracranial pressure (ICP) and blood pressure (BP) were recorded, cerebral perfusion pressure (CPP) was deduced. Animals were sacrificed at 1, 3 and 6 hours after SAH or sham surgery. Coronal brain sections were immunostained for collagen-IV; major protein of basal lamina. The internal diameter of major cerebral arteries and the area fraction of collagen-IV positive microvessels (<100μm) were determined. Initial ICP rise and CPP fall at SAH induction was similar but CBF fall was significantly smaller in A2AR-KO as compared to WT cohorts. The internal diameter of major cerebral vessels decreased progressively after SAH. The extent of diameter reduction was significantly less in A2AR-KO than in WT mice. Collagen-IV immunostaining decreased progressively after SAH. The decrease was significantly less in A2AR-KO than in WT. Our results demonstrate that global inactivation of A2AR decreases the intensity of the early vascular response to SAH. Early inhibition of A2AR after SAH might reduce cerebral injury.
