Role of monoamines in experimental spinal cord injury in rats. Relationship between Na+-K+-ATPase and lipid peroxidation.

Abstract

A spinal cord injury was produced in Wistar rats by extradural compression of the cord with a Sugita aneurysm clip for 5 seconds. During a 2-week observation period following the injury, the tissue norepinephrine (NE), dopamine (DA), and serotonin (5-HT) concentrations decreased uniformly at and below the injured site. The chemical denervation of NE or 5-HT neurons produced by the intraspinal injection of 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT) 2 weeks before the injury did not cause a marked difference in the extent of hemorrhagic necrosis of the spinal cord after trauma as compared to control animals without pretreatment. In the rats pretreated with 6-OHDA, NE was decreased to less than 30% of control (non-pretreated) values, and, beginning at 5 days after injury, motor performance (assessed quantitatively with the inclined-plane method) was significantly improved compared to results in the non-pretreated control rats. The rats pretreated with 5,7-DHT showed no change from control animals. Spinal cord samples from non-pretreated control animals obtained at the injury site 30 minutes after the compression injury showed a marked decrease in the activity of synaptosomal Na+-K+-ATPase (adenosine triphosphatase) of about 50%, and an increase in both thiobarbituric acid reaction substance (about 170%) and cyclic guanine monophosphate (about 150%). The NE-denervated rats showed no significant changes in these three parameters. The results indicated that NE released after crush injury may impair the neuronal cell membrane around the lesion site by induction of lipid peroxidation. The possible mechanisms by which released NE may alter membrane function are discussed.