Metformin attenuates sepsis-induced neuronal injury and cognitive impairment

BMC Neurosci. 2021 Dec 15;22(1):78. doi: 10.1186/s12868-021-00683-8.

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.

Keywords: Cecum ligation and puncture; Cognitive impairment; Inflammatory factors; Metformin; Sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cecum / drug effects
  • Cecum / injuries
  • Cecum / metabolism
  • Cecum / pathology
  • Cognition / drug effects*
  • Cognition / physiology
  • Cognition Disorders / drug therapy
  • Cognition Disorders / metabolism
  • Cognitive Dysfunction / complications
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / physiopathology
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Ligation / adverse effects
  • Male
  • Metformin / pharmacology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / complications*
  • Sepsis / drug therapy
  • Sepsis / metabolism

Substances

  • Metformin