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1.
J Craniofac Surg ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682949

RESUMO

The natural history of spinal cord cavernous malformation (SCM) may be characterized by recurrent episodes of hemorrhage resulting in a range of neurologic deficits, most of which are microhemorrhage and subsequent gliosis that can lead to progressive myelopathy. Macrohemorrhage with acute onset of symptoms is extremely rare and leads to irreversible neurologic deficits. In this article, we present an unusual case of ruptured cavernous malformation (CM) in the cervical spinal cord with large extralesional hemorrhage. The patient underwent an operation of posterior longitudinal myelotomy and had a good neurologic recovery. A histologic examination revealed the typical features of cavernous angioma.

2.
J Craniofac Surg ; 31(2): e173-e175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31895860

RESUMO

Chordoid glioma (CG) is a world health organization classified grade II tumor whose typical localization is in the anterior part of the third ventricle. It's clinical, neuroimaging, and pathologic features may vary and furthermore mimic other types of benign lesions usually associated with a better outcome, thus representing a potential radiological and diagnostic pitfall. In this article, the authors present a novel case of a 51-year-old male who underwent gross total removal of the tumor of the third ventricle with high calcification. The imaging studies and the intraoperative examination led at first to a hypothesis of craniopharyngioma. In this case, the patient underwent successful operative management and has remained well throughout follow-up.


Assuntos
Neoplasias do Ventrículo Cerebral/diagnóstico por imagem , Craniofaringioma/diagnóstico por imagem , Diagnóstico Diferencial , Glioma/diagnóstico por imagem , Calcinose/patologia , Neoplasias do Ventrículo Cerebral/cirurgia , Glioma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Terceiro Ventrículo/cirurgia , Resultado do Tratamento
3.
BMC Neurosci ; 18(1): 42, 2017 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-28490320

RESUMO

BACKGROUND: Astaxanthin (ATX) is a carotenoid pigment with pleiotropic pharmacological properties that is seen as a possible drug for treating cerebral ischemic injury and subarachnoid hemorrhage. Na+-K+-2Cl- co-transporter-1 (NKCC1), an intrinsic membrane protein expressed by many cell types, is activated by various insults, leading to the formation of cell swelling and brain edema. We previously established that ATX attenuated brain edema and improved neurological outcomes by modulating NKCC1 expression after traumatic brain injury in mice. This paper explored the molecular mechanism of ATX-mediated inhibition of NKCC1 utilizing an in vitro astrocyte stretch injury model. RESULTS: Stretch injury in cultured astrocytes lowered cell viability time-dependently, which was substantially reducing by pretreating with ATX (50 µmol/L). Stretch injury increased Bax level and cleaved caspase-3 activity, and decreased Bcl-2 level and pro-caspase 3 activity, resulting in the apoptosis of astrocytes. Additionally, stretch injury substantially raised the gene and protein expressions of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α and prompted the expression and nuclear translocation of NF-κB. Pretreatment with ATX remarkably prevented the trauma-induced initiation of NF-κB, expressions of pro-inflammatory cytokines, and cell apoptosis. Moreover, stretch injury markedly elevated the gene and protein expression of NKCC1, which was partly blocked by co-treatment with ATX (50 µmol/L) or an NF-κB inhibitor (PDTC, 10 µmol/L). Cleaved caspase-3 activity was partially reduced by PDTC (10 µmol/L) or an NKCC1 inhibitor (bumetanide, 50 µmol/L). CONCLUSIONS: ATX attenuates apoptosis after stretch injury in cultured astrocytes by inhibiting NKCC1 expression, and it acts by reducing the expression of NF-κB-mediated pro-inflammatory factors.


Assuntos
Astrócitos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Membro 2 da Família 12 de Carreador de Soluto/biossíntese , Animais , Apoptose/efeitos dos fármacos , Astrócitos/patologia , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais , Membro 2 da Família 12 de Carreador de Soluto/efeitos dos fármacos , Xantofilas/farmacologia
4.
Mol Carcinog ; 55(12): 2268-2277, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26840621

RESUMO

Methylation of the neurofibromatosis type 2 (NF2) gene in low-grade meningioma (WHO grade I) has crucial roles in tumorigenesis and development. Meningioma formation might also occur in the setting of an inflammatory microenvironment. However, the association between inflammation and the methylation of NF2 remains unclear. The present study investigates the role and regulatory mechanism of IL-1ß, one of the most important pro-inflammatory cytokines, in the methylation of NF2 in benign meningioma. Three primary low-grade meningioma cells and leptomeningeal cells were cultured. CCK-8 and BrdU assays demonstrated that proliferation of meningioma/leptomeningeal cells treated with IL-1ß occurred in a dose- and time-dependent manner. Methylation-specific PCR verified that IL-1ß induced methylation of the NF2 promoter and decreased NF2/merlin expression in meningioma/leptomeningeal cells. Real-time PCR, western blotting, and immunofluorescence showed that IL-1ß up-regulated DNMT1 in meningioma cells and DNMT1/3b in leptomeningeal cells but did not up-regulate DNMT3a. After co-treatment with the DNMT inhibitor 5-Aza-2'-deoxycytidine and DNMT siRNA, methylation of NF2 induced by IL-1ß was attenuated and merlin expression was restored. Furthermore, we showed that DNMT1 in meningiomas and DNMT1/3b in leptomeninges were regulated via activation of the MAPK (p38, ERK, JNK) and NF-κB pathways. These results suggest that IL-1ß induces methylation of NF2 by up-regulating DNMT1 in benign meningioma cells and DNMT1/3b in leptomeningeal cells via MAPK and NF-κB pathways. Therefore, NF2 methylation is a linker between IL-1ß and tumor development, and DNMTs might be potential therapeutic targets in meningioma for regulating NF2 and inhibiting tumor development. © 2016 Wiley Periodicals, Inc.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Interleucina-1beta/imunologia , Neoplasias Meníngeas/genética , Meningioma/genética , Neurofibromatose 2/genética , Animais , Proliferação de Células , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , Genes da Neurofibromatose 2 , Humanos , Neoplasias Meníngeas/imunologia , Meningioma/imunologia , Neurofibromina 2/genética , Regiões Promotoras Genéticas , Ratos Sprague-Dawley , Células Tumorais Cultivadas
5.
BMC Neurosci ; 17(1): 60, 2016 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-27581370

RESUMO

BACKGROUND: Astaxanthin is a carotenoid pigment that possesses potent antioxidative, anti-inflammatory, antitumor, and immunomodulatory activities. Previous studies have demonstrated that astaxanthin displays potential neuroprotective properties for the treatment of central nervous system diseases, such as ischemic brain injury and subarachnoid hemorrhage. This study explored whether astaxanthin is neuroprotective and ameliorates neurological deficits following traumatic brain injury (TBI). RESULTS: Our results showed that, following CCI, treatment with astaxanthin compared to vehicle ameliorated neurologic dysfunctions after day 3 and alleviated cerebral edema and Evans blue extravasation at 24 h (p < 0.05). Astaxanthin treatment decreased AQP4 and NKCC1 mRNA levels in a dose-dependent manner at 24 h. AQP4 and NKCC1 protein expressions in the peri-contusional cortex were significantly reduced by astaxanthin at 24 h (p < 0.05). Furthermore, we also found that bumetanide (BU), an inhibitor of NKCC1, inhibited trauma-induced AQP4 upregulation (p < 0.05). CONCLUSIONS: Our data suggest that astaxanthin reduces TBI-related injury in brain tissue by ameliorating AQP4/NKCC1-mediated cerebral edema and that NKCC1 contributes to the upregulation of AQP4 after TBI.


Assuntos
Aquaporina 4/metabolismo , Edema Encefálico/tratamento farmacológico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Edema Encefálico/etiologia , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Bumetanida/farmacologia , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Masculino , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Distribuição Aleatória , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia , Xantofilas/farmacologia
6.
Cell Mol Neurobiol ; 36(8): 1343-1351, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26961543

RESUMO

Neural stem cell (NSC) transplantation is a promising approach to repair the damaged brain after hemorrhagic stroke; however, it is largely limited by the poor survival of donor cells. Breakdown products of the hematoma and subsequent iron overload contribute to the impairment of survival of neural cells. There is little information regarding the mechanism involved in the death of grafted cells. Furthermore, therapeutic research targeted to improving the survival of grafted neural stem cells (NSCs) is strikingly lacking. Here, we showed that iron overload induced apoptosis of C17.2 cells, a cell line originally cloned from mouse NSCs and immortalized by v-myc. Pretreatment with carbon monoxide-releasing molecule-2 (CORM-2) markedly protected C17.2 cells against iron overload in a dose-dependent manner. Moreover, CORM-2 interfered with NF-κB signaling, including inhibition of nuclear translocation and down-regulation of NF-κB p65. TUNEL staining showed that preconditioning C17.2 cells with CORM-2 enhanced their resistance to apoptosis induced by iron overload, which was concomitant with down-regulation of the pro-apoptotic proteins (Bax and cleaved caspase-3) and up-regulation of the anti-apoptotic protein Bcl2. The protective effect of CORM-2 could be simulated by BAY11-7082, a special inhibitor of NF-κB p65. These results provide a novel and effective strategy to enhance the survival of NSCs after transplantation and, therefore, their efficacy in repairing brain injury due to hemorrhagic stroke.


Assuntos
Apoptose/efeitos dos fármacos , Sobrecarga de Ferro/patologia , Células-Tronco Neurais/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Transdução de Sinais , Fator de Transcrição RelA/metabolismo , Animais , Linhagem Celular , Camundongos , Células-Tronco Neurais/metabolismo , Nitrilas/farmacologia , Sulfonas/farmacologia , Fator de Transcrição RelA/antagonistas & inibidores
7.
J Biochem Mol Toxicol ; 30(8): 396-403, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27037625

RESUMO

Free radical damage caused by ferrous iron is involved in the pathogenesis of secondary brain injury after intracerebral hemorrhage (ICH). NF-E2-related factor 2 (Nrf2), a major phase II gene regulator that binds to antioxidant response element, represents an important cellular cytoprotective mechanism against oxidative damage. We hypothesized that Nrf2 might protect astrocytes from damage by Fe(2+) . Therefore, we examined cytotoxicity in primary astrocytes induced by iron overload and evaluated the effects of Fe(2+) on Nrf2 expression. The results demonstrated that 24-h Fe(2+) exposure exerted time- and concentration-dependent cytotoxicity in astrocytes. Furthermore, Fe(2+) exposure in astrocytes resulted in time- and concentration-dependent increases in Nrf2 expression, which preceded Fe(2+) toxicity. Nrf2-specific siRNA further knocked down Nrf2 levels, resulting in greater Fe(2+) -induced astrocyte cytotoxicity. These data indicate that induction of Nrf2 expression could serve as an adaptive self-defense mechanism, although it is insufficient to completely protect primary astrocytes from Fe(2+) -induced neurotoxicity.


Assuntos
Astrócitos/efeitos dos fármacos , Compostos Ferrosos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio/metabolismo , Animais , Animais Recém-Nascidos , Astrócitos/citologia , Astrócitos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , L-Lactato Desidrogenase/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/metabolismo , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
8.
J Neurochem ; 134(2): 340-53, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25872793

RESUMO

Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metallopeptidase found mainly in the nervous system, prostate and small intestine. In the nervous system, glia-bound GCPII mediates the hydrolysis of the neurotransmitter N-acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate. Inhibition of GCPII has been shown to attenuate excitotoxicity associated with enhanced glutamate transmission under pathological conditions. However, different strains of mice lacking the GCPII gene are reported to exhibit striking phenotypic differences. In this study, a GCPII gene knockout (KO) strategy involved removing exons 3-5 of GCPII. This generated a new GCPII KO mice line with no overt differences in standard neurological behavior compared to their wild-type (WT) littermates. However, GCPII KO mice were significantly less susceptible to moderate traumatic brain injury (TBI). GCPII gene KO significantly lessened neuronal degeneration and astrocyte damage in the CA2 and CA3 regions of the hippocampus 24 h after moderate TBI. In addition, GCPII gene KO reduced TBI-induced deficits in long-term spatial learning/memory tested in the Morris water maze and motor balance tested via beam walking. Knockout of the GCPII gene is not embryonic lethal and affords histopathological protection with improved long-term behavioral outcomes after TBI, a result that further validates GCPII as a target for drug development consistent with results from studies using GCPII peptidase inhibitors.


Assuntos
Comportamento Animal/fisiologia , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Glutamato Carboxipeptidase II/deficiência , Animais , Lesões Encefálicas/enzimologia , Modelos Animais de Doenças , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Knockout
9.
Acta Pharmacol Sin ; 36(8): 939-48, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26119880

RESUMO

AIM: Aquaporins (AQPs) are the water-channels that play important roles in brain water homeostasis and in cerebral edema induced by brain injury. In this study we investigated the relationship between AQPs and a neuroprotective agent curcumin that was effective in the treatment of brain edema in mice with intracerebral hemorrhage (ICH). METHODS: ICH was induced in mice by autologous blood infusion. The mice immediately received curcumin (75, 150, 300 mg/kg, ip). The Rotarod test scores, brain water content and brain expression of AQPs were measured post ICH. Cultured primary mouse astrocytes were used for in vitro experiments. The expression of AQP1, AQP4 and AQP9 and NF-κB p65 were detected using Western blotting or immunochemistry staining. RESULTS: Curcumin administration dose-dependently reduced the cerebral edema at d 3 post ICH, and significantly attenuated the neurological deficits at d 5 post ICH. Furthermore, curcumin dose-dependently decreased the gene and protein expression of AQP4 and AQP9, but not AQP1 post ICH. Treatment of the cultured astrocytes with Fe(2+) (10-100 µmol/L) dose-dependently increased the expression and nuclear translocation of NF-κB p65 and the expression of AQP4 and AQP9, which were partly blocked by co-treatment with curcumin (20 µmol/L) or the NF-κB inhibitor PDTC (10 µmol/L). CONCLUSION: Curcumin effectively attenuates brain edema in mice with ICH through inhibition of the NF-κB pathway and subsequently the expression of AQP4 and AQP9. Curcumin may serve as a potential therapeutic agent for ICH.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aquaporina 4/genética , Aquaporinas/genética , Edema Encefálico/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Curcumina/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Animais , Aquaporina 4/análise , Aquaporinas/análise , Astrócitos/efeitos dos fármacos , Astrócitos/imunologia , Astrócitos/metabolismo , Astrócitos/patologia , Encéfalo/imunologia , Encéfalo/metabolismo , Encéfalo/patologia , Edema Encefálico/genética , Edema Encefálico/imunologia , Edema Encefálico/patologia , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/imunologia
10.
Acta Pharmacol Sin ; 36(12): 1426-36, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26592517

RESUMO

AIM: Carvacrol (2-methyl-5-isopropylphenol), a phenolic monoterpene in the essential oils of the genera Origanum and Thymus, has been shown to exert a variety of therapeutic effects. Here we examined whether carvacrol protected neuroblastoma SH-SY5Y cells against Fe(2+)-induced apoptosis and explored the underlying mechanisms. METHODS: Neuroblastoma SH-SY5Y cells were incubated with Fe(2+) for 24 h, and the cell viability was assessed with CCK-8 assay. TUNEL assay and flow cytometric analysis were performed to evaluate cell apoptosis. The mRNA levels of pro-inflammatory cytokines and NF-κB p65 were determined using qPCR. The expression of relevant proteins was determined using Western blot analysis or immunofluorescence staining. RESULTS: Treatment of SH-SY5Y cells with Fe(2+) (50-200 µmol/L) dose-dependently decreased the cell viability, which was significantly attenuated by pretreatment with carvacrol (164 and 333 µmol/L). Treatment with Fe(2+) increased the Bax level and caspase-3 activity, and decreased the Bcl-2 level, resulting in cell apoptosis. Furthermore, treatment with Fe(2+) significantly increased the gene expression of IL-1ß, IL-6 and TNF-α, and induced the nuclear translocation of NF-κB. Treatment with Fe(2+) also significantly increased the phosphorylation of p38, ERK, JNK and IKK in the cells. Pretreatment with carvacrol significantly inhibited Fe(2+)-induced activation of NF-κB, expression of the pro-inflammatory cytokines, and cell apoptosis. Moreover, pretreatment with carvacrol inhibited Fe(2+)-induced phosphorylation of JNK and IKK, but not p38 and ERK in the cells. CONCLUSION: Carvacrol protects neuroblastoma SH-SY5Y cells against Fe(2+)-induced apoptosis, which may result from suppressing the MAPK/JNK-NF-κB signaling pathways.


Assuntos
Apoptose/efeitos dos fármacos , Ferro/toxicidade , MAP Quinase Quinase 4/imunologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , Monoterpenos/uso terapêutico , NF-kappa B/imunologia , Fármacos Neuroprotetores/uso terapêutico , Cátions Bivalentes/toxicidade , Linhagem Celular Tumoral , Cimenos , Humanos , Transdução de Sinais/efeitos dos fármacos
11.
J Craniofac Surg ; 26(2): e118-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25699526

RESUMO

Spinal subdual hematoma (SDH) is an uncommon pathology, and its simultaneous occurrence with cranial SDH is even rarer. We report a unique case of spinal SDH combined with bilateral intracranial SDH, in which the cranial lesion was detected after the evacuation of spinal SDH. The undiagnosed chronic SDH developed acute-on-chronic SDH after the evacuation of spinal SDH. The patient had an uneventful clinical course, and a satisfactory outcome was achieved. The reason for reporting this case is to draw attention to the possibility of concurrent cranial SDH in patients with unexplained spinal SDH. The removal of the spinal SDH may exacerbate intracranial hemorrhage and consequently lead to the potential occurrence of tentorial herniation in patients with accompanied cranial SDH.


Assuntos
Erros de Diagnóstico , Hematoma Subdural Intracraniano/diagnóstico , Hemorragias Intracranianas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Hematoma/complicações , Hematoma/diagnóstico , Humanos , Hemorragias Intracranianas/complicações , Masculino , Pessoa de Meia-Idade
12.
Ageing Res Rev ; 95: 102242, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38387517

RESUMO

Diseases of the central nervous system (CNS), including stroke, brain tumors, and neurodegenerative diseases, have a serious impact on human health worldwide, especially in elderly patients. The brain, which is one of the body's most metabolically dynamic organs, lacks fuel stores and therefore requires a continuous supply of energy substrates. Metabolic abnormalities are closely associated with the pathogenesis of CNS disorders. Post-translational modifications (PTMs) are essential regulatory mechanisms that affect the functions of almost all proteins. Succinylation, a broad-spectrum dynamic PTM, primarily occurs in mitochondria and plays a crucial regulatory role in various diseases. In addition to directly affecting various metabolic cycle pathways, succinylation serves as an efficient and rapid biological regulatory mechanism that establishes a connection between metabolism and proteins, thereby influencing cellular functions in CNS diseases. This review offers a comprehensive analysis of succinylation and its implications in the pathological mechanisms of CNS diseases. The objective is to outline novel strategies and targets for the prevention and treatment of CNS conditions.


Assuntos
Doenças do Sistema Nervoso Central , Lisina , Humanos , Idoso , Lisina/metabolismo , Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Doenças do Sistema Nervoso Central/terapia , Redes e Vias Metabólicas
13.
Front Immunol ; 15: 1397475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979407

RESUMO

Monocytes are pivotal immune cells in eliciting specific immune responses and can exert a significant impact on the progression, prognosis, and immunotherapy of intracranial aneurysms (IAs). The objective of this study was to identify monocyte/macrophage (Mo/MΦ)-associated gene signatures to elucidate their correlation with the pathogenesis and immune microenvironment of IAs, thereby offering potential avenues for targeted therapy against IAs. Single-cell RNA-sequencing (scRNA-seq) data of IAs were acquired from the Gene Expression Synthesis (GEO) database. The significant infiltration of monocyte subsets in the parietal tissue of IAs was identified using single-cell RNA sequencing and high-dimensional weighted gene co-expression network analysis (hdWGCNA). The integration of six machine learning algorithms identified four crucial genes linked to these Mo/MΦ. Subsequently, we developed a multilayer perceptron (MLP) neural model for the diagnosis of IAs (independent external test AUC=1.0, sensitivity =100%, specificity =100%). Furthermore, we employed the CIBERSORT method and MCP counter to establish the correlation between monocyte characteristics and immune cell infiltration as well as patient heterogeneity. Our findings offer valuable insights into the molecular characterization of monocyte infiltration in IAs, which plays a pivotal role in shaping the immune microenvironment of IAs. Recognizing this characterization is crucial for comprehending the limitations associated with targeted therapies for IAs. Ultimately, the results were verified by real-time fluorescence quantitative PCR and Immunohistochemistry.


Assuntos
Aneurisma Intracraniano , Aprendizado de Máquina , Macrófagos , Monócitos , Análise de Célula Única , Humanos , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/imunologia , Análise de Célula Única/métodos , Monócitos/imunologia , Monócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , Microambiente Celular/imunologia , Microambiente Celular/genética , Masculino , Feminino , Redes Reguladoras de Genes , Biologia Computacional/métodos
14.
Front Neurol ; 14: 1282683, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38020622

RESUMO

Objective: In recent years, more and more cases of intracranial aneurysms (IAs) have been found in elderly patients, and neurosurgical interventions have increased, but there is still no consensus on the best treatment strategy for elderly patients. In elderly patients, endovascular coiling (EC) is more popular than surgical clipping (SC) due to its advantages of less trauma and faster recovery. However, SC has made great progress in recent years, significantly improving the prognosis of elderly patients. Therefore, it is necessary to further explore the effects of different treatment modalities on clinical prognosis, hospital stay, and hospital cost of elderly IA patients, and select the most appropriate treatment modalities. Methods: The authors retrospectively analyzed 767 patients with intracranial aneurysms admitted to the facility between August 2017 and December 2022. Prognostic risk factors and multivariate logistic regression were analyzed for elderly patients treated with EC or SC. The area under the receiver operating characteristic (ROC) curve was used to calculate the predictive power of each independent predictor between the treatment groups. Results: Our study included 767 patients with aneurysms, of whom 348 (45.4%) were elderly, 176 (22.9%) underwent endovascular coiling, and 172 (22.4%) underwent microsurgical clipping. A comparison of elderly patients treated with EC and SC showed a higher prevalence of hypertension in the EC group (P = 0.011) and a higher Hunt-Hess score on admission in the SC group (P = 0.010). Patients in the EC group had shorter hospital stays but higher costs (P = 0.000 and P = 0.000, respectively). Patients treated with SC had a higher incidence of postoperative cerebral infarction and poor prognosis (P = 0.002 and P = 0.008, respectively). Through multi-factor logistic analysis, it was found that age (OR 1.209, 95% CI 1.047-1.397, P = 0.010), length of stay (LOS) (OR 1.160, 95 CI% 1.041-1.289, P = 0.007), and complications (OR 31.873, 95 CI% 11.677-320.701, P = 0.000) was an independent risk factor for poor prognosis in elderly patients with EC. In elderly patients treated with SC, age (OR 1.105, 95% CI 1.010-1.209, P = 0.029) was an independent risk factor for poor prognosis. Conclusion: EC and SC interventions in elderly adults carry higher risks compared to non-older adults, and people should consider these risks and costs when making a decision between intervention and conservative treatment. In elderly patients who received EC or SC treatments, EC showed an advantage in improving outcomes in elderly patients although it increased the economic cost of the patient's hospitalization.

15.
Clin Neurol Neurosurg ; 210: 106963, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34715556

RESUMO

OBJECTIVES: This study aimed to analyze the difference between cerebral salt-wasting syndrome (CSWS) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in patients with hyponatremia after hypothalamic tumor surgery, and to explore a convenient and effective way to identify CSWS and SIADH. METHODS: Patients undergoing craniotomy of hypothalamic tumor admitted to the Department of The Affiliated Hospital of Qingdao University from December 2018 to May 2020 were enrolled in this study. Plasma brain natriuretic peptide (BNP), 24-h urine sodium, 24-h urine volume, and the diameter of the inferior vena cava (IVCD) were measured daily before operation and 1-7 days after operation, to analyze differences in plasma BNP, 24-h urinary sodium excretion, 24-h urine volume, and IVCD between the CSWS and SIADH. RESULTS: The medical data of 31 patients with hypothalamic tumors were collected. Fifteen of these patients (48%) had postoperative hyponatremia, nine patients (29%) had CSWS, and six patients (19%) had SIADH. Plasma BNP, 24-h urinary sodium excretion, and 24-h urine volume in the CSWS group were significantly higher than those in the SIADH group. IVCD decreased in the CSWS group and increased in the SIADH group. CONCLUSIONS: When hyponatremia occurs after hypothalamic tumor surgery, plasma BNP, 24-h urinary sodium excretion, 24-h urine volume, and IVCD are of great help in identifying CSWS and SIADH.


Assuntos
Craniotomia/efeitos adversos , Hiponatremia/etiologia , Neoplasias Hipotalâmicas/cirurgia , Hipotálamo/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia
16.
Cell Cycle ; 19(24): 3468-3479, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33269647

RESUMO

Store-operated Ca2+ entry (SOCE) plays an important role in regulating Ca2+ influx, which participates in tumor cell survival and motility. We aim to elucidate the role of SOCE in the behavior of C6 glioma cells. Lentiviral vector inserted with the Orai1-targeting shRNA was used to inhibit SOCE in C6 glioma cells. The down-regulation of Orai1 was confirmed by western blot. The ability of shOrai1 or SOCE inhibitor (SKF96365) in regulating SOCE inhibition was evaluated by measuring Ca2+ concentration. Additionally, its effect on cell behavior was assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, transwell assay, and adhesion assay. Focal adhesions were visualized by immunofluorescence assay. Further, the expression of proline-rich tyrosine kinase 2 (Pyk2) and phosphorylated Pyk2 (p-Pyk2) was analyzed using western blot. Both, SKF96365 treatment and the Orai1 down-regulation inhibited SOCE by perturbing Ca2+ influx. The inhibitory effects of shOrai1 on C6 cell proliferation, migration, and invasion were similar to that of SKF96365. Moreover, Orai1 inhibition enhanced C6 cell adhesion by increasing the size of focal adhesion plaques. The down-regulation of Pyk2 was observed in both SKF96365-treated and Orai1-silenced C6 cells. Additionally, Orai1 inhibition blocked AKT/mTOR, NFAT, and NF-κB pathways. The silencing of Orai1 inhibited the C6 glioma cell migration, invasion and contributed to focal adhesion.


Assuntos
Neoplasias Encefálicas/metabolismo , Sinalização do Cálcio/genética , Cálcio/metabolismo , Movimento Celular/genética , Quinase 2 de Adesão Focal/metabolismo , Adesões Focais/metabolismo , Glioma/metabolismo , Proteína ORAI1/genética , Interferência de RNA , Animais , Neoplasias Encefálicas/patologia , Sinalização do Cálcio/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo/genética , Adesões Focais/genética , Glioma/patologia , Imidazóis/farmacologia , Invasividade Neoplásica/genética , Proteína ORAI1/metabolismo , Ratos
17.
Cell Death Differ ; 25(10): 1870-1884, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29880858

RESUMO

Reactive astrogliosis is a common response to insults to the central nervous system, but the mechanism remains unknown. In this study, we found the temporal and spatial differential expression of glial fibrillary acidic protein (GFAP) and Vimentin in the intracerebral hemorrhage (ICH) mouse brain, indicating that the de-differentiation and astroglial-mesenchymal transition (AMT) of astrocytes might be an early event in reactive astrogliosis. Further we verified the AMT finding in purified astrocyte cultures exposed to hemoglobin (Hb). Additionally, Connexin 43 (Cx43) downregulation and YAP nuclear translocation were observed in Hb-activated astrocytes. Knocking down Cx43 by siRNA triggered YAP nuclear translocation. Cx43 and YAP were physically associated as determined by immunofluorescence and co-immunoprecipitation. We propose that astrocytes undergo AMT during Hb-induced activation where Cx43 downregulation facilitates YAP nuclear translocation is a novel mechanism involved in this process. Cx43-YAP interaction may represent a potential therapeutic target for modulating astrocyte activation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Conexina 43/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Hemoglobinas/farmacologia , Fosfoproteínas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Proteínas de Ciclo Celular , Núcleo Celular/metabolismo , Proliferação de Células , Células Cultivadas , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Conexina 43/antagonistas & inibidores , Conexina 43/genética , Regulação para Baixo/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Camundongos , Microscopia de Fluorescência , Fosfoproteínas/química , Ligação Proteica , Transporte Proteico/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas de Sinalização YAP
18.
Am J Infect Control ; 43(7): e23-32, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25934064

RESUMO

BACKGROUND AND PURPOSE: External ventricular drainage (EVD) is one of the most common and effective procedures in neurosurgery practice. However, catheter-related infection (CRI), which is associated with significant mortality and morbidity, plagues this procedure. We evaluated the efficacy of antibiotic-impregnated EVD (AI-EVD) and silver-impregnated EVD (SI-EVD) catheters compared with plain EVD catheters for the prevention of CRI. METHODS: The authors performed an independent search of Medline, Embase, and the Cochrane Library to identify eligible studies published between January 2002 and August 2014. We searched all relevant literature using an exhaustive search strategy. Randomized controlled trials or observational studies that compared AI-EVD catheters with plain EVD catheters for the prevention of CRI were included. The quality of each included study was assessed using a risk of bias assessment tool and the Newcastle-Ottawa Scale. RevMan5.3 software (The Cochrane Collaboration, Oxford, UK) was used to perform this meta-analysis, and publication bias was investigated using funnel plot constructions and Egger test. RESULTS: A total of 4 randomized and 10 observational studies involving 4,399 patients were included in this meta-analysis. Pooled results comparing AI-EVD catheters with plain EVD catheters in the management of patients with acute high intracranial pressure demonstrated the superiority of antimicrobial EVDs for the prevention of CRI with a risk induction of 62% (95% confidence interval [CI], 0.25-0.58; P < .00001). Subgroup analyses of pooled data from separate analyses of AI-EVDs and SI-EVDs showed the efficacy of both measures for CRI prevention, with a risk ratio (RR) of 0.31 (95% CI, 0.18-0.55; P < .0001) and an RR of 0.59 (95% CI, 0.40-0.88; P = .010), respectively. The protective effects of these AI-EVD catheters remained significant in the subgroup of randomized controlled trials with an RR of 0.48 (95% CI, 0.25-0.90; P = .02). A similar result was also seen after a pooled analysis of observational studies with an RR of 0.35 (95% CI, 0.21-0.60; P = .0001). The heterogeneity among studies was moderate (I(2) = 49%) and was primarily attributed to the inclusion of 1 large, positive cohort study. Publication bias was unlikely in the current meta-analysis. CONCLUSIONS: Our restults indicate that both AI-EVDs and SI-EVDs are more effective than plain EVDs for the prevention of CRI. There is no conclusive evidence on the preference of AI-EVDs vs SI-EVDs because of insufficient data. Further well-designed, multicenter randomized controlled trials are required to confirm the findings of this meta-analysis.


Assuntos
Anti-Infecciosos/farmacologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres de Demora/efeitos adversos , Drenagem/efeitos adversos , Meningite/prevenção & controle , Procedimentos Neurocirúrgicos/métodos , Prata/farmacologia , Estudos de Coortes , Humanos , Resultado do Tratamento
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