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  • 1
    ISSN: 1432-0533
    Keywords: Ganglioglioma ; Hamartia ; Proliferation ; Ki-67 ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gangliogliomas are tumors composed of intimately admixed neuronal and glial components and account for approximately 1% of all brain tumors. Here we report the histopathological findings in 61 gangliogliomas. Epilepsy was the most common presenting symptom. Most gangliogliomas were located in the temporal lobes (74%). Thirteen percent of the gangliogliomas were associated with glioneuronal hamartias. There was considerable variation in neuronal size and density, presence of binucleated neurons, calcifications, desmoplasia, lymphocytic infiltrate, pilocytic differentiation, Rosenthal fibers, location, or histological uniformity. Fifteen percent of the gangliogliomas contained areas of purely astrocytic differentiation. All tumors were examined immunohistochemically for an aberrant p53 tumor suppressor gene product and for the presence of nuclear antigens associated with cell proliferation (Ki-67, Ki-S1, proliferating cell nuclear antigen). In 45 of 61 cases (74%) labeling indices for Ki-67 were less than 1%. Nuclear labeling for Ki-67 was observed exclusively in the astrocytic component. Gangliogliomas with very large neurons had higher Ki-67 labeling indices and occurred in younger patients than gangliogliomas with small-or intermediate-sized neurons. None of the tumors had an aberrant expression of p53. The observations suggest that gangliogliomas may arise from glioneuronal hamartias through neoplastic transformation of the astrocytic component.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Key words: Ganglioglioma ; Hamartia ; Proliferation ; Ki-67 ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gangliogliomas are tumors composed of intimately admixed neuronal and glial components and account for approximately 1   % of all brain tumors. Here we report the histopathological findings in 61 gangliogliomas. Epilepsy was the most common presenting symptom. Most gangliogliomas were located in the temporal lobes (74 %). Thirteen percent of the gangliogliomas were associated with glioneuronal hamartias. There was considerable variation in neuronal size and density, presence of binucleated neurons, calcifications, desmoplasia, lymphocytic infiltrate, pilocytic differentiation, Rosenthal fibers, location, or histological uniformity. Fifteen percent of the gangliogliomas contained areas of purely astrocytic differentiation. All tumors were examined immunohistochemically for an aberrant p53 tumor suppressor gene product and for the presence of nuclear antigens associated with cell proliferation (Ki-67, Ki-S1, proliferating cell nuclear antigen). In 45 of 61 cases (74   %) labeling indices for Ki-67 were less than 1   %. Nuclear labeling for Ki-67 was observed exclusively in the astrocytic component. Gangliogliomas with very large neurons had higher Ki-67 labeling indices and occurred in younger patients than gangliogliomas with small – or intermediate – sized neurons. None of the tumors had an aberrant expression of p53. The observations suggest that gangliogliomas may arise from glioneuronal hamartias through neoplastic transformation of the astrocytic component.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Key words Epilepsy ; Gamma aminobutyric acid ; Receptor ; Ammon's horn sclerosis ; Hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alterations of gamma aminobutyric acid (GABA)-mediated neurotransmission have been implicated in the pathogenesis of epilepsies. Here we examine the distribution of the GABAA receptor in the hippocampus of 78 surgical specimens from patients with chronic pharmacoresistant focal epilepsies. The receptor was localized immunohistochemically with the monoclonal antibody bd-24 which selectively recognizes the α1 subunit of the GABAA receptor. The results were compared with the receptor distribution of 28 normal hippocampal specimens obtained at autopsy. In the great majority of the surgical specimens a loss of GABAA receptor immunoreactivity was present in CA1 (92.3  %), CA4 (78.2  %), the dentate granular cell layer (70.5  %) and the molecular layer of the dentate gyrus (65.4  %). The subiculum revealed a normal staining pattern in all but 4 cases. In no instance did we observe an increase of immunoreactivity in any region or cell population. The decrease of GABAA receptor immunoreactivity was closely related to neuronal loss in the respective specimen and to Ammon's horn sclerosis. There was no correlation between GABAA receptor loss and the patient's age at surgery, duration of seizures, age at onset of seizures and to the presence or absence of secondary generalized tonic clonic seizures. The data suggest that the observed loss of GABAA receptor immunoreactivity is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Disturbances in serotonergic neurotransmission have been suggested to be closely interlinked with hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system, and are likely to be involved in the pathophysiology of anxiety disorders and major depression. We therefore investigated markers of serotonergic transmission and their modulation by chronic paroxetine in rats selectively bred for high (HAB) or low (LAB) anxiety-related behaviour, both under basal conditions and in response to emotional stress. Hippocampal serotonin 1 A (5-HT1A) receptor mRNA expression was reduced in HAB rats, whereas 5-HT concentrations in hippocampal microdialysates did not differ between HAB and LAB rats under basal conditions. In the hippocampus, overall expression of serotonin transporter binding sites was increased in HAB compared with LAB rats. Exposure to emotional stress failed to increase intrahippocampal 5-HT release in HAB rats whereas LAB rats displayed a physiological, albeit small rise. Chronic paroxetine treatment markedly increased the stress-induced rise in hippocampal 5-HT in HAB, but not LAB rats. This effect may be (at least in part) related to a greater down-regulation of hippocampal serotonin transporter binding sites by paroxetine in HABs compared with LABs, while 5-HT1A receptor expression remained unaffected in this brain area. The findings indicate reduced hippocampal serotonergic transmission in HAB rats as compared with LAB rats, which is evident both at the presynaptic (5-HT release) and the postsynaptic (5-HT1A receptor) level. Chronic paroxetine enhanced the presynaptic responsivity in HAB rats, but not LAB rats, pointing to a preferential efficacy of paroxetine in rats with enhanced anxiety/depression-related behaviour.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In major depression, decreased hippocampal volume has been attributed to hypercortisolemia, a frequent sign of the disorder, because in animals an excess of corticosteroids has led to dendritic atrophy, astrogliosis and loss of neurons in this brain region. The present study is the first to investigate the structural integrity of the human hippocampus in major depression and following glucocorticoid treatment. Post-mortem hippocampal tissue from 15 patients who had had major depression or bipolar affective disorder, 10 patients who had been treated with glucocorticoids and 16 controls was assessed using haematoxylin-eosin, Nissl and Bodian staining. The patterns of reactive astrogliosis (glial fibrillary acidic protein, GFAP), synaptic density (synaptophysin), synaptic reorganization (growth-associated protein B-50) and early signs of Alzheimer's disease (Alz-50) were examined immunocytochemically. Multivariate analysis, with the patients' age, tissue fixation time and postmortem delay as covariates, was performed. There was no evidence of neuronal cell loss or other major morphological alterations in any of the groups, nor was there a significant change in the distribution pattern of synaptophysin or Alz-50. Changes in B-50 and GFAP staining were observed in the steroid-treated and depressed patients in areas CA1 and CA2 only. The human hippocampus in major depression and after glucocorticoid treatment does not reveal any major morphological changes or signs of neuronal cell death, but does show subtle alterations in B-50 and GFAP expression in selected parts of the pyramidal cell layer.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 11 (1999), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In recent years, repetitive transcranial magnetic stimulation (rTMS) of the human brain has been used as a therapeutic tool in a variety of psychiatric and neurological disorders. However, to understand the mechanisms underlying any potential therapeutic effects, and possible adverse effects, studies are necessary on how magnetic stimuli induced by rTMS interact with central nervous system (CNS) regulation. In the current study, we failed to find cognitive impairments or structural alterations in rat brains after 11 weeks of long-term treatment with rTMS, which if present would indicate neuronal damage. In contrast, our in vitro studies showed that magnetic stimulation analogous to rTMS increased the overall viability of mouse monoclonal hippocampal HT22 cells and had a neuroprotective effect against oxidative stressors, e.g. amyloid beta (Aβ) and glutamate. The treatment increased the release of secreted amyloid precursor protein (sAPP) into the supernatant of HT22 cells and into cerebrospinal fluid from rats. HT22 cells preincubated with cerebrospinal fluid from rTMS-treated rats were found to be protected against Aβ. These findings suggest that neurochemical effects induced by rTMS do not lead to reduced neuronal viability, and may even reduce the detrimental effects of oxidative stress in neurons.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Epilepsy ; Gamma aminobutyric acid ; Receptor ; Ammon's horn sclerosis ; Hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alterations of gamma aminobutyric acid (GABA)-mediated neurotransmission have been implicated in the pathogenesis of epilepsies. Here we examine the distribution of the GABAA receptor in the hippocampus of 78 surgical specimens from patients with chronic pharmacoresistant focal epilepsies. The receptor was localized immunohistochemically with the monoclonal antibody bd-24 which selectively recognizes the α1 subunit of the GABAA receptor. The results were compared with the receptor distribution of 28 normal hippocampal specimens obtained at autopsy. In the great majority of the surgical specimens a loss of GABAA receptor immunoreactivity was present in CA1 (92.3%), CA4 (78.2%), the dentate granular cell layer (70.5%) and the molecular layer of the dentate gyrus (65.4%). The subiculum revealed a normal staining pattern in all but 4 cases. In no instance did we observe an increase of immunoreactivity in any region or cell population. The decrease of GABAA receptor immunoreactivity was closely related to neuronal loss in the respective specimen and to Ammon's horn sclerosis. There was no correlation between GABAA receptor loss and the patient's age at surgery, duration of seizures, age at onset of seizures and to the presence or absence of secondary generalized tonic clonic seizures. The data suggest that the observed loss of GABAA receptor immunoreactivity is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures.
    Type of Medium: Electronic Resource
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