Neuroprotection and Anti-Epileptogenesis with Mitochondria-Targeted Antioxidant
Abstract
The goals of the project were to assess the neuroprotective and antiepiletogenic properties of a mitochondrial-targeted antioxidant, SS-31 in the pilocarpine (PILO) model of status epilepticus (SE), the kindling seizure model and the tetanus toxin (Tx) model. Progress on the project was limited during the initial grant period due to an inability to obtain a sufficient quantity of SS-31 to perform the proposed experiments. As a result a no cost extension was granted in April 2014. More SS-31 was obtained from Stealth Peptides, Inc. on May 29, 2014. The experiments performed during initial grant period focused on Aim#1. In these experiments adult male Sprague-Dawley rats (260-405g) were pretreated with SS-31 (3 or 10mg/kg, sc; n=14) or saline (n=10) 45min before induction of SE with Pilo (365mg/kg, sc). The results suggested that SS-31 had no effect on the latency to SE and that there was no evidence of neuroprotection in hippocampal tissue stained for: Nissl, Fluoro-jade C (FJ), NeuN and heat shock protein (HSP). The insult generated by prolonged seizure activity appeared to be too severe for SS-31 to be effective. For the current reporting period we extended the experiments in Aim#1 and initiated experiments in Aim#2 testing the efficacy of SS-31 in the kindling seizure model. We addressed the possibility that prolonged seizure activity was too severe an insult for SS-31 to be effective by testing SS-31 (10mg/kg, sc) in PILO-treated rats (6 controls; 6 experimentals) where the duration of SE was limited to 5min and the dose of diazepam used to attenuate SE was increased from 5mg/kg, ip to 10mg/kg, ip. The brains from these animals have been sectioned and staining for the markers listed above has been initiated. To date the only marker that has been evaluated is FJ which revealed that despite limiting the duration of SE, SS-31 was not neuroprotective.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA615113
Entities
People
- Jeffrey H. Goodman
Organizations
- Research Foundation For Mental Hygiene