Aggravating effects of treadmill exercises during the early-onset period in a rat traumatic brain injury model: When should rehabilitation exercises be initiated?

[Display omitted] •A traumatic brain injury model was prepared in rats by stab wounding.•Rats were forced to walk slowly on a treadmill once for 10min at 24h or 48h after wounding.•Exercise, particularly at 24h, aggravated motor impairment while increasing the expression of proinflammatory factors.•Exercise for rehabilitation should be initiated after 48h of severe brain injury onset. Physical exercise is one of the best interventions for improving traumatic brain injury (TBI) outcomes. However, an argument has been raised regarding the timing at which physical exercise should be initiated. In this study, male Wistar rats were subjected to stab wounding of the right hemisphere to develop a TBI model and were forced to walk once on a treadmill at a 5-m/min pace at 24h or 48h after TBI for 10min. Injured brain tissue was dissected after TBI to evaluate the effects of exercise. Behavioral abnormalities and motor impairment were assessed by various behavioral tests between 2 and 3 weeks after TBI. Exercise did not affect the circulating corticosterone levels and the weight of the adrenal glands. Exercise particularly that at 24h, worsened the motor impairment of the left forelimbs. Quantitative reverse-transcription polymerase chain reaction showed that exercise at 24h increased proinflammatory cytokines and chemokines on the third day while suppressing the proinflammatory reactions on the fourth day. Exercise at both time points decreased expression of transforming growth factor (TGF) β1 and its receptor TGFβR1. Exercise at 24h increased phosphorylation of IκB kinase on the fourth day, which may be correlated with the decreased effects of TGFβ1. Even a low-intensity exercise activity could cause deleterious effects when it is initiated within 48h after the onset of severe TBI, probably because of the resulting proinflammatory effects. Therefore, rehabilitation exercise programs should be initiated after 48h of TBI onset.