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1.
Hemimegalencephaly (HMEG) is a developmental brain malformation highly associated with epilepsy. Balloon cells (BCs) and cytomegalic neurons (CNs) are frequently observed in HMEG specimens. Cytomegaly in developmental brain malformations may reflect in aberrant activation of the mTOR and β-catenin signaling cascades, known regulators of cell size. We hypothesized that there is aberrant co-expression of phospho-ribosomal S6 (P-S6) protein, a downstream effector of the mTOR cascade, as well as cyclin D1, a downstream effector of the β-catenin pathway, in BCs and cytomegalic neurons in HMEG. We hypothesized that mutations in PTEN (a cause of HMEG associated with Proteus syndrome), TSC1 or TSC2 (tuberous sclerosis complex) genes, which are known to modulate β-catenin and mTOR signaling could cause sporadic HMEG. Expression of cyclin D1, phospho-p70 S6 kinase (P-p70S6K, another mTOR cascade kinase), P-S6, MAP2, NeuN, or GFAP was determined by immunohistochemistry in HMEG brain tissue (n = 7 specimens). Cyclin D1, P-p70S6K, and P-S6 proteins were co-localized in BCs and CNs in the enlarged hemisphere but not in the unaffected hemisphere or in morphologically normal tissue. Cyclin D1 and P-S6 proteins were not detected in GFAP-labeled astrocytes. Sequencing of PTEN, TSC1, and TSC2 genes in cytomegalic cells co-expressing cyclin D1 and P-S6 proteins did not reveal mutations. Selective expression of cyclin D1 and P-S6 in cytomegalic cells in HMEG suggests co-activation of the β-catenin and mTOR cascades. PTEN, TSC1, or TSC2 gene mutations were not detected suggesting that sporadic HMEG is distinct from HMEG associated with Proteus syndrome or tuberous sclerosis complex.  相似文献   

2.
HEMIMEGALENCEPHALY: A CLINICOPATHOLOGICAL STUDY OF FOUR CASES   总被引:2,自引:0,他引:2  
Pathological findings in four cases of hemimegalencephaly are presented. These cases demonstrated diffuse enlargement of the cortex with disappearance of horizontal layering of the neurons restricted to one hemisphere. In all cases there was marked enlargement of a high percentage of neurons. The nosological situation is discussed and is considered to be heterogeneous; cases 1-3 had cerebral lesions without lesions of the skin or viscera. In these three cases, significant glial abnormalities were found in only one. These cases and others quoted in the literature were considered to be a separate entity completely different from Bourneville's tuberous sclerosis. The aetiology of this developmental malformation remains unknown; genetic factors were not found. Case 4 was associated with a cardiac lesion and with a linear sebaceous naevus characteristic of Solomon's syndrome. Periventricular tumours resembling candlewax drippings were noted. This case, close to Bourneville's disease, could be incorporated into the framework of neuroectodermoses together with tuberous sclerosis.  相似文献   

3.
PURPOSE: Hemimegalencephaly (HMEG) is characterized by unilateral hemispheric enlargement and severe cytoarchitectural abnormalities that are highly associated with intractable epilepsy. No studies have defined alterations in neurotransmitter-receptor subunit gene expression in HMEG. We hypothesize that a differential expression of excitatory amino acid and gamma-aminobutyric acid (GABA)A-receptor subunit messenger RNAs (mRNAs) exists in HMEG. METHODS: The expression of mRNAs encoding 20 neurotransmitter-receptor subunits, synthetic enzymes, and uptake sites as well as select additional candidate genes was defined in HMEG samples (n=8) compared with homotopic control cortex specimens by using targeted complementary DNA (cDNA) arrays. Expression of GLT-1 (a glial glutamate transporter), EAAC-1 (neuronal glutamate transporter), and NMDA2B was corroborated by immunohistochemical, Western, and ligand-binding assays. RESULTS: Differential expression of 11 neurotransmitter-related mRNAs was demonstrated in HMEG compared with control cortex. For example, expression of GLT-1 and GluR6 mRNAs was enhanced, whereas diminished expression of the neuronal glutamate transporter EAAC-1, GABAAalpha2, GABAAgamma2, GABAAgamma3, NMDA2B, GluR1, GluR2, GluR4, and GluR5 subunits occurred. Reduced NMDA2B subunit mRNA expression in HMEG was confirmed by receptor ligand-binding assays by using the NMDA2B-receptor antagonist ifenprodil, which revealed barely detectable levels of NMDA2B binding compared with that in control cortex. CONCLUSIONS: Selective alterations occur in distinct neurotransmitter-receptor and -uptake sites in HMEG. Differential expression of neurotransmitter-receptor and -uptake sites in HMEG may contribute to epileptogenesis in HMEG.  相似文献   

4.
OBJECTIVES: Although changes in novelty seeking and harm avoidance have been reported among patients with Parkinson's disease (PD), the findings regarding the neurochemical correlates of such changes are inconsistent. This study was designed to examine the hypothesis that different patterns of motor and neurochemical asymmetry in PD may have contributed to the conflicting results. METHODS: Forty PD patients (divided into two groups according to initial asymmetry in dopamine deficit: left hemisphere, n = 22; right hemisphere, n = 18) and 17 age matched healthy controls completed the Tridimensional Personality Questionnaire (Cloninger, 1987). RESULTS: Only patients with greater dopamine loss in the left hemisphere showed reduced novelty seeking, whereas only patients with reduced dopamine in the right hemisphere reported higher harm avoidance than matched healthy controls. Novelty seeking was not associated with disease duration, current motor symptoms, or medication, whereas harm avoidance was significantly correlated only with the severity of bradykinesia and depression. CONCLUSIONS: Approach and avoidance reflect different patterns of dopaminergic asymmetry. Whereas reduced novelty seeking reflects deficit in the mesolimbic branch of ascending dopamine transmission in the left hemisphere, increased harm avoidance is associated with greater dopamine loss in the right striatum.  相似文献   

5.
Focal cortical dysplasia (FCD), which is often associated with intractable epilepsy, is a form of abnormal structure of the cerebral cortex caused by a disorder of normal neocortical development. In such cerebral lesions obtained from four patients (two male, two female; average age 32.3 years at operation), the immunohistochemical expression of Trk receptors, which interact with neurotrophins and result in both growth and maturational changes in neuronal cells, was investigated in relation to the possible histogenesis of these lesions. In all cases, a derangement of the cortical laminar structure, dysplastic cytomegalic neurones, and large round balloon cells were the characteristic histological features. Immunohistochemically, the TrkA expression was localized in large dysplastic cytomegalic neurones, and TrkB expression was observed in large dysplastic and relatively small neuronal cells within the affected cortex. Although the exact roles of neurotrophins and their receptors in the pathogenesis of FCD remain uncertain, its development might be governed by such neurotrophic influences, and thus possibly prevent the death of abnormal neuronal cells. In addition, Trk receptors in FCDs may also play a role in establishing in the intrinsic epileptogenicity of FCDs.  相似文献   

6.
Intrinsic neurones and associated cells of the guinea-pig heart in culture   总被引:2,自引:0,他引:2  
This paper describes a method for dissociation of intrinsic neurones from the atria and interatrial septum of newborn guinea-pig heart and their maintenance in culture. The appearance of the cultured intracardiac neurones, muscle and other non-neuronal cell types also present in the preparation has been observed by phase-contrast microscopy. Some of the neurochemical properties of the intracardiac neurones in culture have been investigated using histochemical methods. All the neurones studied were shown to contain acetylcholinesterase. No catecholamine-containing neurones were found. Using an indirect immunofluorescence technique, 20-50% of clearly identifiable neurones in culture contained neuropeptide Y-like immunoreactivity. Vasoactive intestinal polypeptide-like immunoreactive neurones were found in only one out of 15 culture preparations; no substance P-, neurotensin-, or enkephalin-like immunoreactivity was observed. These findings are consistent with those described for intracardiac neurones studied in situ, suggesting that the neurochemical differentiation of the intrinsic heart neurones is retained in culture. The culture preparation provides an opportunity to study the properties and role of intrinsic neurones of the heart. The characteristics of the intracardiac neurones may be distinguished from those of the extrinsic nerve fibres which degenerate in culture. Further, the intracardiac neurones are more accessible to experimental manipulation in culture than in situ.  相似文献   

7.
Linear nevus sebaceous syndrome is reported to occur in as many as 1 in 1000 live births, and is hypothesized to result from genetic mosaicism involving a lethal autosomal-dominant gene. The terms "epidermal nevus syndrome" and "linear nevus sebaceous syndrome" are often used interchangeably, although linear nevus sebaceous syndrome more strictly applies to patients with a typical midline nevus, and epidermal nevus syndrome is a more inclusive term that includes all varieties of epidermal nevi. Linear nevus sebaceous syndrome encompasses a broad spectrum of abnormalities that may affect every organ system, including the central nervous system. In these cases, seizures and mental retardation are the main manifestations. Many other organ systems were also reported to be involved in this syndrome, including the cardiovascular, skeletal, ophthalmologic, and urogenital systems, among others. Although linear nevus sebaceous syndrome occurs at a relatively high frequency and may affect different organ systems, many physicians are unaware of the syndrome, which may delay diagnosis and treatment. We present two cases of linear nevus sebaceous syndrome, and we describe their initial presentation and subsequent evolution, incorporating a review of the current literature in this field.  相似文献   

8.
Sphincter of Oddi (SO) ganglia are comprised of two main types of neurones based either on their electrical or neurochemical properties. This study investigated whether any correlation exists between the electrical and neurochemical properties of these cells. SO neurones were characterized electrically as either Tonic or Phasic cells, labelled with neurobiotin, fixed, and processed for β-nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-DA) staining and choline acetyltransferase immunoreactivity to identify whether electrically characterized neurones were nitrergic or cholinergic. A total of 119 cells were analysed in this manner; 45% of cells were Tonic and 37% were Phasic. An equivalent number of Tonic (58.1%, 18/31) and Phasic cells (60%, 21/35) were choline acetyltransferase (ChAT) positive. Three of 34 Phasic cells were NADPH-DA positive, whereas 11/33 Tonic cells were NADPH-DA positive. In none of the preparations was ChAT immunoreactivity and NADPH-DA reactivity ever observed in the same neurone. Calretinin immunoreactivity was present in a subpopulation of both Tonic and Phasic neurones. No correlation was observed between the direction of axon projections and the electrophysiological or neurochemical properties of the cell. These results suggest that there is a lack of correlation between the electrical properties and the neurochemical content of SO neurones. Various explanations for these findings are discussed.  相似文献   

9.
Abstract

An 18-year-old left-handed female with a large left hemisphere arteriovenous malformation in the frontoparietal region underwent brain mapping of the somatosensory cortex using a whole-head neuromagnetometer. Results indicated the presence of two complete somatosensory maps in the unaffected, right hemisphere. A map of contralateral body surface areas was found in the expected location in the anterior parietal lobe. A second map of ipsilateral body surface areas was found inferior to the first, extending from the inferior parietal lobe into peri-insular cortex, including SII. A less topographically organized map of the right side of the body was also found in the left hemisphere. Evoked magnetic flux components associated with right-sided stimulation occurred earlier, were more numerous, and were stronger in the ipsilateral as compared to the contralateral hemisphere, suggesting that the ipsilateral map is functional. These findings are discussed in relationship to other functional imaging studies of reorganization of the functional cortex in response to early trauma or congenital anomaly.  相似文献   

10.
Microdysgenesis is a term describing microscopic cortical cytoarchitectural abnormalities. Histologically this change shows an irregular glioneuronal tissue combination forming an abnormal structure of the cortex. The pathological features of this malformation are subtle and less well defined than other more distinctive cortical malformations. The clinical significance of these discrete glioneuronal malformations is controversial. Microscopic dysgenetic changes have been reported in cases with intractable epilepsy but similar changes may be seen in neurologically normal adults. The purpose of our study was the investigation of microdysgenetic lesions in the developing nervous system with regard to normal neuronal migration, differentiation and maturation. The post-mortem routine investigated foetal and infantile brains which were analysed histologically for the presence of discrete cortical malformations. A wide spectrum of cytoarchitectural glioneuronal malformations was found in the investigated material. We observed leptomeningeal glioneuronal heterotopias, subpial bands of heterotopic neurones, nests of ectopic neurones in the first cortical layer, neuronal and glial clusters, small foci with irregularity of laminar structure of the cortex. Microdysgenetic changes arose from an insult occurring in the later stages of cortical development and influencing the normal fate of neuroglial cells. Various types of focal morphological and cytoarchitectonial developmental abnormalities have been associated with behavioural and neuropsychological deficits in older infants.  相似文献   

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