[Glutamate neurotoxicity during spinal cord ischemia--development of a delayed-onset paraplegia model].

The incidence and severity of spinal cord dysfunction are related to both the depth and duration of the resulting ischemic state. Evidence is accumulating that glutamate, a major neurotransmitter, has potent neurotoxic activity during ischemia. In our laboratory, it has been confirmed that exogenous glutamate has detrimental effects on spinal cord neurons during brief ischemia in vivo. We hypothesized that glutamate neurotoxicity is associated with delayed-neuronal dysfunction. Delayed-onset paraplegia is defined as a neurologic deficit which develops after initial recovery. Infrarenal aortic segments from 12 New Zealand white rabbits, were isolated for 5 minutes and perfused at a rate of 2 ml/min. Group I (n = 6) received normothermic saline (39 degrees C). Group II (n = 6) received normothermic L-glutamate (20 mM). Neurologic function was assessed at 6, 24, and 48 hours after surgery according to the modified Tarlov scale. After 48 hours, the rabbits were euthanized and their spinal cords were harvested for histologic examination. The neurologic function of all group I was fully intact, whereas three rabbits in group II showed acute paraplegia and the other three showed delayed-onset paraplegia. Histologic examination of spinal cords from rabbits in group I revealed no evidence of cord injury, whereas spinal cords from those in group II had evidence of moderate spinal cord injury with central gray matter and adjacent white matter necrosis and axonal swelling. These results indicate that dose-dependent glutamate neurotoxicity is associated with delayed neuronal dysfunction following ischemia in vivo. The severity of the ischemic event, i.e., extracellular glutamate overload, is suspected to be the etiology of delayed-onset paraplegia which, in turn, is thought to be the result of borderline ischemia. This model may allow a pharmacologic approach to the prevention of ischemic spinal cord injury.