Early postinjury exercise reverses memory deficits and retards the progression of closed-head injury in mice

Mei Feng Chen, Tung Yi Huang, Yu Min Kuo, Lung Yu, Hsiun ing Chen, Chauying J. Jen

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Closed-head injury (CHI) usually involves both physical damage of neurons and neuroinflammation. Although exercise promotes neuronal repair and suppresses neuroinflammation, CHI patients currently often remain resting during the post-traumatic period. This study aimed to investigate whether and how postinjury exercise benefited the brain structure and function in mice after CHI. Closed-head injury immediately caused an elevated neurological severity score, with rapid loss of object recognition memory, followed by progressive location-dependent brain damage (neuronal loss and activation of microglia in the cortex and hippocampus). An early exercise protocol at moderate intensity (starting 2 days postimpact and lasting for 7 or 14 days) effectively restored the object recognition memory and prevented the progressive neuronal loss and activation of microglia. However, if the exercise started 9 days postimpact, it was unable to recover recognition memory deficits. In parallel, early exercise intervention drastically promoted neurite regeneration, while late exercise intervention was much less effective. We also tested the possible involvement of brain-derived neurotrophic factor (BDNF) and mitogen-activated protein kinase phosphatase-1 (MKP-1) in the exercise-induced beneficial effects. Exercise gradually restored the impact-abolished hippocampal expression of BDNF and MPK-1, while oral administration of triptolide (a synthesis inhibitor of MKP-1 and an antagonist of nuclear factor-κB) before each bout of exercise blocked the restorative effects of exercise on MKP-1 and recognition memory, as well as the exercise-induced retardation of neuronal loss. Although triptolide treatment alone inhibited activation of microglia and maintained neuronal numbers, it did not recover the injury-hampered recognition memory. Overall, moderate exercise shortly after CHI reversed the deficits in recognition memory and prevented the progression of brain injury.

Original languageEnglish
Pages (from-to)985-1000
Number of pages16
JournalJournal of Physiology
Issue number4
Publication statusPublished - 2013 Feb

All Science Journal Classification (ASJC) codes

  • Physiology


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