Therapy combining exercise and neuroprotective agent shows promise for stroke victims

August 15, 2012
A: This graphic shows the events and mechanisms involved in neurorepair leading to functional recovery by post injury treatment with GSNO and exercise in a rat model of experimental stroke. B: Walking time on a rotating rod is significantly increased with time in exercise and GSNO-treated groups compared with stroke group. However, combination group (exercise+GSNO) shows improved walking time compared with GSNO or exercise group. Sham group (operated without inducing stroke) treated with saline does not show walking deficits. Credit: H. Sakakima et al.

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 provided neuroprotection, reduced , maintained tissue structure, and aided 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 . 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."

Explore further: Newly discovered cell mechanism uses amplified nitric oxide to fight C. diff

More information: “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.

Related Stories

Newly discovered cell mechanism uses amplified nitric oxide to fight C. diff

August 21, 2011
Groundbreaking research encompassing Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, has uncovered a natural defense mechanism that is capable of inactivating the toxin that ...

Hormone improves long-term recovery from stroke

May 16, 2011
Scientists at the Sahlgrenska Academy have discovered an explanation of how stroke patients can achieve better recovery. A hormone that is associated with the growth hormone system has proved to benefit recovery during the ...

Improved recovery of motor function after stroke

April 19, 2011
After the acute treatment window closes, the only effective treatment for stroke is physical/occupational therapy. Now scientists from Children's Hospital Boston report a two-pronged molecular therapy that leads to significant ...

Modifying scar tissue can potentially improve outcome in chronic stroke

May 21, 2012
New research from the Buck Institute for Research on Aging shows that modifying the scar tissue that develops following a stroke is a promising avenue for future treatments. The need for therapeutics for chronic stroke is ...

Recommended for you

Neuroscientists build case for new theory of memory formation

October 23, 2017
Learning and memory are generally thought to be composed of three major steps: encoding events into the brain network, storing the encoded information, and later retrieving it for recall.

Running on autopilot: Scientists find important new role for 'daydreaming' network

October 23, 2017
A brain network previously associated with daydreaming has been found to play an important role in allowing us to perform tasks on autopilot. Scientists at the University of Cambridge showed that far from being just 'background ...

Rhythm of memory: Inhibited neurons set the tempo for memory processes

October 23, 2017
The more we know about the billions of nerve cells in the brain, the less their interaction appears spontaneous and random. The harmony underlying the processing of memory contents has been revealed by Prof. Dr. Marlene Bartos' ...

Researchers demonstrate 'mind-reading' brain-decoding tech

October 23, 2017
Researchers have demonstrated how to decode what the human brain is seeing by using artificial intelligence to interpret fMRI scans from people watching videos, representing a sort of mind-reading technology.

Research revises our knowledge of how the brain learns to fear

October 23, 2017
Our brains wire themselves up during development according to a series of remarkable genetic programs that have evolved over millions of years. But so much of our behavior is the product of things we learn only after we emerge ...

Scientists use supercomputer to search for "memory molecules"

October 23, 2017
Until now, searching for genes related to memory capacity has been comparable to seeking out the proverbial "needle in a haystack." Scientists at the University of Basel made use of the CSCS supercomputer Piz Daint to discover ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.