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Influence of the plasma glucose level on brain damage after systemic kainic acid injection in the rat

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Summary

Systemic administration of kainic acid (KA), 11 mg/kg body weight, to hyperglycemic rats induced lethal seizures in all animals, while 40% of normoglycemic rats survived the KA treatment and all hypoglycemic rats survived. An inverse correlation (P<0.01) between the plasma glucose level and survival during KA-induced seizures was demonstrated (Chi-square-test). Histopathological observations on the surviving rats clearly divided them into a group with severe hippocampal CA-1 damage and a group with mild hippocampal CA-1 damage. Hippocampal pyramidal cells and CA-1 interneurons were counted 3 weeks after the insult. The pyramidal cell loss in the CA-1 region was significant within mildly, as well as severely, affected rats with normo- and with hypoglycemia. CA-1 interneurons and CA-4 interneurons were only lost in the severely affected group. Hypoglycemia seemed to protect those CA-1 interneurons situated close to the alveus and within the stratum radiatum in these animals. The increased mortality in the hyperglycemic rats could be due to increased brain lactate accumulation, but extracerebral damage of hyperglycemia in association with KA is also a possibility. The study indicated a correlation between loss of interneurons and pronounced CA-1 pyramidal cell death and furthermore that hypoglycemia possibly protected some interneurons against KA.

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References

  • Ben-Ari Y, Trembley E, Ottersen OP, Medlrum BS (1980) The role of epileptic activity in hippocampal and “remote” cerebral lesions induced by kainic acid. Brain Res 191:79–107

    Google Scholar 

  • Ben-Ari Y, Trembley E, Riche D, Ghilini G, Naquet R (1981) Electrographic, clinical and pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole: metabolic mapping using the deoxyglucose method with special reference to the pathology of epilepsy. Neuroscience 6:1361–1391

    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 43:1369–1376

    Google Scholar 

  • Berger M, Sperk G, Hornykiewicz O (1982) Serotonergic denervation partially protects rat striatum from kainic acid toxicity. Nature 299:254–256

    Google Scholar 

  • Brierley JB (1984) Cerebral hypoxia. In: Adams JH, Corsellis JAN, Duchen LW (eds) Greenfield's neuropathology. Arnold E, London, pp 125–208

    Google Scholar 

  • Brown AW, Brierley JB (1968) The nature, distribution and earliest stages of anoxic ischemic nerve cell damage in the rat brain as defined by the optical microscope. Br J Exp Pathol 49:87–106

    Google Scholar 

  • Campochiaro P, Coyle JT (1978) Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation. Proc Natl Acad Sci USA 75:2025–2029

    Google Scholar 

  • Chapman AG, Westerberg E, Premanchandra M, Meldrum BS (1984) Changes in regional neurotransmitter amino acid levels in rat brain during seizures induced byl-allylglycine, bicuculline, and kainic acid. J Neurochem 43:62–70

    Google Scholar 

  • Coyle JT, Ferkany J, Zaczek R, Slevin J, Retz K (1983) Kainic acid: insight into its receptor-mediated neurotoxic mechanisms. In: Fuxe K, Roberts P, Schwarcz R (eds) Excitotoxins. Wenner-Gren Center International Symposium series. MacMillan Press, London, pp 112–121

    Google Scholar 

  • Diemer NH, Siemkowicz E (1978) The influence of different glucose levels on brain damage in rats after cerebral ischemia. Neuropathol Appl Neurobiol 4:236

    Google Scholar 

  • Diemer NH, Siemkowicz E (1981) Regionall neurone damage after cerebral ischemia in the normo- and hypoglycaemic rat. Neuropathol Appl Neurobiol 7:217–227

    Google Scholar 

  • Duckrow RB, Beard DC, Brennan RW (1985) Regional cerebral blood flow decreases during hyperglycemia. Ann Neurol 17:267–272

    Google Scholar 

  • Fisher RS, Alger BE (1984) Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice. Brain Res 4:1312–1323

    Google Scholar 

  • Fonnum F (1984) Glutamate: a neurotransmitter in mammalian brain. J Neurochem 42:1–11

    Google Scholar 

  • Foster AC, Fagg GE (1984) Acidic amino acid binding sites in mammalian neuronal membranes: their characteristics and relationship to synaptic receptors. Brain Res Rev 7:103–164

    Google Scholar 

  • Garthwaite J, Garthwaite G (1983) The mechanism of kainic acid neurotoxicity. Nature 305:138–140

    Google Scholar 

  • Gibbs W, Neale EA, Moonen G (1982) Kainic acid sensitivity of mammalian Purkinje cells in monolayer cultures. Dev Brain Res 4:103–108

    Google Scholar 

  • Hillered L (1984) Mitochondrial physiology and pathology. In: Fiskum G (ed) Mechanisms of mitochondrial damage in brain ischemia. Van Nostrand Reinhold, New York, pp 7–45

    Google Scholar 

  • Johansen FF, Jørgensen MB, Diemer NH (1983) Resistance of hippocampal CA-1 interneurons to 20 min of transient ischemia in the rat. Acta Neuropathol (Berl) 61:135–140

    Google Scholar 

  • Johansen FF, Jørgensen MB, Lubitz DKJE, Diemer NH (1984) Selective dendrite damage in hippocampal CA-1 stratum radiatum with unchanged axon ultrastructure and glutamate uptake after transient cerebral ischemia in the rat. Brain Res 291:373–377

    Google Scholar 

  • Kirino T, Tamura A, Sano K (1984) Delayed neuronal death in the rat hippocampus following transient forebrain ischemia. Acta Neuropathol (Berl) 64:139–147

    Google Scholar 

  • Krespan B, Berl S, Nicklas WJ (1982) Alternation in neuronalglia metabolism of glutamate by the neurotoxin kainic acid. J Neurochem 38:509–518

    Google Scholar 

  • Lassmann H, Petsche U, Kitz K, Baran H, Sperk G, Seitelberger F, Hornykiewicz O (1984) The role of brain edema in epileptic brain damage induced by systemic kainic acid injection. Neuroscience 13:691–704

    Google Scholar 

  • Lehmann A, Isacsson H, Hamberger A (1983) Effects of in vivo administration of kainic acid on the extracellular aminoacid pool in the rabbit hippocampus. J Neurochem 40:1314–1320

    Google Scholar 

  • Lothman EW, Collins RC, Ferrendelli JA (1981) Kainic acid-induced limbic seizures: electrophysiologic studies. Neurology 31:806–812

    Google Scholar 

  • Maier-Hauff K, Lange M, Schürer L, Guggenbichler C, Vogt W, Jacob K, Baethmann A (1984) Glutamate and free fatty acid concentrations in extracellular vasogenic edema fluid. In: Go KG, Baethmann A (eds) Recent progress in the study and therapy of brain edema. Plenum Press, New York, pp 183–192

    Google Scholar 

  • Meldrum BS (1981) 17. In: Rose FC (ed) Metabolic disorders of the nervous system. Pitman, London, pp 175–187

    Google Scholar 

  • Myers RE (1979) A unitary theory of causation of anoxic and hypoxic brain pathology. Advances in neurology: cerebral hypoxia and its consequences. Raven Press, New York, pp 195–213

    Google Scholar 

  • Myers RE, Yamaguchi S (1977) Nervous system effects of cardiac arrest in monkeys. Arch Neurol 34:65–74

    Google Scholar 

  • Nadler JV, Cuthbertson GJ (1980) Kainic acid neurotoxicity toward hippocampal formation: dependence on specific excitatory pathways. Brain Res 195:47–56

    Google Scholar 

  • Obata HL, Kubo S, Kinoshita H, Murabe Y, Ibata Y (1981) The effect of small doses of kainic acid on the area CA-3 of the hippocampal formation. An electron microscopic study. Arch Histol Jpn 44:135–149

    Google Scholar 

  • Paljarvi L (1984) Brain lactic acidosis and ischemic cell damage: a topographic study with high-resolution light microscopy of early recovery in a rat model of severe incomplete ischemia. Acta Neuropathol (Berl) 64:89–98

    Google Scholar 

  • Pellegrino LJ, Pellegrino AS, Cushman AJ (1981) A stereotaxic atlas of the rat brain. Plenum Press, New York

    Google Scholar 

  • Pulsinelli WA, Duffy TE (1983) Regional energy balance in the rat brain after transient cerebral forebrain ischemia. J Neurochem 40:1500–1503

    Google Scholar 

  • Pulsinelli WA, Waldman S Rawlinson D, Plum F (1982) Moderate hyperglycaemia augments ischemic brain damage: a neuropathologic study in the rat. Neurology 32:1239–46

    Google Scholar 

  • Ribak CE, Vaughn JE, Saito K (1978) Immunocytochemical localization of glutamic acid decarboxylase in neuronal somata following colchicine inhibition of axonal transport. Brain Res 140:315–332

    Google Scholar 

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

    Google Scholar 

  • Schwob JE, Fuller T, Price JL, Olney JW (1980) Widespread patterns of neuronal damage following systemic or intracerebral injections of kainic acid: a histological study. Neuroscience 5:991–1014

    Google Scholar 

  • Siemkowicz E, Hansen AJ (1982) Clinical restitution following cerebral ischemia in hypo-, normo- and hyperglycaemic rats. Acta Neurol Scand 58:1–8

    Google Scholar 

  • Simon RP, Swan JH, Griffiths T, Meldrum B (1984) Blockade ofN-methyl-d-aspartate receptors may protect against ischemic damage in the brain. Science 226:850–852

    Google Scholar 

  • Sloviter RS, Damino BP (1981) Sustained electrical stimulation of the perforant path duplicates kainate-induced electrophysiological effects and hippocampal damage in the rat. Neurosci Lett 24:279–284

    Google Scholar 

  • Sperk G, Lassmann H, Baran H, Kish SJ, Seitelberger F, Hornykiewicz O (1983) Kainic acid induced seizures: neurochemical and histopathological changes. Neuroscience 10:1301–1315

    Google Scholar 

  • Storm-Mathisen J, Leknes AK, Bore AT, Vaaland JL, Edminson P, Haug FMS, Ottersen OP (1983) First visualization of glutamate and GABA in neurons by immunocytochemistry. Nature 301:517–520

    Google Scholar 

  • Unnerstall JR, Wamsley JK (1983) Autoradiographic localization of high-affinity3H-kainic acid binding sites in the rat forebrain. Eur J Pharmacol 86:361–371

    Google Scholar 

  • Zucker DK, Wooten GF, Lothman EW (1983) Blood-brain barrier changes with kainic acid-induced limbic seizures. Exp Neurol 79:422–433

    Google Scholar 

Download references

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Johansen, F.F., Diemer, N.H. Influence of the plasma glucose level on brain damage after systemic kainic acid injection in the rat. Acta Neuropathol 71, 46–54 (1986). https://doi.org/10.1007/BF00687961

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