Abstract
The neocortex and the hippocampus were examined for lipid peroxidation products and ultrastructural alterations by fluorescence and electron microscopy, respectively, in rats subjected to 10 min of cardiac arrest or 10 min cardiac arrest and either 90 or 360 min reperfusion. Lipid peroxidation products were observed after 90 min reperfusion in the perikarya and proximal dendrites of neocortical pyramidal neurons and in the hippocampal hilar cells and CA1, region; the fluorescene was most intense at the base of the apical dendrite, the region of the Golgi apparatus. After 90 min of reperfusion, the CA1, showed considerable stretches of rough endoplasmic reticulum devoid of ribosomes and the Golgi cisternae were shorter and widely dilated. The neocortex showed similar endoplasmic reticulum changes, but no significant alterations to the Golgi were noted. In addition there were areas where strings of ribosomes appear to be detaching from the endoplasmic reticulum. After 360 min reperfusion in both the neocortex and the hippocampus, the damage appeared more severe. The Golgi was fragmented into vacuoles, membranous whorls had appeared, and dense aggregates of smooth vesicles were seen coalescing with each other and the vacuoles. These observations suggest that early Golgi involvement is a more important marker of lethal injury than ribosome release from the endoplasmic reticulum. The areas of disturbed Golgi ultrastructure correspond to those areas that show evidence of lipid peroxidation and imply that lipid peroxidation may be causally related to the disturbance in Golgi ultrastructure.
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Adelman MR, Sabatini DD, Blobel G (1973) Ribosome-membrane interaction. Nondestructive disassembly of rat liver rough microsomes into ribosomal and membrane component. J Cell Biol 56:206–229
Bryan J, Nagle BW, Doenges KH (1975) Inhibition of tubulin assembly by RNA and other polyanions: evidence for required protein. Proc Natl Acad Sci USA 75:3570–3574
Farquhar MG (1978) Traffic of products and membranes through the Golgi complex. In: Silverstein KSC (ed) Transport of macromolecules in cellular systems. Dahlem Konferenzen, Berlin, pp 341–362
Furuta S, Ohta S, Hatakeyama T, Nakamura K, Saburo S (1993) Recovery of protein synthesis in tolerance-induced hippocampal CA1 neurons after transient forebrain ischemia. Acta Neuropathol 86:329–336
Gonatas NK, Steiber A, Kim SU, Graham DI, Avrameas S (1975) Internalization of neuronal plasma membrane ricin receptors into the Golgi apparatus. Exp Cell Res 94:426–431
Hara H, Kogure K (1990) Prevention of hippocampus neuronal damage in ischemic gerbils by a novel lipid peroxidation inhibitor (quinazoline derivative). J Pharmacol Exp Ther 255: 906–913
Harris ME, Carney JM, Leedle RA (1994) Detection of oxidation products in individual neurons by fluorescence microscopy. Exp Neurol 129:95–102
Hirano A (1978) Changes of the neuronal endoplasmic reticulum in the peripheral nervous system in mutant hamsters with hind leg paralysis and normal controls. J Neuropathol Exp Neurol 37:75–84
Hong SC, Goto Y, Lanzino G, Soleau S, Kassell NF, Lee KS (1994) Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia. Stroke 25:663–669
Hwang KM, Yang LC, Carrico CK, Schulz RA, Schenkman JB, Sartorelli AC (1974) Production of membrane whorls in rat liver by some inhibitors of protein synthesis. J Cell Biol 62: 20–31
Jessus C, Huchon D, Friedrich E, Francon J, Ozon R (1984) Interaction between rat brain microtubule associated proteins (MAPs) and free ribosomes for Xenopus oocyte: a possible mechanism for the in vivo distribution of MAPs. Cell Differ 14: 295–301
Jothy S, Bilodeau JL, Simpkins H (1975) The role of membrane proteins and phospholipids in the interaction of ribosomes with endoplasmic reticulum membranes. Can J Biochem 53:1039–1045
Krieg UC, Walter P, Johnson AE (1986) Photocrosslinking of the signal sequence of nascent preprolactin to the 54 kD polypeptide of the signal recognition particle. Proc Natl Acad Sci USA 83:8604–8608
Kurzchalia TV, Wiedmann M, Girshovich AS, Bochkareva ES, Bielka H, Rapaport TA (1986) The signal sequence of nascent preprolactin interacts with the 54 kD polypeptide of the signal recognition particle. Nature 320:634–636
Marinari UM, Pronzato MA, Cottalasso D, Rolla C, Biasi F, Poli G, Nanni G, Dianzani MU (1987) Inhibition of liver Golgi glycosylation activities by carbonyl products of lipid peroxidation. Free Radic Res Commun 3:319–324
Miglietta A, Gabriel L, Gadoni E (1987) Microtubular protein impairment by pentanal and hexanal. Cell Biochem Funct 5:189–194
Muraoka Y, Yahara I, Nara H, Watanabe H (1981) Steroid-induced concentric membrane whorls in dog liver. Experientia 37: 389–390
Naftolin F, Bruhlmann-Papazyan M, Baetens D, Garcia-Segura M (1985) Neurons with whorl bodies have increased number of synapses. Brain Res 329:289–293
Nickerson PA, Curtis JC (1969) Concentric whorls of rough endoplasmic reticulum in adrenocortical cells of the Mongolian gerbil. J Cell Biol 40:859–862
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, New York
Peters A, Palay SL, deWebster H (1991) The fine structure of the nervous system: neurons and their supporting cells, 3rd edn. Oxford University Press, New York, pp 21–22
Petito CK, Lapinski RL (1986) Post-ischemic alteractions in ultrastructural cytochemistry of neuronal Golgi apparatus. Lab Invest 55:696–702
Petito CK, Pulsinelli WA (1984) Sequential development of reversible and irreversible neuronal damage following cerebral ischemia. J Neuropathol Exp Neurol 43:141–153
Pronzato MA, Cottalasso D, Domenicotti C, Tenca C, Traverso N, Nanni G, Marinari UM (1990) Effects of CCl4 poisoning on metabolism of dolichol in rat liver microsomes and Golgi apparatus. Free Radic Res Commun 11:267–277
Ris H (1985) The cytoplasmic filament system in critical pointdried whole mounts and plastic-embedded sections. J Cell Biol 100:1474–1487
Rordorf G, Uemura Y, Bonventre JV (1991) Characterization of phospholipase A2 (PLA2) activity in gerbil brain: enhanced activities of cytosolic, mitochondrial, and microsomal forms after ischemia and reperfusion. J Neurosci. 11:1829–1836
Schröder HC, Bernd A, Zahn RK, Müller WEG (1982) Interaction of polyribosomal components and polynucleotides with microtubule proteins. Mol Biol Rep 8:233–237
Schröder HC, Bernd A, Zahn RK, Müller WEG (1984) Binding of polyribonucleotides and polydeoxyribonucleotides to bovine brain microtubule protein: age-dependent modulation via phosphorylation of high-molecular weight microtubule-associated proteins and tau proteins. Mech Ageing Dev 24:101–117
Schubert P, Kreutzberg GW, Lux HD (1972) Neuroplasmic transport in dendrites: effect of cholchicine on morphology and physiology of motoneurons in the cat. Brain Res 47:331–343
Simon SM, Blobel G (1991) A protein-conducting channel in the endoplasmic reticulum. Cell 65:371–380
Skjaerlund JM, Krause GS, Feldman DM, White BC (1991) The effect of EMHP on post-cardiac arrest survival of rats. Resuscitation 22:139–149
Sleight GR, Pagano RE (1984) Transport of a fluorescent phosphatidylcholine analog from the plasma membrane to the Golgi apparatus. J Cell Biol 99:742–751
Steinhardt RA, Bi G, Alderton JM (1994) Cel membrane resealing by a vesicular mechanism similar to neurotransmitter release. Science 263:390–393
Suprenant KA Tempero LB, Hammer LE (1989) Association of ribosomes with in vitro assembled microtubules. Cell Motil Cytoskel 14:401–415
Thibaut-Vercruyssen R, Poumay Y, Ronveaux-Dupal MF (1992) Influence of a short oxidative stress on the LDL endocytosis by human endothelial cells: an ultrastructural study. J Submicrose Cytol Pathol 24:61–73
Thyberg J, Moskalewski S (1985) Microtubules and the organization of the Golgi complex. Exp Cell Res 259:1–16
Tomimoto H, Yanagihara T (1992) Electron microscopic investigation of the cerebral cortex after cerebral ischemia and reperfusion in the gerbil. Brain Res 598:87–97
Tomimoto H, Yanagihara T (1992) Immunoelectron microscopic study of tubulin and microtubule-associated proteins after transient cerebral ischemia in gerbils. Acta Neuropathol 84: 394–399
Voelker DR (1990) Lipid transport pathways in mammalian cells. Experientia 46:569–579
Walker PR, Whitfield JF (1985) Cytoplasmic microtubules are essential for the formation of membrane-bound polyribosomes. J Biol Chem 260:765–770
Walter P, Blobel G (1981) Translocation of proteins across the endoplasmic reticulum. III. Signal recognition protein (SRP) causes signal sequence-dependent and site-specific arrest of chain elongation that is released by microsomal membranes. J Cell Biol 91:557–561
Whaley WG, Dauwalder M (1979) The Golgi apparatus, the plasma membrane, and functional integration. Int Rev Cytol 58: 199–245
White BC, Daya A, DeGracia DJ, O'Neil BJ, Skjaerlund JM, Trumble S, Krause GS, Rafols JA (1993) Fluorescent histochemical localization of lipid perocidation during brain reperfusion following cardiac arrest. Act Neuropathol 86:1–9
White BC, Grossman LI, Krause GS (1993) Brain injury by global ischemia and reperfusion: a theoretical perspective on membrane damage and repair. Neurology 43:1656–1665
Yamamoto K, Morimoto K, Yanagihara T (1986) Cerebral ischemia in the gerbil: transmission electron microscopic and immunoelectron microscopic investigation. Brain Res 384: 1–10
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Rafols, J.A., Daya, A.M., O'Neil, B.J. et al. Global brain ischemia and reperfusion: Golgi apparatus ultrastructure in neurons selectively vulnerable to death. Acta Neuropathol 90, 17–30 (1995). https://doi.org/10.1007/BF00294455
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DOI: https://doi.org/10.1007/BF00294455