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.