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

Abstract

Key points• Exercise benefits the brain in many ways, e.g. promoting neuron repair and inhibiting neuroinflammation. However, current clinical practices often advise patients suffering head injury to rest during the post-traumatic period.• This study used a mouse model to investigate whether and how exercise retarded the brain structural and functional losses induced by a head impact.• An early moderate-exercise protocol (starting 2 days postimpact and lasting for 7 or 14 days) reversed the impact-induced rapid loss of recognition memory and prevented most of the delayed neuronal loss and neuroinflammation.• However, the same exercise protocol started 9 days postimpact was unable to restore deficits in the recognition memory, even though it still retarded the late-phase neuroinflammation.• These beneficial effects of exercise were probably mediated by the timely recovery of neurotrophic factors (brain-derived neurotrophic factor and mitogen-activated protein kinase phosphatase-1) in the injured brain.Abstract 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

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

“…Additionally, both diet and exercise has been proven to be an effective remediation technique following TBI (Griesbach et al, 2009; Wu et al, 2011; Ying et al, 2012; Tyagi et al, 2013). Increased exercise in rodents within 2 days after injury improved cognitive deficits associated with object recognition memory (Chen et al, 2012) while an exercise regimen 3 months after injury improved working memory (Piao et al, 2013). Similarly, environmental enrichment has also been shown to improve both recovery and cognition in male and female rats (Matter et al, 2011; Cheng et al, 2012; Monaco et al, 2013).…”

Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation

“…In this study, exercise seems to influence microglia through increased expression of CX3CL1, which confers on microglia the ability to up-regulate NPC proliferation. In other studies, exercise in animals was found to decrease age-related basal microglial proliferation (Kohman et al, 2012), and to lower microglial activation in models of hypoxia (Lin et al, 2012), high-fat diet (Yi et al, 2012), tau overexpression (Leem et al, 2011), and closed-head injury (Chen et al, 2012), further supporting the notion that exercise can play a role in deactivating and de-priming microglia. The molecular mechanisms underlying how exercise mediates these effects will be a fascinating area for future study, and may discover agents that can elicit exercise-induced effects without the need for actual exercise.…”

The neuropathology of sport

“…Treadmill exercise also improves hippocampus-dependent spatial learning and memory as well as aversive memory [2, 3, 25, 97, 112, 174, 186, 187]. Furthermore, in rodent models, BDNF, insulin– like growth factor 1 (IGF-1), mitogen-activated protein kinase phosphatase-1 (MKP-1), and glial-derived neurotrophic factor (GDNP) are elevated by exercise [1, 53, 179] and early post-injury exercise has been shown to reverse memory deficits and inhibit the progression of neurodegeneration following TBI [27]. …”