PT  - JOURNAL ARTICLE
AU  - Erica L. Underwood
AU  - John B. Redell
AU  - Mark E. Maynard
AU  - Nobuhide Kobori
AU  - Michael J. Hylin
AU  - Kimberly N. Hood
AU  - Rebecca K. West
AU  - Jing Zhao
AU  - Anthony N. Moore
AU  - Pramod K. Dash
TI  - Metformin Reduces Repeat Mild Concussive Injury Pathophysiology
AID  - 10.1523/ENEURO.0421-21.2021
DP  - 2022 Jan 01
TA  - eneuro
PG  - ENEURO.0421-21.2021
VI  - 9
IP  - 1
4099  - http://www.eneuro.org/content/9/1/ENEURO.0421-21.2021.short
4100  - http://www.eneuro.org/content/9/1/ENEURO.0421-21.2021.full
SO  - eNeuro2022 Jan 01; 9
AB  - Mild traumatic brain injury (mTBI) can initiate complex pathophysiological changes in the brain. Numerous cellular and molecular mechanisms underlying these pathologic changes are altered after injury, including those involved in energy utilization, excitotoxicity, ionic disturbances, and inflammation. It is thought that targeting multiple mechanisms may be necessary to produce meaningful reductions in brain pathology and to improve outcome. Previous studies have reported that the anti-diabetic drug metformin can also affect inflammatory, cell survival, and metabolic outcomes, possibly by acting on multiple targets and/or pathways. We therefore questioned whether metformin treatment can reduce pathology after repeat mild closed head injury (rmCHI) in male C57Bl/6 mice. We found that metformin, administered acutely after each head impact, resulted in markedly reduced white matter damage, astrogliosis, loss of hippocampal parvalbumin neurons, and improved mitochondrial function. In addition, both motor and cognitive functions were significantly improved when tested after discontinuation of the treatment. These studies suggest that metformin may be beneficial as a treatment for repeat concussion.