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Possible involvement of P2X7 receptor activation in microglial neuroprotection against focal cerebral ischemia in rats.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2008 Jun; Vol. 31 (6), pp. 1121-30. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Adenosine Triphosphate analogs & derivatives
Adenosine Triphosphate pharmacology
Adenosine Triphosphate physiology
Animals
CD11b Antigen metabolism
Fluorescent Antibody Technique, Indirect
Glial Fibrillary Acidic Protein metabolism
Immunohistochemistry
Infarction, Middle Cerebral Artery pathology
Infarction, Middle Cerebral Artery prevention & control
Injections, Intraventricular
Ischemic Attack, Transient pathology
Male
Motor Activity drug effects
Postural Balance drug effects
Purinergic P2 Receptor Antagonists
Rats
Rats, Wistar
Receptors, Purinergic P2X7
Ischemic Attack, Transient prevention & control
Microglia physiology
Purinergic P2 Receptor Agonists
Subjects
Details
- Language :
- English
- ISSN :
- 0918-6158
- Volume :
- 31
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 18520042
- Full Text :
- https://doi.org/10.1248/bpb.31.1121