Zhen Jun-Li, Wang Wei-Ping, Zhou Jing-Jing, Qu Zhen-Zhen, Fang Hai-Bo, Zhao Ran-Ran, Lu Yan, Wang Hong-Chao, Zang Hong-Min
Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China.
Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China.
Brain Res. 2014 May 14;1563:122-30. doi: 10.1016/j.brainres.2014.03.032. Epub 2014 Mar 27.
Mild brief hypoxia can protect against neuronal damage induced by epileptic seizures, at least in part by inhibiting apoptosis. Further elucidation of the antiepileptic mechanisms and optimization of the conditioning protocols are required before this strategy can be considered for clinical intervention. In this study, we compared the effects of different hypoxic preconditioning protocols on spontaneous recurrent seizures (SRS), intracellular free calcium concentration ([Ca(2+)]i), and apoptosis rate following pilocarpine-induced status epilepticus (SE). Male Sprague Dawley rats were subjected to either chronic intermittent hypobaric hypoxia (CIHH) or chronic intermittent normobaric hypoxia (CINH) (both for 6h/day × 28 consecutive days) prior to pilocarpine-induced SE. The possible anticonvulsant and neuroprotective effects of CIHH and CINH were compared by video monitoring of behavioral seizure activity (frequency, delay), Nissl staining and Fluoro-Jade B (FJB) staining to examine changes in the morphology of hippocampal pyramidal neurons, and flow cytometry to detect the quantification of [Ca(2+)]i and cell apoptosis. Both hypoxic preconditioning protocols reduced the frequency and severity of SRS, suppressed post-ictal [Ca(2+)]i elevations, and inhibited neuronal apoptosis in the rat hippocampus compared to pilocarpine alone, but CIHH was more effective than CINH. Thus, mild hypoxic pretreatment, particularly when delivered as CIHH, may be a novel strategy for the clinical prevention and treatment of epilepsy.
轻度短暂缺氧可预防癫痫发作诱导的神经元损伤，至少部分是通过抑制细胞凋亡来实现的。在将该策略考虑用于临床干预之前，需要进一步阐明其抗癫痫机制并优化预处理方案。在本研究中，我们比较了不同缺氧预处理方案对匹罗卡品诱导的癫痫持续状态（SE）后自发反复癫痫发作（SRS）、细胞内游离钙浓度（[Ca(2+)]i）和凋亡率的影响。雄性Sprague Dawley大鼠在匹罗卡品诱导SE之前，接受慢性间歇性低压缺氧（CIHH）或慢性间歇性常压缺氧（CINH）（均为每天6小时×连续28天）。通过视频监测行为性癫痫发作活动（频率、延迟）、尼氏染色和荧光金B（FJB）染色来检查海马锥体神经元形态变化，以及通过流式细胞术检测[Ca(2+)]i和细胞凋亡的定量，比较CIHH和CINH可能的抗惊厥和神经保护作用。与单独使用匹罗卡品相比，两种缺氧预处理方案均降低了SRS的频率和严重程度，抑制了发作后[Ca(2+)]i升高，并抑制了大鼠海马中的神经元凋亡，但CIHH比CINH更有效。因此，轻度缺氧预处理，特别是以CIHH形式进行时，可能是临床预防和治疗癫痫的一种新策略。
