Metformin reduces neuroinflammation and improves cognitive functions after traumatic brain injury

Victoria L. DiBona, Mihir K. Shah, Kayla J. Krause, Wenxin Zhu, Mikayla M. Voglewede, Dana M. Smith, David P. Crockett, Huaye Zhang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Within the brain, traumatic brain injury (TBI) alters synaptic plasticity and increases neuroinflammation and neuronal death. Yet, there lacks effective TBI treatments providing pleiotropic beneficial effects on these diverse cellular processes necessary for functional recovery. Here, we show the diabetes drug, metformin, significantly improves cognitive functions after controlled cortical impact (CCI) injury in mice, showing improved spatial learning and nest building. Furthermore, injured animals treated with metformin exhibit increased ramification of microglia processes, indicating reduced neuroinflammation. Finally, metformin treatment in vitro increased neuronal activation of partitioning defective 1 (Par1), a family of Ser/Thr kinases playing a key role in synaptic plasticity and neuroinflammation. These results suggest metformin is a promising therapeutic agent for targeting multiple cellular processes necessary for functional TBI recovery.

Original languageEnglish (US)
Pages (from-to)99-109
Number of pages11
JournalNeuroscience Research
Volume172
DOIs
StatePublished - Nov 2021

All Science Journal Classification (ASJC) codes

  • General Neuroscience

Keywords

  • Metformin
  • Microglia
  • Neuroinflammation
  • Par1/MARK
  • TBI

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