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1.
Malformations of cortical development (MCDs) are macroscopic or microscopic abnormalities of the cerebral cortex that arise as a consequence of an interruption to the normal steps of formation of the cortical plate. The human cortex develops its basic structure during the first two trimesters of pregnancy as a series of overlapping steps, beginning with proliferation and differentiation of neurons, which then migrate before finally organizing themselves in the developing cortex. Abnormalities at any of these stages, be they environmental or genetic in origin, may cause disruption of neuronal circuitry and predispose to a variety of clinical consequences, the most common of which is epileptic seizures. A large number of MCDs have now been described, each with characteristic pathological, clinical, and imaging features. The causes of many of these MCDs have been determined through the study of affected individuals, with many MCDs now established as being secondary to mutations in cortical development genes. This review will highlight the best-known of the human cortical malformations associated with epilepsy. The pathological, clinical, imaging, and etiologic features of each MCD will be summarized, with representative magnetic resonance imaging (MRI) images shown for each MCD. The malformations tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly, classical lissencephaly, subcortical band heterotopia, periventricular nodular heterotopia, polymicrogyria, and schizencephaly will be presented. 相似文献
2.
Nine cases of marginal glioneuronal heterotopias over the cerebral cortex were reviewed from the morphological point of view. There were developmental disabilities in all cases except one (case 8), who was stillborn. All subjects died before 1 year of age except one (case 5). The common features of small glioneuronal heterotopias and abundant heterotopic glioneuronal proliferation are described. The correlation of glioneuronal heterotopias with polymicrogyria and other cortical malformations, as well as their appearance over a normal cortex, are described. The glioneuronal heterotopias are considered to be a separate type of malformation that could arise during the second half of intrauterine life. A breach of the neuropial border seems to be the most acceptable pathomechanism for our presented cases. Their morphological features indicate that damage to this barrier leads to involvement of glioneuronal heterotopias in fusion of opposite cortical convolutions. 相似文献
3.
Cortical dysplasias (CD) are characterized histologically by disorganized cortical lamination and abnormally shaped neurons.
We hypothesized that neurons within CD have failed to differentiate fully and may express proteins such as cytoskeletal elements
characteristic of immature cells. Disrupted expression of certain cytoskeletal proteins, which have been implicated in neuronal
polarity, process outgrowth, and migration, could result in disorganized cortical lamination. Thus, we probed two CD subtypes,
focal CD (FCD) and hemimegalencephaly (HME), with antibodies specific for cytoskeletal proteins that are developmentally regulated
in neural progenitor cells and neurons to define more fully the developmental phenotype of neurons within CD. Microtubule-associated
protein 1B (MAP1B) and the intermediate filament (IF) protein nestin are enriched in neural progenitors, whereas MAP2B, phosphorylated
and non-phosphorylated forms of medium (NFM) and high (NFH) molecular weight neurofilament (NF) proteins, as well as the light
NF subunit (NFL) and the IF protein α internexin are expressed in developing and mature neurons. Immunolabeling for internexin
and MAP1B was more abundant in the most abnormally shaped neurons that populated dysplastic regions than in adjacent regions
exhibiting milder cytoarchitectural abnormalities or control cortex. Nestin immunoreactivity was noted in large dysplastic
and heterotopic neurons within the deeper cortical layers of CD specimens but not in normal cortex. In contrast, neurons in
CD specimens also expressed cytoskeletal markers characteristic of differentiated neurons such as NF subunits and MAP2B. These
findings suggest that the cytoarchitectural abnormalities in CD may reflect pathophysiological changes in the developing brain
that disrupt expression of several key components of the neuronal cytoskeleton and may contribute to impaired migration of
cortical neurons.
Received: 19 August 1996 / Revised, accepted: 19 November 1996 相似文献
4.
Boyle MP Bernard A Thompson CL Ng L Boe A Mortrud M Hawrylycz MJ Jones AR Hevner RF Lein ES 《The Journal of comparative neurology》2011,519(11):2061-2089
The disrupted cortical lamination phenotype in reeler mice and subsequent identification of the Reelin signaling pathway have strongly informed models of cortical development. We describe here a marker-based phenotyping approach to reexamine the cytoarchitectural consequences of Reelin deficiency, using high-throughput histology and newly identified panels of highly specific molecular markers. The resulting cell-type-level cytoarchitectural analysis revealed novel features of abnormal patterning in the male reeler mouse not obvious with less specific markers or histology. The reeler cortex has been described as a rough laminar inversion, but the data presented here are not compatible with this model. The reeler cortex is disrupted in a more complex fashion, with some regions showing a mirror-image laminar phenotype. Major rostrocaudal and cell-type-specific differences in the laminar phenotype between cortical areas are detailed. These and similar findings in hippocampus and amygdala have implications for mechanisms of normal brain development and abnormalities in neurodevelopmental disorders. 相似文献
5.
Gordana Juric-Sekhar Raj P. Kapur Ian A. Glass Mitzi L. Murray Shawn E. Parnell Robert F. Hevner 《Acta neuropathologica》2011,121(4):545-554
Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct
phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a
distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III
is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings
in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic
lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different
cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated
with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite
cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and
cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical
malformation in MOPD I/III is distinct from other forms of pachygyria–lissencephaly. 相似文献
6.
Becker AJ Blümcke I Urbach H Hans V Majores M 《Journal of neuropathology and experimental neurology》2006,65(2):99-108
Glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) as well as highly differentiated glioneuronal tumors (i.e. gangliogliomas) and constitute frequent findings in patients with pharmacoresistent focal epilepsies. Tailored resection strategies evolved as promising treatment options and allow a systematic neuropathologic and molecular biologic examination of the epileptogenic area in these patients. The histopathologic appearance and immunophenotype of glioneuronal lesions are, however, characterized by numerous similarities and suggest impaired proliferation, migration, and differentiation of neural precursor cells to play a pathogenetic role. Recent studies point toward molecular alterations within a variety of genes and pathways involved in development of the central nervous system, neuronal growth, and maturation. Compromised signaling within insulin- or reelin-transduction cascades are common findings and were associated with specific MCD entities. Unraveling pathogenic mechanisms may advance refined classification systems for epilepsy-associated malformations and open new avenues for the development of targeted treatment strategies in pharmacoresistent focal epilepsies associated with cortical malformations. 相似文献
7.
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
8.
Boer K Troost D Spliet WG Redeker S Crino PB Aronica E 《Neuropathology and applied neurobiology》2007,33(4):455-470
Hemimegalencephaly (HMEG) is a malformation of cortical development characterized by unilateral enlargement of the cerebral hemisphere, severe architectural and cellular abnormalities and association with intractable epilepsy. HMEG may represent an isolated lesion of the central nervous system, but may also be associated with several neurocutaneous syndromes. In the present study we discuss the neuropathological findings of two autopsy cases of HMEG associated with linear naevus sebaceous syndrome. Both cases showed the presence of linear naevus sebaceous on extensive areas of the face. The neurochemical profile of the glial and neuronal components in the affected hemisphere was determined using immunocytochemical markers and was compared with the unaffected contralateral hemisphere and normal control tissue. The observed cytomegalic neurones expressed receptors for distinct neurotransmitters, neuropeptides and growth factors. Analysis of components of the phosphoinositide 3-kinase pathway revealed expression of phospho-S6 ribosomal protein in cytomegalic neurones. Autopsy findings confirm the complexity of the histologic phenotypic manifestations in HMEG and proved useful in determining the spectrum of cytoarchitectural and neurochemical abnormalities, underlying the molecular pathogenesis and epileptogenesis of this brain malformation. 相似文献
9.
Karin Boer Paul J. Lucassen Wim G. M. Spliet Erno Vreugdenhil Peter C. Van Rijen Dirk Troost Floor E. Jansen Eleonora Aronica 《Epilepsia》2009,50(12):2629-2637
Purpose: Focal cortical dysplasia type IIB (FCD IIB) and cortical tubers of patients with tuberous sclerosis complex (TSC) are malformations of cortical development that are frequently associated with intractable epilepsy. Their histopathologic and molecular features suggest developmental abnormalities during the early stages of cortical development, which may involve neural progenitor cells. The aim of our study was to define the expression and cell‐specific distribution of doublecortin‐like (DCL), a protein critically involved in neuronal division and radial migration during early corticogenesis, in both FCD and TSC. Methods: DCL was studied in epilepsy surgery cases with FCD IIB (n = 8) and TSC (cortical tubers; n = 8) using immunocytochemistry, confocal analysis, and Western blotting. Results: Autopsy and surgical control neocortical specimens were characterized by modest DCL immunoreactivity (IR) throughout all cortical layers, but DCL IR was not detectable in the white matter. Balloon cells (BCs) in FCD and giant cells (GCs) in TSC expressed strong DCL IR. Most of the large dysplastic neurons (DNs) were positive for DCL in both FCD and TSC. Coexpression of DCL with the neural progenitor or neuroblast markers nestin, GFAPδ, and doublecortin was observed in both FCD and TSC specimens. The increased DCL expression within the dysplastic cortex, compared to control cortex, was confirmed by Western blot analysis. Discussion: The prominent postnatal expression of DCL by BCs/GCs and DNs in FCD and TSC supports an important role for this microtubule associated protein, also during early human cortical development, which could be relevant to the pathogenesis of these developmental glioneuronal malformations. 相似文献
10.
Inhibitory networks in epilepsy-associated gangliogliomas and in the perilesional epileptic cortex 总被引:3,自引:0,他引:3
Aronica E Redeker S Boer K Spliet WG van Rijen PC Gorter JA Troost D 《Epilepsy research》2007,74(1):33-44
Developmental glioneuronal lesions, such as gangliogliomas (GG) are increasingly recognized causes of chronic pharmaco-resistant epilepsy. It has been postulated that chronic epilepsy in patients with malformations of cortical development is associated with dysfunction of the inhibitory GABA-ergic system. We aimed to identify the subtypes of interneurons present within GG specimens and the expression and cellular distribution patterns of GABA receptors (GABAR) and GABA transporter 1 (GAT1). The expression of the various components of the GABA-ergic system were also analyzed in the perilesional cortex. We investigated the expression of parvalbumin, calbindin, calretinin, GABA(A)R (a1 subunit)(,) GABA(B) (R1 and R2) and GAT-1 using immunocytochemistry in 30 specimens of GG obtained during epilepsy surgery, including 10 cases with sufficient amount of perilesional cortex. Immunocytochemistry for calbindin (CB), calretinin (CR) and parvalbumin (PV) demonstrate the presence of inhibitory neurons of different subtypes within the GG specimens. Calcium-binding protein-positive interneurons represent a small fraction of the total neuronal population. Both GABA(A)R and GABA(B)R (R1 and R2) subtypes were detected within the neuronal component of GG specimens. In addition, GABA(B)R2 immunoreactivity (IR) was observed in glial cells. GG specimens displayed also expression of GAT-1 IR. Compared to normal cortex, the density of PV- and CB-immunoreactive interneurons was reduced in the perilesional cortex of GG patients, whereas CR-labeling was similar to that observed in normal cortex. GAT-1 IR was also significantly reduced in the perilesional specimens. The cellular distribution of components of the GABA-ergic system in GG, together with the perilesional changes suggest that alterations of the GABA-ergic system may contribute to the complex abnormal functional network of these highly epileptogenic developmental lesions. 相似文献
11.
Thom M Holton JL D'Arrigo C Griffin B Beckett A Sisodiya S Alexiou D Sander JW 《Neuropathology and applied neurobiology》2000,26(3):251-257
Microdysgenesis is a microscopic cortical malformation reported to occur with varying incidence in surgical lobectomies from patients with temporal lobe epilepsy (TLE). It may act as a substrate for the seizures. Four patients are reported with TLE, hippocampal sclerosis and cortical microdysgenesis which was also characterized by the presence of abnormal myelinated fibres running tangentially in the superficial cortical laminae and closely associated with abnormal clusters of neurones. Similar abnormal cortical fibres have been described in other malformations of cortical development including polymicrogyria and focal cortical dysplasia and it is therefore likely that these fibres represent part of the microdysgenetic malformation not hitherto reported. The possibility is discussed that they may also be of functional significance in terms of influencing local seizure propagation and the secondary cortical neuronal loss observed, predominantly affecting layer II. Studies of calbindin interneuronal populations showed preservation of these cells in the microdysgenetic cortex, when compared with non-malformed temporal lobes, despite an overall reduction in cortical neuronal density. In addition, prominent numbers of neurogliaform calbindin-positive nerve cells were observed in the microdysgenesis cases and the nature of these cells is speculated upon. 相似文献
12.
Focal cortical dysplasia (FCD) and microdysgenesis (MD) are likely to represent abnormalities of radial neuronal migration during cortical development. We investigated the distribution of reelin-positive Cajal-Retzius cells, known to be important in the later stages of radial neuronal migration and cortical organization, in 12 surgical cases of both MD and FCD. Quantitation revealed significantly higher numbers of these cells in MD cases compared to controls. As the majority of cortical interneurones arise via tangential rather than radial migration, we studied the distribution and morphology of inhibitory interneuronal subsets immunolabelled for calbindin, parvalbumin and calretinin within these malformations. Frequent findings were a reduction of inhibitory interneurones in the region of FCD and abnormally localised hypertrophic or multipolar calbindin-positive interneurones in both FCD and MD. Neuropeptide Y immunostaining showed a striking increase in the density of the superficial plexus of fibres in both MD and FCD cases in addition to labelling of dysplastic neurones, which may represent an adaptive anti-convulsant mechanism to dampen down seizure propagation. 相似文献
13.
Volker Schick Michael Majores Arend Koch †Christian E. Elger ‡Johannes Schramm §Horst Urbach Albert J. Becker 《Epilepsia》2007,48(S5):65-73
Summary: Low-grade glioneuronal lesions involving tumors such as gangliogliomas and focal cortical dysplasias (FCD) predispose individuals to pharmacoresistant epilepsy. A frequent variant of FCD is composed of dysplastic cytomegalic neurons and Taylor-type balloon cells (FCDIIb ). Those are similar to cellular elements, which are present in cortical tubers in the autosomal dominant inherited tuberous sclerosis complex (TSC). This phacomatosis is caused by mutations in the TSC1 or TSC2 genes. Recent data have indicated accumulation of distinct allelic variants of TSC1 also in FCDIIb . TSC1 represents a key factor in the phosphatidylinositol 3-kinase (PI3K) pathway. A variety of alterations in the PI3K-pathway have been recently reported in epilepsy-associated glioneuronal malformations. Here, we discuss pathogenetic similarities and differences between cortical dysplasias as well epilepsy-associated glioneuronal tumors and TSC-associated cortical tubers with a focus on PI3K-pathway components including ezrin, radixin and moesin (ERM), which represent downstream effectors involved in cytoskeleton-membrane interference. No evidence has been found for mutational events of ERM genes to play a major pathogenetic role in epilepsy-associated glioneuronal malformations. In contrast, aberrant expression of ERM proteins in FCDs and gangliogliomas was observed. These alterations may relate to compromised interactions of dysplastic cellular components in epilepsy-associated glioneuronal lesions and be involved in aberrant PI3K-pathway signaling in epilepsy-associated malformations. However, the underlying cause of PI3K-pathway activation and the functional relationship of PI3K-pathway activity to generation of seizures in epilepsy-associated glioneuronal lesions will need to be determined in the future. 相似文献
14.
《Neurodegeneration》1996,5(4):403-407
Studies of the neurochemical pathology of AD have indicated that early in the course of the disease, abnormalities of relatively few neurotransmitters are obvious. The most reliable and consistent changes are those seen in the cholinergic innervation of the cortex and the cortical pyramidal neurones. However, by the time of death there is usually considerable involvement of other neurones. 相似文献
15.
Detailed classification of brain malformations such as lissencephaly has led to the positional cloning of genes required for normal neuronal migration and the identification of unique molecular pathways governing brain structure. While classical magnetic resonance imaging (MRI) patterns of lissencephaly involve primarily the cerebral cortex, malformations in this spectrum can be associated with significant cerebellar underdevelopment and have recently been referred to as lissencephaly with cerebellar hypoplasia (LCH). The phenotypic features of 34 children were found to define 6 subtypes of LCH. Two of these (LCHa and LCHb) were associated with mutation in the LIS1, DCX and RELN genes, respectively. Gene mutations that exemplify four additional classes (LCHc, d, e and f) remained to be determined. Phenotypic features included small head circumference, cortical malformation ranging from agyria to simplification of the gyral pattern and from near normal cortical thickness to marked thickening of the cortical gray matter. Cerebellar manifestations ranged from midline hypoplasia to diffuse volume reduction and disturbed foliation. We conclude that LCH is within the spectrum of DCX and LIS1 mutations, that LCH associated with RELN mutation is distinguished by the severity of cerebellar and hippocampal involvement, and that several distinctive patterns indicate additional genetic mutations that can produce LCH. 相似文献
16.
MacInnes N Iravani MM Perry E Piggott M Perry R Jenner P Ballard C 《Journal of neural transmission (Vienna, Austria : 1996)》2008,115(6):869-878
Dementia with Lewy bodies (DLB) accounts for 15-20% of the millions of people worldwide with dementia. In the current work we investigate the association between proteasome dysfunction and the development of cortical Lewy body pathology. Analysis of post-mortem cortical tissue indicated levels of the alpha-subunit of the 20S proteasome were significantly reduced in DLB cortex, but not Alzheimer's, in comparison to control and this reduction correlated with both the severity and duration of dementia. Application of proteasome inhibitors to rodent cortical primary neurones in vitro and by direct injection onto rodent cholinergic forebrain neurons in vivo gave rise to dose dependent neuronal death and in rodent cortex -- marked cholinergic deficits accompanied by the accumulation of inclusions that stained positive for alpha-synuclein and ubiquitin. These findings suggest that proteasomal abnormalities are present within cortical Lewy body disease and the experimental inhibition of proteasomal function mirrors the neuropathological changes seen within the disorder. 相似文献
17.
Genes that regulate neuronal migration in the cerebral cortex. 总被引:5,自引:0,他引:5
Malformations of cortical development are increasingly recognized as causes of mental retardation and epilepsy. However, little is known about the molecular and biochemical signals that control the proliferation, migration, and organization of the cells involved in normal cerebral cortical development. Analysis of genes required for cortical development will help elucidate the pathogenesis of some epilepsies. In humans, two striking examples of abnormal cortical development, with varying degrees of epilepsy and mental retardation, are 'double cortex' and lissencephaly. Double cortex (DC), also known as subcortical band heterotopia, shows an abnormal band of neurons in the white matter underlying a relatively normal cortex. In pedigrees, DC often occurs in females, whereas affected males show more severe lissencephaly (XLIS), i.e. an abnormally thick cortex with decreased or absent surface convolutions. We and others have identified a novel brain specific gene, doublecortin, that is mutated in Double Cortex/X-linked lissencephaly (DC/XLIS) patients. Although the cellular function of doublecortin (DCX) is unknown, sequence analysis reveals a cytoplasmic protein with potential MAP kinase phosphorylation sites, as well as a site that is likely to be phosphorylated by c-Abl, suggesting that doublecortin functions as an intracellular signaling molecule critical for the migration of developing neurons. Interestingly, the scrambler mouse mutant demonstrates abnormal lamination with some similarity to lissencephaly and reflects a mutation in the murine homolog of the Drosophila disabled gene, mdab1, which binds c-Abl. Although a direct interaction between doublecortin and mDab1 has not been demonstrated, it is plausible that these two proteins may be part of a common signaling pathway. Therefore, abnormalities in signal transduction may be an underlying mechanism for the neuronal migration defects in DC/XLIS and the scrambler mouse, but further research is necessary to determine how such abnormalities give rise to cortical malformations and epilepsy. 相似文献
18.
Cortical thinning in cingulate and occipital cortices in first episode schizophrenia. 总被引:6,自引:0,他引:6
Katherine L Narr Arthur W Toga Philip Szeszko Paul M Thompson Roger P Woods Delbert Robinson Serge Sevy YungPing Wang Karen Schrock Robert M Bilder 《Neuropsychopharmacology》2005,58(1):32-40
BACKGROUND: Postmortem studies examining discrete regions show reduced cortical thickness in schizophrenia. Computational image analysis methods allow spatially detailed cortical thickness measurements across the entire cortex in 3D, but have not addressed thickness changes in cingulate or other cortices bordering the medial walls of the cerebral hemispheres in first episode schizophrenia. METHODS: Magnetic resonance images and cortical pattern matching methods were used to compare gray matter thickness, measured at sub-voxel resolution at thousands of spatially equivalent locations on the medial hemispheric surfaces, between 72 (51m/21f) first episode schizophrenia patients and 78 (37m/41f) healthy controls similar in age. Group differences were mapped in 3D, and their overall significance was confirmed by permutation testing. RESULTS: Patients with little or no prior antipsychotic medication treatment showed significant cortical thinning within cingulate, occipital and frontopolar cortices with no significant increases in any cortical location. Regional sex differences were observed with pronounced thinning in the left paracentral lobule and right posterior cingulate in male and female patients respectively compared to same sex controls. CONCLUSIONS: Cortical thinning may correspond to cytoarchitectural and neurochemical abnormalities observed in similar anatomic locations and may underlie systems-wise disturbances that include heteromodal association cortices, where cortical thinning has been previously observed in first episode schizophrenia. 相似文献
19.
Tubers are cerebral cortical developmental malformations associated with epilepsy and autism in tuberous sclerosis complex
(TSC). The disparity between tuber number and severity of neurological impairment often observed in TSC led us to hypothesize
that microscopic structural abnormalities distinct from tubers may occur in TSC. Serial frontal to occipital lobe sections
were prepared from five postmortem TSC brain specimens. Sections were probed with cresyl violet stain or NeuN antibodies to
define cytoarchitectural abnormalities and phospho-S6 (Ser235/236) antibodies to define mammalian target of rapamycin complex
1 (mTORC1) pathway activation. Tubers identified in all specimens (mean, 5 tubers per brain specimen) were defined by abnormal
cortical lamination, dysmorphic neurons, and giant cells (GCs) and exhibited robust phospho-S6 immunolabeling. Histopathological
analysis of non-tuber cortices demonstrated that 32% of the sections exhibited microscopic cytoarchitectural alterations,
whereas 68% of the sections did not. Four types of morphological abnormalities were defined including: (1) focal dyslamination,
(2) heterotopic neurons, (3) small collections of giant cells (GCs) and neurons we termed “microtubers”, (4) isolated GCs
we termed “sentinel” cells. When compared with control cortex, phospho-S6 labeling was enhanced in microtubers and sentinel
cells and in some but not all areas of dyslamination. There are microscopic cytoarchitectural abnormalities identified in
postmortem TSC brain specimens that are distinct from tubers. mTORC1 cascade activation in these areas supports a widespread
effect of TSC1 or TSC2 mutations on brain development. Tubers may represent the most dramatic developmental abnormality in TSC; however, more regionally
pervasive yet subtle abnormalities may contribute to neurological disability in TSC. 相似文献
20.
To evaluate neuronal cytoarchitectural changes in cortical dysplasia, we examined microtubule-associated protein 2 (MAP2) expression in surgically resected specimens obtained from 20 patients (age range, 3 months to 10 years) treated for intractable epilepsy. Large neurons were investigated in the specimens from all patients and showed significantly strong immunoreactivity with antibodies against MAP2 in the perikaryon and proximal portion of their processes. In situ hybridization with MAP2 antitense riboprobe showed increased hybridization signal intensities in the large neurons, which correlated with the pattern of immunoreactivity for MAP2. We conclude that MAP2 is strongly expressed in the large neurons in cortical dysplasia. The results of preliminary immunoblotting in 1 patient with focal cortical dysplasia showed that the low-molecular-weight form of MAP2 (MAP2c) was strongly expressed in the dysplastic cortex, suggesting that MAP2c may be a major component contributing to the increased expression of MAP2 in the large neurons of cortical dysplasia. Since it has been suggested that MAP2 plays a crucial role in the branching and remodeling of neuronal processes, increased expression of MAP2 may reflect activated plasticity of the large neurons in cortical dyspasia. 相似文献