BDNF is synthesized in the periphery by vascular endothelial cells, T-cells, B cells, monocytes (Kerschensteiner et al., 1999; Nakahashi et al., 2000) and skeletal muscles (Mousavi and Jasmin, 2006). Once released, BDNF can cross the BBB bi-directionally (Pan et al., 1998), resulting in a direct relationship between BDNF levels in plasma and the brain (Karege et al., 2002). While most of the BDNF that is produced peripherally is released into circulation, internalized, and stored in platelets, the BDNF produced by muscles is used locally at the neuromuscular junction (Fujimura et al., 2002; Matthews et al., 2009).