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Mechanisms of hypoglycemic brain damage

Evidence against a significant role of the noradrenergic locus coeruleus system

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Summary

Selective lesions of the noradrenergic locus coeruleus (LC) system have recently been shown to aggravate both ischemic and epileptic brain damage. This study explores the possibility that the LC system also influences hypoglycemic brain injury. Bilateral 6-hydroxydopamine lesions of the LC projection to the forebrain were found to cause no change in the degree of neuronal necrosis in the neocortex, hippocampal formation and caudateputamen following 30 min of reversible insulin-induced hypoglycemic coma. We propose that selective neuronal necrosis in ischemia and status epilepticus is due to the action of excitatory amino acids at synaptic sites, which can be partly counteracted by noradrenaline release from inhibitory LC terminals. In hypoglycemia, excitatory amino acids probably cause brain damage via a local and more diffuse toxic effect which is not significantly influenced by the activation of the LC system.

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References

  • Abdul-Rahman A, Agardh C-D, Siesjö BK (1980) Local cerebral blood flow in the rat during severe hypoglycemia, and in the recovery period following glucose injection. Acta Physiol Scand 109: 307–314

    Google Scholar 

  • 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

    Google Scholar 

  • Amaral DG, Sinnamon HM (1977) The locus coeruleus: neurobiology of a central noradrenergic nucleus. Prog Neurobiol 9: 147–196

    Google Scholar 

  • Auer RN (1986) Progress review: hypoglycemic brain damage. Stroke 17: 699–708

    Google Scholar 

  • Auer RN, Olsson Y, Siesjö BK (1984a) Hypoglycemic brain injury in the rat. Correlation of density of brain damage with the EEG isoelectric time: a quantitative study. Diabetes 33: 1090–1098

    Google Scholar 

  • Auer RN, Wieloch T, Olsson Y, Siesjö BK (1984b) The distribution of hypoglycemic brain damage. Acta Neuropathol (Berl) 64: 177–191

    Google Scholar 

  • Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43: 1369–1374

    Google Scholar 

  • Blomqvist P, Lindvall O, Wieloch T (1985) Lesions of the locus coeruleus system aggravate ischemic damage in the rat brain. Neurosci Lett 58: 353–358

    Google Scholar 

  • Chauvel P, Trottier S (1986) Role of noradrenergic ascending system in extinction of epileptic phenomena. Adv Neurol 44: 475–487

    Google Scholar 

  • Dahlgren N, Lindvall O, Sakabe T, Stenevi U, Siesjö BK (1981) Cerebral blood flow and oxygen consumption in the rat brain after lesions of the noradrenergic locus coeruleus system. Brain Res 209: 11–23

    Google Scholar 

  • Foote SL, Bloom FE, Aston-Jones G (1983) Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev 63: 844–914

    Google Scholar 

  • Ingvar M, Lindvall O, Folbergrova J, Siesjö BK (1983) Influence of lesions of the noradrenergic locus coeruleus system on the cerebral metabolic response to bicuculline-induced seizures. Brain Res 264: 225–231

    Google Scholar 

  • Lindvall O, Björklund A (1983) Dopamine- and norepinephrine-containing neuron systems: their anatomy in the rat brain. In: Emson PC (ed) Chemical neuroanatomy. Raven Press, New York, pp 229–255

    Google Scholar 

  • Lindvall O, Auer RN, Siesjö BK (1986) Selective lesions of mesostriatal dopamine neurons ameliorate hypoglycemic damage in the caudate-putamen. Exp Brain Res 63: 382–386

    Google Scholar 

  • Nevander G, Ingvar M, Lindvall O (1986) Mechanisms of epileptic brain damage: evidence for a protective role of the noradrenergic locus coeruleus system in the rat. Exp Brain Res 63: 439–442

    Google Scholar 

  • Olney JW (1978) Neurotoxicity of excitatory amino acids. In: McGeer EG, Olney JW, McGeer PL (eds) Kainic acid as a tool in neurobiology. Raven Press, New York, pp 95–121

    Google Scholar 

  • Olney JW, Gubareff T, Sloviter RS (1983) “Epileptic” brain damage in rats induced by sustained electrical stimulation of the perforant path. II. Ultrastructural analysis of acute hippocampal pathology. Brain Res Bull 10: 699–712

    Google Scholar 

  • Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11: 491–499

    Google Scholar 

  • Rothman SM (1984) Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci 4: 1884–1891

    Google Scholar 

  • Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19: 105–111

    Google Scholar 

  • Sandberg M, Butcher SP, Hagberg H (1986) Extracellular over-flow of neuroactive amino acids during severe insulin-induced hypoglycemia: in vivo dialysis of the rat hippocampus. J Neurochem 47: 178–185

    Google Scholar 

  • Schmidt RH, Ingvar M, Lindvall O, Stenevi U, Björklund A (1982) Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and (14C)-2-deoxy-D-glucose autoradiography. J Neurochem 38: 737–748

    Google Scholar 

  • Schwarcz R, Foster AC, French ED, Whetsell WO Jr, Köhler C (1984) Excitotoxic models for neurodegenerative disorders. Life Sci 35: 19–32

    Google Scholar 

  • Siesjö BK (1981) Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1: 155–185

    Google Scholar 

  • Simon RP, Swan JH, Griffith T, Meldrum BS (1984) Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science 226: 850–852

    Google Scholar 

  • Sloviter RS (1983) “Epileptic” brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light microscopic studies. Brain Res Bull 10: 675–697

    Google Scholar 

  • Sloviter RS (1987) Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science 235: 73–76

    Google Scholar 

  • Smith M-L, Auer RN, Siesjö BK (1984) The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia. Acta Neuropathol (Berl) 64: 319–332

    Google Scholar 

  • Wieloch T (1985) Hypoglycemia-induced neuronal damage is prevented by a N-methyl-d-aspartate antagonist. Science 230: 681–683

    Google Scholar 

  • Wieloch T, Engelsen B, Westerberg E, Auer R (1985) Lesions of the glutamatergic cortico-striatal projections in the rat ameliorate hypoglycemic brain damage in the striatum. Neurosci Lett 58: 25–30

    Google Scholar 

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Lindvall, O., Auer, R.N. & Siesjö, B.K. Mechanisms of hypoglycemic brain damage. Exp Brain Res 73, 219–223 (1988). https://doi.org/10.1007/BF00279676

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