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Fasting prior to transient cerebral ischemia reduces delayed neuronal necrosis

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Abstract

A transient brain ischemia of 30-min duration was induced by the four-vessel occlusion technique in normally fed and in 48-hr-fasted rats. Evaluation of brain damage 72 hr after ischemia showed that fasting reduced neuronal necrosis in the striatum, the neocortex, and the lateral part of the CA1 sector of hippocampus. Signs of status spongiosis in the pars reticulata of the substantia nigra were seen in 75% of fed rats and in only 19% of fasted rats. The protective effect was associated with reduction in mortality and in postischemic seizure incidence. The metabolic changes induced by fasting were evaluated before and during ischemia. After 30 min of four-vessel occlusion, fasted rats showed a marked decrease in brain lactate level (14.7 vs 22.5 μmol/g in fed rats;P < 0.001). The decrease in brain lactate concentration might explain the beneficial effect of fasting by minimizing the neuropathological consequences of lactic acidosis. Several factors may account for lower lactate production during ischemia in fasted rats: hypoglycemia, reduction in preischemic stores of glucose and glycogen, or increased utilization of ketone bodies aiming at reducing the glycolytic rate.

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References

  • Atkinson, D. E. (1968). The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers.Biochemistry 7: 4030–4034.

    Google Scholar 

  • Blomqvist, P., Lindvall, O., Steveni, U., and Wieloch, T. (1985). Cyclic AMP concentrations in rat neocortex and hippocampus during and following incomplete ischemia: Effects of central noradrenergic neurons, prostaglandins, and adenosine.J. Neurochem. 44: 1345–1353.

    Google Scholar 

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

    Google Scholar 

  • Clarke, D. W., Boyd, F. T., Kappy, M. S., and Raizada, M. K. (1984). Insulin binds to specific receptors and stimulates 2-deoxy-D-glucose uptake in cultured glial cells from rat brain.J. Biol. Chem. 259: 11672–11675.

    Google Scholar 

  • Combs, D. J., and D'Alecy, L. G. (1987). Motor performance in rats exposed to severe forebrain ischemia: Effect of fasting and 1,3-butanediol.Stroke 18: 503–511.

    Google Scholar 

  • Cremer, J. E. (1982). Substrate utilization and brain development.J. Cereb. Blood Flow Metab. 2: 394–407.

    Google Scholar 

  • DiVivo, D. C., Leckie, M. P., Ferrendell, J. S., and McDougal, D. B. (1978). Chronic ketosis and cerebral metabolism.Ann. Neurol. 3: 331–337.

    Google Scholar 

  • Folbergrova, J., MacMillan, V., and Siesjö, B. K. (1972). The effect of moderate and marked hypercapnia upon the energy rate and upon the cytoplasmic NADH/NAD+ ratio of the rat brain.J. Neurochem. 19: 2497–2505.

    Google Scholar 

  • Gardiner, M., Smith, M.-L., Kagström, E., Shohami, E., and Siesjö, B. K. (1982). Influence of blood glucose concentration on brain lactate accumulation during severe hypoxia and subsequent recovery of brain energy metabolism.J. Cereb. Blood Flow Metab. 2: 429–438.

    Google Scholar 

  • Go, K. G., Ptenen, G. H. M., and Korf, J. (1988). Protective effect of fasting upon cerebral hypoxic-ischemic injury.Metab. Brain Dis. 3: 257–263.

    Google Scholar 

  • Hawkins, R. A., Williamson, D. H. and Krebs, H. A. (1971). Ketone body utilization by adult and suckling rat brain in vivo.Biochem. J. 122: 13–18.

    Google Scholar 

  • Hertz, M. M., Paulson, O. B., Barry, D. I., Christiansen, J. S., and Svendsen, P. A. (1981). Insulin increases glucose transfer across the blood brain barrier in man.J. Clin. Invest. 67: 597–603.

    Google Scholar 

  • Iadarola, M. J., and Gale, K. (1982). Substantia nigra: Site of anitconvulsant activity mediated by gamma-aminobutyric acid.Science 218: 1237–1240.

    Google Scholar 

  • Inamura, K., Olsson, Y., and Siesjö, B. K. (1987). Substantia nigra damage induced by ischemia in hyperglycemic rats. A light and electron microscopic study.Acta Neuropathol. 75: 131–139.

    Google Scholar 

  • Kalimo, H., Rehncrona, S., Söderfelt, B., Olsson, Y., and Siesjö, B. K. (1981). Brain lactic acidosis and ischemic cell damage.J. Cereb. Blood Flow Metab. 1: 313–327.

    Google Scholar 

  • Kirino, T. (1982). Delayed neuronal death in the gerbil hippocampus following ischemia.Brain Res. 239: 57–69.

    Google Scholar 

  • Kirsch, J. R., and D'Alecy, L. G. (1979). Effect of altered availability of energy-yielding substrates upon survival from hypoxia in mice.Stroke 10: 288–291.

    Google Scholar 

  • Kirsch, J. R., and D'Alecy, L. G. (1983). Role of tissue lactate and substrate availability in 1,3-butanediolenhanced hypoxic survival in the mouse.Stroke 14: 971–976.

    Google Scholar 

  • Kirsch, J. R., and D'Alecy, L. G. (1984a). Hypoxia induced preferential ketone utilization by rat brain slices.Stroke 15: 319–323.

    Google Scholar 

  • Kirsch, J. R., and D'Alecy, L. G. (1984b). Glucagon stimulates ketone utilization by rat brain slices.Stroke 15: 324–328.

    Google Scholar 

  • Kraig, R.P., Pulsinelli, W. A., and Plum, F. (1985). Hydrogen ion buffering during complete brain ischemia.Brain Res. 342: 281–290.

    Google Scholar 

  • Lowry, O. H., and Passoneau, J. V. (1972).A Flexible System of Enzymatic Analysis, Academic Press, New York.

    Google Scholar 

  • Lucignani, G., Namba, H., Nehlig, A., Porrino, L. J., Kennedy, C., and Sokoloff, L. (1987). Effects of insulin on local cerebral glucose utilization.J. Cereb. Blood Flow Metab. 7: 309–314.

    Google Scholar 

  • Lust, W. D., Passoneau, J. V., and Crites, S. K. (1975). The measurement of glycogen in tissues by amylo-α-1,4-α-1,6-glucosidase after destruction of preexisting glucose.Anal. Biochem. 68: 328–331.

    Google Scholar 

  • MacMillan, V. (1982). Cereral Na+, K+-ATPase activity during exposure to and recovery from acute ischemia.J. Cereb. Blood Flow Metab. 2: 457–465.

    Google Scholar 

  • Marie, C., Bralet, A. M., and Bralet, J. (1987). Protective action of 1,3-butanediol in cerebral ischemia. A neurologic, histologie and metabolic study.J. Cereb. Blood Flow Metab. 7: 794–800.

    Google Scholar 

  • Miller, A. L. (1986). Regional glucose and ß-hydroxybutyrate use by developing rat brain.Metab. Brain Dis. 1: 53–61.

    Google Scholar 

  • Miller, A. L., Kiney, C. A., Corddry, C. H., and Staton, D. M. (1982). Interactions between glucose and ketone body use by developing brain.Dev. Brain Res. 4: 443–450.

    Google Scholar 

  • Myers, R. E. (1979). A unitary theory of causation of anoxic and hypoxic brain pathology. In Fahn, S., Davis, H. N. and Rowland, L. P. (eds.),Advances in Neurology, Vol. 26. Cerebral Hypoxia and Its Consequences, Raven Press, New York, pp. 195–213.

    Google Scholar 

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

    Google Scholar 

  • Owen, O. E., Morgan, A. P., Kemp, H. G., Sullivan, J. M., Herrera, M. G., and Cahill, G. F. (1967). Brain metabolism during fasting.J. Clin. Invest. 46: 1589–1595.

    Google Scholar 

  • Ponten, U., Ratcheson, R. A., Salford, L. G., and Siesjö, B. K. (1973). Optimal freezing conditions for cerebral metabolites in rats.J. Neurochem. 21: 1127–1138.

    Google Scholar 

  • Pulsinelli, W. A., and Brierley, J. B. (1979). A new model of bilateral hemispheric ischemia in the unanesthetized rat.Stroke 10: 267–272.

    Google Scholar 

  • Pulsinelli, W. A., Brierley, J. B., and Plum, F. (1982a). Temporal profile of neuronal damage in a model of transient forebrain ischemia.Ann. Neurol. 11: 491–498.

    Google Scholar 

  • Pulsinelli, W. A., Waldman, S., Rawlinson, D., and Plum, F. (1982b). Moderate hyperglycemia augments ischemic brain damage: A neuropathologic study in the rat.Neurology 32: 1239–1246.

    Google Scholar 

  • Rehncrona, S., Rosen, I., and Siesjö, B. K. (1981). Brain lactic acidosis and ischemic cell damage. 1. Biochemistry and neurophysiology.J. Cereb. Blood Flow Metab. 1: 297–311.

    Google Scholar 

  • Rehncrona, S., Rosen, I., and Smith, M.-L. (1985). Effect of different degrees of brain ischemia and tissue lactic acidosis on the short-term recovery of neurophysiologic and metabolic variables.Exp. Neurol. 87: 458–473.

    Google Scholar 

  • Ruderman, N. B., Ross, P. S., Berger, M., and Goodman, M. N. (1974). Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats.Biochem. J. 138: 1–10.

    Google Scholar 

  • Sabatino, M., Gravante, G., Ferraro, G., Savatteri, V., and La Grutta, V. (1988). Inhibitory control by substantia nigra of generalized epilepsy in the cat.Epilepsy Res. 2: 380–386.

    Google Scholar 

  • Shin, C., Silver, J. M., Bonhaus, D. W., and McNamara, J. O. (1987). The role of substantia nigra in the development of kindling: Pharmacologie and lesion studies.Brain Res. 412: 311–317.

    Google Scholar 

  • Siemkowicz, E., and Hansen, A. J. (1978). Clinical restitution following cerebral ischemia in hypo-, normo- and hyperglycemic rats.Acta Neurol. Scand. 58: 1–8.

    Google Scholar 

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

    Google Scholar 

  • Welsh, F. A., Ginsberg, M. D., Rieder, W., and Budd, W. W. (1980). Deleterious effect of glucose pretreatment on recovery from diffuse cerebral ischemia in the cat. II. Regional metabolite levels.Stroke 11: 355–363.

    Google Scholar 

  • Williamson, D. H., Mellanby, J., and Krebs, H. A. (1962). Enzymic determination of D(-)-β-hydroxybutyric acid in blood.Biochem. J. 82: 90–96.

    Google Scholar 

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Marie, C., Bralet, A.M., Gueldry, S. et al. Fasting prior to transient cerebral ischemia reduces delayed neuronal necrosis. Metab Brain Dis 5, 65–75 (1990). https://doi.org/10.1007/BF01001047

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