Departamento de Neurologia e Neurocirurgia, Neurologia Experimental, Universidade Federal de São Paulo, São Paulo, Brazil.
Epilepsy Behav. 2011 Oct;22(2):207-13. doi: 10.1016/j.yebeh.2011.07.004. Epub 2011 Aug 17.
Aiming at a better understanding of the role of A(2A) in temporal lobe epilepsy (TLE), we characterized the effects of the A(2A) antagonist SCH58261 (7-(2-phenylethyl)-5-amino-2(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) on seizures and neuroprotection in the pilocarpine model. The effects of SCH58261 were further analyzed in combination with the A(1) agonist R-Pia (R(-)-N(6)-(2)-phenylisopropyl adenosine). Eight groups were studied: pilocarpine (Pilo), SCH+Pilo, R-Pia+Pilo, R-Pia+SCH+Pilo, Saline, SCH+Saline, R-Pia+Saline, and R-Pia+SCH+Saline. The administration of SCH58261, R-Pia, and R-Pia+SCH58261 prior to pilocarpine increased the latency to SE, and decreased either the incidence of or rate of mortality from SE compared with controls. Administration of R-Pia and R-Pia+SCH58261 prior to pilocarpine reduced the number of Fluoro-Jade B-stained cells in the hippocampus and piriform cortex when compared with control. This study showed that pretreatment with R-Pia and SCH58261 reduces seizure occurrence, although only R-Pia has neuroprotective properties. Further studies are needed to clarify the neuroprotective role of A(2A) in TLE.
为了更好地了解 A(2A) 在颞叶癫痫 (TLE) 中的作用，我们研究了 A(2A)拮抗剂 SCH58261（7-(2-苯乙基)-5-氨基-2(2-呋喃基)-吡唑并-[4,3-e]-1,2,4-三唑并[1,5-c]嘧啶）对匹罗卡品模型中癫痫发作和神经保护的影响。进一步分析了 SCH58261 与 A(1)激动剂 R-Pia（R(-)-N(6)-(2)-苯基异丙基腺苷）联合使用的效果。共研究了 8 组：匹罗卡品（Pilo）、SCH+Pilo、R-Pia+Pilo、R-Pia+SCH+Pilo、生理盐水、SCH+生理盐水、R-Pia+生理盐水和 R-Pia+SCH+生理盐水。在给予匹罗卡品之前给予 SCH58261、R-Pia 和 R-Pia+SCH58261，可增加 SE 的潜伏期，并降低 SE 的发生率或死亡率。与对照组相比，给予 R-Pia 和 R-Pia+SCH58261 可减少海马和梨状皮质中 Fluoro-Jade B 染色细胞的数量。本研究表明，R-Pia 和 SCH58261 的预处理可减少癫痫发作的发生，尽管只有 R-Pia 具有神经保护作用。需要进一步研究以阐明 A(2A) 在 TLE 中的神经保护作用。
