A new model of acute compressive spinal cord injury in vitro.
A novel in vitro method of spinal cord injury was developed to facilitate the study of cellular and molecular mechanisms underlying neural trauma. A 3-cm length of thoracic spinal cord was removed from the adult Wistar rat. A strip of dorsal column and its associated dorsal horn gray matter was excised and pinned in an in vitro recording chamber where it was constantly perfused with oxygenated Ringer's solution at either 25 degrees C or 33 degrees C. Injury was performed by compressing the dorsal column segment in vitro with a modified aneurysm clip (closing force 2.0 g) for 15 s. Microelectrode and sucrose gap recordings were generated to characterize the physiological effects of compressive injury. Longitudinal thin sections of control and injured dorsal column segments were examined by electron microscopy. At 25 degrees C, injured axons were characterized by a significant reduction in amplitude of the compound action potential (CAP) to 76.9 +/- 2.4% (P < 0.0005) and an increase in response latency to 112.5 +/- 2.5% (P <0.005). At 33 degrees C, the effects of injury on the CAP amplitude were accentuated (P< 0.0001). With the K+ channel blocker, 4-AP (1 mM), there was broadening of the CAP of injured axons and a delay in repolarization of the axonal resting membrane potential, suggesting myelin disruption with exposure of paranodal K+ channels. Ultrastructurally, injured dorsal column segments showed considerable axonal and myelin pathology including splaying of the myelin sheath and vesicular degeneration.
Fehlings
M G
MG
The Toronto Hospital Research Institute, University of Toronto, Ontario, Canada. mfehlings@torhosp.toronto.on.ca
Nashmi
R
R
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000208:Acute Disease; D000818:Animals; D001369:Axons / Q000502:physiology; D004195:Disease Models, Animal; D004594:Electrophysiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013117:Spinal Cord Compression / Q000503:physiopathology*; D013395:Sucrose
D013395:Sucrose; D015761:4-Aminopyridine