Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Brain Res. 2012 Oct 22;1480:81-90. doi: 10.1016/j.brainres.2012.08.018. Epub 2012 Aug 17.
Brain cholesterol homeostasis has been shown to be disrupted in neurodegenerative conditions such as Alzheimer's and Huntington's diseases. Investigations in animal models of seizure-induced brain injury suggest that brain cholesterol levels are altered by prolonged seizures (status epilepticus) and are a feature of the pathophysiology of temporal lobe epilepsy. The present study measured hippocampal sterol levels in a model of unilateral hippocampal injury triggered by focal-onset status epilepticus, and in chronically epileptic mice. Status epilepticus was induced by intra-amygdala microinjection of kainic acid and ipsilateral and contralateral hippocampus analyzed. No significant changes were found for ipsilateral or contralateral hippocampal levels of desmosterol or lathosterol at any time after SE as measured by gas chromatography-mass spectrometry. 24S-hydroxycholesterol and cholesterol levels were unchanged up to 24h after status epilepticus but were decreased in the ipsilateral hippocampus during early epileptogenesis and in chronically epileptic mice. Levels of cholesterol were also reduced in the contralateral hippocampus during epileptogenesis and in chronic epileptic mice. Treatment of mice with the anti-inflammatory cholesterol synthesis inhibitor lovastatin did not alter seizures during status epilepticus or seizure-induced neuronal death. Thus, changes to hippocampal cholesterol homeostasis predominantly begin during epileptogenesis, occur bi-laterally even when the initial precipitating injury is unilateral, and continue into the chronic epileptic period.
脑胆固醇稳态已被证明在神经退行性疾病如阿尔茨海默病和亨廷顿病中受到破坏。在癫痫诱导的脑损伤动物模型中的研究表明，脑胆固醇水平通过长时间的癫痫发作（癫痫持续状态）而改变，并且是颞叶癫痫病理生理学的特征。本研究通过局灶性癫痫持续状态诱导的单侧海马损伤模型和慢性癫痫小鼠测量海马固醇水平。通过在杏仁核内微注射海人酸诱导癫痫持续状态，并分析同侧和对侧海马。通过气相色谱-质谱法测量，在 SE 后任何时间，同侧或对侧海马的去甲胆固醇或羊毛甾醇水平均无明显变化。24S-羟基胆固醇和胆固醇水平在癫痫持续状态后 24 小时内保持不变，但在早期癫痫发生期间和慢性癫痫小鼠中，同侧海马中的胆固醇水平降低。在癫痫发生期间和慢性癫痫小鼠中，对侧海马中的胆固醇水平也降低。用抗炎胆固醇合成抑制剂 lovastatin 治疗小鼠不能改变癫痫持续状态期间或癫痫诱导的神经元死亡。因此，海马胆固醇稳态的变化主要在癫痫发生期间开始，即使初始引发损伤是单侧的，也会双侧发生，并持续到慢性癫痫期。
