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1.
Strahlenther Onkol ; 199(8): 718-726, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36326857

RESUMO

BACKGROUND: Initial tumor enlargement (or pseudoprogression) instead of true tumor progression is a common phenomenon in patients with acoustic neuromas who are treated with stereotactic radiosurgery (SRS). This phenomenon can affect clinical decision-making and patient management. This study assessed the correlation between initial tumor enlargement and magnetic resonance imaging characteristics in patients with acoustic neuromas who were treated with linear accelerator (LINAC)-based SRS. The long-term tumor control outcomes were also analyzed. MATERIALS AND METHODS: In total, 330 patients with sporadic acoustic neuromas who were treated with LINAC SRS between March 2006 and March 2020 were retrospectively evaluated to assess their initial tumor enlargement. The tumors were divided into homogeneously enhanced, heterogeneously enhanced, and cystic types based on the morphological characteristics noted on magnetic resonance images. Tumor control was assessed in 275 patients with a follow-up duration of more than 2 years. RESULTS: Initial enlargement was observed in 137 of 330 (41.5%) tumors as early as 3 months after LINAC SRS. Data analysis revealed that postoperative tumors with a residual volume lower than 2.5 cm3 had a lower incidence of initial enlargement (p = 0.039). No correlation was noted between the initial enlargement and morphological characteristics of tumors. In patients with a mean follow-up duration of 82.8 ± 37.2 months, heterogeneously enhanced tumors exhibited a lower control rate than homogeneously enhanced and cystic tumors (p = 0.045). No correlation was noted between initial enlargement and tumor control. CONCLUSION: Initial enlargement can occur as early as 3 months after SRS. Postoperative residual tumors with a volume lower than 2.5 cm3 exhibit a lower incidence of initial enlargement. Heterogeneously enhanced tumors have a lower local control rate.


Assuntos
Neuroma Acústico , Radiocirurgia , Humanos , Radiocirurgia/métodos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Aceleradores de Partículas , Seguimentos , Resultado do Tratamento
2.
Acta Neurochir (Wien) ; 165(9): 2551-2560, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37553445

RESUMO

BACKGROUND: Programmable valve (PV) has been shown as a solution to the high revision rate in pediatric hydrocephalus patients, but it remains controversial among adults. This study is to compare the overall revision rate, revision cause, and revision-free survival between PV and non-programmable valve (NPV) in adult patients with different hydrocephalus etiologies. METHOD: We reviewed the chart of all patients with hydrocephalus receiving index ventricular cerebrospinal fluid (CSF) shunt operations conducted at a single institution from January 2017 to December 2017. Patients included in the study were followed up for at least 5 years. Statistical tests including independent t-test, chi-square test, and Fisher's exact test were used for comparative analysis, and Kaplan-Meier curve using log-rank test was performed to compare the revision-free survival between the PV and NPV groups. RESULTS: A total of 325 patients were included in the study, of which 181 patients were receiving PVs and 144 patients receiving NPV. There were 23 patients (12.8%) with PV and 22 patients (15.3%) with NPV receiving initial revision. No significant statistical difference in the initial revision rate was observed between the two groups (p = 0.52). No survival difference was found between the PV and NPV groups. However, better revision-free survival was noted in the PV group among idiopathic normal pressure hydrocephalus (iNPH) (p = 0.0274) and post-traumatic hydrocephalus (p = 0.017). CONCLUSIONS: The combination of the different etiologies of hydrocephalus and the features of PV and NPV results in different outcomes-revision rate and revision-free survival. PV use might be superior to NPV in iNPH and post-traumatic hydrocephalus patients. Further studies are needed to clarify the indications of PV use in adult hydrocephalus patients.


Assuntos
Hidrocefalia , Adulto , Humanos , Derivações do Líquido Cefalorraquidiano/métodos , Seguimentos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Próteses e Implantes , Estudos Retrospectivos , Derivação Ventriculoperitoneal/métodos
3.
BMC Emerg Med ; 22(1): 73, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501709

RESUMO

BACKGROUND: Spinal cord injury (SCI) and spinal fracture are major complications in patients with ankylosing spondylitis (AS) who sustain spinal trauma. The purpose of this study was to investigate the incidence, predictors, and sequelae of spinal trauma in patients with AS. METHODS: This retrospective study included patients with AS who were admitted for spinal trauma between January 1, 2006, and June 30, 2016. The study compared clinical outcomes of patients between group 1: SCI alone, group 2: spinal fracture alone (no SCI), and group 3: both SCI and spinal fracture. RESULTS: Of the 6285 patients with AS admitted during the retrospective study period, only 105 suffered from spinal trauma and were enrolled in the study. Case number in group 1, 2, and 3 was 11(10.48%), 45(42.85%), and 49(46.67%), respectively. Among the patients with spinal fractures, 52.1% had SCI. Bamboo spine was significantly more prevalent in the fracture group than in the nonfracture group (78.7% vs. 36.4%; P = 0.006). Patients with SCI had more instances of subluxation or dislocation (48.3% vs. 8.9%; P < 0.001) and more cases of spinal epidural hematoma (SEH; 21.7% vs. 2.2%; P = 0.003) than patients without SCI. The rate of delayed diagnosis for spinal fracture was 31.4%, with one-third of patients developing delayed SCI. Among the patients with incomplete SCI, 58.3% achieved neurological improvement after treatment (P = 0.004). CONCLUSIONS: Patients with AS and bamboo spine at radiograph had a higher rate of spinal fracture, which may be an important factor in SCI in patients with AS. Spinal fractures involving the C3-C7 region, subluxation or dislocation, severe spinal fracture, and SEH were found to be predictive of SCI, and SCI in patients with AS resulted in higher mortality and complication rates.


Assuntos
Fraturas Ósseas , Traumatismos da Medula Espinal , Fraturas da Coluna Vertebral , Espondilite Anquilosante , Humanos , Estudos Retrospectivos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/terapia , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/epidemiologia , Espondilite Anquilosante/complicações , Espondilite Anquilosante/epidemiologia
4.
Int J Mol Sci ; 23(11)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35682853

RESUMO

A dural substitute is frequently used to repair dura mater during neurosurgical procedures. Although autologous or commercially available dural substitutes matched most of the requirements; difficulties during dural repair, including insufficient space for suturing, insufficient mechanical strength, easy tear and cerebrospinal fluid leakage, represent major challenges. To meet this need, a photo-crosslinked hydrogel was developed as a dural substitute/anti-adhesion barrier in this study, which can show sol-to-gel phase transition in situ upon short-time exposure to visible light. For this purpose, hyaluronic acid (HA) and carboxymethyl cellulose (CMC), materials used in abdominal surgery for anti-adhesion purposes, were reacted separately with glycidyl methacrylate to form hyaluronic acid methacrylate (HAMA) and carboxymethyl cellulose methacrylate (CMCMA). The HA/CMC (HC) hydrogels with different HA compositions could be prepared by photo-crosslinking HAMA and CMCMA with a 400 nm light source using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photo-initiator. From studies of physico-chemical and biological properties of HC composite hydrogels, they are bio-compatible, bio-degradable and mechanically robust, to be suitable as a dural substitute. By drastically reducing attachment and penetration of adhesion-forming fibroblasts in vitro, the HC hydrogel can also act as an anti-adhesion barrier to prevent adhesion formation after dural repair. From in vivo study in rabbits, the HC hydrogel can repair dural defects as well as protect the dura from post-operative adhesion, endorsing the possible application of this hydrogel as a novel dural substitute.


Assuntos
Ácido Hialurônico , Hidrogéis , Animais , Carboximetilcelulose Sódica , Ácido Hialurônico/química , Hidrogéis/química , Metacrilatos , Coelhos , Aderências Teciduais/prevenção & controle
5.
Brain Topogr ; 34(2): 234-244, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33420533

RESUMO

Our study aimed to investigate whether changes in brain function measured with functional magnetic resonance imaging (fMRI) can be detected among individuals with depressive disorders and suicidal ideation. The association between depression severity and brain images is also discussed. Our study recruited 111 participants in three groups: 35 depressive patients with suicidal ideation (SI), 32 depressive patients without suicidal ideation (NS), and 44 healthy controls (HCs). All participants were scanned using 3T MRI to obtain resting-state functional images, and functional connectivity (FC), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and graph theoretical analysis (GTA) were performed. We found functional activity differences, such as the hippocampus and thalamus, in the SI group compared with the NS group. We also concluded lower activity in the thalamus and cuneus regions were related to suicidal ideation. We also found several functional connectivity of the brain areas, such as hippocampus, cuneus, and frontal regions, in the SI group correlated with Hamilton Depression Rating Scale (HAM-D) and Hospital Anxiety and Depression Scale (HADS). A graph theoretical analysis (GTA) and network-based statistical (NBS) analysis revealed different topological organization and slightly better local segregation of the brain network in healthy participants compared with those in depressive patients with suicidal ideation. We suggest that brain functional connectivity may be affected in depressive patients with suicidal ideation.


Assuntos
Mapeamento Encefálico , Ideação Suicida , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tálamo
6.
Int J Mol Sci ; 21(19)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987768

RESUMO

Spinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulated that a nanostructured material for controlled delivery of DHA at the lesion site may be well suited for this purpose. Toward this end, we prepare drug-loaded fibrous mats made of core-shell nanofibers by electrospinning, which contained a polylactic acid (PLA) shell for encapsulation of DHA within the core, for delivery of DHA in situ. In vitro study confirmed sustained DHA release from PLA/DHA core-shell nanofiber membrane (CSNM) for up to 36 days, which could significantly increase neurite outgrowth from primary cortical neurons in 3 days. This is supported by the upregulation of brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) neural marker genes from qRT-PCR analysis. Most importantly, the sustained release of DHA could significantly increase the neurite outgrowth length from cortical neuron cells in 7 days when co-cultured with PLA/DHA CSNM, compared with cells cultured with 3 µM DHA. From in vivo study with a SCI model created in rats, implantation of PLA/DHA CSNM could significantly improve neurological functions revealed by behavior assessment in comparison with the control (no treatment) and the PLA CSNM groups. According to histological analysis, PLA/DHA CSNM also effectively reduced neuron loss and increased serotonergic nerve sprouting. Taken together, the PLA/DHA CSNM may provide a nanostructured drug delivery system for DHA and contribute to neuroprotection and promoting neuroplasticity change following SCI.


Assuntos
Ácidos Docosa-Hexaenoicos/uso terapêutico , Crescimento Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Técnicas de Cultura de Células , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Embrião de Mamíferos , Fenômenos Mecânicos , Nanofibras/química , Neurônios/patologia , Poliésteres/química , Ratos , Ratos Sprague-Dawley
7.
Dev Dyn ; 247(12): 1264-1275, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30358936

RESUMO

BACKGROUND: Many molecules and signaling pathways involved in neural development play a role in neurodegenerative diseases and brain tumor progression. Peroxisome proliferator-activated receptor (PPAR) proteins regulate the differentiation of tissues and the progression of many diseases. However, the role of these proteins in neural development is unclear. RESULTS: We examined the function of Pparα in the neural development of zebrafish. Two duplicate paralogs for mammalian PPARA/Ppara, namely pparaa and pparab, are present in the zebrafish genome. Both pparaa and pparab are expressed in the developing central nervous system in zebrafish embryos. Inhibiting the function of Pparα by using either the PPARα/Pparα antagonist GW6471 or pparaa or pparab truncated constructs produced identical phenotypes, which were sufficient to reduce the proliferation of neuronal and glial precursor cells without affecting the formation of neural progenitors. CONCLUSIONS: We demonstrated that both Pparαa and Pparαb proteins are essential regulators of the proliferation of neuronal and glial precursors. This study provides a better understanding of the functions of PPARα/Pparα in neural development and further expands our knowledge of the potential role of PPARα/Pparα in neurological disorders and brain tumors. Developmental Dynamics 247:1264-1275, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Proliferação de Células/efeitos dos fármacos , Sistema Nervoso Central/citologia , Neuroglia/citologia , Neurônios/citologia , PPAR alfa/fisiologia , Células-Tronco/citologia , Animais , Sistema Nervoso Central/embriologia , Neurogênese , PPAR alfa/deficiência , Peixe-Zebra/embriologia
8.
Biochim Biophys Acta Mol Cell Res ; 1864(3): 463-474, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27979767

RESUMO

Neural crest cells are multipotent progenitors that migrate extensively and differentiate into numerous derivatives. The developmental plasticity and migratory ability of neural crest cells render them an attractive model for studying numerous aspects of cell progression. We observed that zebrafish rgs2 was expressed in neural crest cells. Disrupting Rgs2 expression by using a dominant negative rgs2 construct or rgs2 morpholinos reduced GTPase-activating protein activity, induced the formation of neural crest progenitors, increased the proliferation of nonectomesenchymal neural crest cells, and inhibited the formation of ectomesenchymal neural crest derivatives. The transcription of pparda (which encodes Pparδ, a Wnt-activated transcription factor) was upregulated in Rgs2-deficient embryos, and Pparδ inhibition using a selective antagonist in the Rgs2-deficient embryos repaired neural crest defects. Our results clarify the mechanism through which the Rgs2-Pparδ cascade regulates neural crest development; specifically, Pparδ directly binds to the promoter and upregulates the transcription of the neural crest specifier sox10. This study reveals a unique regulatory mechanism, the Rgs2-Pparδ-Sox10 signaling cascade, and defines a key molecular regulator, Rgs2, in neural crest development.


Assuntos
Crista Neural/metabolismo , Neurogênese/genética , PPAR delta/genética , Proteínas RGS/genética , Fatores de Transcrição SOXE/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Sequência de Aminoácidos , Animais , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Crista Neural/crescimento & desenvolvimento , PPAR delta/metabolismo , Regiões Promotoras Genéticas , Proteínas RGS/metabolismo , Fatores de Transcrição SOXE/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Ativação Transcricional , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
9.
Cutan Ocul Toxicol ; 37(1): 41-51, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28614955

RESUMO

PURPOSE: To determine the systemic impact of intravitreal injection of bevacizumab (IVB), an anti-vascular endothelium growth factor antibody, in newborn rabbits. MATERIALS AND METHODS: We used four groups of rabbits. Group 1 rabbits received a single injection of IVB starting from the age of 6 weeks. Group 2 rabbits received a single injection of balanced salt solution (BSS, 0.025 ml) and served as controls for group 1. Group 3 rabbits received two consecutive injections of IVB at the ages of 6 and 10 weeks. Group 4 rabbits received two consecutive injections of BSS at the ages of 6 and 10 weeks and served as controls for group 3. During the experiment, a complete blood count (CBC), clinical biochemistry, weight gain, food intake, body temperature, blood pressure, pulse, and mortality were measured in the animals. Two months after IVB injection, the animals were sacrificed, and histology of the major organs was checked. Immunohistochemistry was assessed to explore the neurons in the central nervous system (CNS). RESULTS: We found there were no morphological or functional changes in the eyes following IVB injection. Furthermore, there were no differences in CBC, biochemistry, or other measured parameters among the four groups of animals. We checked the histology of the major organs and neurons in the CNS and they did not reveal significant differences among the four groups of animals. CONCLUSIONS: Conclusively, IVB of either one or two injections (0.625 mg) in newborn rabbit eyes is well tolerated and does not cause noticeable systemic organ pathology.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Animais , Animais Recém-Nascidos , Olho/anatomia & histologia , Olho/efeitos dos fármacos , Injeções Intravítreas , Fenômenos Fisiológicos Oculares/efeitos dos fármacos , Coelhos
10.
Psychooncology ; 26(11): 1770-1776, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28029721

RESUMO

BACKGROUND: Depression happens commonly in cancer patients. However, there is limited literature on uterine cancer. In this study, we aimed to evaluate the association between uterine cancer and depression as well as the moderating effect of age and hormone replacement therapy (HRT). METHODS: This was a population-based study using Taiwan's National Health Insurance Research Database. We conducted a matched cohort study and identified 6526 patients with uterine cancer and 65 260 controls. We adopted the competing risk analysis model as the statistical method and adjusted for potential confounding factors. RESULTS: From 1997 to 2008, 71 786 patients were included (6526 patients with uterine cancer and 65 260 controls). In the study, uterine cancer was not linked to depression. However, when we stratified the different age groups, those cancer patients aged <40 and 40 to 49 years showed significant higher risk of developing depression (subdistribution hazard ratio 1.64 and 1.41, respectively). In addition, among uterine cancer patients, 4602 patients had never used HRT and 1921 patients were prescribed HRT. The analysis of time-dependent Cox model showed that, compared with no use of HRT, patients with cumulative doses ≥168 DDD had significant lower risk of depression (hazard ratio 0.49, 95% confidence interval = 0.26-0.92). CONCLUSIONS: An increased risk of depression among younger uterine cancer patients was observed. Our preliminary finding suggests a possible protective factor for developing depression after HRT usage.


Assuntos
Neoplasias Uterinas/psicologia , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Depressão/epidemiologia , Depressão/etiologia , Transtorno Depressivo , Feminino , Terapia de Reposição Hormonal , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Taiwan/epidemiologia , Neoplasias Uterinas/complicações , Neoplasias Uterinas/epidemiologia
11.
Dev Biol ; 397(1): 116-28, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25446033

RESUMO

The study of molecular regulation in neural development provides information to understand how diverse neural cells are generated. It also helps to establish therapeutic strategies for the treatment of neural degenerative disorders and brain tumors. The Hairy/E(spl) family members are potential targets of Notch signaling, which is fundamental to neural cell maintenance, cell fate decisions, and compartment boundary formation. In this study, we isolated a zebrafish homolog of Hairy/E(spl), her2, and showed that this gene is expressed in neural progenitor cells and in the developing nervous system. The expression of her2 required Notch activation, as revealed by a Notch-defective mutant and a chemical inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). The endogenous expression of Her2 was altered by both overexpression and morpholino-knockdown approaches, and the results demonstrated that Her2 was both necessary and sufficient to promote the proliferation of neural progenitors by inhibiting the transcription of the cell cycle inhibitors cdkn1a, cdkn1ba, and cdkn1bb. Her2 knockdown caused premature neuronal differentiation, which indicates that Her2 is essential for inhibiting neuronal differentiation. At a later stage of neural development, Her2 could induce glial differentiation. The overexpression of Her2 constructs lacking the bHLH or WRPW domain phenocopied the effect of the morpholino knockdown, demonstrating the essential function of these two domains and further confirming the knockdown specificity. In conclusion, our data reveal that Her2 promotes progenitor proliferation and maintains progenitor characteristics by inhibiting neuronal differentiation. Together, these two mechanisms ensure the proper development of the neural progenitor cell pool.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Neurogênese/fisiologia , Neuroglia/metabolismo , Neurônios/metabolismo , Receptor ErbB-2/fisiologia , Proteínas de Peixe-Zebra/fisiologia , Animais , Ciclo Celular , Diferenciação Celular , Proliferação de Células , Dipeptídeos/química , Perfilação da Expressão Gênica , Genes Dominantes , Receptor ErbB-2/genética , Transdução de Sinais , Fatores de Tempo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
12.
J Neurooncol ; 124(2): 207-14, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26033546

RESUMO

Corpus callosum involvement is associated with poorer survival in high grade glioma (HGG), but the prognostic value in low grade glioma (LGG) is unclear. To determine the prognostic impact of corpus callosum involvement on progression free survival (PFS) and overall survival (OS) in HGG and LGG, the records of 233 glioma patients treated from 2008 to 2011 were retrospectively reviewed. Preoperative magnetic resonance (MR) images were used to identify corpus callosum involvement. Age, sex, preoperative Karnofsky performance scale, postoperative Eastern Cooperative Oncology Group (ECOG) score and extent of resection (EOR) were evaluated with respect to PFS and OS. The incidence of corpus callosum involvement was similar among HGG (14 %) and LGG (14.5 %). Univariate analysis revealed that PFS and OS were significantly shorter in both WHO grade II and grade IV glioma with corpus callosum involvement (both, p < 0.05). Multivariate analysis showed that grade II glioma with corpus callosum involvement have shorter PFS (p = 0.03), while EOR, instead of corpus callosum involvement (p = 0.16), was an independent factor associated with PFS in grade IV glioma (p < 0.05). Corpus callosum involvement was no longer significantly associated with OS after adjusting age, gender, EOR, preoperative and postoperative performance status (p = 0.16, 0.17 and 0.56 in grade II, III and IV gliomas, respectively). Corpus callosum involvement happened in both LGG and HGG, and is associated with lower EOR and higher postoperative ECOG score both in LGG and HGG. Corpus callosum involvement tends to be an independent prognostic factor for PFS in LGG, but not for OS in LGG or in HGG.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Corpo Caloso/fisiopatologia , Glioma/fisiopatologia , Glioma/cirurgia , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Corpo Caloso/patologia , Feminino , Glioma/diagnóstico , Glioma/patologia , Humanos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
13.
Nature ; 458(7237): 529-33, 2009 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-19212323

RESUMO

Epigenetic mechanisms that maintain neurogenesis throughout adult life remain poorly understood. Trithorax group (trxG) and Polycomb group (PcG) gene products are part of an evolutionarily conserved chromatin remodelling system that activate or silence gene expression, respectively. Although PcG member Bmi1 has been shown to be required for postnatal neural stem cell self-renewal, the role of trxG genes remains unknown. Here we show that the trxG member Mll1 (mixed-lineage leukaemia 1) is required for neurogenesis in the mouse postnatal brain. Mll1-deficient subventricular zone neural stem cells survive, proliferate and efficiently differentiate into glial lineages; however, neuronal differentiation is severely impaired. In Mll1-deficient cells, early proneural Mash1 (also known as Ascl1) and gliogenic Olig2 expression are preserved, but Dlx2, a key downstream regulator of subventricular zone neurogenesis, is not expressed. Overexpression of Dlx2 can rescue neurogenesis in Mll1-deficient cells. Chromatin immunoprecipitation demonstrates that Dlx2 is a direct target of MLL in subventricular zone cells. In differentiating wild-type subventricular zone cells, Mash1, Olig2 and Dlx2 loci have high levels of histone 3 trimethylated at lysine 4 (H3K4me3), consistent with their transcription. In contrast, in Mll1-deficient subventricular zone cells, chromatin at Dlx2 is bivalently marked by both H3K4me3 and histone 3 trimethylated at lysine 27 (H3K27me3), and the Dlx2 gene fails to properly activate. These data support a model in which Mll1 is required to resolve key silenced bivalent loci in postnatal neural precursors to the actively transcribed state for the induction of neurogenesis, but not for gliogenesis.


Assuntos
Montagem e Desmontagem da Cromatina , Cromatina/metabolismo , Proteína de Leucina Linfoide-Mieloide/metabolismo , Neurogênese , Neurônios/citologia , Células-Tronco/citologia , Animais , Animais Recém-Nascidos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular , Linhagem da Célula , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Imunoprecipitação da Cromatina , Histona-Lisina N-Metiltransferase , Histonas/metabolismo , Proteínas de Homeodomínio/química , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Metilação , Camundongos , Proteína de Leucina Linfoide-Mieloide/deficiência , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/citologia , Neuroglia/metabolismo , Neurônios/metabolismo , Bulbo Olfatório/citologia , Bulbo Olfatório/metabolismo , Fator de Transcrição 2 de Oligodendrócitos , Células-Tronco/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
Cerebrovasc Dis ; 37(5): 342-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24941898

RESUMO

BACKGROUND: Arteriovenous malformation (AVM) is one of the cerebrovascular diseases that bear a high risk of hemorrhage. The treatment modalities include microsurgical resection, endovascular embolization, stereotactic radiosurgery, or combinations that vary widely. Several large series have been reported, while data from Asian populations were few. The aim of this study was to examine the efficacy of linear accelerator stereotactic radiosurgery (LINAC SRS) for the treatment of intracranial AVMs, to evaluate the hemorrhage rate and to analyze associated factors. METHODS: One hundred and sixteen patients with AVM were treated with LINAC SRS in a single institute between September 1994 and May 2005 and were retrospectively evaluated. The demographics of patients, clinical characteristics of AVM, the treatment modalities, and the parameters of the LINAC SRS were analyzed. Delayed toxicity and hemorrhage rate after treatment were also evaluated. The AVM obliteration and bleed rates were calculated using the Kaplan-Meier method and Cox regression analyses. RESULTS: The efficacy rate with total obliteration after treatment was 81.9% (95 of 116 patients). The median interval to achieve total obliteration was 49 months. Microsurgical resection combined with SRS for residual AVMs achieved better obliteration rates compared to SRS alone (statistically significant, p = 0.001), while no significant difference was found between the embolization group and the group with no prior treatment (p = 0.895). The Spetzler-Martin grade of AVM is a relative factor of obliteration, higher grades resulting in a worse outcome (p = 0.009). Obliteration was significantly influenced by AVM volume in univariate analysis (p = 0.034), and volume <5 cm(3) contributed to improved obliteration (p = 0.01). There was no statistically significant difference in the hemorrhagic rate and the complication rate between ruptured and unruptured AVMs, while the unruptured group had a higher obliteration rate (p = 0.024). The annual hemorrhage rate after LINAC SRS treatment was 1.9%. The bleeding rate was 3.3% in the first year after radiosurgery, 2.1% in the second year, 1.9% between the second and fifth year, and 1.5% between the fifth and tenth year. Patients with hemorrhagic events before radiosurgery appeared to have a higher rebleeding risk during the latency period. Twenty-three patients (19.8%) had late adverse effects with regard to posttreatment radiological follow-up, but only 1 (0.8%) had newly developed neurological deficits. CONCLUSION: LINAC SRS achieved a high obliteration rate and reduced the risk of hemorrhage effectively in ruptured and unruptured intracranial AVMs. Prior microsurgical resection provided better outcome, while embolization showed no benefit. Adverse effects after treatment are acceptable and require long-term follow-up.


Assuntos
Malformações Arteriovenosas Intracranianas/cirurgia , Adolescente , Adulto , Idoso , Animais , Angiografia Cerebral/métodos , Criança , Embolização Terapêutica/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia , Estudos Retrospectivos , Tempo , Resultado do Tratamento , Adulto Jovem
15.
Eur Spine J ; 23(3): 622-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24212479

RESUMO

PURPOSE: Anterior cervical disectomy and fusion (ACDF) is a highly effective and safe method for spinal cord and cervical root decompression. However, vocal cord paralysis (VCP) remains an important cause of postoperative morbidity. The true incidence and recovery course of postoperative VCP is still uncertain. This study is a report on VCP after ACDF to evaluate the incidence, recovery course, and possible risk factors. METHODS: From 2004 to 2008, 1,895 consecutive patients underwent ACDF in our hospital and were followed up for at least 3 years. All surgeons were well trained and used a right-sided exposure. Prolonged VCP, where patients suffered from postoperative VCP lasting more than 3 months, was recorded and analyzed. RESULTS: In this retrospective study, 9 of the 1,895 patients (0.47%) documented prolonged VCP lasting over 3 months. Six of the nine patients had total recovery within 9 months. Only three patients (0.16%) still had symptoms even after 3 years postoperatively. All symptoms of VCP, except hoarseness, could be improved. After matching with 36 non-VCP patients, no differences with regard to longer operative or anesthesia time, shorter neck, obesity, and prevertebral edema. All cases of prolonged course of postoperative VCP occurred in patients who underwent exposure at the C67 level. CONCLUSION: In our study, only 0.47% documented prolonged postoperative VCP, while most patients recovered within 9 months. However, if symptoms last longer, there could be almost permanent VCP (0.16%). In our study, choking and dysphagia subsided mostly within 6 months, but hoarseness remained. The exposure of the C67 level obviously was a risk factor for postoperative VCP.


Assuntos
Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/efeitos adversos , Discotomia/efeitos adversos , Paralisia das Pregas Vocais/etiologia , Idoso , Vértebras Cervicais/patologia , Transtornos de Deglutição/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
16.
Brain Res ; 1846: 149248, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39313168

RESUMO

Central nervous system lesions often cause permanent motility defects in mammals since the injured neurons cannot regenerate. In contrast, lower vertebrates like zebrafish can regenerate lost neurons and restore motor function. This study investigates the efficacy of SC79, a pan-Akt activator, and A674563, a selective Akt1 inhibitor, as potential therapeutic agents for promoting spinal cord recovery post-injury. Spinal cord injury was induced in zebrafish larvae, and the effects of SC79 and A674563 on neuronal and glial regeneration were examined. SC79 promoted neuronal regeneration without affecting glial bridging, while A674563 induced glial bridging but reduced neuronal regeneration. The combination of SC79 and A674563 induced both glial bridging and neuronal regeneration. Optomotor response tests revealed improved motor function recovery with the combined treatment compared to individual treatments. Additionally, these chemical treatments altered the expression of 12 Akt downstream transcriptional target genes, affirming that the combination treatment preferentially regulates spinal cord regeneration through its action on Akt signaling. These findings highlight the complex interplay of Akt signaling pathways in spinal cord regeneration and suggest potential therapeutic strategies for enhancing functional recovery in spinal cord injury patients.

17.
Stem Cells Dev ; 33(19-20): 540-550, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39001828

RESUMO

Traumatic injury to the spinal cord can lead to significant, permanent disability. Mammalian spinal cords are not capable of regeneration; in contrast, adult zebrafish are capable of such regeneration, fully recovering motor function. Understanding the mechanisms underlying zebrafish neuroregeneration may provide useful information regarding endogenous regenerative potential and aid in the development of therapeutic strategies in humans. DELTEX proteins (DTXs) regulate a variety of cellular processes. However, their role in neural regeneration has not been described. We found that zebrafish dtx2, encoding Deltex E3 ubiquitin ligase 2, is expressed in ependymo-radial glial cells in the adult spinal cord. After spinal cord injury, the heterozygous dtx2 mutant fish motor function recovered quicker than that of the wild-type controls. The mutant fish displayed increased ependymo-radial glial cell proliferation and augmented motor neuron formation. Moreover, her gene expression, downstream of Notch signaling, increased in Dtx2 mutants. Notch signaling inactivation by dominant-negative Rbpj abolished the increased ependymo-radial glia proliferation caused by Dtx2 deficiency. These results indicate that ependymo-radial glial proliferation is induced by Dtx2 deficiency by activating Notch-Rbpj signaling to improve spinal cord regeneration and motor function recovery.


Assuntos
Proliferação de Células , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Medula Espinal , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Proliferação de Células/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Células Ependimogliais/metabolismo , Células Ependimogliais/citologia , Neurônios Motores/metabolismo , Transdução de Sinais/genética , Receptores Notch/metabolismo , Receptores Notch/genética , Neuroglia/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Atividade Motora , Regeneração da Medula Espinal , Mutação/genética
18.
Clin Neurol Neurosurg ; 246: 108551, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39288687

RESUMO

PURPOSE: The role of tumor resection remains undetermined in treating primary central nervous system lymphomas (PCNSLs). This study aimed to clarify the impact of tumor resection on survival and functional outcomes, and to identify subgroups benefiting from resection. METHODS: We retrospectively reviewed records from 2010 to 2021 for PCNSL diagnosed at Chang Gung Memorial Hospital, Linkou. Patients were categorized by extent of resection: gross total resection (GTR), partial resection (PR), and biopsy. Univariate and multivariate analyses were performed to identify prognostic factors for survival and functional outcomes. Subgroup analysis was conducted to characterize patients who benefit from tumor resection. RESULTS: Of 88 patients, 12 had GTR, 25 had PR, and 51 received biopsy. GTR correlated with longer progression free survival (PFS) (HR 0.25, p=0.039), remaining significant in multivariate analysis (adjusted HR 0.09, p=0.004). In solitary PCNSLs, GTR also independently predicted longer PFS (adjusted HR 0.13, p= 0.023). Patients with dominant tumors measuring ≥ 3 cm trended towards improved overall survival (OS) with cytoreductive surgery versus biopsy (median survival 38.6 months vs 22.3 months, p=0.083). Age ≥ 60 years (adjusted OR 16.9, p = 0.008) and preoperative Karnofsky Performance Scale ≤ 70 (adjusted OR 4.97, p = 0.049) predicted poorer functional outcomes, while radiation therapy (adjusted OR 0.10, p = 0.033) was protective. CONCLUSIONS: GTR significantly improved PFS in treating PCNSLs, particularly in solitary cases. For patients with dominant tumors measuring ≥ 3 cm, cytoreductive surgery may improve OS. Neither cytoreductive surgery nor GTR correlated with poor functional outcomes.

19.
Acta Neurol Taiwan ; 22(3): 106-11, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24030089

RESUMO

PURPOSE: This clinical study was conducted to evaluate factors affecting outcome in the cases following major intraoperative rupture (MIOR) of the intracranial aneurysms. METHODS: Thirty cases with MIOR in a series of 467 surgeries for ruptured aneurysms were enrolled in this study. Clinical parameters, including: age, Hunt-Hess grading, Fisher grading, aneurysm size, aneurysm contour, operative timing, aneurysm location, and rupture timing were studied and compared with the prognosis in this particular cohort. The outcome was evaluated using the Glasgow Outcome Scale at least 3 months after surgery. Severe disability, vegetative survival, and death were classified as poor outcome. RESULTS: Among the 30 cases with MIOR, 11 resulted in poor outcomes (36.7%). Age was an important prognostic factor in this cohort. Those patients with poor outcome after MIOR were significantly older than those with good outcome (mean age: 64.6 vs 51.4 years, P=0.006). In this study, a trend toward poor outcome was observed in cases with MIOR on internal carotid artery aneurysms (8/14, 57.1% vs 2/9, 22.2% and 1/6, 16.7% on middle cerebral artery and anterior communicating artery aneurysms, P=0.197, after adjustment for age factor). There was a higher incidence of a poor outcome when MIOR occurred during clip application (5/6, 83.3% vs 1/5, 20.0% and 5/19, 26.3% when MIOR happened during brain retraction and aneurysm dissection, P=0.041 after adjustment with the factor of age). CONCLUSION: Although a larger sample population is required for a more conclusive result, MIOR occuring in older age, during clip application, or on an internal carotid artery aneurysm possibly has the trend to bear a worse outcome in the cohort of patients with MIOR during aneurysm surgery.


Assuntos
Aneurisma Roto/epidemiologia , Aneurisma Roto/etiologia , Aneurisma Intracraniano/cirurgia , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/cirurgia , Adulto , Fatores Etários , Idoso , Feminino , Escala de Resultado de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Índice de Gravidade de Doença , Estatísticas não Paramétricas
20.
Asian J Surg ; 46(2): 705-711, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35868963

RESUMO

BACKGROUND: The prognosis of syringomyelia is not yet established. Syringomyelia derived from different etiologies contributes to similar symptoms. OBJECTIVE: Assess the syringomyelia in our medical institutes and describe the etiologies and clinical appearance of the disorder. And identify the predictors of a good outcome and to find the most suitable timing of surgical intervention according to our results. METHODS: This retrospective cohort study used databases in our hospitals to analyze 70 cases of syringomyelia between 1997 and 2014. All available information was obtained from medical records and radiological reports. We used American Spinal Injuries Association disability scores (ASIA scores), the modified Nurick classification system, and recorded the number of days the patient was hospitalized, for neurological and functional assessment. Univariate and multivariate analyses were used to evaluate the relationship between clinical factors and outcomes. RESULTS: Non-communicating syringomyelia was the most common type of syringomyelia. In univariate analysis, autonomic dysfunction and motor impairment were strong predictors of poor neurological and functional outcomes. In addition to the above factors, syrinxes at the cervical level predicted better functional outcomes than at any spinal level in multivariate analysis. CONCLUSIONS: Motor impairment, which is commonly seen in patients with syringomyelia in Taiwan, is a strong predictor to poor neurological and functional outcomes. Our study indicates that patients without autonomic dysfunction or motor impairment should receive timely surgical intervention to prevent symptomatic deterioration. We also found that cervical syringomyelia in particular has the potential for good functional recovery after adequate intervention.


Assuntos
Siringomielia , Humanos , Siringomielia/complicações , Siringomielia/diagnóstico por imagem , Estudos Retrospectivos , Prognóstico , Complicações Pós-Operatórias/diagnóstico , Imageamento por Ressonância Magnética , Resultado do Tratamento
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