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 of epilepsy. Progress on the project was limited throughout the grant period due to an inability to obtain a sufficient quantity of SS-31 to perform the proposed experiments. Our last shipment of SS-31 was obtained on May 2014. This resulted in the granting of a second no cost extensions in May 2015. We did complete the experiments proposed in Aim 1, testing the efficacy of SS-31 as a neuroprotectant-antiepileptogenic agent in the PILO model of SE. SS-31 had no effect on the latency to the onset of SE and there was no evidence of neuroprotection in hippocampal tissue assessed 3 days after SE. The insult generated by prolonged seizure activity appeared to be too severe for a single dose of SS-31 to be effective. We observed these negative results despite testing SS-31 at dose of 10mg/kg. s.c., which is higher than what has been reported to be efficacious in other models. In Aim 2 we tested the efficacy of SS-31 on hippocampal kindled after discharge (AD) threshold and duration. Baseline AD threshold and duration were determined for each animal. A minimum of 24hr later SS-31 (10-20mg/kg, s.c.; n=9) was administered 30min before AD testing. In our initial experiments SS-31 had no effect on AD threshold but there was preliminary evidence that SS-31 (20mg/kg) decreased AD duration in some animals. We repeated these experiments with a dose of 30mg/kg, s.c. (n = 5). This significantly higher dose SS-31 had no effect on AD threshold or duration and exhausted our supply of SS-31.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2016
- Accession Number
- AD1020626
Entities
People
- Jeffrey H. Goodman
Organizations
- Research Foundation For Mental Hygiene