Summary
A 10-min long ischemic insult followed by up to 60-min survival results in several changes of the synaptic ultrastructure in the hippocampal CA-1 region. The alternations consist of gradual change of synaptic curvature from neutral to positive, cleavage and decrease in thickness of the postsynaptic densities and, in the case of many terminals, wrinkling of their profiles. The most striking form of damage are membrane discontinuities which begin to appear in very small numbers after 20 min of blood reflow and become much more pronounced after 60 min. The development of those modifications seems to be time-related, whereas decrease in the number of synaptic vesicles, as shown by the morphometric analysis, occurs after 10 min and does not progress any further after 20 and 60 min. This decrease is most pronounced in the immediate vicinity of the presynaptic membrane.
Although the observed signs of ultrastructural alternations of synapses in the postischemic period appear to conform to the general pattern of synaptic degeneration observed under other conditions, the severity of ischemia is underlined with the rate at which those changes develop, thus pointing toward grossly disturbed metabolism of postischemic neurons. Recently, a number of theories have been advanced, discussing significance of ischemic destruction of membrane phospholipids. These theories are discussed in the context of membrane discontinuities reported in this investigation.
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References
Ackert K, Livingston RB, Moor H, Streit P (1974) Ultrastructure of synapses in the waking state. A laboratory report on recent advances. J Neural Transm [Suppl] XI:1–11
Bondareff W (1979) Synaptic atrophy in the senescent hippocampus. Mech Ageing Dev 9:163–171
Bures J, Buresova O (1981) Cerebral (K+)e increase as an index of the differential susceptibility of brain structures to terminal anoxia and electroconvulsive shock. J Neurobiol 12:211–220
Demopoulos HB, Flamm ES, Pietronigro DD, Seligman ML (1980) The free radical pathology and microcirculation in the major central nervous system disorders. Acta Physiol Scand [Suppl] 492:91–119
Diemer NH, Siemkowicz E (1980) Increased 2-deoxyglucose uptake in hippocampus, globus pallidus and substantia nigra after cerebral ischemia. Acta Neurol Scand 61:56–63
Fischer J, Langmeier M (1980) Changes in the number, size and shape of synaptic vesicles in an experimental, projected cortical epileptic focus in the rat. Epilepsia 21:571–585
Fischer J, Langmeier M, Trojan S (1980a) Shortening of presynaptic dense projections produced in the synapses of rat cerebral cortex by prolonged repeated hypoxia in early ontogenesis. Physiol Bohemoslov 29:93–97
Fischer J, Langmeier M, Trojan S (1980b) Changes in the length and width of the postsynaptic density, the width of the intersynaptic density and the synaptic cleft in the cerebral cortex synapses of rats exposed to prolonged aerogenic hypoxia during early ontogenesis. An electron-microscopic morphometric study. Physiol Bohemoslov 29:561–567
Garcia JH, Kalimo H, Mamijyo Y (1977) Cellular events during partial cerebral ischemia. I. Electron microscopy of feline cerebral cortex after middle-cerebral-artery occlusion. Virchows Arch [Cell Pathol] 25:191–206
Garcia JH, Losinsky AS, Kauffman FC, Conger KA (1978) Neuronal ischemic injury: light microscopy, ultrastructure and biochemistry. Acta Neuropathol (Berl) 43:85–95
Gray EG (1977) Presynaptic microtubules, agranular reticulum and synaptic vesicles. In: Cottrell GA, Usherwood PNR (eds) Synapses. Blackie, Glasgow London, pp 6–18
Gutmann E (1977) Trophic effects in nerve-muscle cell relations. In: Cottrell GA, Usherwood PNR (eds) Synapses. Blackie, Glasgow London, pp 291–319
Hubbard JI, Kwanbunbumpen S (1968) Evidence for the vesicle hypothesis. J Physiol 194:407–420
Jenkins LW, Povlishock JT, Becker DP, Miller JD, Sullivan HG (1979) Complete cerebral ischemia. Acta Neuropathol (Berl) 48:113–125
Jones DG (1981) Ultrastructural approaches to the organisation of central synapses. Am Sci 69:200–210
Jones DG, Devon RM (1978) An ultrastructural study into the effect of pentobarbitone on synaptic organisation. Brain Res 147:47–60
Jones DG, Cameron PU, Ellison LT (1977) The uptake of horseradish peroxidase by cortical synapses in rat brain. Cell Tiss Res 178:355–373
Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69
Kalt MR, Tendler B (1971) A study of fixation of early amphibian embryos for electron microscopy. J Ultrastruct Res 36:113–125
Landfield PW, Wurtz C, Lindsey JD (1979) Quantification of synaptic vesicles in hippocampus of aging rats and initial studies of possible relations to neurophysiology. Brain Res Bull 4:757–759
von Lubitz DKJE, Diemer NH (1982) Complete cerebral ischemia in the rat: an ultrastructural and stereological analysis of the distal stratum radiatum in the hippocampal CA-1 region. Neuropathol Appl Neurobiol 8:197–215
Malinsky J (1981) Ultrastructural changes of synapses during hypothermia and hibernation. Activ Nerv Sup (Praha) 23:55–56
Majewska MD, Manning R, Sun Y (1981) Effects of postdecapitative ischemia on arachidonate release from brain synaptosomes. Neurochem Res 6:567–576
Nemoto EM (1979) Studies on pathogenesis of ischemic brain damage and its amelioration by barbiturate therapy. In: Zülch KJ, Kaufmann W, Hossmann K-A, Hassmann V (eds) Brain and heart infarct, vol II. Springer, Berlin Heidelberg New York, pp 306–317
Schuster Th, Saballus R, Ossyra H, Fenske D, Roeseler E (1982) Die Zonierung präsynaptischer Areale im elektronemikroskopischen Bild als Methode zur quantitativen Erfassung der Verteilung von Zellorganellen in der Nachbarschaft synaptischer Membranen. Acta Histol Chem [Suppl] XXVI:397–400
Rehncrona S, Siesjö BK, Smith D (1980) Reversible ischemia in the brain: biochemical factors influencing restitution. Acta Physiol Scand [Suppl] 492:135–140
Siemkowicz E, Hansen AJ (1981) Brain extracellular ion composition and EEG activity following 10 minutes ischemia in normo- and hyperglycemic rats. Stroke 12:236–240
Siemkowicz E, Hansen AJ (1978) Clinical restitution following cerebral ischemia in hypo-, normo- and hyperglycemic rats. Acta Neurol Scand 58:1–8
Siesjö BK (1982) Cell damage in the brain: a speculative synthesis. J Cerebr Blood Flow Metabol 1:155–185
Vogt C, Vogt O (1922) Erkrankungen der Großhirnrinde im Lichte der Topistik, Pathoklise and Pathoarchitektonik. J Psychol Neurol 28:1–71
Westrum LE (1973) Early forms of terminal degeneration in the spin trigeminal nucleus following rhizotomy. J Neurocytol 2:189–215
Williams V, Grossman RG (1969) Ultrastructure of cortical synapses after failure of presynaptic activity in ischemia. Anat Rec 166:131–142
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von Lubitz, D.K.J.E., Diemer, N.H. Cerebral ischemia in the rat: Ultrastructural and morphometric analysis of synapses in stratum radiatum of the hippocampal CA-1 region. Acta Neuropathol 61, 52–60 (1983). https://doi.org/10.1007/BF00688386
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DOI: https://doi.org/10.1007/BF00688386