An ultrastructural analysis of cellular death in the CA1 field in the rat hippocampus after transient forebrain ischemia followed by 2, 4 and 10 days of reperfusion
Tóm tắt
An ultrastructural study was performed to investigate the type of cellular death that occurs in hippocampal CA1 field pyramidal neurons after 10 and 20 min of transient cerebral ischemia in the male adult Wistar rats, followed by 2, 4 and 10 days of reperfusion. The four-vessel occlusion method was used to induce ischemic insult for either 10 or 20 min, following which the animals were submitted to either 2, 4 or 10 days of reperfusion. The animals were then anaesthetised, and their brains removed, dehydrated, embedded, sectioned and examined under a transmission electron microscope. After ischemic insult, neurons from the CA1 field presented alterations, corresponding to the initial, intermediate and final stages of the degenerative process. The only difference observed between the 10 and 20 min ischemic groups was the degree of damage; the reaction was stronger in 20 min groups than in the 10 min groups. While neurons were found in the different stages of oncotic necrosis in all groups, differences were found between the groups in relation to prevalent stages. In both ischemic groups, after 2 days of reperfusion, the initial stage of oncotic necrosis was prevalent and large numbers of neurons appeared normal. In both groups, after 4 days of reperfusion, most of the neurons showed more advanced alterations, typical of an intermediate stage. In both groups, after 10 days of reperfusion, alterations corresponding to the intermediate and final stages of oncotic necrosis were also predominant. However, few intact neurons were identified and the neuropile appeared more organised, with numerous glial cells. In summary, the pyramidal neurons of the CA1 field displayed selective vulnerability and exhibited a morphological death pattern corresponding exclusively to an oncotic necrotic pathway.
Tài liệu tham khảo
Arends MJ, Morris RG, Wyllie AH (1990) Apoptosis: the role of the endonuclease. Am J Pathol 136:593–608
Bicknell GR, Cohen GM (1995) Cleavage of DNA to large kilobase pair fragments occurs in some forms of necrosis as well as apoptosis. Biochem Biophys Res Commun 207:40–47
Block F, Bozdag I, Nolden-Koch M (2001) Inflammation contributes to the postponed ischemic neuronal damage following treatment with a glutamate antagonist in rats. Neurosci Lett 298:103–106
Bredesen DE (1996) Keeping neurons alive: the molecular control of apoptosis. Neuroscientist 2:211–216
Bursch W (2004) Multiple cell death programs: charon’s lifts to Hades. FEMS Yeast Res 5:101–110
Dean RT (1987) Some critical membrane events during mammalian cell death. In: Potten CS (eds) Perspectives on mammalian cell death. Oxford University Press, New York, pp 18–38
Ferrer I, Macaya A, Blanco R, Olive M, Cinós C, Munell F, Planas AM (1995) Evidence of internucleosomal DNA fragmentation and identification of dying cell in X-ray-induced cell death in the developing brain. Int J Dev Neurosci 13:21–28
Fukuda T, Wang H, Nakanishi H, Yamamoto K, Kosaka T (1999) Novel non-apoptotic morphological changes in neurons of the mouse hippocampus following transient hypoxic-ischemia. Neurosci Res 33:49–55
Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W, Schulte-Hermann R (1995) In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. J Faseb 21:1465–1468
Horn M, Schlote W (1992) Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. Acta Neuropathol 85:79–87
Kerr JFR, Harmon BV (1991) Definition and incidence of apoptosis: an historical perspective. In: Tomeil LD, Cope FO (eds) Apoptosis: the molecular basis of cell death. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 5–29
Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetic. Br J Cancer 26:239–257
Kerr JFR, Gobé GC, Winterford CM, Harmon BV (1995) Anatomical methods in cell death. Cell death. Academic, New York
Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69
Kirino T, Sano K (1984) Selective vulnerability in the gerbil hippocampus following transient ischemia. Acta Neuropathol 62:201–208
Krantic S, Mechawar N, Reix S, Quirion R (2005) Molecular basis of programmed cell death involved in neurodegeneration. Neuroscience 28:670–676
Laiko KU, Trump BJ (1975) Studies on the pathogenesis of cell injury. Effects of inhibitors of metabolism and membrane function on the mitochondria of Ehrlich ascites tumor cells. Lab Invest 32:163–182
Laiko KU, Shelburne JD, Trump BJ (1971) Observations on cell volume, ultrastructure, mitochondrial conformation and vital-dye uptake in Ehrlich ascites tumor cells. Am J Pathol 65:203–230
Levin S, Bucci TJ, Cohen SM, Fix AS, Hardisty JF, LeGrand EK, Maronpot RR, Trump BF (1999) The nomenclature of cell death: recommendations of an ad hoc committee of the society of toxicologic pathologists. Toxicol Pathol 27:484–490
Liou AKF, Clark RS, Henshall DC, Yin Y, Chen J (2003) To die or not to die for neurons in ischemia, traumatic brain injury and epilepsy: on the stress-activated signalling pathways. Prog Neurobiol 69:103–142
Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568
Lockshim RA, Zakeri Z (2002) Caspase-independent cell deaths. Curr Opin Cell Biol 14:727–733
Lockshin R, Zakeri Z (2004) Caspase-independent cell death? Oncogene 23:2766–2773
Lookeren Campagne M, Lucassen PJ, Vermeulen JP, Balázs R (1995) NMDA and kainate induced internucleosomal DNA cleavage associated with both apoptotic and necrotic cell death in the neonatal rat brain. Eur J Neurosci 7:1627–1640
Lossi L, Merighi A (2003) In vivo cellular and molecular of neuronal apoptosis in the mammalian CNS. Prog Neurobiol 69:287–312
Majno G, Joris I (1995) Apoptosis, oncosis and necrosis. An overview of cell death. Am J Pathol 146:3–15
Martin LJ, Al-Abdulla NA, Brambrink AM, Kirsch JR, Sieber FE, Portera-Cailliau C (1998) Neurodegeneration in excitotoxicity, global cerebral ischemia and target deprivation: a perspective on the contributions of apoptosis and necrosis. Brain Res Bull 46:281–309
Mergner WJ, Jones RT, Trump BJ (1990) Cell death: mechanisms of acute and lethal cell injury. Field & Wood, New York
Netto CA, Hodges H, Sinden JD, Lepeillet E, Kershau T, Sow Inski P, Meldrum BS, Gray JA (1993) Foetal grafts from hippocampal region superior alleviate ischaemic- induced behavioral deficits. Behav Brain Res 58:107–112
Nitatori T, Sato N, Waguri S, Karasawa Y, Araki H, Shibanai K, Kominami E, Uchiyama Y (1995) Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J Neurosci 15:1001–1011
Oppenheim RM, Prevette D, Tytell M, Homma S (1990) Naturally occurring and induced neuronal death in the chick embryo in vivo requires protein and RNA synthesis: evidence for the role of cell death genes. Dev Biol 138:104–113
Ordy JM, Wengenack TM, Bialobock P, Coleman PD, Rodier P, Baggs RB, Dunlap WP, Katest B (1993) Selective vulnerability and early progression of hippocampal CA1 pyramidal cell degeneration and GFAP positive astrocyte reactivity in the rat four-vessel occlusion model of transient global ischemia. Exp Neurol 119:128–139
Petito CK, Pulsinelli WA (1984) Delayed neuronal recovery and neuronal death in rat hippocampus following severe cerebral ischemia: possible relationship to abnormalities in neuronal processes. J Cereb Blood Flow Metab 4:194–205
Petito CK, Feldmann E, Pulsinelli WA, Plum FA (1987) Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology 37:1281–1286
Petito CK, Torres-Munoz J, Roberts B, Olarte JP, Nowak Jr TS, Pulsinelli WA (1997) DNA fragmentation follows delayed neuronal death in CA1 neurons exposed to transient global ischemia in the rat. J Cereb Blood Flow Metab 17:967–976
Pollard H, Charriaut-Marlangue C, Cantagrel S, Represa A, Robain O, Morau J, Ben-Ari Y (1994) Kainate-induced apoptotic cell death in hippocampal neurons. Neuroscience 63:7–18
Portera-Cailliau C, Hedreen JC, Price DL, Koliatsos VE (1995) Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models. J Neurosci 15:3775–3787
Portera-Cailliau C, Price DL, Martin LJ (1997) Non-NMDA and NMDA receptor-mediated excitotoxic neuronal deaths in adult brain are morphologically distinct: further evidence for na apoptosis-necrosis continuum. J Comp Neurol 378:88–104
Pulsinelli WA, Brierley JB (1979) A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke 10:267–272
Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11:491–498
Raff MC, Barres BA, Burne JF, Coles HS, Ishizaki Y, Jacobson MD (1993) Programmed cell death and the central of cell survival: lesson from the nervous system. Science 262:668–669
Reynolds ES (1963) The use of lead citrate of high pH as an electron opaque stain in electron microscopy. J Cell Biol 17:208–212
Rodrigo J, Peinado MA, Sanchez E, Pedrosa JA, Bentura ML, Esteban FJ, Torres MI, Martínez-Murillo R (1996) Técnicas immunocitoquímicas aplicadas a la microscopía electrónica. In: Peinado MA, Rodrigo J, Pedrosa JA (eds) Avances en immunocitoquímica y técnicas relacionadas. Editorial de la Universidad de Jaén, Jaén, pp 177–201
Ruan Y-W, Ling G-Y, Zhang J-L, Xu ZC (2003) Apoptosis in the striatum after transient forebrain ischemia and the effects of the ischemic severity. Brain Res 982:228–240
Sauders JW (1966) Death in embryonic systems. Science 154:604–612
Schreiber SS, Baudry M (1995) Selective neuronal vulnerability in the hippocampus: a role for genes expression. TINS 18:446–451
Spielmeyer W (1925) Zür pathogenese ortlich elektiven gehirnveranderungen.Z Ges Neurol Psychiatr 99:756–776, quoted by Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568
Steller H, White K (1995) The control of apoptosis in Drosophila. Trends Cell Biol 5:74–78
Trump BF, Berezesky IK (1996) The role of altered [Ca 2+] regulation in apoptosis, oncosis, and necrosis. Biochim Biophys Acta 1313:173–178
Trump BJ, Goldblatt PJ, Stowell RE (1965) Studies of mouse liver necrosis in vitro. Ultrastructural and cytochemical alterations in hepatic parenchymal cell nuclei. Lab Invest 14:1969–1999
Vergoni A V, Ottani A, Botticelli A, Guano L, Loche A, Genedani S, Gessa G.L, Bertolini A (2000) Neuroprotective effect of gamma-hydroxybutyrate in transient global cerebral ischemia in rat. Eur J Pharmacol 397:75–84
Weishaupt JH, Neusch C, Bähr M (2003) Cyclin-dependent kinase 5 (CDK5) and neuronal death. Cell Tissue Res 312:1–8
Wyllie AH, Kerr JFR, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306
Yuan J, Lipinski M, Degterev A (2003) Diversity in the mechanisms of neuronal cell death. Neuron 40:401–403
Zeng YS, Xu ZC (2000) Co-existence of necrosis and apoptosis in rat hippocampus following transient forebrain ischemia. Neurosci Res 37:113–125