Stroke is the second most common single cause of death worldwide, with over five million deaths per year globally. So far, conventional therapy has failed to restore neurological function poststroke. Neurorestorative strategy has provided therapeutic benefit for the treatment of stroke. This review outlines the clinical advances, in which cell-based neurorestorative strategies offer the broadest range of potential treatments for stroke.
Stroke is identified by the sudden occurrence of a nonconvulsive, focal neurologic deficit.1 Among all the neurologic diseases of adult life, stroke ranks first in frequency and impact on disability. Stroke, after ischemic heart disease, is the second commonest single cause of death worldwide, with over five million deaths per year globally. The US Census Bureau has forecasted the distribution of incident stroke cases for the years 2010–2050. Over these 40 years, the number of incident strokes is expected to more than double, with the majority of the increase among the elderly (age .75 years) and minority groups (particularly Hispanics).2
Cerebral infarction basically comprises two pathophysiologic processes: 1) a loss in the supply of oxygen and glucose secondary to vascular occlusions and 2) an array of changes in cellular metabolism as a consequence of the collapse of energy-producing processes, with damage to cell membranes. Of potential therapeutic importance are the observations that some of the cellular processes leading to neuronal death are not irrevocable and may be reversed by early intervention, either restoration of blood flow or prevention of the influx of calcium into the cell. In the early stage, the most important therapy that can be taken into consideration is thrombolysis with tissue plasminogen activator, which is now a well-established treatment for acute ischemic stroke and is associated with significant improvements in outcomes.3 Unfortunately, the time window of 4.5 hours is its limitation. Other therapies for stroke are vascular revascularization and secondary prevention strategies. Vascular revascularization includes carotid endarterectomy and stenting. Secondary prevention strategies are mainly for hypertension, heart disease, atrial fibrillation, diabetes mellitus, cigarette smoking, hyperlipidemia, and antiplatelet, statin, and anticoagulant treatment. Together with the primary prevention concept for stroke, the main purpose of current therapies for stroke patients is to prevent stroke event other than to restore neurological impairment caused by the stroke.
However, when a stroke event really happens after all the possible treatments mentioned above, what can we do for the brain tissue lesion and how can we restore the functional impairment left by stroke? At first, neuroprotection is the important direction with a purpose to save the dying neuron with no encouraging results. Recently, a trend of switching from neuroprotectant toward neurorestorative approaches has been set on the fact that cerebral plasticity and neurological recovery can be stimulated in the post-acute ischemic brain. Neurorestorative processes include neurogenesis, angiogenesis, and synaptic plasticity, which have been shown to be beneficial for the functional improvement after stroke. In general, neurorestorative therapy includes pharmacological, cell-based, and neuromodulating therapy.4 In this review, we outline the clinical neurorestorative strategies with emphasis on cell-based therapy as a promising option for stroke.
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