ABSTRACT
Stroke is one of the most common causes of death and severe disability in adults of developed countries,1 accounting for a large proportion of health care costs. About 200 per 100,000 adults per year will have their first stroke. Because the incidence of stroke increases with age, the absolute number of patients with stroke is likely to increase even further, given that the population of aged adults is also increasing.2,3 However, ischemic brain injury does not only affect the adult population, it is a major cause of mortality and severe neurodevelopmental disability (cerebral palsy, mental retardation, epilepsy, neurological handicap, and learning disability) in the pediatric, especially the newborn, population.4,5 Although the etiologies of hypoxic-ischemic (HI) brain injury in adults and children may differ, much of the pathophysiology
underlying neural cell death and dysfunction is quite similar. In the case of newborn infants, despite advances in perinatal monitoring, obstetric and neonatal care, and a deeper understanding of the pathophysiology of perinatal asphyxia, the incidence of hypoxic-ischemic encephalopathy (HIE) in neonates has remained essentially unchanged over the last few decades. Except for thrombolysis therapy for acute stroke in the adult, current clinical management of both adult stroke and perinatal HIE has been limited to supportive measures; it is not directed toward preventing or interrupting the processes underlying brain injury or promoting regeneration.1,4,5 Given the absence of effective therapies for stroke and perinatal HIE, it is important to derive new strategies. There has been an intense search recently for new approaches that might be rooted in the growing knowledge of the molecular mechanisms that mediate neural cell death and degeneration. Unfortunately, despite recent substantial research in neuroprotection, to date, no neuroprotective agents have been shown conclusively to be clinically effective.1,5-8
Recently, there has been a growing interest in the therapeutic potential of neural stem cells (NSCs) and progenitors for therapy in stroke, HIE, and other central nervous system (CNS) dysfunctions. NSCs are the primordial, multipotent, self-renewing cells that, during the earliest stages of development, are believed to give rise to the vast array of specialized cells of the nervous system. They are thought to persist all throughout life, not only in a few discrete regions but probably throughout the brain, serving homeostatic and perhaps self-repair functions. The growing interest in NSC biology, as it might apply to HIE and stroke, represents a somewhat different focus on CNS injury. While most strategies under investigation seek to short-circuit cell death and/or promote neuroprotection — i.e., to combat progression of neuropathological processes, stem cell biology shines the spotlight instead on a nonpathological process — i.e., on reinvoking developmental processes for purposes of regeneration. In other words, a putative stem cell-mediated strategy would be rooted not so much in “combating” pathology as in abetting natural self-repair processes postulated — at least based on data emerging from our lab — to exist in the CNS in response to a wide range of injury and degenerative processes.
