RT Journal Article
SR Electronic
T1 Metformin Reduces Repeat Mild Concussive Injury Pathophysiology
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0421-21.2021
DO 10.1523/ENEURO.0421-21.2021
VO 9
IS 1
A1 Erica L. Underwood
A1 John B. Redell
A1 Mark E. Maynard
A1 Nobuhide Kobori
A1 Michael J. Hylin
A1 Kimberly N. Hood
A1 Rebecca K. West
A1 Jing Zhao
A1 Anthony N. Moore
A1 Pramod K. Dash
YR 2022
UL http://www.eneuro.org/content/9/1/ENEURO.0421-21.2021.abstract
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.