Exploring novel pharmacological targets to reveal neuroprotective mechanisms of postconditioning

Abstract

The current study explored the pharmacological targets to reveal newlineneuroprotective mechanisms of pharmacological postconditioning (pPoCo) with newlineCGS21680 (PubChem CID: 3086599), SF1670 (PubChem CID: 9926586), newlineResveratrol (PubChem CID: 445154) and Piclamilast (PubChem CID: 154575). newlineThe study design consisted of induction of global cerebral ischemia (17 min.) and newlinereperfusion (24 hr.). For the reperfusion intervention, pharmacological agents (i.e. newlinepPoCo) CGS21680, SF1670, Resveratrol, Piclamilast were administered 5 min. newlinebefore reperfusion of 24 hrs, to animals divided in various groups, so that the newlinepharmacological agents would be in circulation at the time of onset of reperfusion. newlineLY294002 (a selective PI3K Inhibitor), Istradefylline (selective A2A antagonist), newlineSirtinol (a selective SIRT1 inhibitor) and 666-15 (a selective CREB inhibitor) newlinewere administered to elucidate the role of various signaling pathways in pPoCo. newlineVaried biochemical, behavioral parameters and histopathological changes were newlineassessed to examine the effect of pPoCo. Infarct size was estimated using newlineTriphenyltetrazolium chloride (TTC) staining. It was established that pPoCo with newlineabove mentioned pharmacological interventions abrogated the deleterious effects newlineof IR injury expressed with regard to infarct size, behavioual parameters newline(memory, motor coordination, neurological severity score (NSS), biochemical newlineparameters of oxidative stress (TBARS, SOD, GSH, catalase, AChE), newlineinflammatory parameter (MPO) and histopathological changes. We conclude that newlineinduced neuroprotective benefits of pPoCo with CGS21680, SF1670, Resveratrol, newlinePiclamilast in all probability, may be the consequence of PI3K pathway, SIRT1 newlineand CREB activation and these agents can be considered, for further studies, as newlinepotential agent inducing pPoCo in clinical situations. newline