In the present study we analyzed aquaporin-4 (AQP4) immunoreactivity in the piriform cortex (PC) and the hippocampus of pilocarpine-induced rat epilepsy model to elucidate the roles of AQP4 in brain edema following status epilepticus (SE). In non-SE-induced animals, AQP4 immunoreactivity was diffusely detected in the PC and the hippocampus. AQP4 immunoreactivity was mainly observed in the endfeet of astrocytes. Following SE the AQP4-deleted area was clearly detected in the PC, not in the hippocampus. Decreases in dystrophin and α-syntrophin immunoreactivities were followed by reduction in AQP4 immunoreactivity. These alterations were accompanied by the development of vasogenic edema and the astroglial loss in the PC. In addition, acetazolamide (an AQP4 inhibitor) treatment exacerbated vasogenic edema and astroglial loss both in the PC and in the hippocampus. These findings suggest that SE may induce impairments of astroglial AQP4 functions via disruption of the dystrophin/α-syntrophin complex that worsen vasogenic edema. Subsequently, vasogenic edema results in extensive astroglial loss that may aggravate vasogenic edema.

BackgroundIn the present study, we investigated the roles of P2X7 receptor in recruitment and infiltration of neutrophil during epileptogenesis in rat epilepsy models.MethodsStatus epilepticus (SE) was induced by pilocarpine in rats that were intracerebroventricularly infused with either saline, 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP), or IL-1Ra (interleukin 1 receptor antagonist) prior to SE induction. Thereafter, we performed immunohistochemical studies for myeloperoxidase (MPO), CD68, interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2).ResultsIn saline-infused animals, neutrophils and monocytes were observed in frontoparietal cortex (FPC) at 1 day and 2 days after SE, respectively. In BzATP-infused animals, infiltrations of neutrophils and monocytes into the FPC were detected at 12 hr and 1 day after SE, respectively. In OxATP-infused animals, neutrophils and monocytes infiltrated into the FPC at 1 day and 2 days after SE, respectively. However, the numbers of both classes of leukocytes were significantly lower than those observed in the saline-infused group. In piriform cortex (PC), massive leukocyte infiltration was detected in layers III/IV of saline-infused animals at 1-4 days after induction of SE. BzATP or OxATP infusion did not affect neutrophil infiltration in the PC. In addition, P2X7 receptor-mediated MCP-1 (released from microglia)/MIP-2 (released from astrocytes) regulation was related to SE-induced leukocyte infiltration in an IL-1β-independent manner.ConclusionsOur findings suggest that selective regulation of P2X7 receptor-mediated neutrophil infiltration may provide new therapeutic approaches to SE or epilepsy.

Recently, it has been reported that astroglial loss/dysfunction plays a role in epileptogenesis. In addition, astroglial loss is accompanied by up-regulation of P2X7 receptor expression in microglia. Therefore, we investigated whether P2X7 receptor is involved in astroglial damages induced by status epilepticus (SE). In the present study, astroglial loss showed the regional-specific manner and the differential responses to P2X7 receptor functions. Both OxATP and brilliant blue G (P2X7 receptor antagonists) infusion prevented apoptotic astroglial loss in the molecular layer of the dentate gyrus and the frontoparietal cortex, while it promoted clasmatodendrosis in the CA1 region as compared to saline treatment. In contrast, BzATP (a P2X7 receptor agonist) treatment exacerbated apoptotic astroglial loss in the molecular layer of the dentate gyrus and the frontoparietal cortex, but alleviated SE-induced astroglial swelling in the CA1 region. Astroglial loss in the piriform cortex was not affected by P2X7 receptor agonist- or antagonist-infusion. These findings suggest that P2X7 receptor function differently modulates SE-induced astroglial loss in distinct brain regions.

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