Ischemic stroke is a leading cause of long-term motor disabilities. Other than tissue type plasminogen activator, there is no effective treatment for stroke and patients must rely on rehabilitation therapy to optimize recovery. Currently, there is increased emphasis on methods that intensify rehabilitation such as treadmill exercise with and without body Everolimus support. However, the biochemical mechanisms that underlie the benefits of exercise on the brain are still to be completely elucidated. It is clear that uncovering these mechanisms could lead to the optimization of exercise paradigms for the treatment of stroke. Animal research can directly examine the cellular and molecular cascades that are triggered by exercise. Brain-Derived Neurotrophic Factor is central to many facets of adult brain function including synaptogenesis, neurogenesis, vasculogenesis and activity-dependent plasticity. It is present in high amount in neurons of the central nervous system where it is initially synthesized as a precursor protein that is subsequently cleaved into proBDNF and mature BDNF. Once released, mBDNF activates TrkB receptors, thereby impacting positively brain function. BDNF has emerged as the main chemical translator of the neurophysiological effects of exercise on the intact brain. However, the crucial role of BDNF was identified from studies that have used free access to a running wheel during the animal’s dark cycle as a model of voluntary exercise. In contrast, the most popular form of exercise used in stroke patients is treadmill exercise, a form of forced exercise. As voluntary and forced exercises are not equivalent for their effect on brain and behavior, the possibility that these two forms of exercise may act through distinct pathways cannot be excluded. In addition, whether a given exercise paradigm impacts brain functioning through the same biochemical mechanisms in intact versus stroke brain has never been explored. Furthermore, despite increasing clinical evidence that task-repetitive training can induce adaptive neuroplasticity in the cortex, most studies on BDNF after exercise have focused on the hippocampus, a region which is however more involved in learning/memory than in motor function. The present study was designed to investigate the regional effect of treadmill exercise on brain BDNF in intact and stroke brains. For this purpose, a 7 day-long treadmill walk was induced in rats with or without ischemic stroke. Infarction was induced to the motor cortex by the photothrombotic ischemic stroke model that results in a lesion reproducible in volume and localization, and exercise was started after complete infarct maturation. The day SCH772984 942183-80-4 following the last boot of exercise, the levels of mBDNF and proBDNF in different brain regions including the lesion, the surrounding cortical areas, the hippocampus and the striatum were assessed using Western blotting analysis. Histological experiments were performed to investigate cellular BDNF localization and lesion volume. Synaptophysin was used as a marker of BDNF-dependent plasticity. Using a model of cortical ischemic stroke, the present study is the first to compare the effects of treadmill exercise on the levels of mature BDNF and its precursor proBDNF in control versus stroke brain.