| Summary: | 碩士 === 國立臺灣大學 === 解剖學研究所 === 88 === In this study, we used rat rubrospinal neurons as an intrinsic central neuron model and investigated their responses related to reactive oxygen and reactive nitrogen species synthesis following spinal axonal injury and compared this to that of the peripheral nerve model, facial neurectomy. In the red nucleus, the number of nitric oxide synthase (NOS)-immunoreactive cells started to increase at 3 days, reached maximum at 1-2 weeks, and decreased to baseline level at 1? years following axonal injury. Labeled neurons appeared only in the caudal pole and the ventrolateral, but not the dorsomedial, area of the caudal nucleus. In addition, almost all NOS-immunoreactive cells were found to contain the retrograde tracer Fast blue applied at the lesion site to identify axotomized rubrospinal neurons. These suggest that only axotomized rubrospinal neurons projecting to the lumbar spinal cord were induced to express high levels of NOS although cervical projection neurons were also axotomized. On the contrary, middle nucleus, which contains mainly neurons not projecting to the spinal cord, was filled with fine NOS-immunoreactive axon profiles with boutons in both normal and injured animals. Very few similar axon profiles were found in the caudal nucleus of both normal and injured nucleus. These suggest that NOS-immunoreactive axons reaching the middle nucleus were probably originated from source(s) different from those innervating the caudal nucleus and they were not altered by rubrospinal tractotomy.
Concomitant with the changes of NOS immunoreactivity, neuronal mitochondrial superoxide dismutase, Mn-SOD and cytoplasmic superoxide dismutase, Cu/Zn-SOD were unchanged following spinal axotomy suggesting a lack of protection of injured neurons since SOD can compete with NO for superoxide thus reducing its neurotoxic effect. To complicate this further, the expression of calcineurin, which can up-regulate NOS activity upon calcium entry was also maintained in rubrospinal neurons following spinal axotomy.
Unlike rubrospinal neurons, facial nerve cut resulted in an increase of mitochondrial Mn-SOD, but not Cu/Zn-SOD in injured facial neurons while NOS immunoreactivity was also increased. Thus, both central and peripheral neurons increase NO production to cope with axonal injury. However injured peripheral neurons also increase their expression of Mn-SOD simultaneously to prevent the consequent generation of peroxynitrite, thus more likely to save the cells from toxic influences. The lack of an increase of SOD in intrinsic central neurons following axotomy is likely to result in their eventual cell death.
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