08:22pm Saturday 19 August 2017

Therapy Combining Exercise and Neuroprotective Agent Shows Promise for Stroke Victims

In a study published in the current issue of Restorative Neurology and Neuroscience scientists report that a therapy combining exercise with the neurovascular protective agent S-nitrosoglutathione (GSNO) improved recovery from stroke in a rat model. GSNO is a compound found naturally in the body and it has no known side effects or toxicity.

“In our study, GSNO or motor exercise provided neuroprotection, reduced neuronal cell death, maintained tissue structure, and aided functional recovery by stimulating the expression of neuronal repair mediators,” says lead investigator Avtar K. Singh, MD, of the Medical University of South Carolina (MUSC) and the Ralph H. Johnson VA Medical Center, Charleston.  “GSNO in combination with exercise accelerated the rate and enhanced the degree of recovery.” 

Stroke is both an acute disease and a chronic condition.  While the acute phase is associated with cell death and secondary injury, the chronic phase is characterized by insufficient neurorepair mechanisms. Most monotherapies fail because the drugs are not effective in the chronic phase.  Rehabilitation has been used to improve neurofunction in the chronic phase, but its efficacy is slow and limited.  An ideal therapy would ameliorate the injury in both phases and therefore include a combination of rehabilitation and an agent that provides both neuroprotection and repair, such as GSNO.

Dr. Singh and her colleagues from MUSC (Drs. Mushfiquddin Khan, Harutoshi Sakakima and Inderjit Singh) induced stroke in rats, which were then assigned to one of five treatment groups.  The first group received no treatment; the second group was treated with exercise; the third group with GSNO; the fourth group received both exercise and GSNO treatment; and the fifth group received a sham treatment.  In the exercise treatment, rats were required to run on a rotating rod motor unit at a constant speed for 20 minutes a day.  GSNO was administered throughout the treatment period.

Animals in each group were evaluated for neurological function, motor behavior, and locomotor function before and after the procedure.  The size of the infarct was measured.  At 7 and 14 days after stroke was induced, brain tissue samples were removed and tested. 

Administration of GSNO not only reduced brain injury but also improved neurological scores.  Exercise alone could not significantly reduce infarct volume, because the exercise started 72 hours post procedure and infarctions occur before then.  However, exercise did improve neurobehavioral functions. Combining the therapies had a synergistic effect, and provided greater functional improvement than either GSNO or exercise alone.

Analysis of the brain tissue found that GSNO accelerates the recovery of neurological and motor functions and enhances the benefit of exercise by stimulating the expression of neurotrophic factor BDNF and its receptors, which play critical roles in neurorepair processes, and by activating Akt, a protein involved in cell proliferation.  Dr. Singh and her collaborators Drs. Mushfiquddin Khan and Inderjit Singh conclude, “GSNO is an attractive candidate to be investigated in humans for neurorepair and rehabilitation following stroke.” 

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NOTES FOR EDITORS

“Stimulation of functional recovery via the mechanisms of neurorepair by S-nitrosoglutathione and motor exercise in a rat model of transient cerebral ischemia and reperfusion,” by H. Sakakima, M. Khan, T.S. Dhammu, A. Shunmugavel, Y. Yoshida, I. Singh, A.K. Singh.  Restorative Neurology and Neuroscience, 30: 5 (September 2012). DOI: 10.3233/RNN-2012-110209. Published by IOS Press online ahead of issue.

Full text of the article is available to credentialed journalists.  Contact Daphne Watrin, IOS Press, +31 20 688 3355, d.watrin@iospress.nl. Journalists wishing to interview the authors should contact Dr. Inderjit Singh at 843-792-7542 or singhi@musc.edu.

ABOUT RESTORATIVE NEUROLOGY AND NEUROSCIENCE (RNN)

An interdisciplinary journal, Restorative Neurology and Neuroscience publishes papers relating the plasticity and response of the nervous system to accidental or experimental injuries and their interventions, transplantation, neurodegenerative disorders and experimental strategies to improve regeneration or functional recovery and rehabilitation. Experimental and clinical research papers adopting fresh conceptual approaches are encouraged. The overriding criteria for publication are novelty, significant experimental or clinical relevance and interest to a multidisciplinary audience. www.iospress.nl/journal/restorative-neurology-and-neuroscience

ABOUT IOS PRESS

Commencing its publishing activities in 1987, IOS Press (www.iospress.com)serves the information needs of scientific and medical communities worldwide. IOS Press now (co-)publishes over 100 international journals and about 130 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.

IOS Press continues its rapid growth, embracing new technologies for the timely dissemination of information. All journals are available electronically and an e-book platform was launched in 2005.

Headquartered in Amsterdam with satellite offices in the USA, Germany, India and China, IOS Press has established several strategic co-publishing initiatives. Notable acquisitions included Delft University Press in 2005 and Millpress Science Publishers in 2008. 

Contact:
Daphne Watrin
IOS Press
Tel: +31 20 688 3355
Fax: +31 20 687 0019
Email: d.watrin@iospress.nl


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