Neuroprotective effects of combined trimetazidine and progesterone on cerebral reperfusion injury

Cerebral ischemia-reperfusion injury induces multi-dimensional damage to neuronal cells through exacerbation of critical protective mechanisms.Targeting more than one mechanism simultaneously namely, inflammatory responses and metabolic energy homeostasis could provide additional benefits to restrict or manage cerebral injury. Being proven neuroprotective agents both, progesterone (PG) and trimetazidine (TMZ) has the potential to add on the individual therapeutic outcomes.We hypothesized the simultaneous administration of PG and TMZ could complement each other to synergize, or at least enhance neuroprotection in reperfusion injury. We investigated the combination of PG and TMZ on middle cerebral artery occlusion (MCAO) induced cerebral reperfusion injury in rats. Molecular docking on targets of energy homeostasis and apoptosis assessed the initial viability of PG and TMZ for neuroprotection. Animal experimentation with MCA induced ischemia-reperfusion (I/R) injury in rats was performed on five randomized groups.Sham operated control group received vehicle (saline) while the other four I-R groups were pre-treated with vehicle (saline), PG (8 ​mg/kg), TMZ treated (25 ​mg/kg), and PG ​+ ​TMZ (8 and 25 ​mg/kg) for 7 days by intraperitoneal route. Neurological deficit, infarct volume, and oxidative stress were evaluated to assess the extent of injury in rats. Inflammatory reactivity and apoptotic activity were determined with alterations in myeloperoxidase (MPO) activity, blood-brain barrier (BBB) permeability, and DNA fragments. Reperfusion injury inflicted cerebral infarct, neurological deficit, and shattered BBB integrity.The combination treatment of PG and TMZ restricted cellular damage indicated by significant (p ​< ​0.05) decrease in infarct volume and improvement in free radical scavenging ability (SOD activity and GSH level). MPO activity and LPO decreased which contributed in improved BBB integrity in treated rats. We speculate that inhibition of inflammatory and optimum energy utilization would critically contribute to observed neuroprotection with combined PG and TMZ treatment. Further exploration of this neuroprotective approach for post-recovery cognitive improvement is worth investigating

Abstracts of National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020

This book presents the abstracts of the papers presented to the Online National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020 (RDMPMC-2020) held on 26th and 27th August 2020 organized by the Department of Metallurgical and Materials Science in Association with the Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, India. Conference Title: National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020Conference Acronym: RDMPMC-2020Conference Date: 26–27 August 2020Conference Location: Online (Virtual Mode)Conference Organizer: Department of Metallurgical and Materials Engineering, National Institute of Technology JamshedpurCo-organizer: Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, IndiaConference Sponsor: TEQIP-