RETRACTED: Metformin prevents brain injury after cardiopulmonary resuscitation by inhibiting the endoplasmic reticulum stress response and activating AMPK-mediated autophagy

Abstract

Background and aims The neurological damage caused by cardiac arrest (CA) can seriously affect quality of life. We investigated the effect of metformin pretreatment on brain injury and survival in a rat CA/cardiopulmonary resuscitation (CPR) model. Methods and results After 14 days of pretreatment with metformin, rats underwent 9 minutes of asphyxia CA/CPR. Survival was evaluated 7 days after restoration of spontaneous circulation; neurological deficit scale (NDS) score was evaluated at days 1, 3, and 7. Proteins related to the endoplasmic reticulum (ER) stress response and autophagy were measured using immunoblotting. Seven-day survival was significantly improved and NDS score was significantly improved in rats pretreated with metformin. Metformin enhanced AMPK-induced autophagy activation. AMPK and autophagy inhibitors removed the metformin neuroprotective effect. Although metformin inhibited the ER stress response, its inhibitory effect was weaker than 4-PBA. Conclusion In a CA/CPR rat model, 14-day pretreatment with metformin has a neuroprotective effect. This effect is closely related to the activation of AMPK-induced autophagy and inhibition of the ER stress response. Long-term use of metformin can reduce brain damage following CA/CPR.

Resurgence of Covid-19 pandemic: Challenging situation of economics vs. healthcare

“…Although, we continue to publish articles on Covid-9 pandemic, 6 there is urgent need for us to establish a balance of continuity with publication of non-covid urgent research. Whether that is related to diagnostic test 7,8 or basic research aimed at understanding molecular aspects of drug action 9 or novel innovation in treatment. 10 All that is responsibility of any peerreviewed multidisciplinary journal such as SMJ.…”