Therapeutic options to enhance poststroke recovery in aged humans

Abstract

In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. It thus appears that H2S-induced hypothermia has pleiotropic effect by: (i) reducing the metabolic rate, (ii) inducing a hibernation-like state; (iii) reducing the epileptic forms of EEG activity; and (iv) inducing a sleep-deprivation state. Therefore, recent results suggest that H2S-induced hypothermia, via targeting multiple points of intervention, could have a higher probability of success in treating stroke as compared to other monotherapies. However, the optimal conditions for therapeutic hypothermia, such as temperature, as well as the initiation and duration of cooling, must be individualized. It has been noted that the potential for neurogenesis is also preserved in aged, stroke-injured brains and the environment of the aged brain is not hostile to cell therapies. However, there are significant developmental and translational issues that remain to be resolved in future studies such as (i) understanding the differentiation into specific phenotypes. Upon transplantation, the differentiated cells often de-differentiate; (ii) tumorigenesis remains a significant concern; (iii) anti-neuroinflammatory therapies are a potential target to promote regeneration and repair in diverse injury and neurodegenerative conditions by stem cell therapy; (iv) efficacy of cell therapy can be enhanced by physical rehabilitation. We recommend that in a real clinical practice involving older poststroke patients, successful regenerative therapies would have to be carried out for a much longer time. The BM MSC therapy in aged rodents warrants further investigation including repeated administrations of therapeutic cells at several time points after stroke and using various combinations with G-CSF or other relevant growth factors/cytokines. Finally, a better understanding of potential risks of stem cell therapies in strokes shall make the translation of cell therapies safer. Likewise, awareness of may help improve their efficacy to achieve therapeutic success.