The effect of the sodium channel blocker QX-314 on recovery after acute spinal cord injury

Sandeep K. Agrawal, Michael G. Fehlings

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

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 μL) into the injury site 15 min after SCI. Injury was performed by compression of the spinal cord at C7-T1 for I 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.

Original languageEnglish (US)
Pages (from-to)81-88
Number of pages8
JournalJournal of Neurotrauma
Volume14
Issue number2
DOIs
StatePublished - Feb 1997

Keywords

  • QX-314
  • axons
  • fluorogold
  • rat
  • red nucleus
  • rostral ventrolateral medulla
  • sodium channels

ASJC Scopus subject areas

  • Clinical Neurology

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