目的：观察比较不同脉冲波形的低频率电刺激对海马电点燃癫痫模型小鼠的作用差异。方法：采用电点燃刺激法建立小鼠癫痫模型，观察正弦波、单相方波、双相方波低频率电刺激对模型小鼠癫痫行为发作及后放电持续时间的影响，并比较不同时...目的：观察比较不同脉冲波形的低频率电刺激对海马电点燃癫痫模型小鼠的作用差异。方法：采用电点燃刺激法建立小鼠癫痫模型，观察正弦波、单相方波、双相方波低频率电刺激对模型小鼠癫痫行为发作及后放电持续时间的影响，并比较不同时间点给予正弦波低频率电刺激的抗癫痫作用。结果：与对照组比较，正弦波低频率电刺激30 s能降低小鼠海马电点燃癫痫发作等级（2．85±0．27 vs 4．75±0．12，P＜0．05）、减少大发作概率（53．6％ vs 96．5％，P＜0．01）和缩短后放电持续时间[（16．22±1．69）s vs （30．29±1．12）s，P＜0．01]，而单相方波和双相方波低频率电刺激30 s没有明显的抗癫痫作用。常用的单相方波低频率电刺激15 min能降低小鼠海马电点燃发作等级（3．58±0．16，P＜0．05）、减少大发作概率（66．7％，P＜0．01）；但对海马后放电持续时间及大发作持续时间无影响（均P＞0．05）。此外，电点燃刺激前预先给予或结束后3 s内给予正弦波低频率电刺激具有明显的抗癫痫作用（ P＜0．05或P＜0．01） ，而电点燃刺激结束10 s给予正弦波低频率电刺激则无上述抗癫痫作用。结论：低频率电刺激抗癫痫作用受波形参数的影响，其中正弦波低频率电刺激能有效抑制小鼠海马电点燃癫痫的发作。展开更多
OBJECTIVE Temporal lobe epilepsy(TLE) is one of the most common types of human epilepsy,and they are often resistant to current treatments. METHODS By using optogenetic,electrophysiological,imaging and pharmacology st...OBJECTIVE Temporal lobe epilepsy(TLE) is one of the most common types of human epilepsy,and they are often resistant to current treatments. METHODS By using optogenetic,electrophysiological,imaging and pharmacology strategies,we aimed toinvestigate the underlying circuit mechanism of TLE and tried to developthe novel and efficient approach to control epilepsy. RESULTS(1) Deep brain stimulation,especially low frequency stimulation,targeted the epileptic focus and the areas outside of the focus(critical regions for seizure spread),such as entorhinal cortex or subiculum,reduced seizure severity in TLE. Its anti-epileptic effect is time-window dependent and polarity dependent,which shows a promising strategy for treating epileptic seizures.(2) Using an optogenetic strategy,we demonstrated that excitatory projection from entorhinal cortex to hippocampus instructs the brain-stimulation treatments of epilepsy.(3) Our data from both the clinical and experimental studies further demonstrated that a disinhibitory GABAergic neuron-mediated microcircuit in the subiculum contributes to secondary generalized seizures in TLE.(4) Finally,based on abnormal synchronization of the electrical activity in epileptic circuit,we developed electro-responsive hydrogel nanoparticles modified with angiopep-2to facilitate the delivery of the antiepileptic drug phenytoin sodium,which greatly improves the therapeutic index. CONCLUSION Our findings may update the current view of epileptic neuronal networks and suggest possible promising ways for epilepsy treatment.展开更多
文摘目的：观察比较不同脉冲波形的低频率电刺激对海马电点燃癫痫模型小鼠的作用差异。方法：采用电点燃刺激法建立小鼠癫痫模型，观察正弦波、单相方波、双相方波低频率电刺激对模型小鼠癫痫行为发作及后放电持续时间的影响，并比较不同时间点给予正弦波低频率电刺激的抗癫痫作用。结果：与对照组比较，正弦波低频率电刺激30 s能降低小鼠海马电点燃癫痫发作等级（2．85±0．27 vs 4．75±0．12，P＜0．05）、减少大发作概率（53．6％ vs 96．5％，P＜0．01）和缩短后放电持续时间[（16．22±1．69）s vs （30．29±1．12）s，P＜0．01]，而单相方波和双相方波低频率电刺激30 s没有明显的抗癫痫作用。常用的单相方波低频率电刺激15 min能降低小鼠海马电点燃发作等级（3．58±0．16，P＜0．05）、减少大发作概率（66．7％，P＜0．01）；但对海马后放电持续时间及大发作持续时间无影响（均P＞0．05）。此外，电点燃刺激前预先给予或结束后3 s内给予正弦波低频率电刺激具有明显的抗癫痫作用（ P＜0．05或P＜0．01） ，而电点燃刺激结束10 s给予正弦波低频率电刺激则无上述抗癫痫作用。结论：低频率电刺激抗癫痫作用受波形参数的影响，其中正弦波低频率电刺激能有效抑制小鼠海马电点燃癫痫的发作。
基金The project supported by National Natural Science Foundation of China(91332202,81630098)
文摘OBJECTIVE Temporal lobe epilepsy(TLE) is one of the most common types of human epilepsy,and they are often resistant to current treatments. METHODS By using optogenetic,electrophysiological,imaging and pharmacology strategies,we aimed toinvestigate the underlying circuit mechanism of TLE and tried to developthe novel and efficient approach to control epilepsy. RESULTS(1) Deep brain stimulation,especially low frequency stimulation,targeted the epileptic focus and the areas outside of the focus(critical regions for seizure spread),such as entorhinal cortex or subiculum,reduced seizure severity in TLE. Its anti-epileptic effect is time-window dependent and polarity dependent,which shows a promising strategy for treating epileptic seizures.(2) Using an optogenetic strategy,we demonstrated that excitatory projection from entorhinal cortex to hippocampus instructs the brain-stimulation treatments of epilepsy.(3) Our data from both the clinical and experimental studies further demonstrated that a disinhibitory GABAergic neuron-mediated microcircuit in the subiculum contributes to secondary generalized seizures in TLE.(4) Finally,based on abnormal synchronization of the electrical activity in epileptic circuit,we developed electro-responsive hydrogel nanoparticles modified with angiopep-2to facilitate the delivery of the antiepileptic drug phenytoin sodium,which greatly improves the therapeutic index. CONCLUSION Our findings may update the current view of epileptic neuronal networks and suggest possible promising ways for epilepsy treatment.
