32^nd European Neurology Congress

Stroke is the leading cause of disability worldwide. It immediately sets into motion various neurodegenerative mechanisms including excitotoxicity and calcium dysregulation leading to infl ammatory/nitoxidative-mediated injury mechanisms. Our studies with a rat model of ischemia and reperfusion (1/R) show that an exogenous treatment with S-nitrosoglutathione (GSNO), a multi-targeting naturally-occurring compound provides neuroprotection as well as stimulates neurorepair and aids functional recovery. Stroke was induced by middle cerebral artery occlusion for 60 min followed by reperfusion followed by drug (GSNO) treatment at various time points after reperfusion. The studies show that GSNO-mediated targeting of neuronal nitric oxide synthase/peroxynitrite/calpains and inflammatory NF-KB mechanisms provides protection against neurodegeneration during acute stroke injury. Furthermore, GSNO-mediated mechanisms also stimulated neurorepair process via targeting HIF-la/VEGF/PECAM-1 as well as BDNF/CNTF signaling pathways to promote recovery of motor and neurological functions during the chronic disease of stroke. These studies document that targeting of S-nitrosylating mechanisms is potentially attractive therapy for stroke patients. In clinical settings, GSNO is of even greater relevance to stroke therapy because it additionally shows antiplatelet, anti-embolization and vasodilatory properties in humans. Based on the efficacy of GSNO in our preclinical studies using animal models of stroke and absence of toxicity in human uses, we submit that GSNO is a promising drug candidate to be evaluated for human stroke therapy and other neurodegenerative diseases treatment.