Temporal lobe epilepsy is associated with astrogliosis. Notchl signaling can induce astrogliosis in glioma. However, it remains unknown whether Notchl signaling is involved in the pathogenesis of epilepsy. This study ...Temporal lobe epilepsy is associated with astrogliosis. Notchl signaling can induce astrogliosis in glioma. However, it remains unknown whether Notchl signaling is involved in the pathogenesis of epilepsy. This study investigated the presence of Notchl, hairy and enhancer of split-l, and glial fibrillary acidic protein in the temporal neocortex and hippocampus of lithium-pilocar- pine-treated rats. The presence of Notchl and hairy and enhancer of split-1 was also explored in brain tissues of patients with intractable temporal lobe epilepsy. Quantitative electroencephalo- gram analysis and behavioral observations were used as auxiliary measures. Results revealed that the presence of Notchl, hairy and enhancer of split-l, and glial fibriUary acidic protein were en- hanced in status epilepticus and vehicle-treated spontaneous recurrent seizures rats, but remain unchanged in the following groups: control, absence of either status epilepticus or spontaneous recurrent seizures, and zileuton-treated spontaneous recurrent seizures. Compared with patient control cases, the presences of Notch1 and hairy and enhancer of split- 1 were upregulated in the temporal neocortex of patients with intractable temporal lobe epilepsy. Therefore, these results suggest that Notchl signaling may play an important role in the onset of temporal lobe epilepsy via astrogliosis. Furthermore, zileuton may be a potential therapeutic strategy for temporal lobe epilepsy by blocking Notchl signaling.展开更多
The Na+-K+-CI- cotransporter 1 and K+-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophys...The Na+-K+-CI- cotransporter 1 and K+-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of CI- homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na+-K+-CI- cotransporter 1 and K+-CI- cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na+-K+-Cl- cotransporter 1 expression and decreased K+-CI- cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na+-K+-CI- cotransporter 1 than for the K+-CI- cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na+-K+-CI-cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.展开更多
目的探讨颞叶脑创伤的手术指征和手术时机。方法回顾分析628例颞叶脑创伤患者的临床资料。结果628例患者术后3年GOS评分:良好531例(84.6%),中度残疾47例(7.4%),重度残疾33例(5.3%),死亡17例(2.7%);幕上血肿量≥30 ml 178例(28.3%)。结...目的探讨颞叶脑创伤的手术指征和手术时机。方法回顾分析628例颞叶脑创伤患者的临床资料。结果628例患者术后3年GOS评分:良好531例(84.6%),中度残疾47例(7.4%),重度残疾33例(5.3%),死亡17例(2.7%);幕上血肿量≥30 ml 178例(28.3%)。结论颞叶脑创伤的手术指征不能硬用幕上血肿量≥30 ml、中线结构移位>10 mm的标准,要根据患者的意识、GCS评分、CT动态观察脑室系统、基底池改变情况而确定手术时机。展开更多
基金funded by the Natural Science Foundation of Hubei Province in China,No.02.02.040458
文摘Temporal lobe epilepsy is associated with astrogliosis. Notchl signaling can induce astrogliosis in glioma. However, it remains unknown whether Notchl signaling is involved in the pathogenesis of epilepsy. This study investigated the presence of Notchl, hairy and enhancer of split-l, and glial fibrillary acidic protein in the temporal neocortex and hippocampus of lithium-pilocar- pine-treated rats. The presence of Notchl and hairy and enhancer of split-1 was also explored in brain tissues of patients with intractable temporal lobe epilepsy. Quantitative electroencephalo- gram analysis and behavioral observations were used as auxiliary measures. Results revealed that the presence of Notchl, hairy and enhancer of split-l, and glial fibriUary acidic protein were en- hanced in status epilepticus and vehicle-treated spontaneous recurrent seizures rats, but remain unchanged in the following groups: control, absence of either status epilepticus or spontaneous recurrent seizures, and zileuton-treated spontaneous recurrent seizures. Compared with patient control cases, the presences of Notch1 and hairy and enhancer of split- 1 were upregulated in the temporal neocortex of patients with intractable temporal lobe epilepsy. Therefore, these results suggest that Notchl signaling may play an important role in the onset of temporal lobe epilepsy via astrogliosis. Furthermore, zileuton may be a potential therapeutic strategy for temporal lobe epilepsy by blocking Notchl signaling.
基金supported by the Science and Technology Foundation of Guangdong Province,No.2008B060600063the National Natural Science Foundation of China,No. 81071050the Natural Science Foundation of Guangdong Province,No. S2011020005483
文摘The Na+-K+-CI- cotransporter 1 and K+-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of CI- homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na+-K+-CI- cotransporter 1 and K+-CI- cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na+-K+-Cl- cotransporter 1 expression and decreased K+-CI- cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na+-K+-CI- cotransporter 1 than for the K+-CI- cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na+-K+-CI-cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.
文摘目的探讨颞叶脑创伤的手术指征和手术时机。方法回顾分析628例颞叶脑创伤患者的临床资料。结果628例患者术后3年GOS评分:良好531例(84.6%),中度残疾47例(7.4%),重度残疾33例(5.3%),死亡17例(2.7%);幕上血肿量≥30 ml 178例(28.3%)。结论颞叶脑创伤的手术指征不能硬用幕上血肿量≥30 ml、中线结构移位>10 mm的标准,要根据患者的意识、GCS评分、CT动态观察脑室系统、基底池改变情况而确定手术时机。