Suppressive effects of levetiracetam on neuroinflammation and phagocytic microglia: A comparative study of levetiracetam, valproate and carbamazepine
Suppressive effects of levetiracetam on neuroinflammation and phagocytic microglia: A comparative study of levetiracetam, valproate and carbamazepine
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DOI：
10.1016/j.neulet.2019.134363
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发表时间：
2019-08-24
影响因子：
2.5
通讯作者：
Ishihara, Yasuhiro
中科院分区：
文献类型：
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作者：
Itoh, Kouichi;Taniguchi, Ruri;Ishihara, Yasuhiro
我们以前报道，左乙拉西坦（LEV）治疗后，癫痫持续状态（SE）终止地西泮（DZP）防止自发性复发性癫痫发作的发展。LEV抑制SE后癫痫发生过程中促炎介质的表达水平增加，但LEV如何在神经炎症过程中起作用尚不清楚。在这项研究中，我们研究了LEV在体内和体外对神经炎症和吞噬性小胶质细胞的影响，并将LEV与代表性抗癫痫药物丙戊酸盐（VPA）和卡马西平（CBZ）的影响进行了比较。用DZP终止匹罗卡品诱发的SE后，用LEV重复治疗30天几乎完全防止了自发复发性癫痫发作的发生，而VPA或CBZ的给药对癫痫发作没有影响。LEV明显抑制单核吞噬细胞的吞噬作用，SE后2天观察到细胞因子表达。VPA仅减轻神经炎症，CBZ对SE后的变化无影响。用LEV治疗显著抑制BV-2小胶质细胞活化，其通过形态学变化、吞噬活性和细胞因子表达来定义。相比之下，VPA和CBZ不影响BV-2小胶质细胞的活性。总之，LEV直接抑制癫痫发生过程中过度的小胶质细胞吞噬作用，这可能会防止SE后自发复发性癫痫发作的发生。
We previously reported that treatment with levetiracetam (LEV) after status epilepticus (SE) termination by diazepam (DZP) prevents the development of spontaneous recurrent seizures. LEV suppresses increased expression levels of proinflammatory mediators during epileptogenesis after SE, but how LEV acts in neuroinflammatory processes is not yet known. In this study, we examined the effects of LEV on neuroinflammation and phagocytic microglia in vivo and in vitro and compared the effects of LEV with those of representative anti-epileptic drugs valproate (VPA) and carbamazepine (CBZ). Repeated treatment with LEV for 30 days after the termination of pilocarpine-induced SE by DZP almost completely prevented the incidence of spontaneous recurrent seizures, while administration of VPA or CBZ showed no effect on the seizures. LEV clearly suppressed phagocytosis of mononuclear phagocytes, and cytokine expression was observed 2 days after SE. VPA attenuated neuroinflammation only, and CBZ showed no effect on changes after SE. Treatment with LEV significantly suppressed BV-2 microglial activation, which was defined by morphological changes, phagocytic activity and cytokine expression. By contrast, VPA and CBZ did not affect BV-2 microglial activity. In summary, LEV directly suppresses excess microglial phagocytosis during epileptogenesis, which might prevent the occurrence of spontaneous recurrent seizures after SE.