NOVEL THERAPEUTIC INTERVENTIONS FOR NEUROPROTECTION IN CENTRAL AND PERIPHERAL NEUROLOGICAL DISORDERS

Abstract

Neuroprotective strategies are emerging as promising therapies for advancing disease outcomes in neurological disorders, however, with limited translational success. Despite enormous scientific efforts to address this growing challenge, there still remains a great need for novel treatment strategies. The overall goal of this thesis was to identify non-drug, non-invasive therapeutic interventions for neuroprotection and demonstrate that they are potentially clinically translatable. We targeted two critical neurological disorders (central and peripheral): Theme 1) Peripheral sensory stimulation (PSS) as adjuvant therapy for thrombolysis in hyperacute ischemia, and Theme 2) Hypothermia for preventing chemotherapy-induced peripheral neuropathy. In theme 1 we demonstrated that PSS was neuroprotective in a rat model of hyperacute ischemia and prolongs the thrombolysis time window. Our results in theme 2 established that limb hypothermia was safe, tolerable and preserved motor nerve function in breast cancer patients undergoing paclitaxel chemotherapy. Collectively, the concepts presented here suggest novel, exciting potential avenues for improving disease outcomes with compelling evidence.