Inhibition of neurotoxic events that lead to delayed cellular damage may prevent motor function loss after transient
spinal cord ischemia. An important effect of the neuroprotective substance
aminoguanidine (AG) is the inhibition of
inducible nitric oxide synthase (iNOS), a perpetrator of focal ischemic damage. The authors studied the protective effects of AG on hind limb motor function and histopathologic outcome in an experimental model for
spinal cord ischemia, and related these findings to the
protein content of iNOS in the spinal cord. Temporary
spinal cord ischemia was induced by 28 minutes of infrarenal balloon occlusion of the aorta in 40 anesthetized New Zealand White rabbits. Animals were assigned randomly to two treatments: saline (n = 20) or AG (n = 20; 100 mg/kg intravenously before occlusion). Postoperatively, treatment was continued with
subcutaneous injections twice daily (saline or 100 mg/kg AG). Normothermia (38 degrees C) was maintained during
ischemia, and rectal temperature was assessed before and after
subcutaneous injections. Animals were observed for 96 hours for neurologic evaluation (Tarlov score), and the lumbosacral spinal cord was examined for ischemic damage after perfusion and fixation. Lastly, iNOS
protein content was determined using Western blot analysis 48 hours after
ischemia in five animals from each group. Neurologic outcome at 96 hours after reperfusion was the same in both groups. The incidence of
paraplegia was 67% in the saline-treated group versus 53% in the AG-treated group. No differences in
infarction volume, total number of viable motoneurons, or total number of eosinophilic neurons were present between the groups. At 48 hours after reperfusion, iNOS
protein content in the spinal cord was increased in one animal in the AG-treated group and in three animals in the control group. The data indicate that peri-ischemic treatment with high-dose AG in rabbits offers no protection against a period of normothermic
spinal cord ischemia. There was no conclusive evidence of spinal cord iNOS inhibition
after treatment with AG.