Brain Monoamines in Cerebral Infarction and Coma
Dopamine (DA), serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) and tryptophan (Trp) were assayed spectrofluorometrically in various brain regions of eight human patients who died after acute and old cerebral infarction, in 17 cases of acute metabolic (hepatic, uremic and diabetic) coma, and in three patients with liver cirrhosis without coma. The results were as follows: (1) In both recent and older cerebral infarction a total depletion of DA and 5-HT was associated with slight reduction of DA and 5-HT levels in remote non-ischemic areas and various nuclei of both the injured and contralateral hemispheres. 5-HIAA was significantly reduced in acute ischemic necrosis, while the perifocal edema zone showed accumulation of both 5-HT and 5-HIAA. The degradation zone surrounding old infarcts showed a mild decrease of both 5-HT and 5-HIAA, indicating normalization of 5-HT metabolism after decrease of the complicating edema. (2) In metabolic coma brain DA showed a mild general decrease, while brain Trp was significantly increased in hepatic coma. 5-HT and 5-HIAA were generally increased in all types of coma, most significantly in the brainstem tegmentum and in parts of the limbic system. (3) In liver cirrhosis without coma, brain 5-HT was within normal range, while Trp and 5-HIAA were significantly elevated in the brainstem, their increase being less severe than in hepatic coma.
The data presented in human stroke which confirm previous findings in experimental cerebral ischemia and infarction indicate that disorders of brain monoamine metabolism are contributing to the development of post-ischémie brain damage and the complicating cerebral edema. The results in endotoxic coma which are in keeping with the findings in experimental porto-caval and uremic encephalopathies suggest some common disorders of central monoamine neurotransmitter metabolism in endotoxic coma of different etiology usually accompanied by cerebral edema. Increased 5-HT synthesis and turnover in the ascending serotonergic brainstem systems are considered an important biochemical substrate of clinical disorders of consciousness.
KeywordsCerebral Ischemia Cerebral Infarction Hepatic Encephalopathy Brain Edema Cerebral Edema
Unable to display preview. Download preview PDF.
- 1.Anton, A.H., Sayre, D.F. (1964): The distribution of dopamine and dopa in various animals and a method for their determination in diverse biological material.J. Pharm, exp. Ther. 145: 326–336.Google Scholar
- 4.Birkmayer, W., Jellinger, K., Riederer, P. (1977): Striatal and extrastriatal dopaminergic functions. In: Psychobiology of the Striatum (Cools, A.R., Lohman, A.H.M., Van den Bercken, J.H.L. eds.) Amsterdam-New York-Oxford: North Holland Publ. Comp. 141–153.Google Scholar
- 9.DiReda, N., Livrea, P., De Blas, A. (1977): Effects of premortem conditions on HVA and 5-HIAA levels in human brain areas at autopsy. Abstr. 11th World Congr. Neurol. W.A.den Hartog-Jager, G.W. Bruyn, A.P.J. Heijstee (eds): Excerpta medica, Amsterdam, ICS Nr. 427: 215.Google Scholar
- 11.Fischer, J.E., Baldessarini, R.J. (1976): Pathogenesis and therapy of hepatic coma. In: Progress in Liver Disease, Popper, H., Schaffner, F. (eds) New York: Grune & Stratton.Google Scholar
- 14.Hamon, M., Bourgoin, S., Morot-Gaudry, Y., Hery, F., Flowinski, J. (1974): Role of active transport of tryptophan in the control of 5-hydroxytryptamine synthesis. Adv. Biochem. Psychopharmac. 11: 153–162.Google Scholar
- 16.Hess, S., Udenfried, S. (1959): A fluorometric procedure for the measurement of tryptophan in tissues. J. Pharm, exp. Ther. 127: 175–181.Google Scholar
- 17.Holm, E. (1975): Ammoniak und hepatische Enzephalopathie. Biochemie, Elektrophysiologie, Toxikologie. Stuttgart: G. Fischer.Google Scholar
- 18.Jakoby, W.B., Scott, E.M. (1959): Aldehyde oxidation. III. Succinic semialdehyde dehydrogenase. J. Biol. Chem. 234: 936–940.Google Scholar
- 20.Jellinger, K., Riederer, P., Kothbauer, P.: Brain monoamines in human cerebral infarction. A preliminary study. Acta neuropath. (Berl.) 41: (in press).Google Scholar
- 22.Klatzo, I. (1075): Pathophysiologic aspects of cerebral ischemia. In: The nervous system, D.B. Tower, ed. New York: Raven Press, 313–321.Google Scholar
- 25.Lavyne, M., Moskowitz, M.A., Larin, F., Zervas, N. and Wurtman, R.J. (1975): Brain 3H-catecholamine metabolism in experimental cerebral ischemia. Neurology (Min.) 25: 483–485.Google Scholar
- 30.Moskowitz, M.A. and Wurtman, R.J. (1976): Acute stroke and brain monoamines. In:Cerebrovascular diseases, P. Scheinberg (ed.) New York: Raven Press: 153–166.Google Scholar
- 35.Plum, F., Hindfelt, B. (1976): The neurological complications of liver disease. In: Handbook of Clinical Neurology (Binken, P.J., Gruyn, G.W. eds,) vol. 25 Amsterdam-New York: North Holland, 349–377.Google Scholar
- 39.Riederer, P., Jellinger, K., Wuketich, St. (1978): Postmortem changes of tryptophan in human brain. In preparation.Google Scholar
- 44.Sourkes, T.L., Young, S.N., Garelis, E., Lal, S.(1975): Gradients of concentrations of tryptophan and 5-hy-droxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Acta vitam. enzym.(Milano) 29: 97–99.Google Scholar
- 46.Welch, K.M.A., Chabi, E., Dodson, R.F., Wang, T.P.F., Nell, J. and Bergin, B. (1976): The role of biogenic amines in the progression of cerebral ischemia and edema: modification by p-chlorophenylalanine, methy-sergide and pentoxyfilline. In:Dynamics of Brain Edema, H.H. Pappius and W. Feindell (eds). Berlin-Heidelberg-New York: Springer-Verlag, 193–202.CrossRefGoogle Scholar
- 48.Wurtman, R.J., Lavyne, M.H. and Zervas, N.T. (1975): Brain catecholamines in relation to cerebral blood vessels. In: Cerebral Vascular Disease, J.P. Whisnant and B.A. Sandok (eds). New York: Grune and Stratton: 13–27.Google Scholar