calpain-inhibitor-iii and Seizures

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.

Topics: Animals; Anticonvulsants; Calpain; Cerebral Cortex; Dipeptides; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsy, Temporal Lobe; Glycoproteins; Hippocampus; Inflammation; Male; Neurodegenerative Diseases; Neurons; Pilocarpine; Random Allocation; Rats, Sprague-Dawley; Seizures