Secondary injury mechanisms of spinal cord trauma: a novel therapeutic approach for the management of secondary pathophysiology with the sodium channel blocker riluzole.
Traumatic spinal cord injury is a consequence of a primary mechanical insult and a sequence of progressive secondary pathophysiological events that confound efforts to mitigate neurological deficits. Pharmacotherapy aimed at reducing the secondary injury is limited by a narrow therapeutic window. Thus, novel drug strategies must target early pathological mechanisms in order to realize the promise of efficacy for this form of neurotrauma. Research has shown that an accumulation of intracellular sodium as a result of trauma-induced perturbation of voltage-sensitive sodium channel activity is a key early mechanism in the secondary injury cascade. As such, voltage-sensitive sodium channels are an important therapeutic target for the treatment of spinal cord trauma. This review describes the evolution of acute spinal cord injury and provides a rationale for the clinical utility of sodium channel blockers, particularly riluzole, in the management of spinal cord trauma.
Schwartz
Gwen
G
Toronto Western Research Institute, Division of Cell and Molecular Biology, Division of Neurosurgery, University of Toronto, Toronto, Canada.
Fehlings
Michael G
MG
D000818:Animals; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019782:Riluzole / Q000627:therapeutic use*; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*
D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D019782:Riluzole