Downregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures

Abstract Unregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE). Our aim was to determine the effect of CD40–CD40L activation in experimental seizures. CD40 deficient mice (CD40KO) and control mice (wild type, WT) received pentenyltetrazole (PTZ) or pilocarpine to evaluate...

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Autores principales:	Esther Pototskiy, Katherine Vinokuroff, Andrew Ojeda, C. Kendall Major, Deepak Sharma, Taylor Anderson, Kendall Howard, Alberto E. Musto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d9c70ea7a994ef1a75229f6d984d92f
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spelling	oai:doaj.org-article:6d9c70ea7a994ef1a75229f6d984d92f2021-12-02T15:09:06ZDownregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures10.1038/s41598-021-96760-32045-2322https://doaj.org/article/6d9c70ea7a994ef1a75229f6d984d92f2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96760-3https://doaj.org/toc/2045-2322Abstract Unregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE). Our aim was to determine the effect of CD40–CD40L activation in experimental seizures. CD40 deficient mice (CD40KO) and control mice (wild type, WT) received pentenyltetrazole (PTZ) or pilocarpine to evaluate seizures and status epilepticus (SE) respectively. In mice, anti-CD40L antibody was administered intranasally before PTZ. Brain samples from human TLE and post-seizure mice were processed to determine CD40–CD40L expression using histological and molecular techniques. CD40 expression was higher in hippocampus from human TLE and in cortical neurons and hippocampal neural terminals after experimental seizures. CD40–CD40L levels increased after seizures in the hippocampus and in the cortex. After SE, CD40L/CD40 levels increased in cortex and showed an upward trend in the hippocampus. CD40KO mice demonstrated reduction in seizure severity and in latency compared to WT mice. Anti-CD40L antibody limited seizure susceptibility and seizure severity. CD40L–CD40 interaction can serve as a target for an immuno-therapy for TLE.Esther PototskiyKatherine VinokuroffAndrew OjedaC. Kendall MajorDeepak SharmaTaylor AndersonKendall HowardAlberto E. MustoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Esther Pototskiy Katherine Vinokuroff Andrew Ojeda C. Kendall Major Deepak Sharma Taylor Anderson Kendall Howard Alberto E. Musto Downregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures
description	Abstract Unregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE). Our aim was to determine the effect of CD40–CD40L activation in experimental seizures. CD40 deficient mice (CD40KO) and control mice (wild type, WT) received pentenyltetrazole (PTZ) or pilocarpine to evaluate seizures and status epilepticus (SE) respectively. In mice, anti-CD40L antibody was administered intranasally before PTZ. Brain samples from human TLE and post-seizure mice were processed to determine CD40–CD40L expression using histological and molecular techniques. CD40 expression was higher in hippocampus from human TLE and in cortical neurons and hippocampal neural terminals after experimental seizures. CD40–CD40L levels increased after seizures in the hippocampus and in the cortex. After SE, CD40L/CD40 levels increased in cortex and showed an upward trend in the hippocampus. CD40KO mice demonstrated reduction in seizure severity and in latency compared to WT mice. Anti-CD40L antibody limited seizure susceptibility and seizure severity. CD40L–CD40 interaction can serve as a target for an immuno-therapy for TLE.
format	article
author	Esther Pototskiy Katherine Vinokuroff Andrew Ojeda C. Kendall Major Deepak Sharma Taylor Anderson Kendall Howard Alberto E. Musto
author_facet	Esther Pototskiy Katherine Vinokuroff Andrew Ojeda C. Kendall Major Deepak Sharma Taylor Anderson Kendall Howard Alberto E. Musto
author_sort	Esther Pototskiy
title	Downregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures
title_short	Downregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures
title_full	Downregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures
title_fullStr	Downregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures
title_full_unstemmed	Downregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures
title_sort	downregulation of cd40l–cd40 attenuates seizure susceptibility and severity of seizures
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6d9c70ea7a994ef1a75229f6d984d92f
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Downregulation of CD40L–CD40 attenuates seizure susceptibility and severity of seizures

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