Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage

Rufinamide (RUF) is a structurally unique anti-epileptic drug, but its protective mechanism against brain injury remains unclear. In the present study, we validated how the RUF protected mice with kainic acid (KA)-induced neuronal damage. To achieve that, a mouse epilepsy model was established by KA...

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Autores principales:	Yu Huaxu, He Bin, Han Xu, Yan Ting
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2021
Materias:	ruf neuronal damage neuroinflammation blood–brain barrier Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6d0d23485c104afd97f40409ac49d0b5
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spelling	oai:doaj.org-article:6d0d23485c104afd97f40409ac49d0b52021-12-05T14:10:41ZRufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage2391-541210.1515/biol-2021-0090https://doaj.org/article/6d0d23485c104afd97f40409ac49d0b52021-08-01T00:00:00Zhttps://doi.org/10.1515/biol-2021-0090https://doaj.org/toc/2391-5412Rufinamide (RUF) is a structurally unique anti-epileptic drug, but its protective mechanism against brain injury remains unclear. In the present study, we validated how the RUF protected mice with kainic acid (KA)-induced neuronal damage. To achieve that, a mouse epilepsy model was established by KA intraperitoneal injection. After Nissl staining, although there was a significant reduction in Nissl bodies in mice treated with KA, 40, 80, and 120 mg/kg, RUF significantly reduced KA-induced neuronal damage, in a dose-dependent manner. Among them, 120 mg/kg RUF was most pronounced. Immunohistochemistry (IHC) and western blot analysis showed that RUF inhibited the IBA-1 overexpression caused by KA to block microglia cell overactivation. Further, RUF treatment partially reversed neuroinflammatory cytokine (IL-1β, TNFα, HMGB1, and NLRP3) overexpression in mRNA and protein levels in KA mice. Moreover, although KA stimulation inhibited the expression of tight junctions, RUF treatment significantly upregulated expression of tight junction proteins (occludin and claudin 5) in both mRNA and protein levels in the brain tissues of KA mice. RUF inhibited the overactivation of microglia, suppressed the neuroinflammatory response, and reduced the destruction of blood–brain barrier, thereby alleviating the excitatory nerve damage of the KA-mice.Yu HuaxuHe BinHan XuYan TingDe Gruyterarticlerufneuronal damageneuroinflammationblood–brain barrierBiology (General)QH301-705.5ENOpen Life Sciences, Vol 16, Iss 1, Pp 845-855 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ruf neuronal damage neuroinflammation blood–brain barrier Biology (General) QH301-705.5
spellingShingle	ruf neuronal damage neuroinflammation blood–brain barrier Biology (General) QH301-705.5 Yu Huaxu He Bin Han Xu Yan Ting Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
description	Rufinamide (RUF) is a structurally unique anti-epileptic drug, but its protective mechanism against brain injury remains unclear. In the present study, we validated how the RUF protected mice with kainic acid (KA)-induced neuronal damage. To achieve that, a mouse epilepsy model was established by KA intraperitoneal injection. After Nissl staining, although there was a significant reduction in Nissl bodies in mice treated with KA, 40, 80, and 120 mg/kg, RUF significantly reduced KA-induced neuronal damage, in a dose-dependent manner. Among them, 120 mg/kg RUF was most pronounced. Immunohistochemistry (IHC) and western blot analysis showed that RUF inhibited the IBA-1 overexpression caused by KA to block microglia cell overactivation. Further, RUF treatment partially reversed neuroinflammatory cytokine (IL-1β, TNFα, HMGB1, and NLRP3) overexpression in mRNA and protein levels in KA mice. Moreover, although KA stimulation inhibited the expression of tight junctions, RUF treatment significantly upregulated expression of tight junction proteins (occludin and claudin 5) in both mRNA and protein levels in the brain tissues of KA mice. RUF inhibited the overactivation of microglia, suppressed the neuroinflammatory response, and reduced the destruction of blood–brain barrier, thereby alleviating the excitatory nerve damage of the KA-mice.
format	article
author	Yu Huaxu He Bin Han Xu Yan Ting
author_facet	Yu Huaxu He Bin Han Xu Yan Ting
author_sort	Yu Huaxu
title	Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
title_short	Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
title_full	Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
title_fullStr	Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
title_full_unstemmed	Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
title_sort	rufinamide (ruf) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
publisher	De Gruyter
publishDate	2021
url	https://doaj.org/article/6d0d23485c104afd97f40409ac49d0b5
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Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage

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