Abstract：
BACKGROUND: One of the mechanisms of epileptgenesis is impairment of inhibitory neural circuits. Several studies have compared neural changes among subtypes of gamma-aminobutyric acid-related (GABAergic) neurons after acquired epileptic seizure. However, it is unclear that GABAergic neural modifications that occur during acquisition process of epileptic seizure.
METHODS: Male rats were injected with pentylenetetrazole (PTZ kindling: n = 30) or saline (control: n = 15) every other day to observe the development of epileptic seizure stages. Two time points were identified: the point at which seizures were most difficult to induce, and the point at which seizures were most easy to induce. The expression of GABAergic neuron-related proteins in the hippocampus was immunohistochemically compared among GABAergic subtypes at each of these time points.
RESULTS: Bimodal changes in seizure stages were observed in response to PTZ kindling. The increase of seizure stage was transiently suppressed after 8 or 10 injections, and then progressed again by the 16th injection. Based on these results, we defined 10 injections as a short-term injection period during which seizures are less likely to occur, and 20 injections as a long-term injection period during which continuous seizures are likely to occur. The immunohistochemical analysis showed that hippocampal glutamic acid decarboxylase 65 (GAD65) expression was increased after short-term kindling but unchanged after long-term kindling. Increased GAD65 expression was limited to somatostatin-positive (SOM+) cells among several GABAergic subtypes. By contrast, GAD, GABA, GABAAR α1, GABABR1, and VGAT cells showed no change following short- or long-term PTZ kindling.
CONCLUSIONS: PTZ kindling induces bimodal changes in the epileptic seizure stage. Seizure stage is transiently suppressed after short-term PTZ injection with GAD65 upregulation in SOM+ cells. The seizure stage is progressed again after long-term PTZ injection with GAD65 reduction to baseline level.
METHODS: Male rats were injected with pentylenetetrazole (PTZ kindling: n = 30) or saline (control: n = 15) every other day to observe the development of epileptic seizure stages. Two time points were identified: the point at which seizures were most difficult to induce, and the point at which seizures were most easy to induce. The expression of GABAergic neuron-related proteins in the hippocampus was immunohistochemically compared among GABAergic subtypes at each of these time points.
RESULTS: Bimodal changes in seizure stages were observed in response to PTZ kindling. The increase of seizure stage was transiently suppressed after 8 or 10 injections, and then progressed again by the 16th injection. Based on these results, we defined 10 injections as a short-term injection period during which seizures are less likely to occur, and 20 injections as a long-term injection period during which continuous seizures are likely to occur. The immunohistochemical analysis showed that hippocampal glutamic acid decarboxylase 65 (GAD65) expression was increased after short-term kindling but unchanged after long-term kindling. Increased GAD65 expression was limited to somatostatin-positive (SOM+) cells among several GABAergic subtypes. By contrast, GAD, GABA, GABAAR α1, GABABR1, and VGAT cells showed no change following short- or long-term PTZ kindling.
CONCLUSIONS: PTZ kindling induces bimodal changes in the epileptic seizure stage. Seizure stage is transiently suppressed after short-term PTZ injection with GAD65 upregulation in SOM+ cells. The seizure stage is progressed again after long-term PTZ injection with GAD65 reduction to baseline level.
摘要：
背景：癫痫发生的机制之一是抑制性神经回路的损伤。一些研究比较了获得性癫痫发作后γ-氨基丁酸相关（GABA能）神经元亚型之间的神经变化。然而,尚不清楚在癫痫发作的获取过程中发生的GABA能神经修饰。
方法：雄性大鼠每隔一天注射戊四唑（PTZ点燃：n=30）或生理盐水（对照：n=15），观察癫痫发作阶段的发展。确定了两个时间点：癫痫发作最难诱发的时间点，以及癫痫发作最容易诱发的点。在这些时间点的每个时间点，对GABA能亚型之间的海马中GABA能神经元相关蛋白的表达进行了免疫组织化学比较。
结果：观察到对PTZ点燃反应的癫痫发作阶段的双峰变化。8或10次注射后，癫痫发作阶段的增加被短暂抑制，然后再次进行第16次注射。基于这些结果,我们将10次注射定义为短期注射期，在此期间癫痫发作的可能性较小，和20次注射作为一个长期注射期，在此期间可能发生持续的癫痫发作。免疫组织化学分析显示，短期点燃后海马谷氨酸脱羧酶65（GAD65）表达增加，但长期点燃后无变化。在几种GABA能亚型中，GAD65表达的增加仅限于生长抑素阳性（SOM）细胞。相比之下,GAD,GABA,短期或长期PTZ点燃后，GABAARα1，GABABR1和VGAT细胞无变化。
结论：PTZ点燃引起癫痫发作阶段的双峰变化。短期PTZ注射后，SOM+细胞中GAD65上调，癫痫发作期被短暂抑制。长期PTZ注射后癫痫发作阶段再次进展，GAD65降低至基线水平。
方法：雄性大鼠每隔一天注射戊四唑（PTZ点燃：n=30）或生理盐水（对照：n=15），观察癫痫发作阶段的发展。确定了两个时间点：癫痫发作最难诱发的时间点，以及癫痫发作最容易诱发的点。在这些时间点的每个时间点，对GABA能亚型之间的海马中GABA能神经元相关蛋白的表达进行了免疫组织化学比较。
结果：观察到对PTZ点燃反应的癫痫发作阶段的双峰变化。8或10次注射后，癫痫发作阶段的增加被短暂抑制，然后再次进行第16次注射。基于这些结果,我们将10次注射定义为短期注射期，在此期间癫痫发作的可能性较小，和20次注射作为一个长期注射期，在此期间可能发生持续的癫痫发作。免疫组织化学分析显示，短期点燃后海马谷氨酸脱羧酶65（GAD65）表达增加，但长期点燃后无变化。在几种GABA能亚型中，GAD65表达的增加仅限于生长抑素阳性（SOM）细胞。相比之下,GAD,GABA,短期或长期PTZ点燃后，GABAARα1，GABABR1和VGAT细胞无变化。
结论：PTZ点燃引起癫痫发作阶段的双峰变化。短期PTZ注射后，SOM+细胞中GAD65上调，癫痫发作期被短暂抑制。长期PTZ注射后癫痫发作阶段再次进展，GAD65降低至基线水平。
