Blockade of P2X receptor prevents astroglial death in the dentate gyrus following pilocarpine-induced status epilepticus

Objective: The P-2 receptor is involved in diverse signal cascades, including the initiation of the rapid release and processing of proinflammatory cytokines, the induction of cytoskeletal rearrangements and transcription factor activation. Therefore, we investigated whether blocking the P-2 receptor would prevent the astroglial death induced by status epilepticus (SE). Methods: We performed seizure induction and drug treatments. After tissue processing, we executed immunoreactivities: mouse anti-glial fibrillary acidic protein (GFAP) IgG (diluted 1 : 200; Chemicon, Billerica, MA, USA rabbit anti-P2X7 receptor IgG (diluted 1 : 200; Chemicon). Results: In control animals, P2X7 receptor-immunoreactive (P2X7+) microglia had small cell bodies with thin ramified processes. Seven days after SE, P2X7 receptor immunoreactivity in microglia was significantly elevated in the dentate gyrus, and the microglia appeared amoeboid or phagocytic. At this point, loss of GFAP immunoreactivity in the dentate gyrus was even more pronounced, indicating that the network of astrocytes was disrupted and a large empty zone was observed. Treatment with pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid and suramin (2, 20 and 200 mg/kg, i.p., respectively) markedly, but not completely, inhibited microglial activation following SE. The morphology of microglia was similar to that of the astrocytes in that they appeared hyper-ramified. In addition, P2X7 receptor antagonist treatments effectively prevented astroglial degeneration. Discussion: These findings suggest that astroglial death induced by ATP-mediated microglia activation may be an important pathophysiological pathway in epileptogenesis. [Neurol Res 2009; 31: 982-988]