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Neurobiol Dis. 2017 Jun;102:1-10. doi: 10.1016/j.nbd.2017.02.003. Epub 2017 Feb 22.

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

Author information

1
Department of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO 80045, USA.
2
Department of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: marco.gonzalez@ucdenver.edu.

Abstract

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.

KEYWORDS:

Calpain; Epilepsy; Epileptogenesis; Proteolysis; Spontaneous seizures

PMID:
28237317
PMCID:
PMC5640433
DOI:
10.1016/j.nbd.2017.02.003
[Indexed for MEDLINE]
Free PMC Article

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