Thymosin beta4: a candidate for treatment of stroke?

Neurorestorative therapy is the next frontier in the treatment of stroke. An expanding body of evidence supports the theory that after stroke, certain cellular changes occur that resemble early stages of development. Increased expression of developmental proteins in the area bordering the infarct suggest an active repair or reconditioning response to ischemic injury. Neurorestorative therapy targets parenchymal cells (neurons, oligodendrocytes, astrocyes, and endothelial cells) to enhance endogenous neurogenesis, angiogenesis, axonal sprouting, and synaptogenesis to promote functional recovery. Pharmacological treatments include statins, phosphodiesterase 5 inhibitors, erythropoietin, and nitric oxide donors that have all improved functional outcome after stroke in the preclinical arena. Thymosin beta4 (Tbeta4) is expressed in both the developing and adult brain and it has been shown to stimulate vasculogenesis, angiogenesis, and arteriogenesis in the postnatal and adult murine cardiac myocardium. In this manuscript, we describe our rationale and techniques to test our hypothesis that Tbeta4 may be a candidate neurorestorative agent.