New therapeutic approaches to reduce neuronal damage in mouse model of focal ischemic injury.
Stroke is a leading cause of death and disabilities in developed countries and causes more serious long-term disabilities than any other disease. Focal ischemic injury is induced by injection of the vasoconstrictor Endothelin-1 into the striatum of mice as a preclinical model of stroke. Animals in this model, display significant long-term neurological deficits, associated with excitotoxicity, inflammatory response and oxidative stresses. My research shows two different approaches to minimize neuronal damage and improve functional outcome. First approach is peptide therapy using a DJ-1 based peptide called ND-13, that protects against glutamate toxicity, neurotoxic insults and oxidative stress. Second approach is gene therapy using lentiviruses encoding EAAT2, GDH2 and NRF2 genes. These genes act synergistically to address the effected excito-oxidative axis, thereby reducing extracellular-glutamate and glutamate availability while improving the metabolic state and the anti-oxidant response. By reducing the harmful responses after stroke and increasing neuroprotection, we can improve recovery and functional outcome.