Metformin attenuates sepsis-induced neuronal injury and cognitive impairment

Abstract

Background Sepsis is considered to be a high-risk factor for cognitive impairment in the brain. The purpose of our study is to explore whether sepsis causes cognitive impairment and try to evaluate the underlying mechanisms and intervention measures. Methods Here, we used cecum ligation and puncture (CLP) to simulate sepsis. Open field, Novel Objective Recognition, and Morris Water Maze Test were used to detect cognitive function, long-term potentiation was used to assess of synaptic plasticity, and molecular biological technics were used to assess synaptic proteins, ELISA kits were used to detect inflammatory factors. Metformin was injected into the lateral ventricle of SD rats, and we evaluated whether metformin alleviated CLP-mediated cognitive impairment using behavioral, electrophysiological and molecular biological technology experiments. Results Here we report hippocampal-dependent cognitive deficits and synaptic dysfunction induced by the CLP, accompanied by a significant increase in inflammatory factors. At the same time, metformin was able to improve cognitive impairment induced by CLP in adult male rats. Conclusion These findings highlight a novel pathogenic mechanism of sepsis-related cognitive impairment through activation of inflammatory factors, and these are blocked by metformin to attenuate sepsis-induced neuronal injury and cognitive impairment.

Metformin Alleviates Sepsis-associated Myocardial Injury by Enhancing AMPK/mTOR Signaling Pathway-mediated Autophagy

“…21 In addition, metformin is known to exert a therapeutic effect on sepsis. Metformin appears to be a treatment option for postsepsis immunosuppression, 22 septic brain injury, 23 and sepsis-associated liver injury 24 ; therefore, metformin could be a useful agent against sepsis-related organ damage as well. 25 Various mechanisms, including oxidative stress, are involved in sepsis.…”

Inflammation associated with sepsis and correlation with neural and cognitive disorders

“…No presente estudo foi identificado concentrações muito altas de citocinas, em contrapartida não foi encontrado aumento de proteínas especificas do cérebro e nem danos cognitivos. Tal resultado obtido contradiz resultados de outros estudos que correlacionam danos cognitivos desenvolvidos após a sepse (CHUNG et al, 2020;MAZERAUD et al, 2020;GOTZ et al, 2014;ANDONEGUI et al, 2018;QIN et al, 2021).…”

“…Conforme evidenciado nos artigos encontrados a sepse a longo prazo pode desencadear danos cognitivos Qin et al (2021),. usaram a ligadura e punção de ceco (CLP) para simular a sepse.…”

The biological alterations of synapse/synapse formation in sepsis-associated encephalopathy

“…Thus, inhibition of synaptic plasticity can affect learning and memory function. Investigators observed that presynaptic proteins synapsin (SYN), synaptophysin (SYP), postsynaptic density protein 95 (PSD 95), and N-methyl-D-aspartate receptor subunit 2B (NR2B), Amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor subunit (GluR1) were downregulated, and hippocampal LTP inhibition in SAE animals (Zong et al, 2019b;Qin et al, 2021). Lin et al found that microglia activation and…”