The Effects of Exercise Pattern and Intensity on Flk-1 and Flt-1 Expression in the Hippocampus

Aerobic exercise has been found to promote brain function through the facilitation of angiogenesis: the growth of new capillaries from preexisting blood vessels. A more diverse vascular network allows for more efficient delivery of glucose and oxygen to preexisting and newly birthed neurons in the hippocampus. One of the primary regulators of angiogenesis is vascular endothelial growth factor (VEGF), which exerts its effect via binding to Flk-1 and Flt-1 receptors. Though exercise is typically considered to be beneficial, there is considerable variation in exercise paradigms employed across experiments. The intent of this study was to better characterize the difference in vascular response to various exercise models. Rats were assigned to either a voluntary of forced wheel running exercise condition, and within these condition rats exercised at either a high (1000 revolutions) or low (500 revolutions) intensity for up to 24 hours. In addition, another group of rats were allowed unlimited access to running wheels for 24 hours. These animals were compared to an inactive control group, which remained sedentary for the duration of the experiment. After completing their respective exercise regimens all animals were scarified, and brains were extracted and prepared for immunohistochemical labeling of Flk-1 and Flt-1 receptors in the hippocampus. Area fraction of Flk-1 and Flt-1 labeling was quantified using unbiased stereology. Preliminary results indicate that voluntary exercise animals in the unlimited access group expressed greater Flk-1 labeling in the CA1 region of the hippocampus compared to both high intensity forced exercise animals and inactive controls. These results suggest that animals allowed to control the duration and intensity of exercise display the most robust angiogenic response. This information has implications for the role of exercise implementation in the recovery process following traumatic brain injury and ischemic stroke