Ephrin-Eph Signaling as a Novel Neuroprotection Path in Ischemic Stroke

The search for novel neuroprotection strategies in ischemic stroke continues, as revascularization using tissue-plasminogen activator is the only pharmacological method currently available to patients. The purpose of this review article is to summarize research findings regarding the erythropoietin-producing hepatocellular receptor pathway as an emerging novel molecular target for neuroprotection in ischemic stroke. Ephrin-Eph interactions represent a new strategy in neuroprotection. Potential therapeutic targets include the different cellular locations within the neurovascular unit (e.g. astrocytes and neurons) and the different ephrin receptor subtypes. In particular, ephrin-B2/EphB4 receptor stimulation seems to exert neuroprotective effects, while stimulation of other ligands/receptors results in deleterious effects, during the post-ischemic stroke recovery phase. Neuroprotection, assessed by either a decrease in neurovascular unit injury markers or improvement in motor function tests, can be achieved by modulating the activity of different ephrin-Eph receptor subtypes. These novel molecular targets provide multiple potential neuroprotective therapeutic benefits, with meaningful clinical outcomes.