Adenosine A2A receptors in early ischemic vascular injury after subarachnoid hemorrhage: Laboratory investigation

Fatima A. Sehba, Rowena Flores, Artur Muller, Victor Friedrich, Jiang Fan Chen, Gavin W. Britz, H. Richard Winn, Joshua B. Bederson

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Object. The role of adenosine A2A receptors in the early vascular response after subarachnoid hemorrhage (SAH) is unknown. In other forms of cerebral ischemia both activation and inhibition of A2A 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 A2A receptor knockout mice to study the role of A2A receptors in the early vascular response to SAH. Methods. Subarachnoid hemorrhage was induced in wild-type mice (C57BL/6) and A2A 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 A2A 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 A2A receptor knockout mice than in wild-type mice. Type IV collagen immunostaining decreased progressively after SAH. This decrease was significantly less in A2A receptor knockout mice than in wild-type mice. Conclusions. These results demonstrate that global inactivation of A2A receptors decreases the intensity of the early vascular response to SAH. Early inhibition of A2A receptors after SAH might reduce cerebral injury.

Original languageEnglish (US)
Pages (from-to)826-834
Number of pages9
JournalJournal of Neurosurgery
Volume113
Issue number4
DOIs
StatePublished - Oct 2010

Keywords

  • Adenosine
  • Microvessels
  • Mouse
  • Stroke
  • Subarachnoid hemorrhage
  • Type IV collagen

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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