Novel mechanisms to manipulate endogenous neural stem cells after stroke

Stroke remains a leading cause of death and disability in the world (775,000 in the US, 1,000,000 in Europe and 15,000 in Israel per year). A person who suffers a stroke loses 1.9 million neurons every minute if untreated. During the last decades, especially in developing countries, its morbidity and mortality keep increasing, unfortunately bringing severe social and economic burdens to patients and their families. Over the past few decades, our understanding of the pathophysiology of stroke has significantly increased and this led to the development of new clinical treatments in the acute time window. However, the fear experienced by patients and their families after the stroke is brain damage, including long-term sensorimotor and language deficits, cognitive impairment to vegetative state for which the therapeutic options are usually limited in scope.

Prof. Ronen Leker, Director of the Stroke Unit and Center at Hebrew University's Hadassah Medical Center, is working on understanding the precise mechanism of action needed to replace dead cells and rejuvenate surviving cells in order to restore brain function. If successful, this approach could give a new lease on life to hundreds of thousands of stroke survivors. The work done at the Cerebrovascular Research Laboratory focuses on harnessing the healing power of neural stem cells. These cells normally reside in our brains and are capable of producing a variety of neural cell types; however, their numbers and activity decrease with age. Endogenous neural stem cells (eNSC), cells already residing in certain sections of the brain, are activated in response to disease or trauma, constituting an innate physiological regenerative response of the brain. However, this spontaneous regeneration is not sufficient for structural or functional restoration of the injured brain. Moreover, the capacity of eNSC to compensate for lost cells is limited probably due to lack of stimulation to support their survival and differentiation. To circumvent this problem, Prof. Leker’s important research allows for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs. His research endeavor aims to manipulate these endogenous or innate-type of neural stem cells as an effective strategy to mobilize and produce new neurons and glia. In this way, he avoids the risk of treatment based on the transplantation of stem cells which harbor several disadvantages including tumor formation. Prof. Leker’s research laboratory will benefit with the use of the newly established small animal-PET/MRI at Hadassah which will allow him to visualize and monitor in vivo eNSC activation and mobilization, thus making it possible to facilitate a translation into the clinical setting. As a separate research endeavor, albeit complementary to this research, Prof. Leker is collaborating with the Department of Hematology for the use of platelets which his laboratory has shown to significantly increase the proliferation of neural stem cells and the growth of new blood vessels in the rat model coupled with a reduction in the stroke-induced behavioral deficits.

Since post stroke patients represent the leading cause of disability in adults and each year millions of stroke survivors have to adapt to a life with restrictions in activities of daily living, it is of the utmost importance to support Prof. Leker’s research endeavors which uses the brain’s already existing ability to respond when it is injured. This research has the potential, if successful, to develop novel and radical therapeutic approaches to mobilize, invigorate and increase this natural response after a stroke.

Prof. Leker also serves as Head of the Academic Department of Neurology and Neurosurgery. He has been actively involved in clinical and basic stroke research for the last fifteen years both at Hadassah and at the U.S. National Institutes of Neurological Disorders and Stroke – National Institutes of Health in Bethesda, MD, where he served as a staff scientist at the Molecular Biology Laboratory and worked on the use of neural stem cells as a novel therapy for stroke.