Role of sodium in the pathophysiology of secondary spinal cord injury.
METHODS
Experimental study using an in vitro model of compressive injury to isolated adult rat dorsal column axons.


OBJECTIVE
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.


BACKGROUND
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.
Spinal Cord Injury Neurophysiology Laboratory, Playfair Neuroscience Unit, Toronto Hospital Research Institute, Canada.
M G
MG
Fehlings
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S
Agrawal
D000200:Action Potentials / Q000187:drug effects; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D008297:Male; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology*; D026941:Sodium Channel Blockers; D000254:Sodium-Potassium-Exchanging ATPase; D013117:Spinal Cord Compression / Q000503:physiopathology* / Q000517:prevention & control
D026941:Sodium Channel Blockers; C013407:benzamil; D011343:Procaine; D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase