Moderate Intensity Treadmill Exercise Increases Survival of Newborn Hippocampal Neurons and Improves Neurobehavioral Outcomes after Traumatic Brain Injury

Physician-prescribed rest after traumatic brain injury (TBI) is both commonplace and an increasingly scrutinized approach to TBI treatment. Although this practice remains a standard of patient care for TBI, research of patient outcomes reveals little to no benefit of prescribed rest after TBI, and in some cases prolonged rest has been shown to interfere with patient well-being. In direct contrast to the clinical advice regarding physical activity after TBI, animal models of brain injury consistently indicate that exercise is neuroprotective and promotes recovery. Here, we assessed the effect of low and moderate intensity treadmill exercise on functional outcome and hippocampal neural proliferation after brain injury. Using the controlled cortical impact (CCI) mouse model of TBI, we show that 10 days of moderate intensity treadmill exercise initiated after CCI reduces anxiety-like behavior, improves hippocampus-dependent spatial memory, and promotes hippocampal proliferation and newborn neuronal survival. Pathophysiological measures including lesion volume and axon degeneration were not altered by exercise. Taken together, these data reveal that carefully titrated physical activity may be a safe and effective approach to promoting recovery after brain injury.