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  • 1
    Keywords: brain ; CELLS ; tumor ; Germany ; PATHWAY ; PATHWAYS ; CLASSIFICATION ; SYSTEM ; SYSTEMS ; GENE ; GENES ; TUMORS ; PATIENT ; MECHANISM ; CONTRAST ; mechanisms ; FREQUENCY ; polymorphism ; POLYMORPHISMS ; VARIANTS ; IDENTIFICATION ; LESIONS ; WHITE-MATTER ; SERIES ; pathology ; NEOPLASTIC TRANSFORMATION ; molecular ; VARIANT ; MUTATIONAL ANALYSIS ; ALLELES ; DYSPLASIA ; epilepsy ; focal cortical dysplasia ; FOCAL EPILEPSIES ; GANGLIOGLIOMAS ; glio-neuronal lesion ; GLIONEURONAL TUMORS ; tuberous sclerosis ; TUBEROUS SCLEROSIS COMPLEX
    Abstract: Epilepsy-associated malformations of cortical development (MCDs) comprise a variety of dysplastic and neoplastic lesions of yet undetermined molecular pathology. Histopathologic similarities between MCDs and dysplastic brain lesions in the autosomal inherited neurocutaneous phacomatosis tuberous sclerosis (TSC), which affects the TSC1 and/or TSC2 genes, suggest common pathogenetic mechanisms. Previous studies revealed different alterations of TSC1 and TSC2 in epilepsy-associated malformations and glio-neuronal tumors despite histopathologic similarities. In order to examine current clinico-pathologic classification systems of cortical malformations on the molecular level, we carried out a mutational analysis of TSC1 and TSC2 in a series of surgical specimens obtained from patients with FCD without Taylor type balloon cells (FCDIIa; n = 20), architectural dysplasias (FCDI; n = 15), nodular cortical heterotopias (NCH; It = 4), and heterotopic white matter neurons (WMNH; It = 19). In FCDIIa, abundant genomic polymorphisms were detected in TSC2 (intron 4) but no allelic variants observed in exon 17 of TSCL This allelic distribution pattern is in contrast to findings in FCDI and WMNH but also to those previously reported in FCDIIb (Taylor's balloon cell type). The latter revealed increased frequencies of specific alleles only in TSCL The determination of characteristic molecular genetic alterations in specific epilepsy-associated malformations will support a comprehensive clinico-pathologic classification system and help to identify molecular pathways with potential pathogenetic relevance. Our work is supported by DFG (SFB TRB [AJB], DFG B1 42 1/1-1 [113]), BONFOR, and Deutsche Krebshilfe
    Type of Publication: Journal article published
    PubMed ID: 16042315
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN); 20120912-20120915; Erlangen; DOC12dgnnPP6.9 /20120911/
    Publication Date: 2012-09-12
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN); 20120912-20120915; Erlangen; DOC12dgnnPP6.12 /20120911/
    Publication Date: 2012-09-12
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 4
    ISSN: 1432-1106
    Keywords: Thalamus ; Visual system ; HRP ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present experiments were undertaken to define the areas of projection of pretectum and superior colliculus to the pulvinar and n. lateralis posterior, respectively, and to define other brain stem structures projecting to these thalamic nuclei in cats. For this purpose the technique of retrograde transport of horseradish peroxidase (HRP) has been used. After injection of the enzyme in the pulvinar, neurons were labeled in all subdivisions of the pretectal area. The majority of the labeled cells were located in the n. pretectalis posterior and n. tractus opticus although cells filled with HRP were present also in the n. pretectalis anterior pars compacta and area pretectalis medialis. Neurons projecting to the pulvinar were also found in the periaqueductal gray, reticular formation and locus coeruleus. When HRP was injected in the n. lateralis posterior, labeled neurons were present in the II and III subdivisions of the second layer of the superior colliculus. The location of these cells shifted from medial to lateral as the injections were shifted from posterior to anterior within the lateralis posterior. Neurons projecting to this nucleus were also present in the intermediate layers of the superior colliculus, lateral hypothalamus and parabigeminal nucleus. The possible role of the pretectal area and superior colliculus in mediating somesthetic input to the pulvinar and lateralis posterior, respectively, and the role of these structures in the control of ocular movements, are discussed.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1106
    Keywords: Key words Excitatory amino acids ; Calcium-binding proteins ; Thalamic nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Topographical and quantitative features of medial thalamic neurons in which aspartate (ASP) or glutamate (GLU) might act as neurotransmitters were investigated in the rat. The calcium-binding protein calbindin D-28k (CB) was exploited as a marker of neuronal subsets, thus allowing us to study also the relationships between the CB-containing neurons and those immunoreactive to excitatory amino acids. Double immunocytochemistry of ASP and CB or GLU and CB was performed in 40-μm-thick sections. The three markers were distributed in the thalamic midline, mediodorsal, anterior intralaminar and ventromedial nuclei, with regional variations. ASP-immunoreactive neurons appeared more numerous than the GLU-immunoreactive ones throughout these structures; ASP-CB or GLU-CB double-immunostained neurons were evident. ASP-, GLU- and CB-immunoreactive cells were then quantitatively evaluated in 5-μm-thick consecutive sections. Interindividual variations and different anti-ASP and anti-GLU antibodies did not result in significant differences. ASP and GLU were not co-localized. Single ASP- or GLU-immunoreactive neurons accounted for 60% of the total number of immunostained cells, and single ASP-immunopositive cells represented more than half of these neurons. Among the CB-immunoreactive cells (40% of the total), half were double immunostained; the proportion of double CB-ASP-immunopositive neurons was sevenfold higher than that of the CB-GLU-immunoreactive ones. These results indicate that ASP may act as excitatory neurotransmitter in a relatively high proportion of medial thalamic neurons, in which ASP frequently coexists with CB. Approximately 50% of the CB-immunoreactive cells did not contain either ASP or GLU, suggesting that some medial thalamic neurons may utilize a different neurotransmitter.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1106
    Keywords: Thalamus ; Intralaminar nuclei ; GABA ; Inhibition ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemistry using antibodies to glutamic acid decarboxylase (GAD) was used to investigate the intralaminar nuclei of the thalamus in rat, cat and monkey. Antibodies to gamma aminobutyric acid (GABA) were also used in the cat. Intralaminar immunoreactive cell bodies were not detected in the rat, but were clearly present in cat and monkey. In the latter species, GABA- or GAD-immunopositive perikarya were distributed throughout the anterior intralaminar nuclei, whereas in the posterior intralaminar complex they prevailed in the lateral part of the centre median nucleus and around the fasciculus retrofiexus. Measurements of the area of immunostained intralaminar cell bodies in cat and monkey indicated that they are represented by small neurons. Experiments in the cat, based on retrograde tracers injections involving large sectors of the frontal and parietal cortices and the head of the caudate nucleus, revealed that the GABA- or GAD-immunoreactive cells and the retrogradely labeled projection neurons represented two separate intralaminar cell populations, although the latter also included small cells. Considerable differences were observed in the immunoreactive GABAergic neuropil of the anterior and posterior intralaminar nuclei. Clusters of densely packed bouton-like immunoreactive elements were detected in the former structures in the rat, cat and monkey, and were especially evident in the central lateral nucleus; immunopositive varicose fibers and puncta were diffusely distributed in the posterior intralaminar structures. Taken together with data from the literature, the present findings indicate that in cat and monkey local circuit inhibitory cells regulate not only the activity of principal thalamic nuclei which project densely upon restricted cortical fields, but also of the intralaminar structures which are widely connected with the cerebral cortex and the striatum. Regional variations in the distribution of GABAergic fibers and terminals suggest major differences in the organization of inhibitory circuits and synaptic arrangements of the anterior and posterior intralaminar thalamus.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0568
    Keywords: Thalamus ; Somatosensory system ; Synaptogenesis ; Nervous system ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Electron microscopy has been employed to analyze the normal maturationai sequence that characterizes the postnatal development of synaptic circuits in the ventrobasal (VB) and reticular (Rt) thalamic nuclei of rats at different ages (from birth to the end of the third postnatal week). Throughout the first postnatal week, similar signs of immaturity are observed in both nuclei, mainly consisting in scarcity of cytoplasmic organelles, presence of wide extracellular spaces, and absence of myelinated fibers. Several synaptic terminals are however present from birth, thus indicating that some of the afferents have already reached and contacted their thalamic target during embryonic life. Most of the terminals are small and contain only a few round, clear vesicles, and therefore their cytological features do not allow the identification of their origin. In particular, in both nuclei, terminals with flat vesicles and symmetric specialization are only rarely observed, and in VB the ascending terminals are not distinguishable from terminals of other sources as they are in adults. During the second postnatal week, progressive maturationai changes in VB and Rt lead to neurons having well-developed cytoplasmic organelles and to an elaborate neuropil containing myelinated fibers and synaptic terminals that are morphologically heterogeneous and resemble the adult ones. The permanence of growth cone-like profiles and of numerous somatic and dendritic protrusions, often contacted by synaptic terminals, indicates that a certain degree of reorganization is still taking place in both nuclei. By the end of the third postnatal week the synaptic organization of VB and Rt is indistinguishable from that observed in adults. This ultrastructural study shows that the appearance of the neuropil of VB and Rt and the morphological complexity of the synaptic arrangements characteristic of the adult rat are not present in neonates, but are gradually acquired during the first three postnatal weeks, and that they result from progressive modifications in circuit organization involving both pre- and postsynaptic elements.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Knockout Otx1 mice present a microcephalic phenotype mainly due to reduced deep neocortical layers and spontaneous recurrent seizures. We investigated the excitable properties of layer V pyramidal neurons in neocortical slices prepared from Otx1–/– mice and age-matched controls. The qualitative firing properties of the neurons of Otx1–/– mice were identical to those found in wild-type controls, but the proportion of intrinsically bursting (IB) neurons was significantly smaller. This is in line with the lack of the Otx1 gene contribution to the generation and differentiation of neurons destined for the deep neocortical layers, in which IB neurons are located selectively in wild-type rodents. The pyramidal neurons recorded in Otx1–/– mice responded to near-threshold electrical stimulation of the underlying white matter, with aberrant polysynaptic excitatory potentials often leading to late action potential generation. When the strength of the stimulus was increased, the great majority of the Otx1–/– neurons (78%) responded with a prominent biphasic inhibitory postsynaptic potential that was significantly larger than that observed in the wild-type mice, and was often followed by complex postinhibitory depolarizing events. Both late excitatory postsynaptic potentials and postinhibitory excitation were selectively suppressed by NMDA receptor antagonists, but not by AMPA antagonists. We conclude that the cortical abnormalities of Otx1–/– neocortex due to a selective loss of large projecting neurons lead to a complex rearrangement of local circuitry, which is characterized by an excess of N-methyl-d-aspartate-mediated polysynaptic excitation that is counteracted by GABA-mediated inhibition in only a limited range of stimulus intensity. Prominent postsynaptic inhibitory potentials may also act as a further pro-epileptogenic event by synchronizing abnormal excitatory potentials.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Neurological sciences 13 (1992), S. 171-176 
    ISSN: 1590-3478
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Neurological sciences 13 (1992), S. 700-703 
    ISSN: 1590-3478
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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