Fig 3.

The potential mechanism underlying the role of PDE4 inhibitors in neuroplasticity after stroke. Under the condition of ischemic stroke, the expression and activity of PDE4 are extensively increased in neural cells, which subsequently lead to decreased level of cAMP and the inhibition of PKA/CREB and Epac/ERK1/2 signaling pathways. cAMP/PKA/CREB pathway plays a critical role in promoting the expression of BDNF, which is a potent factor triggering neuroplasticity. Activation of Epac/ERK1/2 and cAMP/PKA/CREB pathways inhibits the expression of pro-inflammtory factors, such as IL-1β, which are viewed as negative factors delaying the process of neuroplasticity, especially at the early stage of stroke. PDE4 inhibition is supposed to enhance neuroplasticity through increasing the levels of cAMP and BDNF, and decreasing the expression of pro-inflammatory factors.