Exploring Novel Pharmacological approaches to Reveal Neuroprotective Mechanisms of Remote postconditioning

Abstract

The current study explored the pharmacological approaches to reveal newlineneuroprotective mechanisms of remote postconditioning (RIPoCo) with polycomb, newlinesonic-hedgehog and PI3K/Akt/mTOR/P70S6K Pathway. The study design consisted of newline3 cycles of 5-min occlusion/5-min release of the bilateral femoral arteries immediately newlineafter global ischemia (17 min, BCAO) followed by 24hrs reperfusion. GSK 343 (a newlineselective polycomb Inhibitor), CUR61414 (selective Shh inhibitor) and LY294002 (a newlineselective PI3K inhibitor) were administered to elucidate the role of various signaling newlinepathways in RIPoCo. Varied biochemical, behavioral parameters and histopathological newlinechanges were assessed to examine the effect of RIPoCo. Infarct size was estimated newlineusing triphenyltetrazolium chloride (TTC) staining. It was established that RIPoCo newlineabrogated the deleterious effects of IR injury expressed regarding biochemical newlineparameters of oxidative stress (TBARS, SOD, GSH, catalase), inflammatory parameter newline(TNF-and#945;, IL-6 and IL 1and#946;, MPO), learning and memory (AChE) behavioual parameters newline(motor coordination, neurological severity score (NSS), infarct size and newlinehistopathological changes. We conclude that induced neuroprotective benefits of newlineRIPoCo may be the consequence of polycomb, sonic-hedgehog and newlinePI3K/Akt/mTOR/P70S6K in all probability. This research will assist in the translation newlineof the paradigm into a clinically applicable one for use in the hospital setting. newline