A calpain inhibitor ameliorates seizure burden in an experimental model of temporal lobe epilepsy

Neurobiology of Disease

Marco I. González¹  Jessica Carlsen²  Philip M. Lam² 

[1] Corresponding author at: Pharmacy Building (V20), Mail Stop 8605, 12850 E. Montview Blvd, Room 3117, Aurora, CO 80045, USA.;Department of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO 80045, USA;

关键词: Epileptogenesis;    Calpain;    Proteolysis;    Epilepsy;    Spontaneous seizures;   

DOI  :  

来源: DOAJ

【 摘 要 】

In this study, we used the pilocarpine model of epilepsy to evaluate the involvement of calpain dysregulation on epileptogenesis. Detection of spectrin breakdown products (SBDPs, a hallmark of calpain activation) after induction of pilocarpine-induced status epilepticus (SE) and before appearance of spontaneous seizure suggested the existence of sustained calpain activation during epileptogenesis. Acute treatment with a cell permeable inhibitor of calpain, MDL-28170, resulted in a partial but significant reduction on seizure burden. The reduction on seizure burden was associated with a limited reduction on the generation of SBDPs but was correlated with a reduction in astrocytosis, microglia activation and cell sprouting. Together, these observations provide evidence for the role of calpain in epileptogenesis. In addition, provide proof-of-principle for the use of calpain inhibitors as a novel strategy to prevent epileptic seizures and its associated pathologies.

【 授权许可】

Unknown