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Links between Immune Cells from the Periphery and the Brain in the Pathogenesis of Epilepsy: A Narrative Review
Authors:Gaku Yamanaka  Shinichiro Morichi  Tomoko Takamatsu  Yusuke Watanabe  Shinji Suzuki  Yu Ishida  Shingo Oana  Takashi Yamazaki  Fuyuko Takata  Hisashi Kawashima
Affiliation:1.Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo 160-8402, Japan; (S.M.); (T.T.); (Y.W.); (S.S.); (Y.I.); (S.O.); (T.Y.);2.Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan; (F.T.); (H.K.)
Abstract:Accumulating evidence has demonstrated that the pathogenesis of epilepsy is linked to neuroinflammation and cerebrovascular dysfunction. Peripheral immune cell invasion into the brain, along with these responses, is implicitly involved in epilepsy. This review explored the current literature on the association between the peripheral and central nervous systems in the pathogenesis of epilepsy, and highlights novel research directions for therapeutic interventions targeting these reactions. Previous experimental and human studies have demonstrated the activation of the innate and adaptive immune responses in the brain. The time required for monocytes (responsible for innate immunity) and T cells (involved in acquired immunity) to invade the central nervous system after a seizure varies. Moreover, the time between the leakage associated with blood–brain barrier (BBB) failure and the infiltration of these cells varies. This suggests that cell infiltration is not merely a secondary disruptive event associated with BBB failure, but also a non-disruptive event facilitated by various mediators produced by the neurovascular unit consisting of neurons, perivascular astrocytes, microglia, pericytes, and endothelial cells. Moreover, genetic manipulation has enabled the differentiation between peripheral monocytes and resident microglia, which was previously considered difficult. Thus, the evidence suggests that peripheral monocytes may contribute to the pathogenesis of seizures.
Keywords:epilepsy   cytokine   monocytes   pericytes
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