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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 79 (1990), S. 409-417 
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Hippocampus ; Dentate gyrus ; Perforant path ; Electron-dense degeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Silver impregnation performed 1–2 days after transient forebrain ischemia in the Mongolian gerbil demonstrated terminal-like granular deposits in the outer two-thirds of the hippocampal dentate molecular layer (perforant path terminal zone), even though neither the cell bodies of origin of the perforant path nor the dentate granule cells were destroyed. Electron microscopic studies of the dentate gyrus were performed in an effort to discover the identity of these degenerating structures. Electron microscopy revealed that the granular silver deposits corresponded to electron-dense profiles. Many of these were degenerating boutons and some were degenerating postsynaptic dendritic fragments, but most of them could not be identified with certainty. Electron-dense profiles were less numerous than expected from the density of granular silver deposits. These structures were probably the degenerating axons, axon terminals and dendrites of CA4 neurons. The granular silver deposits and electron-dense boutons observed in the inner third of the dentate molecular layer 5 days after transient ischemia can probably be explained by the ischemia-induced degeneration of CA4 mossy cells, which give rise to the dentate associational-commissural projection. Finally, most mossy fiber boutons in area CA4 and some boutons in the molecular layer appeared watery and enlarged on postischemia days 1 and 2. Mossy fiber boutons with this ultrastructural appearance have previously been observed in seizure-prone animals and in animals undergoing convulsant-induced seizures. Although no postischemic seizures occur under the conditions of this study, these findings support the idea that excitatory pathways become hyperactive after transient ischemia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Hippocampus ; CA1 pyramidal cells ; Neuropathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Transient forebrain ischemia produces a spatially and temporally selective pattern of neuronal degeneration in the hippocampal formation of the Mongolian gerbil. Ischemic neuronal death has been suggested to depend on the activation of excitatory hippocampal pathways that project to the vulnerable neurons. This idea was tested by examining the effect of a unilateral entorhinal cortical lesion or a unilateral knife cut lesion of intrahippocampal pathways on the neuropathology produced by 5 min of complete fore-brain ischemia. A prior lesion of either the ipsilateral entorhinal cortex or the mossy fiber and Schaffer collateral-commissural pathways partially prevented the destruction of CA1b pyramidal cells in most animals. It did not, however, reduce the extent of ischemic neuronal death in any other hippocampal subfield. Within area CA1b, an entorhinal lesion protected an average of 23% of the pyramidal cells and a transection of both mossy and Schaffer collateral-commissural fibers protected an average of 36.5%. CA1b pyramidal cells saved from ischemia-induced degeneration appeared clearly abnormal when stained with cresyl violet or by silver impregnation. It is suggested that lesions of excitatory pathways attenuate ischemic damage to area CA1b by directly or indirectly reducing the level of synaptic excitation onto the vulnerable neurons. However, only a relatively small percentage of hippocampal neurons can be protected by these lesions in the gerbil ischemia model and there is reason to believe that the neurons protected in this manner may not be electrophysiologically competent. Synaptic excitation therefore appears to play an important, but not an essential, role in this model of ischemic brain damage.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 19 (1972), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Abstract-Tumors of the human nervous system were utilized to investigate the cellular distribution of N-acetyl-L-aspartic acid (NAA). Astroglial tumours contained about 0.144 μmol/g. Oligodendrogliomas and medulloblastomas contained somewhat larger amounts. However, the level of NAA in all gliomas studied was less than that of normal human white matter. NAA was undetectable in meningiomas and acoustic neurinomas. If these results may be taken as representative of normal tissue, they imply a predominantly neuronal localization for NAA.Substantial amounts of NAA were found in peripheral nervous tissues and retina. Neurons seem to vary widely in NAA content.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 19 (1972), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A subconvulsant dose of sodium fluoroacetate inhibited the metabolic utilization of intracerebrally-administered N-acetyl-l-[U-14C]asparticacid and the labelling of glutamine from this precursor in mouse brain, but not the labelling of glutamate or aspartate. A convulsant dose also inhibited the utilization of l-[U-14C]aspartic acid. When intraperitoneal injection of a convulsant dose of sodium fluoroacetate was followed by intracerebral injection of N-acetyl-l-[U-14C]asparticacid, the levels of N-acetylaspartate, aspartate and glutamate in brain were lowered, while the glutamine content was increased. The specific radioactivity of glutamine relative to that of glutamate was much lower when these compounds were labelled from l-[U-14C]aspartic acid than when N-acetyl-l-[U-14C]aspartic acid was used as the precursor. Intracerebral injection of tracer amounts of l-[U-14C]aspartic acid reduced the content of N-acetylaspartate in brain and raised the glutamine content. Sodium fluoroacetate had no additional effect on the relative specific radioactivity of glutamine or the content of N-acetylaspartate, aspartate, glutamate or glutamine when l-[U-14C]aspartic acid was the precursor. We consider the results to be consistent with a selective inhibition both by sodium fluoroacetate and by exogenous aspartic acid of the tricarboxylic acid cycle in brain associated with the biosynthesis of glutamine. We suggest that the activity of this pathway may regulate the metabolism of N-acetylaspartate and aspartate.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 19 (1972), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The metabolism of N-acetyl-l-aspartic acid (NAA) was studied in rat brain. [Aspartyl-U-14C]NAA was metabolized predominantly by deacylation. Studies of NAA biosynthesis from l-[U-14C]aspartic acid have confirmed previous reports that NAA turns over slowly in rat brain. However, intracerebrally-injected N-acetyl-l-[U-14C]asparticacid was rapidly metabolized. Exogenous NAA appears to be taken up rapidly into a small, metabolically-active pool. This pool serves as substrate for a tricarboxylic acid cycle associated with the production of glutamate for the biosynthesis of glutamine. The bulk of the NAA content in brain appears to be relatively inactive metabolically.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 31 (1978), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Glutamate and aspartate probably serve as transmitters of hippocampal perforant path and commissural afferents, respectively. We therefore used slices of hippocampal regions to evaluate certain biochemical properties as markers for sites of transmission mediated by these amino acids. In these studies content and accumulation of glutamate and aspartate were compared with their Ca2+-dependent effluxes.Hippocampal regions varied little in their contents of glutamate and aspartate, but slices of regio superior and dentate gyrus accumulated and released more of each than slices of regio inferior. A commissurotomy or bilateral entorhinal lesion altered Ca2+-dependent efflux and accumulation in the same direction, but did not affect the glutamate or aspartate content of any hippocampal region. Elimination of hippocampal mossy fibers reduced the Ca2+-dependent efflux of glutamate and probably aspartate from slices of dentate gyrus, but not of regio inferior, where most mossy fiber synapses are located. The mossy fibers appeared relatively deficient in aspartate in both strains tested, but only in Purdue-Wistar rats were they enriched in glutamate. Removal of the perforant path input to the fascia dentata did not significantly change the activity of any of the enzymes most actively involved in glutamate synthesis.These results suggest that accumulation or high affinity transport of glutamate or aspartate can be employed to localize afferents which use these amino acids as transmitters, although it is not so reliable or selective a marker as Ca2+-dependent efflux. Enrichment in either glutamate or aspartate content or in the activity of enzymes which synthesize them is not a reliable marker. Neither amino acid is likely to be used as a transmitter by the hippocampal mossy fibers.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 29 (1977), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Superfused slices of the rat dentate gyrus were employed to study the release of GABA, glutamate and aspartate, which are considered strong neurotransmitter candidates in this region. The introduction of Ca2+ to a Ca2+-free superfusion medium containing a depolarizing agent augmented the efflux of all three amino acids. The response to application of Ca2+ nearly always occurred within 30 s, the shortest interval tested in these studies. The efflux rate reached a peak within 90 s and then declined to a level slightly greater than the prestimulation baseline. The failure to maintain the maximal rate with continued exposure to Ca2+ and depolarizing influences appeared not to result from a reduction in Ca2+ permeability caused by continuous depolarization. Ca2+ also stimulated the efflux of exogenously loaded radiolabeled GABA, glutamate and aspartate, but not proline. Exogenously loaded GABA was more readily released than endogenous GABA. Otherwise the effects of various treatments on their efflux rates were qualitatively similar.Mg2+ inhibited Ca2+-dependent efflux. Ba2+, but not Mg2+, stimulated amino acid efflux in the absence of Ca2+. Extracellular Na+ was not required to support Ca2+-dependent efflux. Addition of Ca2+ to a Ca2+-free medium in the absence of a depolarizing agent released GABA from the slices, but not glutamate or aspartate.K+-enriched medium and the depolarizing alkaloid, veratridine, stimulated both Ca2+-dependent and Ca2+-independent release processes. Na+-free medium enhanced the Ca2+-independent releasing action of elevated K+. Ca2+-independent release was inhibited by raising the Mg2+ concentration by 15 or 30 mM and appeared to be inhibited by Ca2+ as well. Amino acid output in the absence of Ca2+ is probably not directly related to transmission and is considered to result partially from a general increase in membrane permeability induced by depolarization in a Ca2+-free medium and partially from stimulation of carrier-mediated amino acid efflux.These results support previously suggested transmitter roles for GABA, glutamate and aspartate in the rat dentate gyrus.
    Type of Medium: Electronic Resource
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