Abstract
Electron microscopy and terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick end-labelling (TUNEL) were used to illustrate the different stages and subcellular alterations of cell degeneration that occur in the striatum of the rat after transient focal ischemia. Degenerating neurons exhibited different morphological types: apoptosis Type 1 (aggregation of dense masses of chromatin beneath the 'intact' nuclear membrane) and Type 2 (high cytoplasmic vacuolization), and necrosis. These profiles were localized in different part of the striatum. Type 1 was found in the head of the caudate putamen, Type 2 in the middle part of the striatum and necrosis in the striatal core. These ultrastructural results demonstrated that apoptosis occurs in neurons following focal ischemia in the striatal penumbra. In contrast, necrosis can be observed in the ischemic core, the region maximally affected by the ischemia. Finally, the presence of astrocytes throughout both the penumbra and ischemic core displaying numerous cytoplasmic vacuoles suggested an activation of glial cells.
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References
Wyllie A. Cell death: a new classification separating apoptosis from necrosis. In: Bowen I, Locksin RA, eds. Cell Death in Biology and Pathology. New York, NY: Chapman & Hall 1981: 9–34.
Arends M, Morris R, Wyllie A. Apoprosis: The role of the endonuclease. Am J Pathol 1990; 136: 593–600.
Oppenheim R. Cell death during development of the nervous system. Annu Rev Neurosci 1991; 14: 453–501.
Kerr J, Wyllie A, Currie A. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239–257.
Trump B, Berezesky I, Osornio-Vargas A. Cell death and the disease process. The role of calcium. In: Bowen I, Locksin RA, eds. Cell Death in Biology and Pathology. New York, NY: Chapman & Hall 1981: 209–225.
Heron A, Pollard H, Dessi F, Lasbennes F, Moreau J, Ben-An Y, Charnaut-Marlangue C. Regional variability in DNA fragmentation after global ischemia evidenced by combined histological and electrophoresis observations in the rat brain. J Neurochem 1993; 61: 1973–1976.
Linnik MD, Zobrist RH, Hatfield MM. Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke 1993; 24: 2002–2009.
MacManus I, Buchan A, Hill I, Rasquinha I, Preston E. Global ischemia can cause DNA fragmentation indicative of apoptosis in rat brain. Neurosci Lett 1993; 164: 89–92.
Charnaut-Marlangue C, Aggoun-Zouaoui D, Represa A, Ben-An Y. Apoprotic features in Ischemia, epilepsy and gpl20 toxicity. Trends Neurosci 1996; 19: 109–114.
Choi D, Ischemia-induced neuronal apoptosis. Current Opin Neurobiol 1996; 6: 667–672.
Ferrer I, Martin F, Serrano T, et al. Both apoptosis and necrosis occur following intrastriatal administration of excitotoxins. Acta Neuropathol 1995; 90: 504–510.
Nitatori T, Sato N, Waguri S, et al. Delayed neuronal death in the CAI pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J Neurosci 1995; 15: 1001–1011.
Charnaut-Marlangue C, Margaill I, Represa A, Popovici T, Plotkine M, Ben-An Y. Apoptosis and necrosis following reversible focal ischemia: an in situ DNA fragmentation analysis. J Cereb Blood Flow Metabol. 1996; 16: 186–194.
Pollard H, Charnaut-Marlangue C, Cantagrel S, et al. Kainate induced apoptocic cell death in hippocampal neurons. Neurosci 1994; 63: 7–18.
Li Y, Victor C, Jiang N, Zaioga C, Sabbah H, Chopp M. Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 1995; 146: 1045–1051.
Van Lookeren Campagne M, Gill R. Ultrastructural morphological changes are not characteristic of apoptotic cell death following focal cerebral ischemia in the rat. Neurosci Lett 1996; 213: 111–114.
Margaill I, Parmentier S, Callebert J, Allix M, Boulu R, Plotkine M. Short therapeutic window for MK-801 in transient focal cerebral ischemia in normotensive rats. J Cereb Blood Flow Metab 1996; 16: 107–113.
Charnaut-Marlangue C, Ben-An Y. A cautionary note on the use of TUNEL stain to describe apoptosis. NeuroRep 1995; 7:61–64.
Charnaut-Marlangue C, Margaill I, Plotkine M, Ben-An Y. Early endonuclease activation following reversible focal ischemia. J Cereb Blood Flow Metabol 1995; 15: 385–388.
Clarke P. Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol 1990; 181: 195–213.
Server A, Mobley W. Neuronal cell death and the role of apopcosis. In: Tomei L, Cope F, eds. Apoptosis: The Molecular Basis of Cell Death. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1991: 263–278.
Portera-Cailleau C, Hedren J, Price D, Koliatos W. Evidence of apoptotic cell death in Huntington disease and excitotoxic animal models. J Neurosci 1995; 15: 3775–3787.
Sloviter R, Dean E, Neubort S. Electron microscopic analysis of adrenalectomy-induced hippocampal granule cell degeneration in the rat: apoptosis in the adult central nervous system. J Comp Neurol 1993; 330: 337–351.
Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 1982; 239: 57–69.
Deshpande J, Bergstedt K, Linden T, Kalimo H, Wieloch T. Ultrastructural changes in the hippocampal CAI region following transient cerebral ischemia evidence against programmed cell death. Exp Brain Res 1992; 88: 91–105.
Tominaga T, Kure S, Yoshimoto T. DNA fragmentation in focal cortical freeze injury of rats. Neurosci Lett 1992; 139: 265–268.
Pollard H, Cantagrel S, Charnaut-Marlangue C, Moreau I, Ben-An Y. Apoptosis associated DNA fragmentation in epileptic brain damage. Neurorep 1994; 5: 1053–1055.
Sloviter R, Dean E, Sollas A, Goodman J. Apoptosis and necrosis induced in different hippocampal neuron populations by repetitive perforant path stimulation in the rat. J Camp Neurol 1996; 366: 516–533.
Bonfoco E, Krainc D, Ankarcrona M, Nicotera P, Lipton S. Apoptosis and necrosis: two distinct events induced, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA 1995; 92: 7162–7166.
Choi D. Calcium: still center-stage in hypoxic-ischemic neuronal death. Trends Neurosci 1995; 18: 58–60.
Rothman SM. Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci 1984; 4: 1884–1891.
Buchan A, Li H, Cho S, Pulsinelli W. Blockade of the AMPA receptor prevents CAI hippocampal injury following severe but transient forebrain ischemia in adult rats. Neunsci Lett 1991, 132: 255–258.
Nellgard B, Wieloch T. Cerebral protection by AMPA-and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia. Exp Brain Res 1992; 92: 259–266.
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Aggoun-Zouaoui, D., Margalli, I., Borrega, F. et al. Ultrastructural Morphology of Neuronal Death Following Reversible Focal Ischemia in the Rat. Apoptosis 3, 133–141 (1998). https://doi.org/10.1023/A:1009653126347
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DOI: https://doi.org/10.1023/A:1009653126347