Intranasal Administration of PEGylated Transforming Growth Factor-α Improves Behavioral Deficits in a Chronic Stroke Model

We previously demonstrated that infusion of transforming growth factor (TGF)-α after chronic middle cerebral artery occlusion (MCAO) stimulates stem and progenitor cell proliferation, migration, and neuronal differentiation associated with the amelioration of neurologic impairment. But the use of TGF-α in humans is impeded by impracticality of intracranial infusion and the inability of intravenous TGF-α to cross the blood-brain barrier. Here we investigated whether intranasal delivery of PEGylated TGF-α (PEG-TGF-α) is a viable alternative. We found that intranasal PEG-TGF-α can also induce the proliferation of neural progenitors and their migration to the damaged striatum, and that this is associated with significant behavioral improvement in the MCAO model. This nonsurgical approach represents a potential therapeutic strategy for human patients.