Purinergic Signaling Induces Cyclooxygenase-1-Dependent Prostanoid Synthesis in Microglia: Roles in the Outcome of Excitotoxic Brain Injury
Figure 7
In vivo inhibition of P2X7 receptors blocks NMDA induced PGE2 production and reverts the protective effect of NS398.
(A) Animals were injected i.c.v. with saline (ve; 3 µl) or the P2X7 receptor blocker oxATP (300 nmol in 3 µl). Thirty minutes later NMDA was delivered stereotaxically to the parietal cortex. Brain tissue was collected 10 minutes after end of NMDA injection and PGE2 tissue levels were determined (n = 5/group; * p<0.05 from NMDA+ve). (B) Animals were treated as in A and both groups received NS398 (20 mg/kg i.p.). Lesion volumes were determined 24 hours after NMDA injections (n = 5/group; * p<0.05 from NMDA+ve). Note the slightly increased lesion volumes in NS398+ve treated as compared to animals presented in Fig. 2A and 7C, a fact that could be related to surgical procedures associated with i.c.v. injections. (C) Animals received NS398 (20 mg/kg i.p.) together with A438079 (200 µmol/kg in physiol. saline; i.p.) or vehicle (100 µl physiol. saline; i.p.). Lesion volumes were determined 24 hours after NMDA injections (n = 4/group; * p<0.05 from NMDA+ve).