Experimental Brain Research

, Volume 160, Issue 4, pp 473–486

“Dark” (compacted) neurons may not die through the necrotic pathway

  • Ferenc Gallyas
  • Attila Csordás
  • Attila Schwarcz
  • Mária Mázló
Research Article

Abstract

“Dark” neurons were produced in the cortex of the rat brain by hypoglycemic convulsions. In the somatodendritic domain of each affected neuron, the ultrastructural elements, except for disturbed mitochondria, were remarkably preserved during the acute stage, but the distances between them were reduced dramatically (ultrastructural compaction). Following a 1-min convulsion period, only a few neurons were involved and their environment appeared undamaged. In contrast, 1-h convulsions affected many neurons and caused swelling of astrocytic processes and neuronal dendrites (excitotoxic neuropil). A proportion of “dark” neurons recovered the normal structure in 2 days. The non-recovering “dark” neurons were removed from the brain cortex through two entirely different pathways. In the case of 1-h convulsions, their organelles swelled, then disintegrated and finally dispersed into the neuropil through large gaps in the plasma membrane (necrotic-like removal). Following a 1-min convulsion period, the non-recovering “dark” neurons fell apart into membrane-bound fragments that retained the compacted interior even after being engulfed by astrocytes or microglial cells (apoptotic-like removal). Consequently, in contrast to what is generally accepted, the “dark” neurons produced by 1-min hypoglycemic convulsions do not die as a consequence of necrosis. As regards the case of 1-h convulsions, it is assumed that a necrotic-like removal process is imposed, by an excitotoxic environment, on “dark” neurons that previously died through a non-necrotic pathway. Apoptotic neurons were produced in the hippocampal dentate gyrus by intraventricularly administered colchicine. After the biochemical processes had been completed and the chromatin condensation in the nucleus had reached an advanced phase, the ultrastructural elements in the somatodendritic cytoplasm of the affected cells became compacted. If present in an apparently undamaged environment such apoptotic neurons were removed from the dentate gyrus through the apoptotic sequence of morphological changes, whereas those present in an impaired environment were removed through a necrotic-like sequence of morphological changes. This suggests that the removal pathway may depend on the environment and not on the death pathway, as also assumed in the case of the “dark” neurons produced by hypoglycemic convulsions.

Keywords

Hypoglycemic convulsions “Dark” neurons Cell death Silver staining Electron microscopy 

References

  1. Attilo A, Söderfeldt B, Kalimo H, Olsson Y, Siesjö BK (1983) Pathogenesis of brain lesions caused by experimental epilepsy. Light and electron-microscopic changes in the rat hippocampus following bicuculline-induced status epilepticus. Acta Neuropathol 59:11–24PubMedGoogle Scholar
  2. Auer RN, Kalimo H, Olsson Y, Siesjö BK (1985a) The temporal evolution of hypoglycemic brain damage. I. Light- and electron-microscopic findings in the rat cerebral cortex. Acta Neuropathol 67:13–24PubMedGoogle Scholar
  3. Auer RN, Kalimo H, Olsson Y, Siesjö BK (1985b) The temporal evolution of hypoglycemic brain damage. II. Light- and electron-microscopic findings in the hippocampal gyrus and subiculum of the rat. Acta Neuropathol 67:25–36PubMedGoogle Scholar
  4. Cammermeyer J (1961) The importance of avoiding “dark” neurons in experimental neuropathology. Acta Neuropathol 1:245–270Google Scholar
  5. Ceccatelli S, Ahlbom E, Diana A, Zhivotovsky B (1997) Apoptosis in rat hippocampal dentate gyrus after intraventricular administration of colchicine. Neuroreport 8:3779–3783PubMedGoogle Scholar
  6. Csordás A, Mázló M, Gallyas F (2003) Recovery versus death of “dark” (compacted) neurons in non-impaired parenchymal environment. Light and electron microscopic observations. Acta Neuropathol 106:37–49PubMedGoogle Scholar
  7. Dietrich WD, Halley M, Alonso 0, Globus MYT, Busto R (1992) Intraventricular infusion of N-methyl-d-aspartate. Acute neuronal consequences. Acta Neuropathol 84:630–637PubMedGoogle Scholar
  8. Ferrer I, Martin F, Serrano T, Reiriz J, Pérez-Navarro E, Alberch J, Macaya A, Planas AM (1995) Both apoptosis and necrosis occur following intrastriatal administration of excitotoxins. Acta Neuropathol 90:504–510CrossRefPubMedGoogle Scholar
  9. Formingli R, Papucci L, Tani A, Schiavone N, Tempestini A, Orlandini GE, Capaccioli S, Orlandini SZ (2000) Aponecrosis: morphological and biochemical exploration of a syncretic process of cell death sharing apoptosis and necrosis. J Cell Physiol 182:41–49CrossRefPubMedGoogle Scholar
  10. Gallyas F, Güldner FH, Zoltay G, Wolff JR (1990) Golgi-like demonstration of “dark” neurons with an argyrophil III method for experimental neuropathology. Acta Neuropathol 79:620–628PubMedGoogle Scholar
  11. Gallyas F, Zoltay G, Horváth Z (1992) Light microscopic response of neuronal somata, dendrites and axons to post mortem concussive head injury. Acta Neuropathol 83:499–503PubMedGoogle Scholar
  12. Gallyas F, Farkas O, Mázló M (2004) Gel-to-gel phase transition may occur in mammalian cells: mechanism of formation of “dark” (compacted) neurons. Biol Cell 96:313–324CrossRefPubMedGoogle Scholar
  13. Goldschmidt RB, Steward O (1980) Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat. Proc Nat Acad Sci U S A 88:3048–3151Google Scholar
  14. Goldschmidt RB, Steward O (1982) Neurotoxic effects of colchicine: differential susceptibility of CNS neuronal populations. Neuroscience 8:695–814CrossRefGoogle Scholar
  15. Graeber MB, Blakemore WF, Kreutzberg GW (2002) Cellular pathology of the central nervous system. In: Graham DI, Lantos PL (eds) Greenfield’s neuropathology, vol 1. Arnold, London, p 126Google Scholar
  16. Harmon BV (1987) An ultrastructural study of spontaneous cell death in mouse mastocytoma with particular reference to dark cells. J Pathol 153:345–355PubMedGoogle Scholar
  17. Ishida K, Shimizu H, Hida H, Urakawa S, Ida K, Nishino H (2004) Argyrophilic dark neurons represent various states of neuronal damage in brain insults: some come to die and others to survive. Neuroscience 125:633–644CrossRefPubMedGoogle Scholar
  18. Kalimo H, Auer RN, Siesjö BK (1985) The temporal evolution of hypoglycemic brain damage. III. Light- and electron-microscopic findings in the rat caudoputamen. Acta Neuropathol 67:37–50PubMedGoogle Scholar
  19. Kerr JFR, Harmon BV (1991) Definition and incidence of apoptosis: an historical perspective. In: Tomel LD, Cope FO (eds) Apoptosis: the molecular basis of cell death. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 5–29Google Scholar
  20. Kiernan JA, Macpherson CM, Price A, Sun T (1998) A histochemical examination of the staining of kainate-induced neuronal degeneration by anionic dyes. Biotech Histochem 73:244–254PubMedGoogle Scholar
  21. Kubova H, Druga R, Lukasiuk K, Suchomelova L, Haugvicova R, Pitkanen A (2001) Status epilepticus causes necrotic damage in the mediodorsal nucleus of the thalamus in immature rats. J Neurosci 15:3593–3599Google Scholar
  22. Liposits ZS, Kalló I, Hrabovszky E, Gallyas F (1997) Ultrastructural pathology of degenerating “dark” granule cells in the hippocampal dentate gyrus of adrenalectomized rats. Acta Biol Hung 48:173–187PubMedGoogle Scholar
  23. Newman GR, Jasani AB (1998) Silver development in microscopy and bioanalysis: past and present. J Pathol 186:119–125CrossRefPubMedGoogle Scholar
  24. Obernier JA, Bouldin TW, Crews FT (2002) Binge ethanol exposure in adult rats causes necrotic cell death. Alcohol Clin Exp Res 26:547–557CrossRefPubMedGoogle Scholar
  25. Petito CK, Pulsinelli WA (1984) Sequential development of reversible and irreversible neuronal damage following cerebral ischemia. J Neuropathol Exp Neurol 43:141–153PubMedGoogle Scholar
  26. Pozas E, Aguado F, Ferrer I (1999) Localization and expression of Jun-like immunoreactivity in apoptotic neurons induced by colchicine administration in vivo and in vitro depends on the antisera used. Acta Neuropathol 98:119–128CrossRefPubMedGoogle Scholar
  27. Tan S, Wood M, Maher P (1998) Oxidative stress induces a form of programmed cell death with characteristics of both apoptosis and necrosis. J Neurochem 71:95–105PubMedGoogle Scholar
  28. Tóth ZS, Hollriegel GS, Soltesz I (1997) Instantaneous perturbation of dentate interneuronal networks by a pressure wave-transient delivered to the neocortex. J Neurosci 17:8106–8117PubMedGoogle Scholar
  29. Turmaine M, Raza A, Mahal A, Mangiarini L, Bates GP, Daves SW (2000) Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington’s disease. Proc Natl Acad Sci U S A 97:8093–8097CrossRefPubMedGoogle Scholar
  30. Wyllie AH (1987) Apoptosis: cell death in tissue relations. J Pathol 153:313–316PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Ferenc Gallyas
    • 1
  • Attila Csordás
    • 1
  • Attila Schwarcz
    • 1
  • Mária Mázló
    • 2
  1. 1.Department of Neurosurgery, Faculty of MedicinePécs UniversityPécsHungary
  2. 2.Central Electron Microscopic Laboratory, Faculty of MedicinePécs UniversityPécsHungary

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