Perineuronal net degradation in epilepsy

• DOI: 10.1111/epi.13026
• Publication Date: 2015-05-29T18:45:30Z
• Authors: Elyse K. Rankin‐Gee; Paulette A. McRae; Esther Baranov; Stephanie Rogers; Luke Wandrey; Brenda E. Porter
• Keywords: Male; Rats, Sprague-Dawley; Mice; Oligodendroglia; 0303 health sciences; 03 medical and health sciences; Status Epilepticus; Pilocarpine; Animals; Nerve Net; Hippocampus; Rats

SummaryObjectiveWe previously reported loss of perineuronal net (PN) immunohistochemical staining around parvalbumin‐positive interneurons in the hippocampus of rats after an episode of status epilepticus (SE). We hypothesized that the loss of thePNcould alter seizure susceptibility and that matrix metalloproteinases (MMPs) were candidates for degradation of thePNfollowingSE.MethodsThe pilocarpine chemoconvulsant rodent epilepsy model was used to characterize the degradation of the aggrecan component of thePNin the hippocampus following SE. ChondroitinaseABC(ChABC) was used to degrade thePNin mice. Onset, number, and duration of pentylenetetrazole (PTZ)–induced seizures were assessed.ResultsThe loss of thePNin the hippocampus followingSEis at least partially related to degradation of the aggrecanPNcomponent byMMPactivity. Forty‐eight hours afterSE, a neoepitope created byMMPcleavage of aggrecan was present and concentrated around parvalbumin‐positive interneurons. The increase in aggrecan cleavage products was found at 48 h, 1 week, and 2 months afterSE, with different fragments predominating over time. We demonstrate ongoing aggrecan proteolysis and fragment accumulation in the hippocampus of adult control rats, as well as inSE‐treated animals. Degradation of thePNalters the seizure response toPTZ. ChABC treatment caused an increase in myoclonic seizures followingPTZadministration, a delayed onset of Racine stage 4/5 seizure, and a decreased duration of Racine stage 4/5 seizure.SignificanceStatus epilepticus increasesMMPproteolysis of aggrecan, pointing toMMPactivity as one mechanism ofPNdegradation post‐SE. There is accumulation of aggrecan fragments in adult rat hippocampus of both control andSE‐exposed animals. Loss of thePNwas associated with increased numbers of myoclonic seizures; it also, delayed and shortened the duration of Racine stage 4/5 seizures, suggesting a complex relationship between thePNand seizure susceptibility.