An electrophysiological study on the mechanism of seizure generation in rat brain slices : the effect of adenosine on epileptiformactivities.

含海马（HC）和内嗅皮质（EC）的大鼠脑切片在无镁（0-Mg）培养基中浸泡可引起电痉挛。它们最终被间性发作（iib）所取代，这已被证明在海马区CA3出现并抑制EC的癫痫发作。我们已经报道，在这个IIB阶段，缺氧暴露抑制CA3的IIB，并促进EC的癫痫复发。这些数据表明，缺氧可能在iib和癫痫发作之间的转变中起重要作用。另一方面，有报道称腺苷抑制缺氧时的神经元活动。鉴于这些发现，本研究检测了腺苷及其拮抗剂茶碱对癫痫样活动的影响，以研究该模型中从iib到癫痫发作转变的机制。Sprague-Dawley大鼠CA3区、EC区或HC/EC区切片进行细胞外记录。在0-Mg培养基中，癫痫发作首先出现，但最终在两个区域都被iib所取代。在癫痫发作完全被iib取代后，将腺苷（50-100muM）应用于细胞外溶液。CA3区的iib在所有切片中均被抑制（n=33），而EC区的28片（85%）再次出现癫痫发作。在茶碱实验中，在IIB阶段，通过将氧化气体从95%O_2+5%CO_2切换为30%O_2+65%N_2+5%CO_2来引入缺氧，然后在溶液中加入100muM茶碱（n=14）。缺氧条件下再次出现ec -癫痫发作，但茶碱阻断了这一作用，再次被iib所取代。综上所述，腺苷是在O-Mg/缺氧模型中促进iib向癫痫发作转变的调节因子之一。

Bathing rat brain slice containing hippocampus(HC) and entorhinal cortex(EC) in magnesium-free(0-Mg) medium elicits electrographic seizures. They are eventually replaced by interictal bursts(IIBs), which have been shown to arise in hippocampal area CA3 and suppress seizure generation in EC.We have reported that during this IIB phase, the exposure to hypoxia suppresses IIBs in CA3 and promotes seizure reappearance in EC.These data suggest that hypoxia may play an important role in the transition between IIBs and seizures. On the other hand, it has been reported that adenosine suppresses the neuronal activity during hypoxia. Given these findings, the present study examined the effect of adenosine and its antagonist theophylline on the epileptiform activities in order to investigate the mechanisms underlying the transition from IIBs to seizures in this model.Extracellular recordings were made in area CA3 and EC or HC/EC slices from Sprague-Dawley rats. In the 0-Mg medium, seizures appeared first but eventually they gave way to IIBs in both regions. After the seizures were completely replaced by IIBs, adenosine(50-100muM) was applied to the extracellularsolution. The IIBs in CA3 were suppressed in all the slices tested(n=33), while in EC the seizures reappeared in 28 slices(85%). In the theophylline experiments, hypoxia was introduced by switcihg the oxygenation gas from 95%O_2+5%CO_2 to 30%O_2+65%N_2+5%CO_2 during the IIB phase, then 100muM theophylline was added to the solutino(n=14). The EC-seizures reappeared in the hypoxic condition, however, theophylline blocked the effect and they were replaced by IIBs again.In conclusion, adenosine is one of the modulatory factors withch can promote the transition from IIBs to seizures in this O-Mg/hypoxia model.