Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 519
Filtrar
1.
J Neuroinflammation ; 21(1): 255, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39385253

RESUMEN

Ependymal cells are arranged along the inner surfaces of the ventricles and the central canal of the spinal cord, providing anatomical, physiological and immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found that alterations in gene expression, cell junctions, cytokine secretion and metabolic disturbances can lead to dysfunction of ependymal cells, thereby participating in the onset and progression of central nervous system (CNS) infections. Additionally, ependymal cells can exhibit proliferative and regenerative potential as well as secretory functions during CNS injury, contributing to neuroprotection and post-injury recovery. Currently, studies on ependymal cell primarily focus on the basic investigations of their morphology, function and gene expression; however, there is a notable lack of clinical translational studies examining the molecular mechanisms by which ependymal cells are involved in disease onset and progression. This limits our understanding of ependymal cells in CNS infections and the development of therapeutic applications. Therefore, this review will discuss the molecular mechanism underlying the involvement of ependymal cells in CNS infections, and explore their potential for application in clinical treatment modalities.


Asunto(s)
Infecciones del Sistema Nervioso Central , Epéndimo , Humanos , Epéndimo/patología , Epéndimo/metabolismo , Animales , Infecciones del Sistema Nervioso Central/terapia
2.
Acta Neuropathol ; 148(1): 39, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254862

RESUMEN

Mature multiciliated ependymal cells line the cerebral ventricles where they form a partial barrier between the cerebrospinal fluid (CSF) and brain parenchyma and regulate local CSF microcirculation through coordinated ciliary beating. Although the ependyma is a highly specialized brain interface with barrier, trophic, and perhaps even regenerative capacity, it remains a misfit in the canon of glial neurobiology. We provide an update to seminal reviews in the field by conducting a scoping review of the post-2010 mature multiciliated ependymal cell literature. We delineate how recent findings have either called into question or substantiated classical views of the ependymal cell. Beyond this synthesis, we document the basic methodologies and study characteristics used to describe multiciliated ependymal cells since 1980. Our review serves as a comprehensive resource for future investigations of mature multiciliated ependymal cells.


Asunto(s)
Encéfalo , Cilios , Epéndimo , Epéndimo/patología , Humanos , Animales , Cilios/patología , Cilios/fisiología , Encéfalo/patología , Adulto
3.
Acta Neuropathol Commun ; 12(1): 143, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39228008

RESUMEN

Neuroepithelial tumors with fusion of PLAGL1 or amplification of PLAGL1/PLAGL2 have recently been described often with ependymoma-like or embryonal histology respectively. To further evaluate emerging entities with PLAG-family genetic alterations, the histologic, molecular, clinical, and imaging features are described for 8 clinical cases encountered at St. Jude (EWSR1-PLAGL1 fusion n = 6; PLAGL1 amplification n = 1; PLAGL2 amplification n = 1). A histologic feature observed on initial resection in a subset (4/6) of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement was the presence of concurrent ependymal and ganglionic differentiation. This ranged from prominent clusters of ganglion cells within ependymoma/subependymoma-like areas, to interspersed ganglion cells of low to moderate frequency among otherwise ependymal-like histology, or focal areas with a ganglion cell component. When present, the combination of ependymal-like and ganglionic features within a supratentorial neuroepithelial tumor may raise consideration for an EWSR1-PLAGL1 fusion, and prompt initiation of appropriate molecular testing such as RNA sequencing and methylation profiling. One of the EWSR1-PLAGL1 fusion cases showed subclonal INI1 loss in a region containing small clusters of rhabdoid/embryonal cells, and developed a prominent ganglion cell component on recurrence. As such, EWSR1-PLAGL1 neuroepithelial tumors are a tumor type in which acquired inactivation of SMARCB1 and development of AT/RT features may occur and lead to clinical progression. In contrast, the PLAGL2 and PLAGL1 amplified cases showed either embryonal histology or contained an embryonal component with a significant degree of desmin staining, which could also serve to raise consideration for a PLAG entity when present. Continued compilation of associated clinical data and histopathologic findings will be critical for understanding emerging entities with PLAG-family genetic alterations.


Asunto(s)
Proteína EWS de Unión a ARN , Neoplasias Supratentoriales , Factores de Transcripción , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Adulto Joven , Diferenciación Celular , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genética , Epéndimo/patología , Reordenamiento Génico/genética , Neoplasias Neuroepiteliales/genética , Neoplasias Neuroepiteliales/patología , Proteínas de Fusión Oncogénica/genética , Proteína EWS de Unión a ARN/genética , Neoplasias Supratentoriales/genética , Neoplasias Supratentoriales/patología , Factores de Transcripción/genética
4.
Fluids Barriers CNS ; 21(1): 53, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956598

RESUMEN

AQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4-/- mice (KO) due to stenosis of Silvio's aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice. We compared periaqueductal samples from wild-type and KO mice. The microarray-based transcriptome analysis reflected a large number of genes with differential expression (809). Gene sets (GS) associated with ependymal development, ciliary function and the immune system were specially modified qPCR confirmed reduced expression in the KO mice genes: (i) coding for transcription factors for ependymal differentiation (Rfx4 and FoxJ1), (ii) involved in the constitution of the central apparatus of the axoneme (Spag16 and Hydin), (iii) associated with ciliary assembly (Cfap43, Cfap69 and Ccdc170), and (iv) involved in intercellular junction complexes of the ependyma (Cdhr4). By contrast, genes such as Spp1, Gpnmb, Itgax, and Cd68, associated with a Cd11c-positive microglial population, were overexpressed in the KO mice. Electron microscopy and Immunofluorescence of vimentin and γ-tubulin revealed a disorganized ependyma in the KO mice, with changes in the intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane. These structural alterations translate into reduced cilia beat frequency, which might alter cerebrospinal fluid movement. The presence of CD11c + microglia cells in the periaqueductal zone of mice during the first postnatal week is a novel finding. In AQP4-/- mice, these cells remain present around the aqueduct for an extended period, showing peak expression at P11. We propose that these cells play an important role in the normal development of the ependyma and that their overexpression in KO mice is crucial to reduce ependyma abnormalities that could otherwise contribute to the development of obstructive hydrocephalus.


Asunto(s)
Acuaporina 4 , Epéndimo , Hidrocefalia , Ratones Noqueados , Microglía , Animales , Epéndimo/metabolismo , Epéndimo/patología , Hidrocefalia/metabolismo , Hidrocefalia/genética , Hidrocefalia/patología , Microglía/metabolismo , Acuaporina 4/metabolismo , Acuaporina 4/genética , Ratones , Acueducto del Mesencéfalo/metabolismo , Acueducto del Mesencéfalo/patología , Antígenos CD11/metabolismo , Antígenos CD11/genética , Ratones Endogámicos C57BL
5.
Cytopathology ; 35(5): 556-560, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38988178

RESUMEN

Ependymal and choroid plexus tumours arise in anatomically related regions. Their intraoperative differential diagnosis is large and depends on factors such as age, tumour site and clinical presentation. Squash cytology can provide valuable information in this context. Cytological features of conventional ependymomas, subependymomas and myxopapillary ependymomas as well as choroid plexus tumours are reviewed and illustrated. Differential diagnostic considerations integrating morphological and clinical information are discussed.


Asunto(s)
Neoplasias del Plexo Coroideo , Ependimoma , Humanos , Neoplasias del Plexo Coroideo/patología , Neoplasias del Plexo Coroideo/diagnóstico , Ependimoma/patología , Ependimoma/diagnóstico , Citodiagnóstico/métodos , Diagnóstico Diferencial , Plexo Coroideo/patología , Epéndimo/patología , Femenino
6.
Proc Natl Acad Sci U S A ; 121(27): e2314702121, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38916997

RESUMEN

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). KATNAL2, a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of Katnal2 (Katnal2Δ17) in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, KATNAL2 is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in Katnal2Δ17 mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Katnal2Δ17 mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in KATNAL2 in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest KATNAL2 pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting.


Asunto(s)
Cilios , Hidrocefalia , Microtúbulos , Animales , Femenino , Humanos , Masculino , Ratones , ATPasas Asociadas con Actividades Celulares Diversas/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Trastorno del Espectro Autista/metabolismo , Cilios/metabolismo , Cilios/patología , Epéndimo/metabolismo , Epéndimo/patología , Hidrocefalia/genética , Hidrocefalia/patología , Hidrocefalia/metabolismo , Katanina/metabolismo , Katanina/genética , Microtúbulos/metabolismo , Neuronas/metabolismo , Células Piramidales/metabolismo , Células Piramidales/patología
7.
J Neurochem ; 168(10): 3449-3466, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38702968

RESUMEN

Ependymal cells form a specialized brain-cerebrospinal fluid (CSF) interface and regulate local CSF microcirculation. It is becoming increasingly recognized that ependymal cells assume a reactive state in response to aging and disease, including conditions involving hypoxia, hydrocephalus, neurodegeneration, and neuroinflammation. Yet what transcriptional signatures govern these reactive states and whether this reactivity shares any similarities with classical descriptions of glial reactivity (i.e., in astrocytes) remain largely unexplored. Using single-cell transcriptomics, we interrogated this phenomenon by directly comparing the reactive ependymal cell transcriptome to the reactive astrocyte transcriptome using a well-established model of autoimmune-mediated neuroinflammation (MOG35-55 EAE). In doing so, we unveiled core glial reactivity-associated genes that defined the reactive ependymal cell and astrocyte response to MOG35-55 EAE. Interestingly, known reactive astrocyte genes from other CNS injury/disease contexts were also up-regulated by MOG35-55 EAE ependymal cells, suggesting that this state may be conserved in response to a variety of pathologies. We were also able to recapitulate features of the reactive ependymal cell state acutely using a classic neuroinflammatory cocktail (IFNγ/LPS) both in vitro and in vivo. Taken together, by comparing reactive ependymal cells and astrocytes, we identified a conserved signature underlying glial reactivity that was present in several neuroinflammatory contexts. Future work will explore the mechanisms driving ependymal reactivity and assess downstream functional consequences.


Asunto(s)
Astrocitos , Encefalomielitis Autoinmune Experimental , Epéndimo , Ratones Endogámicos C57BL , Animales , Astrocitos/metabolismo , Astrocitos/patología , Epéndimo/metabolismo , Epéndimo/patología , Ratones , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/inmunología , Femenino , Enfermedades Neuroinflamatorias/patología , Transcriptoma
8.
Neurochirurgie ; 70(4): 101553, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38547561

RESUMEN

BACKGROUND: Ependymal cysts (EC) typically present supra-tentorially near the lateral ventricle, juxta ventricular, or temporoparietal regions. Previous cases have also identified infratentorial EC of the brainstem, cerebellum, and subarachnoid spaces. They are mostly asymptomatic. In this paper, we present the first-ever case of a symptomatic medullary ependymal cyst treated with surgery, along with a comprehensive review of the literature on EC of other parts of the brain stem. CASE DESCRIPTION: This 51-year-old female presented with hearing loss, dizziness, diplopia, and ataxia. Radiographic imaging indicated the presence of a non-enhancing lesion in the medulla with a mass effect on the brainstem. Pathological examination confirmed its characterization as an ependymal cyst. The patient underwent a suboccipital craniotomy for the fenestration of the medullary ependymal cyst under neuro-navigation, Intra-op ultrasound and intra-operative neuro-monitoring. Histopathological examination confirmed the diagnosis of an ependymal cyst. At one month follow-up, her KPS is 90, ECOG PS 1, and her ataxia has improved with complete resolution of diplopia. CONCLUSION: Due to their rarity and potential similarity to other cystic structures, EC may be overlooked or incorrectly diagnosed resulting in mismanagement and surgical disaster. Therefore, a comprehensive understanding and awareness of their distinct characteristics are essential for accurate diagnosis and appropriate management.


Asunto(s)
Bulbo Raquídeo , Humanos , Femenino , Persona de Mediana Edad , Bulbo Raquídeo/cirugía , Bulbo Raquídeo/patología , Epéndimo/cirugía , Epéndimo/patología , Quistes del Sistema Nervioso Central/cirugía , Quistes del Sistema Nervioso Central/diagnóstico , Neoplasias del Tronco Encefálico/cirugía , Neoplasias del Tronco Encefálico/diagnóstico , Neoplasias Infratentoriales/cirugía , Neoplasias Infratentoriales/diagnóstico , Imagen por Resonancia Magnética , Craneotomía/métodos
9.
Stroke ; 55(4): 1062-1074, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38436063

RESUMEN

BACKGROUND: In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells. METHODS: GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student t or Wilcoxon-Mann-Whitney U test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively. RESULTS: PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 [forkhead box J1] transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema). CONCLUSIONS: In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.


Asunto(s)
Enfermedades Fetales , Hidrocefalia , Células-Madre Neurales , Nacimiento Prematuro , Humanos , Femenino , Animales , Ratones , Epéndimo/patología , Hidrocefalia/cirugía , Hidrocefalia/metabolismo , Hemorragia Cerebral/terapia , Hemorragia Cerebral/metabolismo , Edema
11.
Methods Cell Biol ; 176: 103-123, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37164533

RESUMEN

Cilia are well conserved hair-like structures that have diverse sensory and motile functions. In the brain, motile ciliated cells, known as ependymal cells, line the cerebrospinal fluid (CSF) filled ventricles, where their beating contribute to fluid movement. Ependymal cells have gathered increasing interest since they are associated with hydrocephalus, a neurological condition with ventricular enlargement. In this article, we highlight methods to identify and characterize motile ciliated ependymal lineage in the brain of zebrafish using histological staining and transgenic reporter lines.


Asunto(s)
Hidrocefalia , Pez Cebra , Animales , Pez Cebra/genética , Encéfalo/patología , Epéndimo/metabolismo , Epéndimo/patología , Hidrocefalia/genética , Hidrocefalia/metabolismo , Hidrocefalia/patología , Animales Modificados Genéticamente , Cilios/metabolismo
12.
Biomolecules ; 13(5)2023 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-37238624

RESUMEN

The neuron loss caused by the progressive damage to the nervous system is proposed to be the main pathogenesis of neurodegenerative diseases. Ependyma is a layer of ciliated ependymal cells that participates in the formation of the brain-cerebrospinal fluid barrier (BCB). It functions to promotes the circulation of cerebrospinal fluid (CSF) and the material exchange between CSF and brain interstitial fluid. Radiation-induced brain injury (RIBI) shows obvious impairments of the blood-brain barrier (BBB). In the neuroinflammatory processes after acute brain injury, a large amount of complement proteins and infiltrated immune cells are circulated in the CSF to resist brain damage and promote substance exchange through the BCB. However, as the protective barrier lining the brain ventricles, the ependyma is extremely vulnerable to cytotoxic and cytolytic immune responses. When the ependyma is damaged, the integrity of BCB is destroyed, and the CSF flow and material exchange is affected, leading to brain microenvironment imbalance, which plays a vital role in the pathogenesis of neurodegenerative diseases. Epidermal growth factor (EGF) and other neurotrophic factors promote the differentiation and maturation of ependymal cells to maintain the integrity of the ependyma and the activity of ependymal cilia, and may have therapeutic potential in restoring the homeostasis of the brain microenvironment after RIBI or during the pathogenesis of neurodegenerative diseases.


Asunto(s)
Lesiones Encefálicas , Enfermedades Neurodegenerativas , Humanos , Epéndimo/metabolismo , Epéndimo/patología , Factores de Crecimiento Nervioso/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Encéfalo/metabolismo , Lesiones Encefálicas/metabolismo
13.
PLoS Biol ; 21(3): e3002008, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36862758

RESUMEN

Idiopathic scoliosis (IS) is the most common spinal deformity diagnosed in childhood or early adolescence, while the underlying pathogenesis of this serious condition remains largely unknown. Here, we report zebrafish ccdc57 mutants exhibiting scoliosis during late development, similar to that observed in human adolescent idiopathic scoliosis (AIS). Zebrafish ccdc57 mutants developed hydrocephalus due to cerebrospinal fluid (CSF) flow defects caused by uncoordinated cilia beating in ependymal cells. Mechanistically, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells through regulating the organization of microtubule networks and proper positioning of basal bodies. Interestingly, ependymal cell polarity defects were first observed in ccdc57 mutants at approximately 17 days postfertilization, the same time when scoliosis became apparent and prior to multiciliated ependymal cell maturation. We further showed that mutant spinal cord exhibited altered expression pattern of the Urotensin neuropeptides, in consistent with the curvature of the spine. Strikingly, human IS patients also displayed abnormal Urotensin signaling in paraspinal muscles. Altogether, our data suggest that ependymal polarity defects are one of the earliest sign of scoliosis in zebrafish and disclose the essential and conserved roles of Urotensin signaling during scoliosis progression.


Asunto(s)
Hidrocefalia , Escoliosis , Urotensinas , Animales , Cilios/metabolismo , Epéndimo/metabolismo , Epéndimo/patología , Hidrocefalia/genética , Hidrocefalia/metabolismo , Hidrocefalia/patología , Escoliosis/genética , Escoliosis/metabolismo , Escoliosis/patología , Urotensinas/metabolismo , Pez Cebra
14.
Neurobiol Dis ; 175: 105913, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36341771

RESUMEN

Dysfunction of motile cilia in ependymal cells has been proposed to be a pathogenic cause of cerebrospinal fluid (CSF) overaccumulation leading to ventricular expansion in hydrocephalus, primarily based on observations of enlarged ventricles in mouse models of primary ciliary dyskinesia. Here, we review human and animal evidence that warrants a rethinking of the cilia hypothesis in hydrocephalus. First, we discuss neuroembryology and physiology data that do not support a role for ependymal cilia as the primary propeller of CSF movement across the ventricles in the human brain, particularly during in utero development prior to the functional maturation of ependymal cilia. Second, we highlight that in contrast to mouse models, motile ciliopathies infrequently cause hydrocephalus in humans. Instead, gene mutations affecting motile cilia function impact not only ependymal cilia but also motile cilia found in other organ systems outside of the brain, causing a clinical syndrome of recurrent respiratory infections and situs inversus, symptoms that do not typically accompany most cases of human hydrocephalus. Finally, we postulate that certain cases of hydrocephalus associated with ciliary gene mutations may arise not necessarily just from loss of cilia-generated CSF flow but also from altered neurodevelopment, given the potential functions of ciliary genes in signaling and neural stem cell fate beyond generating fluid flow. Further investigations are needed to clarify the link between motile cilia, CSF physiology, and brain development, the understanding of which has implications for the care of patients with hydrocephalus and other related neurodevelopmental disorders.


Asunto(s)
Cilios , Hidrocefalia , Animales , Ratones , Humanos , Cilios/patología , Hidrocefalia/etiología , Hidrocefalia/patología , Epéndimo/patología , Encéfalo/patología , Modelos Animales de Enfermedad
15.
Br J Neurosurg ; 36(3): 329-339, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35579079

RESUMEN

Congenital hydrocephalus affects approximately one in 1000 newborn children and is fatal in approximately 50% of untreated cases. The currently known management protocols usually necessitate multiple interventions and long-term use of healthcare resources due to a relatively high incidence of complications, and many of them mostly provide a treatment of the effect rather than the cause of cerebrospinal fluid flow reduction or outflow obstruction. Future studies discussing etiology specific hydrocephalus alternative treatments are needed. We systematically reviewed the available literature on the effect of ciliary abnormality on congenital hydrocephalus pathogenesis, to open a discussion on the feasibility of factoring ciliary abnormality in future research on hydrocephalus treatment modalities. Although there are different forms of ciliopathies, we focused in this review on primary ciliary dyskinesia. There is growing evidence of association of other ciliary syndromes and hydrocephalus, such as the reduced generation of multiple motile cilia, which is distinct from primary ciliary dyskinesia. Data for this review were identified by searching PubMed using the search terms 'hydrocephalus,' 'Kartagener syndrome,' 'primary ciliary dyskinesia,' and 'immotile cilia syndrome.' Only articles published in English and reporting human patients were included. Seven studies met our inclusion criteria, reporting 12 cases of hydrocephalus associated with primary ciliary dyskinesia. The patients had variable clinical presentations, genetic backgrounds, and ciliary defects. The ependymal water propelling cilia differ in structure and function from the mucus propelling cilia, and there is a possibility of isolated non-syndromic ependymal ciliopathy causing only hydrocephalus with growing evidence in the literature for the association ependymal ciliary abnormality and hydrocephalus. Abdominal and thoracic situs in children with hydrocephalus can be evaluated, and secondary damage of ependymal cilia causing hydrocephalus in cases with generalized ciliary abnormality can be considered.


Asunto(s)
Hidrocefalia , Síndrome de Kartagener , Cilios/genética , Cilios/patología , Epéndimo/patología , Humanos , Hidrocefalia/etiología , Hidrocefalia/patología , Recién Nacido , Síndrome de Kartagener/complicaciones , Síndrome de Kartagener/genética , Síndrome de Kartagener/patología
16.
Neurosci Res ; 181: 22-38, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35452717

RESUMEN

The adult mammalian central nervous system has limited regenerative ability, and spinal cord injury (SCI) often causes lifelong motor disability. While regeneration is limited in adults, injured spinal cord tissue can be regenerated and neural function can be almost completely restored in neonates. However, difference of cellular composition in lesion has not been well characterized. To gain insight into the age-dependent cellular reaction after SCI, we performed single-nucleus RNA sequencing, analyzing 4076 nuclei from sham and injured spinal cords from adult and neonatal mice. Clustering analysis identified 18 cell populations. We identified previously undescribed cells with ependymal cell-like gene expression profile, the number of which was increased in neonates after SCI. Histological analysis revealed that these cells line the central canal under physiological conditions in both adults and neonates. We confirmed that they were enriched in the lesion only in neonates. We further showed that these cells were positive for the cellular markers of ependymal cells, astrocytes and radial glial cells. This study provides a deeper understanding of neonate-specific cellular responses after SCI, which may determine regenerative capacity.


Asunto(s)
Personas con Discapacidad , Trastornos Motores , Traumatismos de la Médula Espinal , Animales , Animales Recién Nacidos , Epéndimo/metabolismo , Epéndimo/patología , Humanos , Mamíferos , Ratones , Trastornos Motores/metabolismo , Análisis de Secuencia de ARN , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología
17.
J Clin Neurosci ; 99: 10-16, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35228087

RESUMEN

BACKGROUND: Intracranial ependymal cysts (IECs) are rare, histologically benign neuroepithelial cysts that mostly occur in the cerebral parenchyma. The majority of these cysts are clinically silent and discovered incidentally, but when symptomatic they may compress surrounding structures, thus surgical intervention is needed. The current data in the literature about ECs is very scarce, and many are misdiagnosed, once they share many radiological characteristics with a variety of intracranial benign cysts. Also their terminology is confusing, and its definitive diagnosis can only be made through a thorough histopathological study, hence a detailed description about these uncommon lesions is necessary. The correct identification of the lesion lead to our better understanding of the condition and further improvement of the patient's prognosis. METHODS: A descriptive case is presented; moreover, a detailed PubMed search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was performed. The data found was analyzed by various criteria in order to correctly describe the characteristics of this lesion. RESULTS: The literature review gathered 9 descriptions of patients with IECs with a diverse range anatomopathological and clinical manifestations. All of the included studies found were case reports. Moreover, the authors suggest an updated classification of the lesion, involving their immunohistochemical characteristics. CONCLUSIONS: The information obtained from this study highlights IECs rarity and their inaccurately classification. We propose that the definitive diagnosis of IECs shall be made upon histopathological confirmation of an ependyma-lined cyst along with a positive glial fibrillary acidic protein (GFAP).


Asunto(s)
Quistes del Sistema Nervioso Central , Quistes , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/patología , Quistes/diagnóstico por imagen , Quistes/patología , Epéndimo/patología , Epéndimo/cirugía , Humanos
18.
Sci Rep ; 11(1): 21956, 2021 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-34753951

RESUMEN

Deep and periventricular white matter hyperintensities (dWMH/pvWMH) are bright appearing white matter tissue lesions in T2-weighted fluid attenuated inversion recovery magnetic resonance images and are frequent observations in the aging human brain. While early stages of these white matter lesions are only weakly associated with cognitive impairment, their progressive growth is a strong indicator for long-term functional decline. DWMHs are typically associated with vascular degeneration in diffuse white matter locations; for pvWMHs, however, no unifying theory exists to explain their consistent onset around the horns of the lateral ventricles. We use patient imaging data to create anatomically accurate finite element models of the lateral ventricles, white and gray matter, and cerebrospinal fluid, as well as to reconstruct their WMH volumes. We simulated the mechanical loading of the ependymal cells forming the primary brain-fluid interface, the ventricular wall, and its surrounding tissues at peak ventricular pressure during the hemodynamic cycle. We observe that both the maximum principal tissue strain and the largest ependymal cell stretch consistently localize in the anterior and posterior horns. Our simulations show that ependymal cells experience a loading state that causes the ventricular wall to be stretched thin. Moreover, we show that maximum wall loading coincides with the pvWMH locations observed in our patient scans. These results warrant further analysis of white matter pathology in the periventricular zone that includes a mechanics-driven deterioration model for the ventricular wall.


Asunto(s)
Epéndimo/patología , Sustancia Blanca/patología , Anciano , Epéndimo/diagnóstico por imagen , Femenino , Humanos , Ventrículos Laterales/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Sustancia Blanca/diagnóstico por imagen
19.
Nat Commun ; 12(1): 5887, 2021 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-34620853

RESUMEN

TRIP6, a member of the ZYXIN-family of LIM domain proteins, is a focal adhesion component. Trip6 deletion in the mouse, reported here, reveals a function in the brain: ependymal and choroid plexus epithelial cells are carrying, unexpectedly, fewer and shorter cilia, are poorly differentiated, and the mice develop hydrocephalus. TRIP6 carries numerous protein interaction domains and its functions require homodimerization. Indeed, TRIP6 disruption in vitro (in a choroid plexus epithelial cell line), via RNAi or inhibition of its homodimerization, confirms its function in ciliogenesis. Using super-resolution microscopy, we demonstrate TRIP6 localization at the pericentriolar material and along the ciliary axoneme. The requirement for homodimerization which doubles its interaction sites, its punctate localization along the axoneme, and its co-localization with other cilia components suggest a scaffold/co-transporter function for TRIP6 in cilia. Thus, this work uncovers an essential role of a LIM-domain protein assembly factor in mammalian ciliogenesis.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Encéfalo/metabolismo , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Animales , Encéfalo/patología , Epéndimo/patología , Adhesiones Focales/metabolismo , Regulación de la Expresión Génica , Ratones , Ratones Noqueados , Interferencia de ARN , Transcriptoma
20.
Cell Rep ; 37(1): 109775, 2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-34610312

RESUMEN

Motile cilia defects impair cerebrospinal fluid (CSF) flow and can cause brain and spine disorders. The development of ciliated cells, their impact on CSF flow, and their function in brain and axial morphogenesis are not fully understood. We have characterized motile ciliated cells within the zebrafish brain ventricles. We show that the ventricles undergo restructuring through development, involving a transition from mono- to multiciliated cells (MCCs) driven by gmnc. MCCs co-exist with monociliated cells and generate directional flow patterns. These ciliated cells have different developmental origins and are genetically heterogenous with respect to expression of the Foxj1 family of ciliary master regulators. Finally, we show that cilia loss from the tela choroida and choroid plexus or global perturbation of multiciliation does not affect overall brain or spine morphogenesis but results in enlarged ventricles. Our findings establish that motile ciliated cells are generated by complementary and sequential transcriptional programs to support ventricular development.


Asunto(s)
Encéfalo/metabolismo , Cilios/metabolismo , Epéndimo/metabolismo , Animales , Animales Modificados Genéticamente/metabolismo , Encéfalo/citología , Encéfalo/patología , Linaje de la Célula , Líquido Cefalorraquídeo/fisiología , Cilios/patología , Embrión no Mamífero/metabolismo , Epéndimo/citología , Epéndimo/patología , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Edición Génica , Morfogénesis , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Columna Vertebral/crecimiento & desarrollo , Columna Vertebral/metabolismo , Telencéfalo/citología , Telencéfalo/metabolismo , Telencéfalo/patología , Tubulina (Proteína)/metabolismo , Pez Cebra , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...