Downregulation of CD40L-CD40 attenuates seizure susceptibility and severity of seizures.

Autor: Pototskiy E; Department of Pathology and Anatomy, Eastern Virginia Medical School, 700 W. Olney Road, Lewis Hall, Office 2174, Norfolk, VA, 23507, USA., Vinokuroff K; Eastern Virginia Medical School, Norfolk, VA, USA., Ojeda A; Department of Pathology and Anatomy, Eastern Virginia Medical School, 700 W. Olney Road, Lewis Hall, Office 2174, Norfolk, VA, 23507, USA., Major CK; Eastern Virginia Medical School, Norfolk, VA, USA., Sharma D; Eastern Virginia Medical School, Norfolk, VA, USA., Anderson T; Eastern Virginia Medical School, Norfolk, VA, USA., Howard K; Eastern Virginia Medical School, Norfolk, VA, USA., Borenstein R; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, 23507, USA., Musto AE; Department of Pathology and Anatomy, Eastern Virginia Medical School, 700 W. Olney Road, Lewis Hall, Office 2174, Norfolk, VA, 23507, USA. mustoae@evms.edu.; Department of Neurology, Eastern Virginia Medical School, 700 W. Olney Road, Lewis Hall, Office 2174, Norfolk, VA, 23507, USA. mustoae@evms.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Aug 26; Vol. 11 (1), pp. 17262. Date of Electronic Publication: 2021 Aug 26.
DOI: 10.1038/s41598-021-96760-3
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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