|
Schwartz G, Fehlings, MG
Division of Cell and Molecular Biology
The Toronto Western Research Institute
Ontario, Canada
Object:
Persistent activation of voltage-sensitive Na+ channels is associated with cellular toxicity and may contribute to the degeneration of neural tissue following traumatic brain and spinal cord injury (SCI). Pharmacologic blockade of these channels can attenuate second pathophysiology and reduce functional deficits acutely.
Methods:
To determine the therapeutic effects of Na+ channel blockers on long-term tissue sparing and functional neurological recovery after traumatic SCI, the authors injected Wistar rats intraperitoneally with riluzole (5mg/kg), Phenytoin (30 mg/kg), CNS5546A, a novel Na+ channel block (15 mg/kg), or vehicle (2-HP3CD; 5mg/kg) 15 minutes after induction of compressive SCI at C7-T1. Functional neurological recovery of coordinated hindlimb function and strength, assessed one week postinjury and weekly thereafter for six weeks, was significantly enhanced in animals treated with riluzole compared with other treatment groups. Seven weeks postinjury the preservation of residual tissue and integrity of descending axons were determined with digital morphometrical and fluorescent histochemical analysis. All three Na+ channel blockers significantly enhanced residual tissue area at the injury epicenter compared with control. Riluzole significantly reduced tissue loss in rostrocaudal regions surrounding the epicenter, with overall sparing of gray matter and selective sparing of white matter. Also, counts of red nuclei neurons retrogradely labeled with fluorogold introduced caudal to the injury site were significantly increased in the riluzole group. Conclusions:
Systemic Na+ channel blockers, in particular riluzole, can confer significant neuroprotection after in vivo SCI and result in behaviorial recovery and sparing of both gray and white matter.
|
