Epilepsy is a neurological condition distinguished by recurrent and unexpected seizures. Astrocytic channels and transporters are essential for maintaining normal neuronal functionality. The astrocytic water channel, aquaporin-4 (AQP4), which plays a pivotal role in regulating water homeostasis, is a potential target for epileptogenesis. In present study, we examined the effect of different doses (10, 50, 100 μM and 5 mM) of AQP4 inhibitor, 2-nicotinamide-1, 3, 4-thiadiazole (TGN-020), during kindling acquisition, on seizure parameters and seizure-induced cognitive impairments. Animals were kindled by injection of pentylenetetrazole (PTZ: 37.5 mg/kg, i.p.). TGN-020 was administered into the right lateral cerebral ventricle 30 min before PTZ every alternate day. Seizure parameters were assessed 20 min after PTZ administration. One day following the last PTZ injection, memory performance was investigated using spontaneous alternation in Y-maze and novel object recognition (NOR) tests. The inhibition of AQP4 during the kindling process significantly decreased the maximal seizure stage and seizure duration (two-way ANOVA, = 0.0001) and increased the latency of seizure onset and the number of PTZ injections required to induce different seizure stages (one-way ANOVA, = 0.0001). Compared to kindled rats, the results of the NOR tests showed that AQP4 inhibition during PTZ-kindling prevented recognition memory impairment. Based on these results, AQP4 could be involved in seizure development and seizure-induced cognitive impairment. More investigation is required to fully understand the complex interactions between seizure activity, water homeostasis, and cognitive dysfunction, which may help identify potential therapeutic targets for these conditions.

中文翻译：

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Aquaporin-4 抑制可减轻戊四唑诱导的点燃大鼠的行为癫痫发作和认知障碍

癫痫是一种神经系统疾病，其特征是反复发作和意外发作。星形细胞通道和转运蛋白对于维持正常的神经元功能至关重要。星形细胞水通道水通道蛋白 4 (AQP4) 在调节水稳态中发挥着关键作用，是癫痫发生的潜在靶点。在本研究中，我们检查了不同剂量（10、50、100 μM 和 5 mM）AQP4 抑制剂 2-烟酰胺-1,3,4-噻二唑 (TGN-020) 在引火采集过程中对癫痫参数的影响和癫痫引起的认知障碍。通过注射戊四唑(PTZ：37.5mg/kg，腹膜内注射)来点燃动物。每隔一天在 PTZ 前 30 分钟将 TGN-020 注入右侧脑室。 PTZ 给药后 20 分钟评估癫痫发作参数。最后一次 PTZ 注射后一天，使用 Y 迷宫中的自发交替和新物体识别 (NOR) 测试来研究记忆表现。点燃过程中 AQP4 的抑制显着降低了最大癫痫发作阶段和癫痫发作持续时间（双向方差分析，= 0.0001），并增加了癫痫发作的潜伏期和诱导不同癫痫发作阶段所需的 PTZ 注射次数（单向方差分析） , = 0.0001)。与点燃大鼠相比，NOR 测试结果表明，PTZ 点燃过程中 AQP4 抑制可防止识别记忆损伤。基于这些结果，AQP4 可能参与癫痫发作和癫痫引起的认知障碍。需要更多的研究来充分了解癫痫活动、水稳态和认知功能障碍之间的复杂相互作用，这可能有助于确定这些疾病的潜在治疗靶点。