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

Frontiers in Pharmacology

Min Li¹  Xuemin Feng¹  Teng Zhao¹  Chao Wang¹  Lexiang Cui¹  Ying Ding²  Lijie Wang³  Yinmeng Zhang⁴ 

[1] Department of Neurology, The First Hospital of Jilin University, Changchun, China;Department of Radiology, The First Hospital of Jilin University, Changchun, China;Department of Traditional Chinese Medicine, General Hospital of FAW, Fourth Hospital of Jilin University, Changchuan, China;Major in Clinical Medicine, Medical College of Nanchang University, Nanchang, China;

关键词: losmapimod;    mitogen-activated protein kinase;    epilepsy;    hippocampus;    pilocarpine;   

DOI  :  10.3389/fphar.2019.00625

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown