Jefferson R Wilson1, Michael G Fehlings2. 1. Department of Surgery, Division of Neurosurgery and Spinal Program, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada. 2. Department of Surgery, Division of Neurosurgery and Spinal Program, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada. Electronic address: Michael.Fehlings@uhn.on.ca.
Abstract
BACKGROUND: Over the years, understanding of the specific secondary injury mechanisms that follow traumatic spinal cord injury (SCI) has improved. These pathologic mechanisms collectively serve to increase the extent of neural tissue injury, reducing prospects for neurologic recovery. An enhanced understanding of the pathobiology of SCI has permitted investigation of therapies targeting specific elements of this pathologic cascade. It is now known that the continuous posttraumatic activation of neuronal voltage-gated sodium ion channels leads to increased rates of cell death through the development of cellular swelling, acidosis, and glutaminergic excitotoxicity. The objective herein is to provide an update regarding the current status of the potential neuroprotective drug riluzole in the treatment of traumatic SCI. METHODS: Narrative review and summary paper. RESULTS: Riluzole is a sodium channel-blocking benzothiazole anticonvulsant drug that is approved by the U.S. Food and Drug Administration for the treatment of amyotrophic lateral sclerosis and has shown efficacy in preclinical models of SCI in reducing the extent of sodium and glutamate mediated secondary injury. This drug is currently under early stages of clinical investigation in SCI and shows promise as an acute neuroprotective therapy in this context. CONCLUSION: This article reviews the biologic rationale, existing preclinical evidence, and emerging clinical data for riluzole in the treatment of traumatic SCI.
BACKGROUND: Over the years, understanding of the specific secondary injury mechanisms that follow traumatic spinal cord injury (SCI) has improved. These pathologic mechanisms collectively serve to increase the extent of neural tissue injury, reducing prospects for neurologic recovery. An enhanced understanding of the pathobiology of SCI has permitted investigation of therapies targeting specific elements of this pathologic cascade. It is now known that the continuous posttraumatic activation of neuronal voltage-gated sodium ion channels leads to increased rates of cell death through the development of cellular swelling, acidosis, and glutaminergic excitotoxicity. The objective herein is to provide an update regarding the current status of the potential neuroprotective drug riluzole in the treatment of traumatic SCI. METHODS: Narrative review and summary paper. RESULTS:Riluzole is a sodium channel-blocking benzothiazole anticonvulsant drug that is approved by the U.S. Food and Drug Administration for the treatment of amyotrophic lateral sclerosis and has shown efficacy in preclinical models of SCI in reducing the extent of sodium and glutamate mediated secondary injury. This drug is currently under early stages of clinical investigation in SCI and shows promise as an acute neuroprotective therapy in this context. CONCLUSION: This article reviews the biologic rationale, existing preclinical evidence, and emerging clinical data for riluzole in the treatment of traumatic SCI.
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