Mg. Fehlings et R. Nashmi, ASSESSMENT OF AXONAL DYSFUNCTION IN AN IN-VITRO MODEL OF ACUTE COMPRESSIVE INJURY TO ADULT-RAT SPINAL-CORD AXONS, Brain research, 677(2), 1995, pp. 291-299
An in vitro model of spinal cord injury was developed to study the pat
hophysiology of posttraumatic axonal dysfunction. A 25 mm length of th
oracic spinal cord was removed from the adult male rat (n = 27). A dor
sal column segment was isolated and pinned in a recording chamber and
superfused with oxygenated (95%O-2/5% CO2) Ringer. The cord was stimul
ated with a bipolar electrode, while two point responses were recorded
extracellularly. Injury was accomplished by compression with a modifi
ed aneurysm clip which applied a 2 g force for 15 s. With injury the c
ompound 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 injur
y from 1.7 +/- 0.1 ms to 2.1 +/- 0.1 ms (P < 0.001). With train stimul
ation (200 and 400 Hz), injured axons showed evidence of high frequenc
y conduction failure (P < 0.05). The infusion of 5 mM 4-aminopyridine
(4-AP), a blocker of voltage-sensitive 'fast' K channels confined to i
nternodal regions, resulted in broadening of the CAP of injured axons
to 114.9 +/- 3.1% of control (P < 0.05). Ultrastructural analysis of t
he injured dorsal column segments revealed marked axonal and myelin pa
thology, including considerable myelin disruption. In conclusion, we h
ave developed and characterized an in vitro model of mammalian spinal
cord injury which simulates many of the features of in vivo trauma. In
jured axons display characteristic changes in physiological function i
ncluding a shift in refractory period and high frequency conduction fa
ilure. The ultrastructural data and response of injured axons to 4-AP
suggest that myelin disruption with exposure of 'fast' K+ channels con
tributes to posttraumatic axonal dysfunction.