Abstract
The changes in acetylcholine (ACh), monoamine and monoamine metabolite levels following cerebral ischemia in Mongolian gerbils were examined. In addition, the effects of Sho-saiko-to-go-keishi-ka-shakuyaku-to (TJ-960), which is a spray-dried mixture of 9 herbal drugs, on these changes were also examined. The dramatic decrement of ACh levels in ischemic gerbils was significantly inhibited by p.o. administration of TJ-960 at a daily dose of 3.5 g/kg or 700 mg/kg for one month. Norepinephrine (NE) was also reduced in all ischemic brain regions, and TJ-960 also recovered the level of NE. In ischemic gerbil brains, the dopamine (DA) levels decreased and its metabolites increased in the striatum, but DA and its metabolites in the thalamus+midbrain region increased. The serotonin (5HT) level was reduced in the cerebral cortex and hippocampus. TJ-960 inhibited these monoaminergic changes in ischemic gerbils. This suggests that TJ-960 may provide anti-ischemic action and beneficial effects on various symptoms induced by ischemia.
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Wurtman, R. J., and Zervas, N. T., 1974. Monoamine neurotransmitters and the pathophysiology of stroke and central nervous system trauma. J. Neurosurg. 40:34–36.
Harrison, M. J. G., and Ellam, L. D., 1981. Role of 5HT in the morbidity of cerebral infarction—a study in the gerbil stroke model. J. Neurol. Neurosurg. Psych. 44:140–143.
Nilson, B., and Ponten, U. 1977. Expermental head injury in the rat. Part 2: Regional brain energy metabolism in concussive trauma. J. Neurosurg. 47:252–261.
Lust, D. W., Mrsulja, B. B., Mrsulja, B. J., Passonneau, J. V., and Klatzo, I. 1975. Putative neurotransmitters and cyclic nucleotides in prolonged ischemia of the cerebral cortex. Brain Res. 98:394–399.
Levy, D. E., and Duffy, T. E. 1975. Cerebral energy metabolism during transient ischemia and recovery in the gerbils. J. Neurochem. 28:63–70.
Kobayashi, M., Lust, W. D., and Passonnean, J. V. 1977. Concentration of energy metabolites and cyclic nucleotides during and after bilateral ischemia in the gerbil cerebral cortex. J. Neurochem. 29:53–59.
Cvejic, V., Micic, D. V., Djuricic, B. M., Mrsulja, B. J., and Mrsulja, B. B. 1980. Monoamines and related enzymes in cerebral cortex and basal ganglia following transient ischemia in gerbils. Acta. Neuropathol. (Berl), 51:71–77.
Mrsulja, B. B., Mrsulja, B. J., Spatz, M., and Klatzo, I. 1976. Catecholamines in brain ischemia-effects of alpha-methyl-p-tyrosine and pargyline. Brain Res. 104:373–378.
Welch, K. M. A., Chabi, E., Gaudet, R. J., and Wang, T-P. 1979. Recemphasis of the role of 5-hydroxytryptamine incerbral ischemia. Pages 109–119.in Mrsuljia, B. B., Rakic, L. M., Klatzo, I., Spaty, M. (eds.) Pathophysiology of cerebral energy metabolism. Plenum Press, New York London.
Gaudet, R., Welch, K. M. A., Chali, E., and Wang, T-P 1978. Effect of transient ischemia on monoamine levels in the cerebral cortex of gerbils. J Neurochem. 30:751–757.
Sara, S. J., and Lefevre, P. 1972. Hypoxia-induced amnesia in one-trial learning and pharmacological protection, by piracetam. Psychopharmacologia 25:32–40.
Ogawa, N., Haba, K., Yoshikawa, H., Ono, T., and Mizukawa, K. 1988. Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine hydrochloride on ischemia-induced depletion of brain acetylcholine levels in gerbils. Res. Comm. Chem. Pathol. Pharm. 61:285–288.
Hoffmeister, F., Benz, U., Heise, A., Krause, H. P., and Neuser, V. 1982. Behavioral effects of nimodipine in animals. Arzneimittelforsch. 32:347–360.
Kakihana, M., Yamazaki, N., and Nagaoka, A. 1984. Effects of idebenone (CV-2619) on the concentrations of acetylcholine and choline in various brain regions of rats with cerebral ischemia. Japan. J. Pharmacol. 36:28–33.
Ogawa, N., Haba, K., Yoshikawa, H., Kawata, M., and Sato, H. 1989. Effects of lisuride hydrogen maleate on ischemia-induced depletion of brain acetylcholine levels in gerbils. Cli. Therapeutics. 11:241–246.
Hiramatsu, M., Edamatsu, R., Kohno, M., and Mori, A. 1986. The possible involvement of free radicals in seizure mechanism. Jpn. J. Psychiat. Neurol. 40:349–352.
Hiramatsu, E. Edamatsu, R., Kabuto, H., and Mori, A. 1989. Effect of Sho-saiko-to-go-keishi-ka-shakuyaku-to on monoamines, amino acids, lipid peroxides, and superoxide dismutase in brains of aged rats. Medical, Biochemical and Chemical Aspects of Free Radicals, Excepta Medica. Ltd. 128–135.
Hiramatsu, M., Kabuto, H., and Mori, A. 1986. Effects of shosaikoto-go-keishikashakuyakuto (TJ-960) on brain catecholamine level of aged rats. IRCS Med. Sci. 14:189–190.
Glowinski, J., and Iversen, L. 1966. Regional studies of catecholamines in the rat brain I. J. Neurochem. 13:655–669.
Fujimori, K., and Yamamoto, K. 1987. Determination of acetylcholine and choline in perchlorate extracts of brain tissue using liquid chromatography-electrochemistry with an immobilized-enzyme reactor. J. Chromatograph. 414:167–173.
Lasley, S. M., Michaelson, I. A., Greenland, R. D., and McGinnis, P. M., 1984. Simultaneous measurement of tyrosine, triptophan and releated monoamines for determination of neurotransmitter turnover in discrete rat brain regions by liquid chromatography with electrochemical detection. J. Chromatograph. 305:27–42.
Kabuto, H., Yokoi, I., and Mori, A. 1988. Effects of muscimol and baclofen on levels of monoamines and their metabolites in the El mouse brain. Neurochem. Res. in press.
Weinberger J., Nieves-Rosa, J., and Cohen, G., 1985. Nerve terminal damage in cerebral ischemia: protective effect of brain dopamine following experimental cerebral ischemia. Nature 274:283–284.
Slivka, A., Brannan, T. S., Weinberger, J., Knott, P. J., and Cohen, G., 1988. Increase in extracellular dopamine in the striatum during cerebral ischemia: a study utilizing corebral microdialysis. J. Neurochem. 50:1714–1718.
Matsumoto, M., Kimura, K., Fujisawa, A., Matsuyama, T., Fukunaga, R., Yoneda, S., Wada, H., and Abe, H. 1984. Differential effect of cerebral ischemia on monoamine content of discrete ischemia on monoamine content of discrete brain regions of the Mongolian gerbils (Meriones unguiculatus). J. Neurochem. 42:647–651.
Bogomir, B., Mrsulja, B. J., Mrsulja, M. S., and Igor K. 1976. Catecholamines in brain ischemia-effects of alpha-methyl-p-tyrosine and pargyline. 104:373–378.
Saito, K., Honda, S., Tobe, A., and Yanagiya, I. 1985. Effects of bifemelane hydrochloride (MCI-2016) on acetylcholine level reduced by scopolamine, hypoxia and ischemia in the rat and mongolian gerbils. Jpn. J. Pharmacol. 38:375–380.
Davis, J. N., and Carlsson, A. 1973. The effect of hypoxia on monoamine synthesis levels and metabolism in rat brain. J. Neurochem. 21:783–790.
Stone, T. W., Taylor, D. A., and Bloom, F. E. 1975. Cyclic AMP and cyclic GMP may mediate opposite neuronal responses in the rat cerebral cortex. Science 187:845–847.
Egawa, M., Mitsuka, M., Umezu, K. and Tobe A. 1984. Effects of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCl-2016) on survival time and brain monoamine levels in bilaterally carotid-artery-ligated gerbils. Japan J. Pharmacol. 34:363–365.
Gibson, G. E. and Shimada, M., and Blass J. P. 1978. Alterations in acetylcholine synthesis and cyclic nucleotides in mild cerebral hypoxia. J. Neurochem. 31:757–760.
Udenfriend, S. 1966. Tyrosine hydroxylase. Pharmacol. Rev. 18:43–51.
Sugaya, E., Ishige, A., Sekiguchi, K., Iizuka, S., Sugimoto, A., Yuzurihara, M., and Hosoya, E. 1988. Inhibitory effect of a mixture of herbal drugs (TJ-960, SK) on pentylenetetrazol-induced convulsions in El mice. Epilipsy Res. 2:337–339.
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Haba, K., Ogawa, N. & Mori, A. The effects of Sho-saiko-to-go-keishi-ka-shakuyaku-to (TJ-960) on ischemia-induced changes of brain acetylcholine and monoamine levels in gerbils. Neurochem Res 15, 487–493 (1990). https://doi.org/10.1007/BF00966205
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DOI: https://doi.org/10.1007/BF00966205