Brain-Derived Neurotrophic Factor and Its Potential Therapeutic Role in Stroke Comorbidities

Figure 4

Summary of approaches to enhance TrkB activation and their effect on stroke treatment and recovery. Multiple strategies could be utilized to activate the TrkB receptor to serve in the treatment and recovery of stroke comorbidities. Direct approaches include the modification and improvement of BDNF for better delivery and the development of BDNF mimetic peptides, small molecule compounds, and specific agonistic antibodies. Indirect approaches include hormones, physical therapies, and natural compounds that can stimulate the endogenous expression of BDNF and gene/cell therapy to overexpress BDNF. TrkB receptor activation directly triggers and stimulates downstream signaling cascades, which subsequently protect neuronal cells and facilitate poststroke brain recovery. While the PLCγ pathway has been suggested to play a role in neuroplasticity and in cell death, the PI3K/Akt and MAPK/ERK pathways mainly protect neurons from excitotoxicity and cell death, chiefly apoptosis. The PI3K/Akt signaling is also reported to support neuronal survival under oxygen/nutrient deprivation and to contribute to neurogenesis during rehabilitation.