Role of sodium in the pathophysiology of secondary spinal cord injury.

STUDY
DESIGN: Experimental study using an in vitro model of compressive injury to isolated adult rat dorsal column axons.
OBJECTIVES: To examine the role of extracellular Na+ (Na+e) in mediating secondary injury to spinal cord axons after compressive trauma. The mechanisms of intracellular sodium entry were examined using ion substitution techniques and pharmacologic blockers. SUMMARY OF BACKGROUND DATA: There is evidence that intracellular Na+ entry potentiates hypoxic-ischemic cell death by causing cytotoxic cell swelling, intracellular acidosis, and gating of Ca++ entry through reverse activation of the Na(+)-Ca++ exchanger. In the present study, we have examined the role of Na+e in the pathophysiology of spinal cord injury.
METHODS: Dorsal column segments isolated from the thoracic cord of adult rats (n = 40) were pinned in a recording chamber and superfused with oxygenated Ringer's solution. Extracellular field potentials were recorded from glass microelectrodes (150 mmol KCl; 5-10 mol). Injury was accomplished in vitro by compression with a modified aneurysm clip (closing force, 2 g) for 15 seconds. The effect of zero Na+e (equimolar substitution with NMDG+), the Na(+)-H+ exchange blocker amiloride, the Na+ channel blocker procaine, and the Na(+)-Ca++ exchanger blocker benzamil on CAP recovery after compressive injury were assessed.
RESULTS: Pretreatment with zero Na+, amiloride and procaine conferred significant neuroprotection (P < 0.05). In contrast, the NCE blocker benzamil was ineffective in attenuation secondary injury.
CONCLUSIONS: Reduction of extracellular Na+, inhibition of the Na(+)-H+ exchanger or blockade of voltage gated Na+ channels is neuroprotective after spinal cord injury. The mechanism of Na(+)-associated cytotocity does not involve reverse gating of the Na(+)-Ca++ exchanger.