Interaction of Hypoxia and Hypothermia on Dorsal Column Conduction in Adult Rat Spinal Cord in Vitro

Abstract

Trauma reduces both action potential amplitudes and conduction velocities, as well as the ability of axons to follow high-frequency stimulation, in spinal cord dorsal columns. Since white matter blood flow falls after spinal cord injury, hypoxia may play a role in post-traumatic axonal dysfunction. We examined the effects of hypoxia on action potential conduction in isolated adult rat dorsal columns under normothermic (37°C) and hypothermic (25°C) conditions. After stabilization in oxygenated Ringer's solution (9.5% O 2 and 5% CO 2), the isolated dorsal columns were superfused with hypoxic Ringer's solution (95% N 2 and 5% CO 2) for 120 min, followed by 90 min of reoxygenation. At 37°C, hypoxia markedly depressed response amplitudes to 25 ± 9% (mean ± SEM, n = 7) of prehypoxic levels but paradoxically increased population conduction velocity to 133 ± 6%. Reoxygenation restored response amplitudes to 57 ± 11% and population conduction velocities returned to prehypoxic levels. At 25°C, the dorsal columns were significantly less sensitive to hypoxia. Response amplitudes fell to 50 ± 6% ( n = 7) after hypoxia and recovered to 77 ± 6% after reoxygenation. Normothermic dorsal columns responded to 500-Hz stimuli with minimal amplitude changes before (-9 ± 3%, n = 7) and after hypoxia (-13 ± 2%). In hypothermic preparations, 500-Hz stimulation depressed response a amplitudes before (-40 ± 8%, n = 7) and after hypoxia ( 56 ± 8%); they were not significantly different from each other. These results suggest that hypoxia selectively impairs slow-conducting axons in dorsal columns, that hypothermia ameliorates the effects of hypoxia, and that hypoxia does not remarkably alter the ability of surviving axons to follow high-frequency stimulation. Hypoxia-induced conduction failure in dorsal columns differs from post-traumatic axonal dysfunction.