The structural underpinning responsible for neuroplasticity and neurorestoration under physiological and pathophysiological conditions is only beginning to be elucidated. It is evident that life-long neurogenesis occurs in the human brain, with experimental data supporting its upregulation following an insult (eg, stroke) and/or in response to pharmacological therapy. Sildenafil, a PDE5 inhibitor currently marketed for the treatment of erectile dysfunction, enhances neurorestoration in rat models of stroke, as measured by neurogenesis, synaptogenesis and angiogenesis. This neurorestorative effect is associated with improved outcome despite no observed effect on brain infarct size. This neurorestorative effect has also been observed in both young and old animals, and is demonstrable even if therapy is initiated 1 week post-stroke. The extended therapeutic window and novel mechanism of action of neurorestorative therapies, such as sildenafil, warrant further investigation for the treatment of stroke.
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