EFFECTS OF PRE-INJURY PHYSICAL EXERCISE ON PLASMA MYOKINE LEVELS BEFORE AND AFTER A TRAUMATIC BRAIN INJURY IN LATE MIDDLE-AGED MALE AND FEMALE RATS

Myokines are muscle-secreted growth factors and cytokines that mediate some of the neuroprotective and neuroplastic effects of physical exercise on the brain. Little is known, however, about the myokine response to exercise in healthy and brain injured aging animals. We examined the effects of 4 weeks voluntary wheel running on myokine levels before and after a traumatic brain injury (TBI) in late middle-aged male and female rats. Levels of brain-derived neurotrophic factor (BDNF), fibroblast growth factor-21 (FGF-21), irisin, and insulin growth factor 1 (IGF-1) were measured in plasma before and after the exercise intervention, and at 24 h and 3 weeks after a controlled cortical impact model of TBI. Females showed a considerably higher amount of running behavior than males. Sex differences were also found in pre-exercise BDNF, irisin and IGF-1 levels and in myokine response to exercise. Thus, female (but not male) exercising rats had reduced BDNF, irisin and IGF-1 levels at the end of the intervention, compared to sedentary animals. After TBI, pre-injury exercise was associated with increased levels of BDNF and irisin 24 h post-injury in both sexes, and to increased levels of IGF-1 only in males. Meanwhile, levels of irisin and FGF-21 decreased 3 weeks after TBI in all groups. These data indicate that late middle-aged rats present sex differences in the basal levels of myokines and in myokine release after exercise and at the acute stage of TBI, presumably related to differences in amount of exercise.