Abstract 2741: S-Nitrosoglutathione Increases Benefit of Motor Exercise on Functional Recovery and Stimulates Neurorepair Mechanisms Following Experimental Stroke in Rats
Background: Stroke is the leading cause of long-term physical disability and life-long neurologic deficits. The disability stems from acute neurovascular injury and injury-induced compromised neuroplasticity. This neuroplasticity can be restored by stimulating neurotrophic factors via two possible modalities: rehabilitation activity and neurorepair therapy. Improvement of neurologic function has been achieved following brain trauma by the neurovascular protective agent S-nitrosoglutathione (GSNO). Therefore, we investigated whether GSNO stimulates the expression neurotrophic factors and enhances the benefits of motor exercise, leading to functional recovery in a rat model of experimental stroke.
Methods: Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) for 60 min followed by reperfusion in adult male rats. Injured animals were either treated with vehicle (IR group), GSNO (0.25 mg/kg, GSNO group) or underwent rotarod exercise (EX group). In the third treatment group, GSNO was combined with rotarod exercise (GSNO+EX group). The groups were compared in terms of brain infarction, neurological score, motor function, cell death, tissue structure, and the expression of the neurotrophic factors BDNF, TrKB, and myelin.
Results: All three treated groups (GSNO, EX and GSNO+EX) showed reduced infarction, improved motor and neurological functions, and decreased apoptotic neuronal cell death compared to the IR group. However, the combination group GSNO+EX showed a trend toward greater recovery than the GSNO or EX group alone. All the three treated groups also showed enhanced expression of neurotrophic factors and improved tissue histology. A delayed intervention (24 h after IR) by GSNO also aided the functional recovery. Furthermore, the protective effect of GSNO and exercise was blunted in another set of animals by an inhibition of AKT activity using the PI3 kinase inhibitor LY 294002 compound.
Conclusion: GSNO, like exercise, aids recovery of functions in a long-term treatment by stimulating the expression of neurotrophic factors, reducing infarctions, and decreasing cell death. A combination of exercise and GSNO shows a greater degree of improvement in neurobehavioral function. Clinical relevance of the therapy is supported by an improved functional recovery even when GSNO was administered 24 h following IR. Mechanistically, the improvements by GSNO and exercise are dependent, at least in part, on AKT activity.
- © 2012 by American Heart Association, Inc.