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1.
Intracellular calcium-binding protein S100A4 influences injury-induced migration of white matter astrocytes 总被引:1,自引:0,他引:1
Fang Z Duthoit N Wicher G Källskog O Ambartsumian N Lukanidin E Takenaga K Kozlova EN 《Acta neuropathologica》2006,111(3):213-219
Astrocytes play a crucial role in central nervous system (CNS) pathophysiology. White and gray matter astrocytes are regionally
specialized, and likely to respond differently to CNS injury and in CNS disease. We previously showed that the calcium-binding
protein S100A4 is exclusively expressed in white matter astrocytes and markedly up-regulated after injury. Furthermore, down-regulation
of S100A4 in vitro significantly increases the migration capacity of white matter astrocytes, a property, which might influence
their function in CNS tissue repair. Here, we performed a localized injury (scratch) in confluent cultures of white matter
astrocytes, which strongly express S100A4, and in cultures of white matter astrocytes, in which S100A4 was down-regulated
by transfection with short interference (si) S100A4 RNA. We found that S100A4-silenced astrocytes rapidly migrated into the
injury gap, whereas S100A4-expressing astrocytes extended hypertrophied processes toward the gap, but without closing it.
To explore the involvement of S100A4 in migration of astrocytes in vivo, we induced focal demyelination and transient glial
cell elimination in the spinal cord white matter by ethidium bromide injection in S100A4 (−/−) and (+/+) mice. The results
show that astrocyte migration into the demyelinated area is promoted in S100A4 (−/−) compared to (+/+) mice, in which a pronounced
glial scar was formed. These data indicate that S100A4 reduces the migratory capacity of reactive white matter astrocytes
in the injured CNS and is involved in glial scar formation after injury. 相似文献
2.
Fang Z Forslund N Takenaga K Lukanidin E Kozlova EN 《Journal of neuroscience research》2006,83(4):619-626
The central nervous system (CNS) is considered a nonpermissive environment for axonal regeneration because of the presence of myelin and associated repulsive molecules. However, neural cells transplanted to the CNS preferably migrate and extend their fibers in white matter areas. We previously showed that white matter astrocytes in vivo express the calcium-binding protein S100A4, which is strongly up-regulated in areas of white matter degeneration. To investigate the role of white matter astrocytes and their specific protein S100A4 in axonal regeneration, we developed white matter astrocyte cultures with strong S100A4 expression and grew dissociated adult dorsal root ganglion (DRG) cells on top of astrocytes for 24 hr. By using small interfering S100A4 RNA, we were able to eliminate S100A4 expression and compare growth of DRG cell neurites on S100A4-silenced and S100A4-expressing astrocytes. In addition, we studied whether extracellular S100A4 has an effect on neurite growth from adult DRG cells cultured on S100A4-expressing white matter astrocytes. Our data show that white matter astrocytes are permissive for neurite growth, although high levels of S100A4 in white matter astrocytes have a negative effect on this growth. Extracellular application of S100A4 induced extensive growth of DRG cell neurites on white matter astrocytes. These findings suggest that white matter astrocytes are able to support axonal regeneration and, furthermore, that administration of extracellular S100A4 provides strong additional support for axonal regeneration. 相似文献
3.
Role of intracellular S100A4 for migration of rat astrocytes 总被引:4,自引:0,他引:4
S100A4 is a member of the EF-hand family of calcium-binding proteins, first identified in tumor cells, and implicated in tumor invasion and metastasis. Intracellular upregulation of S100A4 is associated with increased motility of tumor cells. Extracellular application of S100A4 increases the motility of glioma cells in vitro. We showed previously that astrocytes in spinal cord and brain white matter also express S100A4. This expression is markedly increased in reactive white matter astrocytes after injury. Here, we have explored how changes in intracellular S100A4 affect migration of astrocytes. We produced cultures of white matter, S100A4 expressing astrocytes, and developed a small interfering (si) RNA approach to specifically eliminate S100A4 expression in these cells, and compared the migration of astrocytes expressing S100A4 with astrocytes transfected with S100A4 siRNA. As a "positive control" we used S100A4 expressing C6 glioma cells. In contrast to malignant cells, S100A4 expressing astrocytes increased their migration capacity after S100A4 siRNA treatment. At the same time, and in parallel with increased migration, white matter astrocytes increased their expression of metalloproteinases MMP-9 and MT1-MMP. The addition of MMP-2/MMP-9 inhibitor resulted in a significant inhibition of migration in S100A4 siRNA-treated astrocytes. These findings indicate that S100A4 has a stabilizing function in reactive white matter astrocytes, a function that may contribute to the development of a rigid, growth-inhibitory glial scar. 相似文献
4.
The S100 family of calcium binding proteins has been shown to be involved in a variety of physiological functions, such as regulation of enzyme function, cell motility, modification of extracellular matrix, and cell proliferation. Several members of the S100 family are expressed in the nervous system, but their functional roles are still largely obscure. The Mts1 gene codes for the S100A4 protein, which has been implicated in the control of cell proliferation and metastasis activity of tumor cells. We have used immunohistochemistry to examine the expression pattern of the Mts1 protein in the adult rat spinal cord and how this expression is influenced by peripheral nerve or dorsal root injury. Mts1 immunoreactivity (IR) was present only in white matter astrocytes in the intact spinal cord. Sciatic nerve as well as dorsal root injury induced a marked and prolonged up-regulation of Mts1-IR in astrocytes in the region of the dorsal funiculus containing the central processes of the injured primary sensory neurons. These findings suggest that Mts1 plays a unique physiological role in white matter astrocytes as well as in the response of astrocytes to degeneration of myelinated axons. 相似文献
5.
Olby NJ O'leary MT Targett MP Blakemore WF 《Restorative neurology and neuroscience》1995,7(3):171-174
Bisbenzimide-labelled astrocytes were transplanted into the spinal white matter of the rat using three different injection techniques and the variability of the longitudinal distance over which they were found was compared 30 min later. Cells spread up to 5.02 mm and the greatest variability was seen when they were injected as a bolus (54%), compared with 26% when injected over 2 min. These results show the importance of establishing the extent of passive spread of cells and its variability when performing studies in cell migration. 相似文献
6.
M. Aoyama H. Kakita S. Kato M. Tomita K. Asai 《Journal of neuroscience research》2012,90(12):2272-2280
Cellular activities within the brain display regional specificity and a neuronal and glia interdependence. Components characterizing the regional specificity of neurons have been identified. However, characterization of the astrocyte remains in question. To identify region specific features of astrocytes, we have characterized the molecular phenotype of cells derived from regions with different levels of neuronal excitability, the cortex and striatum. Astrocytes were identified in cryostat sections of adult rat brain by rapid immunostaining for glial fibrillary acidic protein (GFAP), and individual cells were collected from each region by using laser microdissection (LMD). Total RNA was isolated and subjected to DNA microarray analysis. At least eight genes showed a differential expression level. Among them, aquaporin 4 (AQP4), a water channel protein, was expressed at higher levels within the cortex compared with the striatum, as confirmed by immunohistochemistry. Primary cultured astrocytes isolated from rat cortex or striatum also showed a differential expression of AQP4. These data may reflect unique properties of astrocytes across different brain regions. However, they may also reflect the interactive demands of neurons with different activity levels. Further examination of the heterogeneous astrocyte populations within each region will lend additional support to the regional specificity of neuronal functions and neuronal–glial interactions. © 2012 Wiley Periodicals, Inc. 相似文献
7.
To capture patterns of normal age-associated atrophy, we previously used a multivariate statistical approach applied to voxel based morphometry that identified age-associated gray and white matter covariance networks (Brickman et al. [2007]: Neurobiol Aging 28:284-295). The current study sought to examine the stability of these patterns by forward applying the identified networks to an independent sample of neurologically healthy younger and older adults. Forty-two younger and 35 older adults were imaged with standard high-resolution structural magnetic resonance imaging. Individual images were spatially normalized and segmented into gray and white matter. Covariance patterns that were previously identified with scaled subprofile model analyses were prospectively applied to the current sample to identify to what degree the age-associated patterns were manifested. Older individuals were also assessed with a modified version of the Mini Mental State Examination (mMMSE). Gray matter covariance pattern expression discriminated between younger and older participants with high optimal sensitivity (100%) and specificity (90.5%). While the two groups differed in the degree of white matter pattern expression (t (75) = 5.26, P < 0.001), classification based on white matter expression was relatively low (sensitivity = 80% and specificity = 61.9%). Among older adults, chronological age was significantly associated with increased gray matter pattern expression (r (32) = 0.591, P < 0.001) but not with performance on the mMMSE (r (31) = -0.314, P = 0.085). However, gray matter pattern expression was significantly associated with performance on the mMMSE (r (31) = -0.405, P = 0.024). The findings suggest that the previously derived age-associated covariance pattern for gray matter is reliable and may provide information that is more functionally meaningful than chronological age. 相似文献
8.
The in vitro properties of the CG4 cell line have led to its increasing use as a cell line with which to study the behaviour of the O-2A progenitor cell. In this study we have examined the in vivo behaviour of the CG4 cell line following transplantation into areas of adult rat spinal cord white matter which have been permanently depleted of glial cells by the combination of local X-irradiation and direct injection of 0.1% ethidium bromide. Twenty-one days after transplantation, both myelin-forming oligodendrocytes and glial fibrillary acidic protein-positive astrocytes were identified within the lesion, indicating that the CG4 cell line has bipotential differentiation properties when introduced into a pathological environment consisting of demyelinated axons but devoid of oligodendrocytes or astrocytes. In this respect, the CG4 cell line resembles other glial progenitor cell lines that have been transplanted into similar lesions. In some areas of the lesion, remyelination was observed that was similar in extent to that achieved by growth factor-expanded populations of O-2A progenitor cells. The transplant origin of the cell types within the lesion was confirmed by retroviral incorporation of the lacZ marker gene, the expression of which allowed their identification by histochemistry. In conclusion, the in vivo properties of the CG4 cell line make it a highly suitable line with which to study the behaviour of O-2A progenitors following transplantation into normal and damaged CNS. © 1995 Wiley-Liss, Inc. 相似文献
9.
Reali C Scintu F Pillai R Donato R Michetti F Sogos V 《Journal of neuroscience research》2005,81(5):677-686
Central nervous system degenerative diseases are often characterized by an early, strong reaction of astrocytes and microglia. Both these cell types can play a double role, protecting neurons against degeneration through the synthesis and secretion of trophic factors or inducing degeneration through the secretion of toxic molecules. Therefore, we studied the effects of S100B and trimethyltin (TMT) on human astrocytes and microglia with two glial models, primary cultures of human fetal astrocytes and a microglia cell line. After treatment with 10(-5) M TMT, astrocytes showed morphological alterations associated with an increase in glial fibrillary acidic protein (GFAP) expression and changes in GFAP filament organization. Administration of S100B before TMT treatment prevented TMT-induced changes in morphology and GFAP expression. A decrease in inducible nitric oxide synthase expression was observed in astrocytes treated with TMT, whereas the same treatment induced iNOS expression in microglia. In both cases, S100B prevented TMT-induced changes. Tumor necrosis factor-alpha mRNA expression in astrocytes was not modified by TMT treatment, whereas it was increased in microglia cells. S100B pretreatment blocked the TMT-induced increase in TNF-alpha expression in microglia. To trace the mechanisms involved in S100B activity, the effect of BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-kappaB) activation, and of PD98059, an inhibitor of MEK-ERK1/2, were investigated. Results showed that the protective effects of S100B against TMT toxicity in astrocytes depend on NF-kappaB, but not on ERK1/2 activation. These results might help in understanding the role played by glial cells in brain injury after exposure to chemical neurotoxicants and support the view that S100B may protect brain cells in case of injury. (c) 2005 Wiley-Liss, Inc. 相似文献
10.
Current protocols for preparing primary sensory neuron cultures are inadequate when studying individual subpopulations of dorsal root ganglion (DRG) neurons. The DRG is made up of a heterogeneous population of cells, making it difficult to study treatment effects on any given population in mass cultures. Thus, we describe a procedure using magnetic beads from Dynal to select and plate viable populations of neurons based on expression of specific cell surface markers. We show that, by the use of the lectin IB4, we can select a highly enriched viable subpopulation of GDNF-responsive DRG neurons, leaving a viable population of non-selected IB4-ve, Trk+ve neurons. Key factors for successful cultures are (i) quick and careful dissection of DRGs from 4- to 5-week-old Sprague-Dawley rats, (ii) adequate removal of debris and non-neuronal contamination and (iii) gentle handling of bead-bound cells during selection. 相似文献
11.
Profilometry: A new statistical framework for the characterization of white matter pathways,with application to multiple sclerosis 下载免费PDF全文
Michael Dayan Elizabeth Monohan Sneha Pandya Amy Kuceyeski Thanh D. Nguyen Ashish Raj Susan A. Gauthier 《Human brain mapping》2016,37(3):989-1004
Aims: describe a new “profilometry” framework for the multimetric analysis of white matter tracts, and demonstrate its application to multiple sclerosis (MS) with radial diffusivity (RD) and myelin water fraction (MWF). Methods: A cohort of 15 normal controls (NC) and 141 MS patients were imaged with T1, T2 FLAIR, T2 relaxometry and diffusion MRI (dMRI) sequences. T1 and T2 FLAIR allowed for the identification of patients having lesion(s) on the tracts studied, with a special focus on the forceps minor. T2 relaxometry provided MWF maps, while dMRI data yielded RD maps and the tractography required to compute MWF and RD tract profiles. The statistical framework combined a multivariate analysis of covariance (MANCOVA) and a linear discriminant analysis (LDA) both accounting for age and gender, with multiple comparison corrections. Results: In the single‐case case study the profilometry visualization showed a clear departure of MWF and RD from the NC normative data at the lesion location(s). Group comparison from MANCOVA demonstrated significant differences at lesion locations, and a significant age effect in several tracts. The follow‐up LDA analysis suggested MWF better discriminates groups than RD. Discussion and conclusion: While progress has been made in both tract‐profiling and metrics for white matter characterization, no single framework for a joint analysis of multimodality tract profiles accounting for age and gender is known to exist. The profilometry analysis and visualization appears to be a promising method to compare groups using a single score from MANCOVA while assessing the contribution of each metric with LDA. Hum Brain Mapp 37:989–1004, 2016. © 2015 Wiley Periodicals, Inc . 相似文献
12.
Hoyaux D Boom A Van den Bosch L Belot N Martin JJ Heizmann CW Kiss R Pochet R 《Journal of neuropathology and experimental neurology》2002,61(8):736-744
Astrogliosis is one of the earliest pathological changes observed in neurodegenerative diseases in general and in amyotrophic lateral sclerosis (ALS) in particular. ALS is characterized by selective degeneration of motoneurons. There are 2 forms of the disease: sporadic ALS (SALS), comprising 90%-95% of cases, and familial ALS (FALS), comprising 5%-10% of cases. FALS is an age-dependent autosomal dominant disorder in which mutations in the homodimeric enzyme Cu/ Zn superoxide dismutase 1 (SOD1) is linked to the disease. The animal model for this disease is a transgenic mouse expressing the mutated human SOD1(G93A) gene. Here we show by immunohistochemistry and double immunofluorescence that astrocytes located near impaired axons of motoneurons that were selectively programmed to die overexpressed S100A6, a Ca2+/Zn2+ binding protein able to translocate into the nucleus. Transgenic mice overexpressing the mutated human SOD1 gene and patients suffering from SALS showed this selective astrocytic S100A6 expression. For instance, the pyramidal tract could be macroscopically detected on S100A6-labeled spinal cord and brainstem sections from SALS patients. Transgenic mice overexpressing the non-mutated SOD1 gene did not overexpress S100A6, although glial fibrillary associated protein astrogliosis was seen. Although these results do not give any clue about the beneficial or detrimental role played by S100A6, its induction may be assumed to appropriately serve some function(s). 相似文献
13.
Coppens AG Kiss R Heizmann CW Schäfer BW Poncelet L 《Brain research. Developmental brain research》2001,126(2):191-199
The immunolocalization of three members of the S100 calcium-binding protein family was investigated in the dog cochlea during normal postnatal development. Sections of decalcified and paraffin-embedded cochleae from 16 beagle puppies aged from birth to 3 months were treated with polyclonal antisera raised against the human recombinant S100A1, S100A5, and S100A6 proteins. At birth, in the dog cochlea, S100A1 was expressed in the immature Deiter's cells, and slightly in the pillar cells. From the second week, S100A1 was detected in the supporting structures of the organ of Corti, i.e. the Deiter's, the pillar, the border, and the Hensen's cells, and in the reticular membrane. From birth onwards, S100A5 remained a neuronal-specific protein, only located in a subpopulation of neurons in the spiral ganglion. S100A6 was not expressed at birth. From the second week of life, the Schwann cells and nerve sheaths in the modiolus, in the spiral ganglion, and running in the direction of the organ of Corti exhibited S100A6-labeling. From the 12th postnatal day, some scattered intermediate cells started to express S100A6 protein in the stria vascularis. The number of labeled intermediate cells increased during the third week. At adult stage, the intermediate cells were S100A6-stained with cytoplasmic labeling throughout the stria vascularis from the base to the apex of the cochlea. None of the other cochlear structures expressed the S100 proteins under study during the postnatal development of the dog cochlea. The S100A1, S100A5, S100A6 immunostaining was limited to specific cell types in dog cochlea. These S100 proteins were useful markers in the study of supporting cells, neurons, nerve fibers sheaths and stria vascularis (S100A6) during the normal postnatal development of the dog cochlea. 相似文献
14.
Interferon-gamma (IFN-gamma) is a potent lymphokine which can modify a variety of cellular processes. One of the mechanisms involved in these processes is the ability of IFN-gamma to alter the regulation and expression of cellular proteins. Using analytical flow cytometry, we show that recombinant human IFN-gamma can enhance the expression of retinal S-antigen in retinoblastoma cells. This enhancement was selective since two other retinal cell proteins, interphotoreceptor binding protein (IRBP) and photo-6, were not affected by IFN-gamma treatment. Retinal S-antigen plays an important role in vision and is one of the retinal proteins capable of inducing an inflammatory eye disease called experimental autoimmune uveitis. These studies therefore demonstrate an important role for this lymphokine, that is, the enhanced expression of a neuronal cell protein. This finding may also identify additional mechanisms by which IFN-gamma may participate in immunopathologic events in nervous tissue. 相似文献
15.
Takenaga K Nygren J Zelenina M Ohira M Iuchi T Lukanidin E Sjöquist M Kozlova EN 《Neurobiology of disease》2007,25(3):455-463
The calcium-binding Mts1/S100A4 protein plays an important role in motility and metastatic activity of tumor cells. Recently we showed that Mts1/S100A4 is expressed in white matter astrocytes and influences their migration in vitro and in vivo. Here, we have investigated the role of Mts1/S100A4 expression in C6 glioma cells or surrounding astrocytes for migration of C6 cells on astrocytes, using short interference (si) RNA to silence Mts1/S100A4 expression. We find that in vitro, the migration of Mts1/S100A4 expressing and silenced C6 cells on astrocytes is predominantly dependent on the expression of Mts1/S100A4 in astrocytes, i.e. C6 cells preferably migrate on Mts1/S100A4-silenced astrocytes. In vivo, Mts1/S100A4-positive C6 cells preferably migrate in white matter. In contrast Mts1/S100A4-silenced C6 cells avoid white matter and migrate in gray matter and meninges. Thus, the migration pattern of C6 cells is affected by their intrinsic Mts1/S100A4 expression as well as Mts1/S100A4 expression in astrocytes. To investigate if Mts1/S100A4 has a significant role on brain tumor progression, we made quantitative RT-PCR analysis for the expression of S100A4/Mts1 in various grades of astrocytic tumors. Our data showed that high-grade glioblastomas express higher amount of S100A4/Mts1 than low-grade astrocytic tumors. 相似文献
16.
Miguel Marín-padilla 《The Journal of comparative neurology》1995,357(4):554-572
The prenatal developmental histories of layer I, fibrous (white matter), and protoplasmic (gray matter) astrocytes have been studied in the human neocortex by the rapid Golgi method. The developmental route followed by each of these astrocytes is a distinct process which evolves from a specific precursor, occurs at a different time, and is linked to a specific event. The differentiation of layer I astrocytes is linked to the neocortex external glial limiting membrane (EGLM), that of fibrous astrocytes to the early white matter vascularization and maturation, and that of protoplasmic astrocytes to the late gray matter ascending vascularization and maturation. At the start of development, three glial precursors are established in the neocortex: 1) original radial neuroectodermal cells with nuclei above the primordial plexiform layer (PPL) by losing their ependymal and retaining their pial attachments become early astrocytes of layer I and EGLM components; 2) neuroectodermal cells with nuclei below the PPL that retain their pial and ependymal attachments become type I radial glial cells which are committed to the guidance of neurons and the early EGLM maintenance; and, 3) neuroectodermal cells that lose their pial but retain their ependymal attachment are transformed into type II radial glial precursors. By progressively losing their ependymal attachment, type II radial glia precursors become freely migrating cells, establish vascular contacts, and differentiate into fibrous astrocytes (and into oligodendrocytes?) throughout the subplate, developing white matter, and paraventricular regions. After the formation of the gray matter, additional layer I astrocytes are needed for the EGLM late prenatal and postnatal maintenance because type I radial glia cells start to regress and to reabsorb their EGLM endfeet. A late ependyma-to-pia migration of glial precursors progressively repopulates layer I with additional astrocytes and establishes the ephemeral subpial granular layer (SGL) of Ranke. From the 15th week of gestation to the time of birth, late astrocytes of layer I lose their EGLM attachments, migrate freely into the maturing gray matter, establish vascular contacts, and differentiate into protoplasmic astrocytes. The protoplasmic astrocytes of the gray matter evolve from transformation of layer I astrocytes rather than from radial glia cells as is generally believed. © 1995 Wiley-Liss, Inc. 相似文献
17.
Tiu SC Chan WY Heizmann CW Schäfer BW Shu SY Yew DT 《Brain research. Developmental brain research》2000,119(2):159-168
S100B and S100A6 (calcylin) are two members of the S100 Ca(2+)-binding protein family and have been localized in the mammalian nervous system. However, information on their distribution in the human nervous system, especially in the developing human fetal brain, is scarce. In the present study, an immunocytochemical method was used to examine the spatio-temporal protein expression patterns of S100B and S100A6 in normal human fetal hippocampus, entorhinal cortex and occipital cortex. Normal aged adult human brain specimens were also included for comparison. From week 15 onwards, an increase with advancing gestation age in both the number and staining intensity of S100B positive, astrocyte-like cells was found in the pyramidal layer of the hippocampus, while both the molecular and polymorphic layers showed similar S100B immunoreactivities at all stages examined. A decrease in the immunoreactivities was found in the molecular layer of the aged adult hippocampus while other layers exhibited immunoreactivities similar to those of the late fetus. At week 15, the molecular, pyramidal and ganglionic/multiform layers of the entorhinal cortex also showed positive S100B immunoreactivities which were maintained throughout the rest of the gestation and in adult specimens. In the occipital cortex, the numbers of positive cells for all layers were about twofold higher than those found in the hippocampus and entorhinal cortex, and immunoreactivities detected in the granular layer increased from week 21, reaching a plateau at around week 27. S100B positive fibers were also found at week 30 but were not observed in aged adult specimens. S100A6 positive cells were on the whole fewer in number than those of S100B in the brain regions examined. The S100A6 immunoreactivities which were localized in some pyramidal neuron-like and some glial-like cells of the pyramidal and molecular layers of the hippocampus increased by midgestation and became weak in the late fetus and in aged adult specimens. Weakly stained S100A6 positive cells were also observed in the entorhinal cortex throughout the gestation and in aged adult cortex. S100A6 immunoreactivities were weak in the fetal occipital cortex. They were also localized in the glial-like cells of the aged adult occipital cortex. The differential spatio-temporal expression of S100B and S100A6 proteins suggests that the proteins play different roles in different brain regions during development and in adulthood. 相似文献
18.
Extraction of dynamic functional connectivity from brain grey matter and white matter for MCI classification 下载免费PDF全文
Brain functional connectivity (FC) extracted from resting‐state fMRI (RS‐fMRI) has become a popular approach for diagnosing various neurodegenerative diseases, including Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). Current studies mainly construct the FC networks between grey matter (GM) regions of the brain based on temporal co‐variations of the blood oxygenation level‐dependent (BOLD) signals, which reflects the synchronized neural activities. However, it was rarely investigated whether the FC detected within the white matter (WM) could provide useful information for diagnosis. Motivated by the recently proposed functional correlation tensors (FCT) computed from RS‐fMRI and used to characterize the structured pattern of local FC in the WM, we propose in this article a novel MCI classification method based on the information conveyed by both the FC between the GM regions and that within the WM regions. Specifically, in the WM, the tensor‐based metrics (e.g., fractional anisotropy [FA], similar to the metric calculated based on diffusion tensor imaging [DTI]) are first calculated based on the FCT and then summarized along each of the major WM fiber tracts connecting each pair of the brain GM regions. This could capture the functional information in the WM, in a similar network structure as the FC network constructed for the GM, based only on the same RS‐fMRI data. Moreover, a sliding window approach is further used to partition the voxel‐wise BOLD signal into multiple short overlapping segments. Then, both the FC and FCT between each pair of the brain regions can be calculated based on the BOLD signal segments in the GM and WM, respectively. In such a way, our method can generate dynamic FC and dynamic FCT to better capture functional information in both GM and WM and further integrate them together by using our developed feature extraction, selection, and ensemble learning algorithms. The experimental results verify that the dynamic FCT can provide valuable functional information in the WM; by combining it with the dynamic FC in the GM, the diagnosis accuracy for MCI subjects can be significantly improved even using RS‐fMRI data alone. Hum Brain Mapp 38:5019–5034, 2017. © 2017 Wiley Periodicals, Inc. 相似文献
19.
N Girgrah M Letarte L E Becker T F Cruz E Theriault M A Moscarello 《Journal of neuropathology and experimental neurology》1991,50(6):779-792
The CD44 antigen is a proteoglycan recently implicated in several adhesion events including that of lymphocytes to endothelium. The CD44 antigen, reactive with monoclonal antibody (MAb) 44D10, has been shown previously to be expressed in normal human white matter homogenates and to be found at higher concentrations in brain homogenates of victims of multiple sclerosis (MS). The cellular localization of CD44 in human brain of normal individuals and in those afflicted with MS has now been determined. Monoclonal antibody 44D10 reacted with astrocyte-like cells in 40 microns thick paraformaldehyde-fixed sections but not in thin (6 microns) fixed sections. A double labeling experiment performed on a frozen brain section with MAb 44D10 and rabbit anti-glial fibrillary acidic protein (GFAP), a cytoplasmic marker of astrocytes, confirmed the co-localization of these two antigens. The reactivity with brain tissue sections of a rabbit antiserum produced against lymphocyte-CD44 could be absorbed by a preparation of the CD44 glycoprotein, purified 2,100-fold from a white matter homogenate. The antiserum was shown by Western blot analysis to be specific for p80 glycoprotein in brain extracts derived from a normal and MS patients. This antibody reacted with fibrous astrocytes predominantly in white matter; staining was also noted in subependymal and subpial regions. Inhibition studies using a cellular radioimmunoassay indicated that the highest concentrations of CD44 in three MS victims were found in plaques, followed by periplaques and non-involved areas of white matter which were higher than normal white matter. Reactive astrocytes, identified in active lesions, expressed high levels of CD44 on their surfaces. Thus, CD44 is associated with astrocytes in human brain and the increased expression observed in MS brain may reflect activation and/or proliferation of astrocytes implicated in the pathogenesis of this disease. 相似文献
20.
Summary Microglia were demonstrated in paraffinembedded human nervous tissues with an avidinbiotin peroxidase method andRicinus communis agglutinin-1 (RCA-1). Specific staining was observed in cell bodies and processes of microglia. Although endothelial cells and blood cells reacted with RCA-1, they were easily distinguished morphologically from microglia. Astrocytes, oligodendrocytes, and neurons did not react with RCA-1. These results suggest that RCA-1 can be used as a new histochemical marker for microglia in normal human brain. 相似文献