Adult Neurogenesis Following Ischemic Stroke and Implications for Cell-Based Therapeutic Approaches.

Abstract

Ischemic stroke is one of the most intractable diseases of the central nervous system and is also a major cause of mortality and disability in adult humans. Unfortunately, current therapies target vessel recanalization, which has a narrow treatment window, and the potential adverse effects lead to a low rate of clinical employment; in addition, neuroprotective strategies are not effective for stroke treatment. It is necessary to discover new approaches to develop neuroprotective, neuroregenerative treatment strategies for stroke. At present, accumulating evidence suggests that adult neurogenesis is a novel topic with extensive research on its potential to be harnessed for therapy in various neurologic disorders, and the neurogenesis capacity in the subventricular zone was shown to be increased in response to brain ischemic stroke. In this review, we describe the cellular and molecular mechanisms underlying potential adult neurogenesis and review current preclinical and clinical cell-based therapies for enhancing neural regeneration after adult ischemic stroke. Although stroke-induced neurogenesis in humans does not seem to translate to neurofunctional recovery, we also summarize factors of potential treatment strategies with transplanted cells, including transplantation time, cell dosage, and administration route, to achieve optimum and effective cell-based therapy, thereby harnessing this neuroregenerative response to improve neurofunctional recovery after ischemic stroke.