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Updated: May 3, 2026
Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Molecular regulation of exercise training on hippocampal neuroprotection in post-traumatic brain injury: A systematic
Farhan Yousaf1, Sean Kao2, Shahid Ishaq3
1Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan.
Objective:
Traumatic brain injury (TBI) induces oxidative stress, neuroinflammation, programmed cell death, mitochondrial dysfunction, impaired neurotrophic signaling, and neurogenesis, contributing to hippocampal dysfunction. Exercise training is a promising non-pharmacological intervention with potential neuroprotective effects. This systematic review aimed to evaluate the effectiveness of exercise training on the neurobiological mechanisms and cognitive function post-TBI.
Methods:
PubMed, Embase, and Web of Science were searched up to July 2025, following the PRISMA 2020 guidelines. Of 1855 records, 44 studies involving post-TBI animals and exercise training as intervention were included. Exercise protocols varied, including voluntary wheel running, treadmill running, and swimming, with durations ranging from 7 to 94 days, and 4-7 sessions per week. The quality of included studies was appraised on the CAMARADES checklist.
Results:
Exercise training reduced hippocampal reactive oxygen species (ROS), microglial reactivity, pro-inflammatory cytokines, and caspase-3 activity, while increasing total antioxidant capacity (TAC) and anti-apoptotic markers in post-TBI rodents. It elevated PGC-1α, electron transport system activity, BDNF, TrkB, and Synapsin-1 expression, and promoted neurogenesis post-TBI. Functionally, exercise improved cognitive function, spatial learning, and memory, and reduced anxiety and depression-like behaviors in post-TBI rodents.
Conclusion:
Exercise training reduced oxidative stress, neuroinflammation, apoptosis, and enhanced mitochondrial function, neurotrophic signaling, neurogenesis, and cognitive function in post-TBI rodents. (PROSPERO: CRD420251072276).
