Neuroprotection and Anti-Epileptogenesis with Mitochondria-Targeted Antioxidant
Annual rept. 30 Sep 2013-28 Sep 2014
RESEARCH FOUNDATION FOR MENTAL HYGIENE INC STATEN ISLAND NY
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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. 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 Aim1. In these experiments adult male Sprague-Dawley rats 260-405g were pretreated with SS-31 3 or 10mgkg, sc n14 or saline n10 45min before induction of SE with Pilo 365mgkg, 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 Aim1 and initiated experiments in Aim2 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 10mgkg, 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 5mgkg, ip to 10mgkg, 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.
- Medicine and Medical Research