Recovery of Stress Response Coincides with Responsiveness to Voluntary Exercise after Traumatic Brain Injury

Abstract

We have recently shown that there is a heightened stress response after a mild traumatic brain injury (TBI) during the first 2 post-injury weeks. This corresponds to the same post-injury period when exercise does not increase brain-derived neurotrophic factor (BDNF) and autonomic dysfunction becomes evident with exercise. Here we determined stress and autonomic responses to voluntary and forced exercise at a post-injury time window when exercise has been found to elicit beneficial effects. Rats underwent a mild fluid percussion injury and were exercised at post-injury days 28-32 and 35-39. Cardiac and temperature autonomic function were evaluated. Hippocampal tissue was obtained immediately after exercise for analysis of BDNF. In contrast to the sub-acute period, corticosterone and adrenocorticotropic hormone responses to exercise were normalized in the TBI group. Irrespective of injury, forced exercise markedly stimulated the corticotrophic axis and did not increase BDNF. BDNF levels were increased with voluntary exercise in all animals. Rats exposed to forced exercise had lower activity levels during periods of non-exercise. This effect was more pronounced in the TBI rats. Cardiac and temperature autonomic responses to delayed exercise also recuperated. Rats with TBI that underwent forced exercise, however, had higher core body temperatures during experimental manipulations, thus suggesting that exposure to a potent stressor facilitates responsiveness to environmental stimulations.

Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia

“…It has also been shown that forced and voluntary exercise can have different effects on inflammatory response, where forced exercise increases and voluntary exercise decreases levels of pro-inflammatory cytokines after injury in mice (Cook et al., 2013). Moreover, it has been shown that voluntary running leads to higher levels of BDNF compared to forced running (Uysal et al, 2015, Griesbach et al, 2014). However, there are also studies comparing the effect of forced versus voluntary running showing that both regimens can be of equal beneficial effect when it comes to improving cognition, neuronal survival and BDNF levels in different models of brain injury (Lin et al, 2015a, Lin et al, 2015b).…”

A Physiological Approach to Prolonged Recovery From Sport-Related Concussion

“…Rats forced to exercise after concussion markedly stimulated the corticotrophic axis and did not increase BDNF, whereas BDNF levels increased after voluntary exercise. 69,85 Thus, the motivation for exercise appears to be important after concussion, and exercise regimens with strong stress responses (ie, forced exercise) are not beneficial shortly after concussion.…”

Active Rehabilitation of Concussion and Post-concussion Syndrome

“…Rats forced to exercise 28 to 32 days and 35 to 39 days after mTBI markedly stimulated the corticotropic axis and did not increase brain-derived neurotrophic factor (BDNF), which is involved in neuron repair after injury, whereas BDNF levels increased following voluntary exercise. 45 …”