Metformin reduces neuroinflammation and improves cognitive functions after traumatic brain injury

TY - JOUR

T1 - Metformin reduces neuroinflammation and improves cognitive functions after traumatic brain injury

AU - DiBona, Victoria L.

AU - Shah, Mihir K.

AU - Krause, Kayla J.

AU - Zhu, Wenxin

AU - Voglewede, Mikayla M.

AU - Smith, Dana M.

AU - Crockett, David P.

AU - Zhang, Huaye

N1 - Publisher Copyright: © 2021 Elsevier B.V. and Japan Neuroscience Society

PY - 2021/11

Y1 - 2021/11

N2 - 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.

AB - 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.

KW - Metformin

KW - Microglia

KW - Neuroinflammation

KW - Par1/MARK

KW - TBI

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U2 - 10.1016/j.neures.2021.05.007

DO - 10.1016/j.neures.2021.05.007

M3 - Article

C2 - 34023358

SN - 0168-0102

VL - 172

SP - 99

EP - 109

JO - Neuroscience Research

JF - Neuroscience Research

ER -