Gol Mohammad, Ghorbanian Davoud, Hassanzadeh Samaneh, Javan Mohammad, Mirnajafi-Zadeh Javad, Ghasemi-Kasman Maryam
Student Research Committee, Faculty of Medical Sciences, Babol University of Medical Sciences, Babol, Mazandaran, Iran.
Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Eur J Pharm Sci. 2017 Jan 1;96:72-83. doi: 10.1016/j.ejps.2016.09.016. Epub 2016 Sep 12.
Recent evidence indicates that demyelination occurs in epilepsy patients and kindling animal models. Regarding the well-known literature on anti-inflammatory and myelin protective effects of fingolimod (FTY720) in multiple sclerosis patients and animal models, we hypostatized whether FTY720 administration could exert myelin protective effects in pentylenetetrazol (PTZ)-induced kindling model. To end this, animals received 0.3 or 1mg/kg dosage of FTY720, 1h before PTZ injections. In another approach, after achieving fully kindling stage, FTY720 was administrated i.p. once daily for 7 consecutive days. Treatment with FTY720 (especially lower dose) reduced the frequency of seizures and epileptiform discharges in both approaches. We found that FTY720 administration decreases cell death and glial activation in CA1 and CA3 regions of hippocampus. Myelin protection effect was shown by increasing myelin levels. Furthermore, post-treatment of FTY720 enhanced endogenous remyelination and the number of oligodendrocyte precursor cells in fully kindled animals. Together, these results demonstrate that FTY720 behind the anti-inflammatory and neuroprotection effects has beneficial role in myelin protection and remyelination enhancement in PTZ kindling model of seizure and it may be provide a new therapeutic option for demyelination associated with epilepsy.
近期证据表明，癫痫患者和点燃动物模型中会发生脱髓鞘。鉴于关于芬戈莫德（FTY720）在多发性硬化症患者和动物模型中的抗炎和髓鞘保护作用的著名文献，我们假设给予FTY720是否能在戊四氮（PTZ）诱导的点燃模型中发挥髓鞘保护作用。为此，在注射PTZ前1小时，动物接受0.3或1mg/kg剂量的FTY720。在另一种方法中，在达到完全点燃阶段后，连续7天每天腹腔注射FTY720。在两种方法中，FTY720治疗（尤其是低剂量）均降低了癫痫发作频率和癫痫样放电。我们发现，给予FTY720可减少海马CA1和CA3区域的细胞死亡和胶质细胞激活。通过增加髓鞘水平显示出髓鞘保护作用。此外，在完全点燃的动物中，FTY720的治疗后增强了内源性髓鞘再生和少突胶质细胞前体细胞的数量。总之，这些结果表明，FTY720在抗炎和神经保护作用之外，在PTZ点燃癫痫模型的髓鞘保护和髓鞘再生增强方面具有有益作用，并且可能为与癫痫相关的脱髓鞘提供一种新的治疗选择。
