Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Islamic Republic of Iran.
Epilepsy Res. 2013 Sep;106(1-2):54-63. doi: 10.1016/j.eplepsyres.2013.03.016. Epub 2013 Apr 22.
Experimental models of epilepsy, including pentylenetetrazol (PTZ) chemical kindling, are very important in studying the pathophysiology of epilepsy. The aim of the present study was to provide behavioral, electrophysiological and molecular evidences to confirm the similarities between standard and a modified protocol named window- (win-) PTZ kindling method. Standard PTZ kindling model was induced by injection of PTZ (37.5mg/kg) every other days. In win-PTZ kindling method, animals received 4 initial PTZ injections and the time of 3 last PTZ injections were determined according to the number of PTZ injections in standard PTZ kindling model. The behavioral signs of kindled seizures were observed for 20 min after each PTZ injection. Field potential recordings were done from the dentate gyrus granular cells following perforant path stimulation. In addition, the expression of γ2 subunit of GABAA receptor, NR2A subunit of NMDA receptor, adenosine A1 receptor, α-CaMKII and GAP-43 were evaluated in the hippocampus and dentate gyrus using RT-PCR technique. All the animals in win-PTZ kindling method group achieved fully kindled state after 3 last PTZ injections. There was no significant difference in population spike amplitude and expression of the mentioned genes during kindling acquisition between standard PTZ kindling model and win-PTZ kindling method. The similarities in electrophysiological and molecular parameters remained after 8 days post fully kindled state. Obtained data showed the similarities between this win-PTZ kindling method and standard PTZ kindling model. Thus, it may be suggested that not all PTZ injections are need for induction of PTZ induced fully kindled state.
癫痫的实验模型,包括戊四氮(PTZ)化学点燃,在研究癫痫的病理生理学方面非常重要。本研究的目的是提供行为学、电生理学和分子学证据,以确认标准和改良方案(称为窗口(win-)PTZ 点燃法)之间的相似性。标准 PTZ 点燃模型通过每两天注射 PTZ(37.5mg/kg)来诱导。在 win-PTZ 点燃方法中,动物接受 4 次初始 PTZ 注射,根据标准 PTZ 点燃模型中的 PTZ 注射次数确定最后 3 次 PTZ 注射的时间。每次 PTZ 注射后观察 20 分钟点燃性癫痫发作的行为迹象。在强直刺激后,从颗粒细胞层记录场电位。此外,使用 RT-PCR 技术评估海马和齿状回中 GABA A 受体γ2 亚基、NMDA 受体 NR2A 亚基、腺苷 A1 受体、α-CaMKII 和 GAP-43 的表达。在 win-PTZ 点燃方法组中,所有动物在最后 3 次 PTZ 注射后均达到完全点燃状态。在获得点燃过程中,标准 PTZ 点燃模型和 win-PTZ 点燃方法之间,群体峰电位幅度和上述基因的表达没有显著差异。在完全点燃状态后 8 天,电生理和分子参数的相似性仍然存在。获得的数据表明,这种 win-PTZ 点燃方法与标准 PTZ 点燃模型之间存在相似性。因此,可以认为并非所有 PTZ 注射都需要诱导 PTZ 诱导的完全点燃状态。