The potential therapeutic effect of phosphodiesterase 5 inhibitors in the acute ischemic stroke (AIS)

Abstract

AbstractAcute ischemic stroke (AIS) is a focal neurological disorder that accounts for 85% of all stroke types, due to occlusion of cerebral arteries by thrombosis and emboli. AIS is also developed due to cerebral hemodynamic abnormality. AIS is associated with the development of neuroinflammation which increases the severity of AIS. Phosphodiesterase enzyme (PDEs) inhibitors have neuro-restorative and neuroprotective effects against the development of AIS through modulation of the cerebral cyclic adenosine monophosphate (cAMP)/cyclic guanosine monophosphate (cGMP)/nitric oxide (NO) pathway. PDE5 inhibitors through mitigation of neuroinflammation may decrease the risk of long-term AIS-induced complications. PDE5 inhibitors may affect the hemodynamic properties and coagulation pathway which are associated with thrombotic complications in AIS. PDE5 inhibitors reduce activation of the pro-coagulant pathway and improve the microcirculatory level in patients with hemodynamic disturbances in AIS. PDE5 inhibitors mainly tadalafil and sildenafil improve clinical outcomes in AIS patients through the regulation of cerebral perfusion and cerebral blood flow (CBF). PDE5 inhibitors reduced thrombomodulin, P-selectin, and tissue plasminogen activator. Herein, PDE5 inhibitors may reduce activation of the pro-coagulant pathway and improve the microcirculatory level in patients with hemodynamic disturbances in AIS. In conclusion, PDE5 inhibitors may have potential roles in the management of AIS through modulation of CBF, cAMP/cGMP/NO pathway, neuroinflammation, and inflammatory signaling pathways. Preclinical and clinical studies are recommended in this regard. Graphical abstract