Summary
Transient periods of global cerebral ischemia lead to selective neuronal damage in the striatum. We investigated the effects of unilateral 6-hydroxydopamine lesions of the mesostriatal dopamine (DA) system on the density and distribution of neuronal necrosis in the rat striatum following ischemia induced by bilateral occlusion of the common carotid arteries combined with hypotension. After both 12 and 15 min of ischemia, which caused slight and extensive striatal damage, respectively, there was no difference in the density of neuronal necrosis in the striatum between DA-lesioned and shamoperated animals. We conclude that the DA system alone does not modulate injury following complete cerebral ischemia, but may contribute significantly to damage following conditions such as during hypoglycemia and incomplete cerebral ischemia.
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References
Agardh C-D, Folbergrová J, Siesjö BK (1978) Cerebral metabolic changes in profound insulin-induced hypoglycemia and in the recovery period following glucose administration. J Neurochem 31:1135–1142
Agardh C-D, Carlsson A, Lindquist M, Siesjö BK (1979) The effect of pronounced hypoglycemia on monoamine metabolism in rat brain. Diabetes 28:804–809
Albers GW, Goldberg MP, Choi DW (1989) N-methyl-D-aspartate antagonists: ready for clinical trial in brain ischemia? Ann Neurol 25:398–403
Block GA, Pulsinelli WA (1987) Excitatory amino acid receptor antagonists: failure to prevent ischemie neuronal damage. J Cerebr Blood Flow Metabol 7 Suppl 1:149
Blomqvist P, Lindvall O, Wieloch T (1985) Lesions of the locus coeruleus system aggravate ischemie damage in the rat brain. Neurosci Lett 58:353–358
Clemens JA, Phebus LA (1988) Dopamine depletion protects striatal neurons from ischemia-induced cell death. Life Sci 42:707–713
Germano IM, Pitts LH, Meldrum BS, Bartowski HM, Simon RP (1987) Kynurenate inhibition of cell excitation decreases stroke size and deficits. Ann Neurol 22:730–734
Gill R, Foster AC, Woodruff GN (1986) Systemic administration of MK-801 protects against ischaemia-induced hippocampus neurodegeneration in the gerbil. J Neurosci 7:3343–3349
Globus MY-T, Ginsberg MD, Dietrich DT, Busto R, Scheinberg P (1987) Substantia nigra lesion protects against ischemie damage in the striatum. Neurosci Lett 80:251–256
Globus MY-T, Busto R, Dietrich WD, Martinez E, Valdés I, Ginsberg MD (1989a) The role of dopamine and glutamate in the development of ischemie neuronal injury in the striatum. In: Ginsberg MD, Dalton DW (eds) Cerebrovascular diseases. Raven Press, New York, pp 99–110
Goroleva NA, Koroleva VO, Amemori T, Pavlik V, Bures J (1987) Ketamine blockade of cortical spreading depression in rats. Electroencephalogr Clin Neurophysiol 66:440–447
Gustafson I, Miyauchi Y, Wieloch T (1989) Postischemic administration of idazoxan, an beta-blocker adrenergic receptor antagonist, decreases neuronal damage in the rat brain. J Cereb Blood Flow Metab 9:171–174
Hansen AJ, Zeuthen T (1981) Extracellular ion concentrations during spreading depression and ischemia in the rat brain cortex. Acta Physiol Scand 113:437–445
Hansen AJ, Lauritzen M, Wieloch T (1988) NMDA antagonists inhibit cortical spreading depression, but not anoxic depolarisation. In: Turski L, Lehmann J, Cavalheiro EA (eds) Frontiers in excitatory amino acid research. Alan Liss, New York, pp 661–666
Harik SI, Yoshida S, Busto R, Ginsberg MD (1986) Monoamine neurotransmitters in diffuse reversible forebrain ischemia and early recirculation: increased dopaminergic activity. Neurology 36:971–976
Lindvall O, Björklund A (1983) Dopaminean norepinephrine-containing neuron systems: their anatomy in the rat brain. In: Emson PC (eds) Chemical neuroanatomy. Raven Press, New York, pp 229–255
Lindvall O, Auer RN, Siesjö BK (1986) Selective lesions of mesostriatal dopamine neurons ameliorate hypoglycemie damage in the caudate-putamen. Exp Brain Res 63:382–385
Loren I, Björklund A, Falck B, Lindvall O (1980) The aluminium-formaldehyde (ALFA) method for improved visualization of catecholamines and indoleamines. I. A detailed account of the methodology for central nervous tissue, using paraffin, cryostat or vibratome sections. J Neurosci Methods 2:277–300
Nowicki J-P, Assumel-Lurdin C, Duverger D, MacKenzie ET (1988) Temporal evolution of regional energy metabolism following focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 8:462–473
Park CK, Nehls DG, Graham DI, Teasdale GM; McCulloch J (1988) The glutamate antagonist MK-801 reduced focal ischemic brain damage in the rat. Ann Neurol 24:543–551
Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, Sydney
Phebus LA, Perry KW, Clemens JA, Fuller RW (1986) Brain anoxia releases striatal dopamine in rats. Life Sci 38:2447–2453
Pulsinelli WA, Bierley JB (1979) A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke 10:267–272
Siesjö BK and Bengtsson F (1989) Calcium fluxes, calcium antagonists, and calcium related pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis. J Cerebr Blood Flow Metabol 9:127–140
Simon RP, Schmiedly JW, Meldrum BS, Swan JH, Chapman AG (1986) Excitotoxic mechanisms in hypoglycaemic hippocampal injury. Neuropath Appl Neurobiol 12:567–576
Smith A-L, Béndek G, Dahlgren N, Rosén I, Wieloch T, Siesjö BK (1984) Models for studying long-term recovery following forebrain ischemia in the rat. 2. A 2-vessel occlusion model. Acta Neurol Scand 69:385–401
Steinberg GK, George CP, De La Paz R, Shibata DK, Gross T (1988) Dextromethorphan protects against cerebral injury following transient focal ischemia in rabbits. Stroke 19:1112–1118
Swan JH, Evans MC, Meldrum BS (1988) Long-term development of selective neuronal loss and the mechanism of protection by 2-amino-7-phosphonoheptanoate in a rat model of incomplete forebrain ischaemia. J Cereb Blood Flow Metabol 8:64–78
Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotation behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal system. Brain Res 24:485–493
Van Harreveld A (1959) Compounds in brain extracts causing spreading depression of cerebral cortical activity and contraction of crusacean muscle. J Neurochem 3:300–315
Westerberg E, Kehr J, Ungerstedt U, Wieloch T (1988) The NMDA-antagonist MK-801 reduces extracellular amino acid levels during hypoglycemia and prevents striatal damage. Neurosci Res Commun 3:151–158
Wieloch T (1985) Hypoglycemia-induced neuronal damage prevented by an N-methy1-D-aspartate antagonist. Science 230:681–683
Wieloch T, Gustafson I, Westerberg E (1988) Effects of the noncompetitive NMDA receptor antagonist MK-801 on ischemie and hypoglycemie brain damage. In: Turski L, Lehmann J, Cavalheiro EA (eds) Frontiers in excitatory amino acid research. Alan Liss, New York, pp 715–722
Wieloch T, Westerberg E (1989) Mechanisms of glutamate neurotoxicity in cerebral ischemia. In: J Seylaz, R Sercombe (eds) Neurotransmission and cerebrovascular function, II. Elsevier Science Publishers B. V, pp 393–409
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Wieloch, T., Miyauchi, Y. & Lindvall, O. Neuronal damage in the striatum following forebrain ischemia: lack of effect of selective lesions of mesostriatal dopamine neurons. Exp Brain Res 83, 159–163 (1990). https://doi.org/10.1007/BF00232204
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DOI: https://doi.org/10.1007/BF00232204