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Abstract
An in vitro model of spinal cord injury was developed to study the pathophysiology
of posttraumatic axonal dysfunction. A 25 mm length of thoracic spinal cord was removed
from the adult male rat (n = 27). A dorsal column segment was isolated and pinned
in a recording chamber and superfused with oxygenated (95% O2/5% CO2) Ringer. The
cord was stimulated with a bipolar electrode, while two point responses were recorded
extracellularly. Injury was accomplished by compression with a modified aneurysm clip
which applied a 2 g force for 15 s. With injury the compound action potential (CAP)
amplitude decreased to 53.7 +/- 5.4% (P < 0.001), while the latency increased to 115.6
+/- 3.1% (P < 0.0025) of control values. The absolute refractory period increased
with injury from 1.7 +/- 0.1 ms to 2.1 +/- 0.1 ms (P < 0.05). The infusion of 5 mM
4-aminopyridine (4-AP), a blocker of voltage-sensitive 'fast' K channels confined
to internodal regions, resulted in broadening of the CAP of injured axons to 114.9
+/- 3.1% of control (P < 0.05). Ultrastructural analysis of the injured dorsal column
segments revealed marked axonal and myelin pathology, including considerable myelin
disruption. In conclusion, we have developed and characterized an in vitro model of
mammalian spinal cord injury which simulates many of the features of in vivo trauma.
Injured axons display characteristic changes in physiological function including a
shift in refractory period and high frequency conduction failure. The ultrastructural
data and response of injured axons to 4-AP suggest that myelin disruption with exposure
of 'fast' K+ channels contributes to posttraumatic axonal dysfunction.