Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK Pathway

Autor: Min Li, Lexiang Cui, Xuemin Feng, Chao Wang, Yinmeng Zhang, Lijie Wang, Ying Ding, Teng Zhao
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 10 (2019)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2019.00625
Popis: Objective: This research aimed to validate the therapeutic effect of losmapimod and explore the underlying mechanism in its treatment of epilepsy.Methods: A rat model of epilepsy was constructed with an injection of pilocarpine. Microarray analysis was performed to screen aberrantly expressed mRNAs and activated signaling pathways between epileptic rats and normal controls. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to identify cell apoptosis. Hippocampal cytoarchitecture was visualized with Nissl staining. The secretion of inflammatory factors as well as the marker proteins in the mitogen-activated protein kinase (MAPK) pathway were detected by Western blot. A Morris water maze navigation test evaluated the rats’ cognitive functions.Results: Activation of the MAPK signaling pathway was observed in epilepsy rats. A decrease in the MAPK phosphorylation level by application of losmapimod protected against epilepsy by reducing neuron loss. Losmapimod effectively improved memory, reduced the frequency of seizures, protected the neuron from damage, and limited the apoptosis of neurons in epilepsy rats.Conclusion: The application of losmapimod could partly reverse the development of epilepsy.
Databáze: Directory of Open Access Journals