Microglia play important roles in the pathogenic cascade following
cerebral ischemia, since they express
growth factors,
chemokines and regulatory
cytokines as well as
free radicals and other toxic mediators.
P2X7 receptor, a subtype of a family of
P2 purinoceptors, is primarily expressed in microglia and macrophages, suggesting that it regulates immune function and inflammatory responses. However, the involvement of
ATP in such microglial responses after
cerebral ischemia is not yet understood. In this study, we investigated the possible involvement of
ATP, especially through the P2X7 receptors, in a rat model of focal
cerebral ischemia. In immunohistochemical analysis,
P2X7 receptor-like immunoreactivity was predominantly detected in microglia, and then activated microglia accumulated in the ischemic region, in rats subjected to
middle cerebral artery occlusion (MCAO) and reperfusion. Intracerebroventricular injection with
P2X7 receptor agonist 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (
BzATP) improved behavioral dysfunction accessed by rota-rod test and ischemic neural injury induced by MCAO. In contrast,
P2X7 receptor antagonist
adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP) exacerbated ischemic brain damage. These results suggest that microglia play an important role in neuroprotection against rat
cerebral ischemia, which is regulated by a
P2X7 receptor-mediated
ATP signal.