Abstract
Concentrations of acetylcholine and the monoaminergic neurotransmitters dopamine, serotonin and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylacetic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA) and choline were simultaneously determined in the corpus striatum of rats after 15 min. complete cerebral ischemia (CCI) and in different intervals (1, 24, 48, 72, 96 hours) of postischemic cerebral reperfusion. Results were compared to respective sham-operated control animals. After 15 min. CCI acetylcholine concentration decreased to 15%, and dopamine concentration to 56% of the control values. The metabolite levels of DOPAC decreased to 40% and HVA to 64% of the control values. Acetylcholine, dopamine, serotonin and choline concentrations were not changed significantly after reperfusion. The metabolites HVA and 5-HIAA showed their maximum increases after 1 and 24 hours of reperfusion, additionally HVA was decreased both, after 72 and 96 hours of reperfusion. The data indicate that surprisingly little permanent damage could be caused by a 15 min. ischemia in the striatum. Tissue levels of the neurotransmitters appeared differentially altered but similarly regulated during ischemia and subsequent recirculation. Acetylcholine and dopamin levels decreased profoundly during ischemia. However, acetylcholine levels could be compensated rapidly during reperfusion, whereas the dopaminergic system showed a long-lasting change in its turnover rate. Although serotonin levels were unaffected by CCI, there was an increase of its presumed turnover rate during reperfusion.
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Alger, J. R., Brunetti, A., Nagashima, G., and Hossmann, K. A. 1989. Assessment of post-ischemic cerebral energy metabolism in cat by31P NMR: the cumulative effects of secondary hypoxia and ischemia. J. Cereb. Blood Flow Metab. 9:506–514.
Borgström, L., Johansson, H., and Siesjö, B. K. 1975. The influence of acute normovolemic anemia on cerebral blood flow and oxygen consumption of anaesthetized rats. Acta Physiol. Scand. 93:505–514.
Buu, N. T. 1985. Dopamine sulfoconjugation in the rat brain: regulation by monoamine oxidase. J. Neurochem. 45:470–476.
Carlson A. 1974. The in vivo estimation of rats of tryptophan and typrosine hydroxylation: effects of alterations in enzyme environment and neuronal activity. In: Aromatic amino acids in the brain. Ciba Foundation Symposium 22. Elsevier Excerpta Medica North-Holland, 117–134.
Damsma, G., Boiswert, D. P., Mudrick, L. A., Wenkstern, D., Fibiger, H. C. 1990. Effects of transient forebrain ischemia and pargyline on extracellular concentrations of dopamine, serotonin, and their metabolites in the rat striatum as determined by in vivo microdialysis. J Neurochem. 54:801–808.
Davis, J. N., Carlsson, A. 1973. The effect of hypoxia on rat brain tyrosine and tryptophan hydroxylase in vivo. J. Neurochem. 20:913–915.
Ding, A., Nemeth, G., Hoyer, S. 1992. Age influences abnormalities in striatal dopamine metabolism during and after forebrain ischemia. J. Neural Trans. 4:213–215.
Edvinsson L., Owman C. 1980, Noradrenalin and the cerebral circulation. In: A. Bes, G. Geraud (Eds.): Cerebral circulation and Neurotransmitter. Amsterdam. Exc. Med. ICS 507:149–156.
Gibson, G. E., Duffy, T. E. 1981. Impaired synthesis of acetylcholine by mild hypoxia, anoxia or nitrous oxide. J. Neurochem. 36:28–33.
Ginsberg, M. D., Mela, L., Wrobel-Kuhl, K., and Reivich, M. 1977. Mitochondrial metabolism following bilateral cerebral ischemia in the gerbil. Ann. Neurol. 1:519–527.
Globus, M. Y. T., Bosto, R., Dietrich, W. D., Martinez, E., Valdes, I., Ginsberg, M. D. 1988. Effect of ischemia on the in vivo release of striatal dopamine, glutamate and gammaaminobutyric acid studied by intracerebral microdialysis. J. Neurochem. 51:1455–1464.
Haba, K., Ogawa, N., and Mori, A. 1990. The effects of Shosaiko-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.
Harik, S. I., Yoshida, S., Busto, R., Ginsberg, M. D. 1986. Monoamine transmitters in diffuse reversible forebrain ischemia and early recirculation: increased dopaminergic activity. Neurology 36:971–976.
Hoyer, S., and Krier, C. 1986. Ischemia and the aging brain. Studies on glucose and energy metabolism in rat cerebral cortex. Neurobiol. Aging 7:23–29.
Hoyer, S., and Betz, K. 1988. Abnormalities in glucose and energy metabolism are more severe in the hippocampus than in cerebral cortex in postischemic recovery in aged rats. Neurosci. Lett. 94:167–172.
Hoyer, S., and Betz, K. 1989. Elimination of the delayed postischemic energy deficit in cerebral cortex and hippocampus of aged rats with a dried, deproteinized blood extract (ActoveginR). Arch. Gerontol. Geriatr. 9:181–192.
Jellinger, K., Riederer, P. 1983. Zentrale Neurotransmitter bei zerebraler Ischämie und Hirninfarkt. Fortschr. Neurol. Psychiat. 51:91–123.
Kamijo K., Usdin E., Nagatsu T. 1982 (eds.). Monoamine Oxidase, Basic and Clinical Frontiers, Amsterdam-Prinston-Oxford, Excerpta Medica ICS 564.
Ksiezak, H. J., and Gibson, G. E. 1981. Oxygen dependence of glucose and acetylcholine metabolism in slices and synaptosomes from rat brain. J. Neurochem. 37:305–314.
Kumagae, Y., and Matsui, Y. 1991. Output, tissue levels, and synthesis of acetylcholine during and after transient forebrain ischemia in the rat. J. Neurochem. 56:1169–1173.
Nemeth, G., Ding, A., Hoyer, S. 1989. Effects of ischemia on dopamine metabolism in the rat brain striatum: the significance of 3-methoxtyramine. J. Cereb. Blood Flow Metab. 9: Suppl. 1:662.
Paxinos, G., and Watson, C. The rat brain in stereotaxic coordinates, Academic Press, Sydney, 2. Ed., VIII ff.
Phebus, L. A., Clemens, J. A. 1989. Effects of Transient, global, cerebral ischemia on striatal extracellular dopamine serotonin and their metabolites. Life Sci. 44:1335–1342.
Pulsinelli, W. A., and Buchem, A. M. 1988. The four-vessel occlusion rat model: method for complete occlusion of vertebral arteries and control of collateral circulation. Stroke 19 (7):913–914.
Pulsinelli, W. A., Levy, D. E., and Duffy, T. E. 1982. Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia. Ann. Neurol. 11:499–502.
Pulsinelli, W. A., and Duffy, T. E. 1983. Regional energy balance in rat brain after transient forebrain ischemia. J. Neurochem. 40:1500–1503.
Scremin, O., and Jenden, D. J. 1991. Time-dependent changes in cerebral choline and acetylcholine induced by transient global ischemia in rats. Stroke 22:643–647.
Slivka, A., Brannan, T. S., Weinberger, J., Knott, J. P. and Cohen, G. 1988. Increase in extracellular dopamine in the striatum during cerebral ischemia: A study utilizing cerebral microdialysis. J. Neurochem. 50:1714–1718.
Stadler, H., and Nesselhut, T. 1986. A simpel and rapid measurement of acetylcholine and choline by HPLC and enzymatic-electrochemical detection. Neurochem. Int. 9:127–129.
Trendelenburg, U., and Weiner, N. 1988 (eds.). Catecholamines I, Springer-Verlag, Berlin-Heidelberg-New York- Tokyo 119–192.
Trendelenburg, U., and Weiner, N. 1989 (eds.). Catecholamines II, Springer-Verlag, Berlin-Heidelberg-New York- Tokyo, 12–16 and 429–430.
Tuček, S. 1985. Regulation of Acetylcholine in the brain. J. Neurochem., 44:11–24.
Usdin, E., Weiner N., Youdim, G. B. H. 1977. Structure and function of monoamine enzymes, Marcel Dekker, INC. New York-Basel.
Zaidan, E., and Sims, N. R. 1990. Alterations in the production of14CO2 and [14C]-acetylcholine from [U-14C]-glucose in brain subregions following transient forebrain ischemia in the rat. J. Neurochem. 55:1882–1889.
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Frölich, L., Dirr, A., Riederer, P. et al. Effects of long-term recovery from transient cerebral ischemia in rat brain: Tissue levels of acetylcholine, monoamines, and their metabolites. Neurochem Res 18, 1239–1244 (1993). https://doi.org/10.1007/BF00975041
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DOI: https://doi.org/10.1007/BF00975041