癲癇為一種慢性的腦部疾病。百分之七十的病人可以利用抗癲癇藥物控制住病情，但目前仍然有百分之三十的病人無法用藥物控制。因此，發展新的抗癲癇藥物對於患有癲癇的病人是迫切需要的。
過氧化體增生活化受體家族(PPARs family)是第二類型的nucleus receptor，主要的功能為調控細胞分化，發展以及代謝。其中過氧化體增生活化受體γ(PPAR-γ)已經被報告在中樞神經疾病中對於神經具有保護性。在本研究中，我們試圖探討調節過氧化體增生活化受體γ是否會減緩pilocarpine所誘導的癲癇發作以及降低神經的興奮性。
結果發現，在小鼠行為觀察上，給予PPAR-γ親和劑pioglitazone(愛妥糖)會減緩癲癇的嚴重程度。病理切片上，我們發現pioglitazone 減緩pilocarpine所引起神經細胞損傷以及血腦屏障的破壞。。在pilocarpine誘導癲癇發作的情況下，PPAR-γ的缺失會增加老鼠腦部放電的頻率及振幅。此外，在細胞電生理研究的部分發現，在海馬迴神經元中pioglitazone會減少鈉離子電流以及增加BKCa 通道(大電導鈣激活鉀通道)的打開機率與活性。
總結，促進PPAR-γ活性降低動物急性癲癇發作的嚴重程度、急性神經元損傷以及血腦屏障的破壞。PPAR-γ的缺失則會增加腦部放電的程度。在細胞電生理部分發現PPAR-γ會降低海馬迴神經元鈉離子電流以及提高BKCa 通道的打開機率進而調節神經興奮度。

Epilepsy is a chronic brain disorder. Currently, seizures are controllable with antiepileptic drugs (AEDs) in about 70% of cases and approximately 30% of patients are refractory to current therapies. A novel therapy would thus be urgent for patients with epilepsy.
Peroxisome proliferator-activated receptor (PPARs) family is a type II nucleus receptor, it has functions of regulating cellular differentiation, development, and metabolism. To our knowledge, PPAR-γ has been successfully tested for their neuroprotective potential in some central nervous system diseases. We aimed to investigate whether the modulation of PPAR-γ could attenuate pilocarpine-induced seizures and decrease neuronal excitability.
We found that pioglitazone could attenuate pilocarpine-induced seizure severity in mice. Pathologically, pioglitazone significantly attenuated pilocarpine-induced status epilepticus-related hippocampal neuronal loss and blood brain barrier damage. Video-EEG monitoring showed PPAR-γ deficient mice had more frequent spikes during pilocarpine-induced seizure modeling. In addition, with the aid of patch-clamp technology, we found that pioglitazone could decrease sodium current and increase open probability of large conductance Ca2+-activated K+ (BKCa) channels in hippocampal neurons.
In conclusion, promoting PPAR-γ function attenuated seizure severity, acute neuronal loss and BBB damage. Deficiency of PPAR-γ aggravated pilocarpine-induced electrographic hyperexcitability. Pioglitazone could enhance hippocampal BKCa channel activities and thus modulate neuronal excitability.

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