The effect of the sodium channel blocker QX-314 on recovery after acute spinal cord injury.
There is evidence that elevated intracellular sodium ([Na+]i) activity potentiates spinal cord injury (SCI) and the hypoxic/ischemic cell death. In this study, we examined the effect of QX-314, a potent Na+ channel blocker, on recovery after SCI in vivo. QX-314 (2.0 and 10 nmol) or vehicle was microinjected (2 microL) into the injury site 15 min after SCI. Injury was performed by compression of the spinal cord at C7-T1 for 1 min with a modified aneurysm clip exerting a closing force of 35 g. Neurological function was assessed 1 day after injury and weekly thereafter until 6 weeks by the inclined plane method and by the modified Tarlov technique. After 6 weeks of injury, the origin of descending axons at the injury site was determined by retrograde labeling with fluorogold (FG), and a computer-assisted morphometric assessment of the injury site was performed. There was a significant improvement in counts of retrogradely labeled neurons in the red nucleus and rostral ventrolateral medulla (RVLM) in rats treated with either 2 nM (1338 +/- 366 and 28.8 +/- 16) or 10 nM (1390 +/- 511 and 46.3 +/- 31) QX-314 as compared to vehicle (902 +/- 403 and 13.8 +/- 8). There was a trend to increased neuronal counts in the sensorimotor cortex (170.8 +/- 226.8) and vestibular nuclei (1096.2 +/- 970.2) with QX-314 (10 nM) as compared to the vehicle-treated group. There was no significant difference in the extent of neurological recovery between the control and treated groups. Our results suggest that the Na+ channel blocker QX-314 partially preserves the integrity of descending motor axons after SCI. However, in this study, the effects were insufficient to result in sustained improvements in behavioral neurological function.
Agrawal
S K
SK
Spinal Cord Injury Neurophysiology Laboratory, The Toronto Hospital Research Institute, University of Toronto, Ontario, Canada.
Fehlings
M G
MG
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013997:Time Factors
D000779:Anesthetics, Local; C012647:QX-314; D008012:Lidocaine