Abstract
The distribution and changes of catalytic nitric oxid synthase (cNOS) activity in the dorsal, lateral and ventral white matter columns at midthoracic level of the rabbit's spinal cord were studied in a model of surgically-induced spinal cord constriction performed at Th7 segment level and compared with the occurrence of nicotinamide adenine dinucleotide phosphate diaphorase expressing and neuronal nitric oxide synthase immunoreactive axons in the white matter of the control thoracic segments. Segmental and white-column dependent differences of cNOS activity were found in the dorsal (141.5 ± 4.2 dpm/μm protein), lateral (87.3 ± 11.5 dpm/μm protein) and ventral (117.1 ± 7.6 dpm/μm protein) white matter columns in the Th5-Th6 segments and in the dorsal (103.3 ± 15.5 dpm/μm protein), lateral (54.9 ± 4.9 dpm/μm protein), and ventral (86.1 ± 6.8 dpm/μm protein) white matter columns in the Th8-Th9 segments. A surgically-induced constriction of Th7 segment caused a disproportionate response of cNOS activity in the rostrally (Th5-Th6) and caudally (Th8-Th9) located segments in both lateral and ventral white matter columns. While a statistically significant decrease of cNOS activity was detected above the constriction site in the ventral columns, a considerable, statistically significant increase of cNOS activity was noted in the white lateral columns below the site of constriction. It is reasoned that the changes of cNOS activity may have adverse effects on nitric oxide (NO) production in the white matter close to the site of constriction injury, thus broadening the scope of the secondary mechanisms that play a role in neuronal trauma.
Similar content being viewed by others
REFERENCES
Kowall, N. W., Beal, M. F., Ferrante, R. J., and Martin, J. B. 1985. Topography of nicotinamide adenine dinucleotide phosphate-diaphorase staining neurons in rat striatum. Neurosci. Lett. 59:61-66.
Kowall, N. W. and Mueller, M. O. 1988. Morphology and distribution of nicotinamide adenine dinucleotide phosphate (reduced form) diaphorase reactive neurons in human brainstem. Neuroscience 26:645-654.
Mizukawa, K., McGeer, P. L., Vincent, S. R., and McGeer, E. G. 1989. Distribution of reduced-nicotinamide-adenine-dinucleotide-phosphate diaphorase-positive cells and fibers in the cat central nervous system. J. Comp. Neurol. 279:281-311.
Mufson, E. J., Brady, D. R., and Carey, R. G. 1990. Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry in the hippocampal formation of the new world monkey (Saimiri sciureus). Brain Res. 516:237-247.
Dawson, T. M., Bredt, D. S., Fotuhi, M., Hwang, P. M., and Snyder, S. H. 1991. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc. Natl. Acad. Sci. U.S.A. 88:7797-7801.
Valtschanoff, J. G., Weinberg, R. J., and Rustioni, A. 1992. NADPH diaphorase in the spinal cord of rats. J. Comp. Neurol. 321:209-222.
Vincent, S. R. and Kimura, H. 1992. Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience 46:755-784.
Vizzard, M. A., Erdman, S. L., Erickson, V. L., Stewart, R. J., Roppolo, J. R., and de Groat, W. C. 1994. Localization of NADPH diaphorase in the lumbosacral spinal cord and dorsal root ganglia of the cat. J. Comp. Neurol. 339:62-75.
Maršala, J., Kluchová, D., and Maršala, M. 1997. Spinal cord gray matter layers rich in NADPH diaphorase-positive neurons are refractory to ischemia-reperfusion-induced injury: A histochemical and silver impregnation study in rabbit. Expl. Neurol. 145:165-179.
Maršala, J., Vanicky, I., Maršala, M., JalČ, P., OrendáČová, J., and Taira, Y. 1998. NADPH diaphorase in the spinal cord of dogs. Neuroscience 85:847-862.
LukáČová, N., Čížková, D., Maršala, M., JalČ, P., and Maršala, J. 1999. Segmental and laminar distribution of NADPH diaphorase exhibiting and neuronal nitric oxide synthase immunoreactive neurons versus radioassay detection of catalytic nitric oxide synthase activity in the spinal cord of rabbit. Neuroscience 94:229-237.
Maršala, J., Maršala, M., Vanicky, I., and Taira, Y. 1999. Localization of NADPHd-exhibiting neurons in the spinal cord of the rabbit. J. Comp. Neurol. 406:263-284.
LukáČová, N. and Pavel, J. 2000. Catalytic nitric oxide synthase activity in the white and gray matter regions of the spinal cord of rabbits. Physiol. Res. 49:167-173.
Maršala, J. and JalČ, P. 2000. Short-term changes of NADPH-dexhibiting neuronal pools in the spinal cord of rabbit after repeated sublethal ischemia. Physiol. Res. 49:157-165.
Dun, N. J., Dun, S. L., Wu, S. Y., Förstermann, U., Schmidt, H. H. H. W., and Tseng, L. F. 1993. Nitric oxide synthase immunoreactivity in the rat, mouse, cat and squirrel monkey spinal cord. Neuroscience 54:845-857.
Valtschanoff, J. G., Weinberg, R. J., Kharazia, V. N., Schmidt, H. H. H. W., Nakane, M., and Rustioni, A. 1993. Neurons in rat cerebral cortex that synthesize nitric oxide: NADPH diaphorase histochemistry, NOS immunocytochemistry, and colocalization with GABA. Neurosci. Lett. 157:157-161.
Saito, S., Kidd, G. J., Trapp, B. D., Dawson, T. M., Bredt, D. S., Wilson, D. A., Traystmann, R. J., Snyder, S. H., and Hanley, D. F. 1994. Rat spinal cord neurons contain nitric oxide synthase. Neuroscience 59:447-456.
Vizzard, M. A., Erdman, S. L., Roppolo, J. R., Förstermann, U., and de Groat, W. C. 1994. Differential localization of neuronal nitric oxide synthase immunoreactivity and NADPHdiaphorase activity in the cat spinal cord. Cell Tiss. Res. 278:299-309.
Bredt, D. S. 1995. Molecular characterization of nitric oxide synthase. Pages 1-42, in Vincent, S. R. (ed.), Nitric Oxide in the Nervous System, Academic Press, New York.
Kuppusamy, P., Ohnishi, S. T., Numagamy, Y., Ohnishi, T., and Zweier, J. L. 1995. Three-dimensional imaging of nitric oxide production in the rat brain subjected to ischemia-hypoxia. J. Cereb. Blood Flow Metab. 15:904-913.
Salter, M., Duffy, C., Garthwaite, J., and Strijbos, P. J. L. M. 1995. Substantial regional and hemispheric differences in brain nitric oxide synthase (NOS) inhibition following intracerebroventricular administration of N ω-nitro-L-arginine (L-NA) and its methyl ester (L-NAME). Neuropharmacology 34:639-649.
Yezierski, R. P., Liu, S., Ruenes, G. L., Busto, R., and Dietrich, W. D. 1996. Neuronal damage following intraspinal injection of a nitric oxide synthase inhibitor in the rat. J. Cereb. Blood Flow Metab. 16:996-1004.
Ashwal, S., Tone, B., Tian, H. R., Cole, D. J., and Pearce, W. J. 1998. Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion. Stroke 29:1037-1047.
Lee, J.-H., Price, R. H., Williams, F. G., Mayer, B., and Beitz, A. J. 1993. Nitric oxide synthase is found in some spinothalamic neurons and in neuronal processes that appose neurons that express Fos induced by noxious stimulation. Brain Res. 608: 324-333.
Miyazaki, M., Kayama, Y., Kihara, T., Kawasaki, K., Yamaguchi, E., Wada, Y., and Ikeda, M. 1996. Possible release of nitric oxide from cholinergic axons in the thalamus by stimulation of the rat laterodorsal tegmental nucleus as measured with voltammetry. J. Chem. Neuroanat. 10:203-207.
Vizzard, M. A., Erdman, S. L., and de Groat, W. C. 1993. The effect of rhizotomy on NADPH diaphorase staining in the lumbar spinal cord of the rat. Brain Res. 607:349-353.
Vizzard, M. A., Erdman, S. L., and de Groat, W. C. 1995. Increased expression of neuronal nitric oxide synthase (NOS) in visceral neurons after nerve injury. J. Neurosci. 15:4033-4045.
Choi, Y., Raja, S. N., Moore, L. C., and Tobin, J. R. 1996. Neuropathic pain in rats is associated with altered nitric oxide synthase activity in neural tissue. J. Neurol. Sci. 138:14-20.
Lumme, A., Vanhatalo, S., and Soinila, S., 1996. Axonal transport of nitric oxide synthase in autonomic nerves. J. Auton. Nerv. Syst. 56:207-214.
Lin, L. H., Cassell, M. D., Sandra, A., and Talman, W. T. 1998. Direct evidence for nitric oxide synthase in vagal afferents to the nucleus tractus solitarii. Neuroscience 84:549-58.
Wang, W., Inoue, N., Nakayama, T., Ishii, M., and Kato, T. 1995. An assay method for nitric oxide synthase in crude samples by determining product NADP. Anal. Biochem. 227:274-80.
Phul, R. K., Smith, M. E., Shaw, P. J., and Ince, P. G. 1998. Expression of nitric oxide synthase in the spinal cord in amyotrophic lateral sclerosis. J. Neurol. Sci. Suppl. 1601:87-91.
Lynch, D. R. and Dawson, T. M. 1994. Secondary mechanism in neuronal trauma. Curr. Opin. Neurol. 7:510-516.
Guízar-SahagÚ n, G., García-Ló pez, P., Espitia, A. L., Grijalva, I., Franco-Bourland, R. E., and Madrazo, I. 1998. Transitory expression of NADPH diaphorase (NOS) in axonal swellings after spinal cord injury. NeuroReport 9:2899-2902.
Scherer-Singler, U., Vincent, S. R., Kimura, H., and McGeer, E. G. 1983. Demonstration of a unique population of neurons with NADPH diaphorase histochemistry. J. Neurosci. Methods 8:229-234.
Bredt, D. S., Hwang, P. M., and Snyder, S. H. 1990. Localization of nitric oxide synthase indicating a neuronal role for nitric oxide. Nature 347:768-770.
Bredt, D. S. and Snyder, S. H. 1990. Isolation of nitric oxide synthase, a calmodulin-requiring enzyme. Proc. Natl. Acad. Sci. U.S.A. 87:682-685.
Strosznajder, J. and Chalimoniuk, M. 1996. Biphasic enhancement of nitric oxide synthase activity and cGMP level following brain ischemia in gerbils. Acta Neurobiol. Exp. 56:71-81.
Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248-254.
Zivin, J. A., DeGirolami, U., and Hurwitz, E. L. 1982. Spectrum of neurological deficits in experimental CNS ischemia. A quantitative study. Arch. Neurol. 39:408-412.
Garthwaite, J. and Boulton, C. L. 1995. Nitric oxide signaling in the central nervous system. Annu. Rev. Physiol. 57:683-706.
Christopherson, K. S. and Bredt, D. S. 1997. Nitric oxide in excitable tissues: physiological roles and disease. J. Clin. Invest. 100:2424-2429.
Ignarro, L. J. 1991. Signal transduction mechanisms involving nitric oxide. Biochem. Pharmacol. 41:485-90.
Hobbs, A. J. 1997. Soluble guanylate cyclase: the forgotten sibling. Trends Pharmacol. Sci. 18:484-91.
Garthwaite, G., Goodwin, D. A., and Garthwaite, J. 1999. Nitric oxide stimulates cGMP formation in rat optic nerve axons, providing a specific marker of axon viability. Eur. J. Neurosci. 11:4367-4372.
Stys, P. K. 1998. Anoxic and ischemic injury of myelinated axons in CNS white matter: from mechanistic concepts to therapeutics. J. Cereb. Blood Flow Metab. 18:2-25.
Trapp, B. D., Peterson, J., Ransohoff, R. M., Rudick, R., Mörk, S., and Bö, L. 1998. Axonal transection in the lesions of multiple sclerosis. New Engl. J. Med. 338:278-285.
Marcoux, F. W., Morawetz, R. B., Crowell, R. M., DeGirolami, U., and Halsey, J. H. Jr. 1982. Differential regional vulnerability in transient focal cerebral ischemia. Stroke 13:339-46.
Pantoni, L., Garcia, J. H., and Gutierrez, J. A. 1996. Cerebral white matter is highly vulnerable to ischemia. Stroke 27: 1641-1647.
Fehlings, M. G., Tator, C. H., and Linden, R. D. 1989. The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow. Electroencephalogr. Clin. Neurophysiol. 74:241-259.
Follis, F., Scremin, O. U., Blisard, K. S., Scremin, A. M., Pett, S. B., Scott, W. J., Kessler, R. M., and Wernly, J. A. 1993. Selective vulnerability of white matter during spinal cord ischemia. J. Cereb. Blood Flow Metab. 13:170-178.
Garthwaite, G., Brown, G., Batchelor, A. M., Goodwin, D. A., and Garthwaite, J. 1999. Mechanisms of ischaemic damage to central white matter axons: a quantitative histological analysis using rat optic nerve. Neuroscience 94:1219-1230.
Agrawal, S. K. and Fehlings, M. G. 1996. Mechanisms of secondary injury to spinal cord axons in vitro: role of Na+, Na+-K+-ATPase, the Na+-H+ exchanger, and the Na+-Ca2+ exchanger. J. Neurosci. 16:545-552.
Yezierski, R. P., Culberson, J. L., and Brown, P. B. 1980. Cells of origin of propriospinal connections to cat lumbosacral gray as determined with horseradish peroxidase. Exp. Neurol. 69: 493-512.
Sherrington, C. S. and Laslett, E. E. 1903. Observations on some spinal reflexes and the inner connection of spinal segments. J. Physiol. (Lond.) 29:58-96.
Barilari, M. G. and Kuypers, H. G. J. M. 1969. Propriospinal fibers interconnecting the spinal enlargements in the cat. Brain Res. 14:321-330.
Lloyd, D. P. C. 1942. Mediation of descending long spinal reflex activity. J. Neurophysiol. 5:435-458.
Giok, S. P. 1958. The fascilulus intermediolateralis of Loewenthal in man. Brain 81:577-587.
Dado, R. J. and Giesler, G. J. Jr. 1990. Afferent input to nucleus submedius in rats: retrograde labeling of neurons in the spinal cord and caudal medulla. J. Neurosci. 10:2672-2686.
Ralston, H. J. III. and Ralston, D. D. 1992. The primate dorsal spinothalamic tract: evidence for a specific termination in the posterior nuclei (Po/SG) of the thalamus. Pain 48:107-118.
Apkarian, A. V. and Hodge, C. J. 1989. Primate spinothalamic pathways: II. The cells of origin of the dorsolateral and ventral spinothalamic pathways. J. Comp. Neurol. 288:474-492.
Katter, J. T., Dado, R. J., Kostarczyk, E., and Giesler, G. J. Jr. 1996. Spinothalamic and spinohypothalamic tract neurons in the sacral spinal cord of rats. I. Locations of antidromically identified axons in the cervical cord and diencephalon. J. Neurophysiol. 75:2581-2605.
Katter, J. T., Dado, R. J., Kostarczyk, E., and Giesler, G. J. Jr. 1996. Spinothalamic and spinohypothalamic tract neurons in the sacral spinal cord of rats. II. Responses to cutaneous and visceral stimuli. J. Neurophysiol. 75:2606-2628.
Vincent, S. R. 1994. Nitric oxide: a radical neurotransmitter in the central nervous system. Prog. Neurobiol. 42:129-160.
Hobbelen, J. F., Gramsbergen, A., and van Hof, M. W. 1992. Descending pathways and the hopping response in the rabbit. Behav. Brain Res. 51:217-21.
Kamogawa, H. and Bennett, G. J. 1986. Dorsal column postsynaptic neurons in the cat are excited by myelinated nociceptors. Brain Res. 364:386-90.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lukáčová, N., Čížková, D., Maršala, M. et al. Effect of Midthoracic Spinal Cord Constriction on Catalytic Nitric Oxide Synthase Activity in the White Matter Columns of Rabbit. Neurochem Res 25, 1139–1148 (2000). https://doi.org/10.1023/A:1007682315257
Issue Date:
DOI: https://doi.org/10.1023/A:1007682315257