Neuroprotection and Anti-Epileptogenesis with Mitochondria-Targeted Antioxidant
Technical Report,30 Sep 2014,29 Sep 2015
Research Foundation for Mental Hygiene Staten Island United States
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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 has been limited throughout the grant period due to an inability to obtain a sufficient quantity of SS-31 to perform the proposed experiments. This resulted in a no cost extension granted in April 2014. Our last shipment of SS-31 was obtained on May 29, 2014. In this reporting period we completed the experiments proposed in Aim 1, testing the efficacy of SS-31 as a neuroprotectantantiepileptogenic agent in the PILO model of SE and as an antiepileptogenic agent in the kindling seizure model. The results from these experiments confirmed our preliminary results 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, NeuN and heat shock protein. The insult generated by prolonged seizure activity appeared to be too severe for SS-31 to be effective. We observed these negative results despite testing SS-31 at dose of 10mgkg. s.c., which is higher than what has been reported to be efficacious in other models. In Aim2 we tested the efficacy of SS-31 in the kindling model. In our preliminary experiments a kindling stimulus was delivered to the hippocampus of each rat and the stimulus-induced after discharge AD threshold and duration were determined. A minimum of 24hr later SS-31 10-20mgkg, s.c. n9 was administered 30min before AD testing. SS-31 had no effect on AD threshold but there was preliminary evidence that SS-31 20mgkg decreased AD duration in some animals. In this reporting period we repeated these experiments increasing the dose of SS-31 to 30mgkg, s.c. n 5. At this dose SS-31 had no effect on AD threshold or duration.