Acta Neuropathologica

, Volume 72, Issue 1, pp 23–28 | Cite as

Resistance to hypoglycemia of cerebellar transplants in the rat forebrain

  • P. Kleihues
  • M. Kiessling
  • R. Thilmann
  • Y. Xie
  • A. Uozumi
  • B. Volk
Original Works


Prolonged insulin-induced hypoglycemia causes widespread loss of neurons and permanent brain damage with irreversible coma. Although the deprivation of carbohydrate stores affects all brain regions, the breakdown of energy metabolism and cessation of protein synthesis occur predominantly in the cerebral cortex, caudoputamen and hippocampus. The cerebellum, brain stem and hypothalamus are largely resistant. Following transplantation of the cerebellar anlage of rat fetuses (day 15 of gestation) into the caudoputamen of adult rats, the grafts were allowed to differentiate for a period of 8 weeks. The host animals were then subjected to 30 min of severe hypoglycemia with isoelectric EEG (‘coma’). In contrast to the surrounding vulnerable brain structures, protein synthesis was fully preserved within the cerebellar transplant. Grafting of fetal forebrain cortex to the same location did not result in escape from hypoglycemic cell injury. This indicates that resistance to hypoglycemia is part of the programmed differentiation of the cerebellum and develops irrespective of its location and functional integration within the nervous system.

Key words

Hypoglycemia Cerebellum Selective vulnerability Neural grafts Protein synthesis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agardh C-D, Siesjö BK (1981) Hypoglycemic brain injury: phospholipids, free fatty acids, and cyclic nucleotides in the cerebellum of the rat after 30 and 60 min of severe hypoglycemia. J Cereb Blood Flow Metab 1:267–275Google Scholar
  2. Agardh C-D, Rosén I, Ryding E (1983) Persistent vegetative state with high cerebral blood flow following profound hypoglycemia. Ann Neurol 14:482–486Google Scholar
  3. Auer RN, Wieloch T, Olsson Y, Siesjö BK (1984) The distribution of hypoglycemic brain damage. Acta Neuropathol (Berl) 64:177–191Google Scholar
  4. Auer R, Kalimo H, Olsson Y, Wieloch T (1985) The dentate gyrus in hypoglycemia: pathology implicating excitotoxin-mediated neuronal necrosis. Acta Neuropathol (Berl) 67:279–288Google Scholar
  5. Björklund A, Stenevi U (1984) Intracerebral neural transplants: neuronal replacement and reconstruction of damaged circuitries. Annu Rev Neurosci 7:279–308Google Scholar
  6. Brierley JB, Brown AW, Meldrum BS (1971) The nature and time course of the neuronal alterations resulting from oligemia and hypoglycemia in the brain ofMacaca mulatta. Brain Res 25:483–499Google Scholar
  7. Cremer JE, Cunningham VJ, Seville MP (1983) Relationships beween extraction and metabolism of glucose, blood flow, and tissue blood volume in regions of rat brain. J Cereb Blood Flow Metab 3:291–302Google Scholar
  8. Das GD, Hallas BH, Das KG (1979) Transplantation of neural tissues in the brains of laboratory mammals: technical details and comments. Experientia 35:143–153Google Scholar
  9. Fazekas JF, Alman RF, Parrish AE (1951) Irreversible posthypoglycemic coma. Am J Med 222:640–643Google Scholar
  10. Finley KH, Brenner C (1941) Histologic evidence of damage to the brain in monkeys treated with Metrazole and insulin. Arch Neurol Psychiatry 45:403–438Google Scholar
  11. Freed WJ, de Medinaceli L, Wyatt RJ (1985) Promoting functional plasticity in the damaged nervous system. Science 227:1544–1552Google Scholar
  12. Gage FH, Dunnett SB, Brundin P, Isacson O, Björklund A (1983) Intracerebral grafting of embryonic neural cells into the adult host brain: an overview of the cell suspension method and its application. Dev Neurosci 6:137–151Google Scholar
  13. Hawkins RA, Biebuyck JF (1979) Ketone bodies are selectively used by individual brain regions. Science 205:325–327Google Scholar
  14. Himwich HE (1951) Brain metabolism and cerebral disorders. Williams nad Wilkins, Baltimore, pp 257–302Google Scholar
  15. Kalimo H, Olsson Y (1980) Effect of severe hypoglycemia on the human brain. Acta Neurol Scand 62:345–356Google Scholar
  16. Kiessling M, Weigel K, Gartzen D, Kleihues P (1982) Regional heterogeneity ofl-[3-3H]tyrosine incorporation into rat brain proteins during severe hypoglycemia. J Cereb Blood Flow Metab 2:249–253Google Scholar
  17. Kiessling M, Xie Y, Kleihues P (1984) Regionally selective inhibition of cerebral protein synthesis in the rat during hypoglycemia and recovery. J Neurochem 43:1507–1514Google Scholar
  18. Kiessling M, Volk B, Thilmann R, Xie Y, Uozumi A, Wiestler OD, Kleihues P (1985) Neural transplants in the investigation of selective neuronal vulnerability. J Cereb Blood Flow Metab 5:S321-S322Google Scholar
  19. Kiessling M, Auer RN, Kleihues P, Siesjö BK (1986) Cerebral protein synthesis during long-term recovery from severe hypoglycemia. J Cereb Blood Flow Metab 6:42–51Google Scholar
  20. LaManna JC, Harik SI (1985) Regional comparison of brain glucose influx. Brain Res 326:299–305Google Scholar
  21. Lewis LD, Ljunggren B, Ratcheson RA, Siesjö BK (1974) Cerebral energy state in insulin-induced hypoglycemia, related to blood glucose and to EEG. J Neurochem 23:673–679Google Scholar
  22. Meyers RE, Kahn KJ (1971) Insulin-induced hypoglycemia in nonhuman primate. II. Long-term neuropathological consequences. Clin Dev Med 39/40:195–206Google Scholar
  23. Norberg K, Siesjö BK (1976) Oxidative metabolism of the cerebral cortex of the rat in severe insulin-induced hypoglycaemia. J Neurochem 26:345–352Google Scholar
  24. Peters P, Ashley CA (1967) An artefact in radioautography due to binding of free amino acids to tissues by fixatives. J Cell Biol 33:53–60Google Scholar
  25. Ratcheson RA, Blank AC, Ferendelli JA (1981) Regionally selective metabolic effects of hypoglycemia in brain. J Neurochem 36:1952–1958Google Scholar
  26. Siesjö BK (1978) Brain energy metabolism. Wiley, New York, pp 101–125Google Scholar
  27. Siesjö BK (1981) Cell damage in the brain: a speculative hypothesis. J Cereb Blood Flow Metab 1:155–185Google Scholar
  28. Sokoloff L (1973) Metabolism of ketone bodies by the brain. Annu Rev Med 24:271–280Google Scholar
  29. Sternberger LA (1979) Immunocytochemistry, 2nd edn. Wiley, New YorkGoogle Scholar
  30. Stewart PA, Wiley MJ (1981) Developing nervous tissue induced formation of blood-brain-barrier characteristics in invading endothelial cells: a study using quail-chick transplantation chimeras. Dev Biol 84:183–192Google Scholar
  31. Wieloch T, Engelsen B, Westerberg E, Auer R (1985) Lesions of the glutaminergic cortico-striatal projections in the rat ameliorate hypoglycemic brain damage in the striatum. Neuroscience Lett 58:25–30Google Scholar
  32. Wilkinson DS, Prockop LD (1976) Hypoglycemia: effects on the central nervous system. In: Vincken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 27. American Elsevier, New York, pp 53–78Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • P. Kleihues
    • 1
  • M. Kiessling
    • 2
  • R. Thilmann
    • 2
  • Y. Xie
    • 2
  • A. Uozumi
    • 2
  • B. Volk
    • 2
  1. 1.Laboratory of Neuropathology, Institute of PathologyUniversity of ZürichZürichSwitzerland
  2. 2.Laboratory of Neuropathology, Institute of PathologyUniversity of FreiburgFreiburg i. Br.Germany

Personalised recommendations