Assessment of axonal dysfunction in an in vitro model of acute compressive injury to adult rat spinal cord axons.
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.
Fehlings
M G
MG
Playfair Neuroscience Unit, Toronto Hospital Research Institute, University of Toronto, Canada.
Nashmi
R
R
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology*; D004195:Disease Models, Animal; D005071:Evoked Potentials; D008297:Male; D009186:Myelin Sheath / Q000502:physiology; D009408:Nerve Compression Syndromes / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D015221:Potassium Channels / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D015221:Potassium Channels; D015761:4-Aminopyridine