Important role of reverse Na+-Ca2+ exchange in spinal cord white matter injury at physiological temperature

Spinal cord injury is a devastating condition in which most of the clinical disability results from dysfunction of white matter tracts. Excessive cell ular Ca2+ accumulation is a common phenomenon after anoxia/ischemia or mech anical trauma to white matter, leading to irreversible injury because of ov eractivation of multiple Ca2+ dependent biochemical pathways. In the presen t study, we examined the role of Na+-Ca2+ exchange, a ubiquitous Ca2+ trans port mechanism, in anoxic and traumatic injury to rat spinal dorsal columns in vitro. Excised tissue was maintained in a recording chamber at 37 degre es C and injured by exposure to an anoxic atmosphere for 60 min or locally compressed with a force of 2 g for 15 s. Mean compound action potential amp litude recovered to approximate to 25% of control after anoxia and to appro ximate to 30% after trauma. Inhibitors of Na+-Ca2+ exchange (50 mu M beprid il or 10 mu M KB-R7943) improved functional recovery to approximate to 60% after anoxia and approximate to 70% after traumatic compression. These inhi bitors also prevented the increase in calpain-mediated spectrin breakdown p roducts induced by anoxia. We conclude that, at physiological temperature, reverse Na+-Ca2+ exchange plays an important role in cellular Ca2+ overload and irreversible damage after anoxic and traumatic injury to dorsal column white matter tracts.