On the Role of PDE4D in Cerebral Ischemia

In a clinical study conducted a decade ago, it was proposed that different versions of the gene encoding phosphodiesterase 4D, cAMP-specific (pde4d) confer different risks for ischemic stroke. Today, however, there continues to be unresolved global discussion of this issue. This short review summarizes the results of clinical genomic and basic research studies. In the acute phase following experimentally-induced stroke, the microvascular expression of PDE4D is increased in association with increased bloodbrain-barrier (BBB) permeability and neuronal death. Treatment with PDE4 inhibitors ameliorates BBB dysfunction and reduces cerebral ischemic damage. Accordingly, experimental approaches using Pde4d knock-out animals for addressing the role of PDE4D in cerebral ischemia are logical next steps. The results of such studies may determine whether or not enhanced PDE4D expression after cerebral ischemia exacerbates stroke outcome and, thus, may provide at least partial resolution to this issue. More importantly, such an approach may provide enhanced opportunities in the search for stroke therapies.