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Suppressive effects of levetiracetam on neuroinflammation and phagocytic microglia: A comparative study of levetiracetam, valproate and carbamazepine.
Neurosci Lett. 2019 08 24; 708:134363.NL

Abstract

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 antiepileptic 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.

Authors+Show Affiliations

Laboratory for Pharmacotherapy and Experimental Neurology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa, 769-2193, Japan.Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8521, Japan.Laboratory for Pharmacotherapy and Experimental Neurology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa, 769-2193, Japan.Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8521, Japan.Center for Health and the Environment, University of California, Davis, Davis, CA, 95616, USA; Department of Environmental Toxicology, University of California, Davis, Davis, CA, 95616, USA.Program of Life and Environmental Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8521, Japan.Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8521, Japan; Center for Health and the Environment, University of California, Davis, Davis, CA, 95616, USA. Electronic address: ishiyasu@hiroshima-u.ac.jp.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31276728

Citation

Itoh, Kouichi, et al. "Suppressive Effects of Levetiracetam On Neuroinflammation and Phagocytic Microglia: a Comparative Study of Levetiracetam, Valproate and Carbamazepine." Neuroscience Letters, vol. 708, 2019, p. 134363.
Itoh K, Taniguchi R, Matsuo T, et al. Suppressive effects of levetiracetam on neuroinflammation and phagocytic microglia: A comparative study of levetiracetam, valproate and carbamazepine. Neurosci Lett. 2019;708:134363.
Itoh, K., Taniguchi, R., Matsuo, T., Oguro, A., Vogel, C. F. A., Yamazaki, T., & Ishihara, Y. (2019). Suppressive effects of levetiracetam on neuroinflammation and phagocytic microglia: A comparative study of levetiracetam, valproate and carbamazepine. Neuroscience Letters, 708, 134363. https://doi.org/10.1016/j.neulet.2019.134363
Itoh K, et al. Suppressive Effects of Levetiracetam On Neuroinflammation and Phagocytic Microglia: a Comparative Study of Levetiracetam, Valproate and Carbamazepine. Neurosci Lett. 2019 08 24;708:134363. PubMed PMID: 31276728.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppressive effects of levetiracetam on neuroinflammation and phagocytic microglia: A comparative study of levetiracetam, valproate and carbamazepine. AU - Itoh,Kouichi, AU - Taniguchi,Ruri, AU - Matsuo,Taira, AU - Oguro,Ami, AU - Vogel,Christoph F A, AU - Yamazaki,Takeshi, AU - Ishihara,Yasuhiro, Y1 - 2019/07/02/ PY - 2019/04/19/received PY - 2019/06/29/revised PY - 2019/07/02/accepted PY - 2019/7/6/pubmed PY - 2019/7/6/medline PY - 2019/7/6/entrez KW - Epileptogenesis KW - Inflammation KW - Levetiracetam KW - Microglia KW - Phagocytosis SP - 134363 EP - 134363 JF - Neuroscience letters JO - Neurosci. Lett. VL - 708 N2 - 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 antiepileptic 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. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/31276728/Suppressive_effects_of_levetiracetam_on_neuroinflammation_and_phagocytic_microglia:_A_comparative_study_of_levetiracetam_valproate_and_carbamazepine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(19)30466-5 DB - PRIME DP - Unbound Medicine ER -