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1.
BMC Neurol ; 24(1): 254, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048961

RESUMO

OBJECTIVE: The primary objective of this study was to explore the clinical characteristics of apoplectic intratumoral hemorrhage in gliomas and offer insights for improving the diagnosis and treatment of this disease. METHODS: We analyzed the clinical data of 35 patients with glioma and hemorrhage. There were eight cases of multiple cerebral lobe involvement, and 22 cases involved a single lobe. Twenty-one patients had a preoperative Glasgow Coma Scale (GCS) score of ≥ 9 and had a craniotomy with tumor resection and hematoma evacuation after undergoing preoperative preparation. A total of 14 patients with GCS < 9, including one with thalamic hemorrhage breaking into the ventricles and acute obstructive hydrocephalus, underwent craniotomy for tumor resection after external ventricular drainage (EVD). One patient had combined thrombocytopenia, which was surgically treated after platelet levels were normalized through transfusion. The remaining 12 patients received immediate intervention in the form of craniotomy hematoma evacuation and tumor resection. RESULTS: We performed subtotal resection on three tumors of thalamic origin and two tumors of corpus callosum origin, but we were able to successfully resect all the tumors in other locations that were gross total resection Pathology results showed that 71.43% of cases accounted for WHO-grade 4 tumors. Among the 21 patients with a GCS score of ≥ 9, two died perioperatively. Fourteen patients had a GCS score < 9, of which eight patients died perioperatively. CONCLUSIONS: Patients with a preoperative GCS score ≥ 9 who underwent subemergency surgery and received aggressive treatment showed a reasonable prognosis. We found their long-term outcomes to be correlated with the pathology findings. On the other hand, patients with a preoperative GCS score < 9 required emergency treatment and had a high perioperative mortality rate.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/complicações , Glioma/cirurgia , Masculino , Feminino , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/complicações , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Adolescente , Hemorragia Cerebral/cirurgia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/complicações , Criança , Craniotomia/métodos , Escala de Coma de Glasgow , Estudos Retrospectivos , Resultado do Tratamento
2.
Br J Neurosurg ; 37(5): 1167-1170, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33595378

RESUMO

Intraparenchymal meningiomas without dural attachments are extremely rare. A 32-year-old female adult was admitted to our hospital, complaining of occasional dizziness. The patient had no neurological deficits. MRI demonstrated a lesion with mild edema located in the left cerebellar parenchyma. CT revealed calcification within the mass. Gross total resection was achieved. The histopathological examination indicated that the lesion was an atypical meningioma (WHO-II). We herein report an extremely rare case of an intraparenchymal meningioma located in the left cerebellar hemisphere. The significance of the differential diagnosis of lesions in the cerebellum should be emphasized.


Assuntos
Neoplasias Meníngeas , Meningioma , Adulto , Feminino , Humanos , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Imageamento por Ressonância Magnética , Diagnóstico Diferencial
3.
J Neurooncol ; 158(1): 59-67, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35434765

RESUMO

OBJECTIVE: Perioperative antiepileptic drug (AED) prophylaxis for early postoperative seizures (EPSs) in patients with supratentorial meningiomas without preoperative seizures is controversial. This paper discusses the incidence, risk factors, control rate and AED withdrawal indications of EPS in patients undergoing supratentorial convexity and parasagittal/falx meningioma resection without preoperative seizures. METHODS: Patients treated for a histologically confirmed supratentorial convexity and parasagittal/falx meningioma at the authors' institution between 2015 and 2021 were retrospectively examined. Clinical and imaging data were assessed. Variates were analyzed using univariate and multivariate regression analyses. A PubMed review of the literature published between 2011 and 2021 was performed. RESULTS: In total, 517 patients met the selection criteria. EPS (within the first postoperative week) was observed in 30/517 cases (5.8%). Multivariate analysis revealed that surgical/medical complications (OR 16.33, 95% CI 7.07-37.7, P < 0.001) were the only independent predictors of EPS. The dose of valproic was increased and levetiracetam was added based on the frequency of seizures (≤ 2, > 2 times and status epilepticus). EPS control rates were 94.1% (16/17) and 92.3% (12/13), respectively. AEDs were discontinued at 2 weeks and 4-6 weeks, respectively. The authors identified 10 relevant studies in the literature. Based on their review of the literature, the incidence of EPS was 3.7% (47/1282) with AED use and 6.2% (95/1525) without AED use patients in supratentorial meningiomas without preoperative seizures. The incidence of EPS was 9.0% (19/209) in patients without AED use with convexity and parasagittal/falx meningiomas without preoperative seizures. CONCLUSIONS: AED prophylaxis can reduce the incidence of EPS in patients with convexity and parasagittal/falx meningiomas without preoperative seizures. Avoiding postoperative complications is an important means to prevent EPS. Combined medication has a significant effect on controlling repeated EPS. The timing of AED withdrawal was evaluated according to the clinical symptoms and imaging findings.


Assuntos
Neoplasias Meníngeas , Meningioma , Neoplasias Supratentoriais , Anticonvulsivantes/uso terapêutico , Humanos , Neoplasias Meníngeas/complicações , Meningioma/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Convulsões/epidemiologia , Convulsões/etiologia , Convulsões/prevenção & controle , Neoplasias Supratentoriais/terapia
4.
BMC Neurol ; 22(1): 259, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831795

RESUMO

BACKGROUND: Cerebral venous infarction (CVI) is a serious complication after meningioma resection. The risk factors of postoperative cerebral venous infarction after surgical resection of meningioma can be determined through large samples and this study can add evidence to the literature. METHODS: The clinical and imaging data of 1127 patients with intracranial meningiomas who underwent resection in our hospital were retrospectively collected and analyzed. CVI was evaluated by postoperative imaging and clinical manifestations. Univariate and multivariate analyses were performed to identify risk factors associated with CVI. RESULTS: Overall, 4.7% (53/1127) of patients experienced CVI after meningioma resection. Multivariate analysis revealed superficial meningioma, moderate to severe peritumoral edema, peritumoral critical vein and WHO grade II-III as independent predictors of a postoperative CVI. After timely intervention, the symptoms were clearly alleviated in one month, and the prognosis was good, but injury to key veins could cause irreversible neurological disorders. CONCLUSIONS: Intraoperative protection of veins is the primary way to prevent CVI. The present study identified several significant and independent risk factors for postoperative venous infarction, thereby enabling the identification of high-risk patients who require special attention during clinical and surgical management.


Assuntos
Neoplasias Meníngeas , Meningioma , Infarto Cerebral/complicações , Humanos , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/cirurgia , Meningioma/complicações , Meningioma/cirurgia , Estudos Retrospectivos , Fatores de Risco
5.
Biochem Biophys Res Commun ; 556: 149-155, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33839410

RESUMO

Secondary injury is the main cause of high mortality and poor prognosis of TBI, which has recently been suggested to be related to ferroptosis. Polydatin, a monocrystalline compound extracted from the rhizome of Polygonum, has been shown to exert potential neuroprotective effects. However, its role and mechanism in the secondary injury of TBI has not been elucidated. In this study, the inhibition of Polydatin on ferroptosis was observed both in the hemoglobin treated Neuro2A cells in vitro and in TBI mouse model in vivo, characterized by reversion of accumulation or deposition of free Fe2+, increased content of MDA, decreased activity of key REDOX enzyme GPx4, cell death and tissues loss. Although Polydatin corrected the increased mRNA levels of ferroptosis signaling molecules GPX4, SLC7A11, PTGS2, and ATP5G3 after TBI, TBI and Polydatin treatment had no significant effect on their protein expression. Notably, Polydatin could completely reverse the decrease of GPx4 activity after TBI in vivo and in vitro, and the effect was stronger than that of the classical ferroptosis inhibitor FER-1 in vitro. Further, Polydatin has been shown to reduce the severity of acute neurological impairment and significantly improve subacute motor dysfunction in TBI mice. Our findings provided translational insight into neuroprotection with Polydatin in TBI by inhibiting ferroptosis mainly depending on the maintenance of GPx4 activity.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/prevenção & controle , Ferroptose/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Lesões Encefálicas Traumáticas/fisiopatologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Hemina/farmacologia , Ferro/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/uso terapêutico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo
6.
J Neurooncol ; 148(3): 481-488, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32529449

RESUMO

INTRODUCTION: The incidence of meningiomas among the elderly is considered to be high, and are at increased risk of severe morbidity and mortality following surgery due to their aging physiology and unexpected comorbidities. This study aimed to evaluate the optimal management strategies of meningiomas in elderly patients. METHODS: We retrospectively analyzed 150 patients with incidental large (≥ 3 cm) and giant (≥ 6 cm) anterior skull base meningiomas from 2009 to 2018. These patients were divided into elderly group (≥ 65 years, n = 70) and younger group (< 65 years, n = 80). Information of patients with regard to their medical records, operative details, relevant imaging, and follow-up data were obtained from their respective electronic medical records. RESULTS: The elderly patients had significantly longer length of hospital stay (15.9 ± 3.5) compared to younger patients (13.6 ± 3.6, P < 0.001). Karnofsky Performance Scale (KPS) at discharge was significantly lower in elderly group when compared to younger group (P = 0.04). However, the KPS at 1-year after surgery was similar between the two groups. In addition, there was no significant difference in the incidence of surgical complications between the two groups. Multivariate regression analysis of postoperative complications revealed blood loss ≥ 800 mL (P = 0.007) and BMI (< 18.5 or ≥ 24, P < 0.001) as risk factors, rather than age. CONCLUSIONS: Surgical resection in elderly patients with incidental anterior skull base large and giant meningiomas is considered to be a safe and effective therapeutic option owing to acceptable mortality, postoperative complications and postoperative clinical outcomes.


Assuntos
Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Base do Crânio/cirurgia , Idoso , Envelhecimento , China/epidemiologia , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Incidência , Tempo de Internação , Masculino , Neoplasias Meníngeas/epidemiologia , Neoplasias Meníngeas/patologia , Meningioma/epidemiologia , Meningioma/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Base do Crânio/epidemiologia , Neoplasias da Base do Crânio/patologia
7.
Biochim Biophys Acta Mol Basis Dis ; 1864(9 Pt B): 2859-2870, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29842922

RESUMO

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra compacta (SNc). Although mitochondrial dysfunction is the critical factor in the pathogenesis of PD, the underlying molecular mechanisms are not well understood, and as a result, effective medical interventions are lacking. Mitochondrial fission and fusion play important roles in the maintenance of mitochondrial function and cell viability. Here, we investigated the effects of MitoQ, a mitochondria-targeted antioxidant, in 6-hydroxydopamine (6-OHDA)-induced in vitro and in vivo PD models. We observed that 6-OHDA enhanced mitochondrial fission by decreasing the expression of Mfn1, Mfn2 and OPA1 as well as by increasing the expression of Drp1 in the dopaminergic (DA) cell line SN4741. Notably, MitoQ treatment particularly upregulated the Mfn2 protein and mRNA levels and promoted mitochondrial fusion in the presence of 6-OHDA in a Mfn2-dependent manner. In addition, MitoQ also stabilized mitochondrial morphology and function in the presence of 6-OHDA, which further suppressed the formation of reactive oxygen species (ROS), as well as ameliorated mitochondrial fragmentation and cellular apoptosis. Moreover, the activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) was attributed to the upregulation of Mfn2 induced by MitoQ. Consistent with these findings, administration of MitoQ in 6-OHDA-treated mice significantly rescued the decrease of Mfn2 expression and the loss of DA neurons in the SNc. Taken together, our findings suggest that MitoQ protects DA neurons in a 6-OHDA induced PD model by activating PGC-1α to enhance Mfn2-dependent mitochondrial fusion.


Assuntos
Antioxidantes/farmacologia , GTP Fosfo-Hidrolases/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Animais , Antioxidantes/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Neurônios Dopaminérgicos , GTP Fosfo-Hidrolases/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Compostos Organofosforados/farmacologia , Compostos Organofosforados/uso terapêutico , Oxidopamina/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Fosforilação , RNA Mensageiro/metabolismo , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Regulação para Cima
8.
Tumour Biol ; 35(5): 4937-41, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24532427

RESUMO

Glioblastoma (GBM), a deadly brain tumor, is the most malignant glioma. It mainly occurs in adults and occurs significantly more in males than in females. We genotyped 19 tag single nucleotide polymorphisms (tSNPs) from 13 genes in a case-control study of the Han Chinese population to identify genetic factors contributing to the risk of GBM. These tSNPs were genotyped by Sequenom MassARRAY RS1000. Statistical analysis was performed using χ(2) test and SNPStats, a website software. Using χ(2) test, we found that the distribution of two tSNPs (rs2267130 in checkpoint kinase 2 (CHEK2), p = 0.040; rs1695 in GSTP1, p = 0.023) allelic frequencies had significant difference between cases and controls. When we analyzed all of the tSNPs using the SNPStats software, we found that rs1695 in GSTP1 decreased the risk of GBM in log-additive model (OR = 0.56, 95% CI, 0.34-0.94, p = 0.022). Besides, we found that there is an interaction between rs3212986 in excision repair cross-complementing group 1 (ERCC1) and gender under codominant and recessive models. The gene polymorphisms in CHEK2, GSTP1, and ERCC1 may be involved in GBM in the Han Chinese population. Since our sample size is small, further investigation needs to be performed.


Assuntos
Neoplasias Encefálicas/genética , Quinase do Ponto de Checagem 2/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Glioblastoma/genética , Glutationa S-Transferase pi/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , China/etnologia , Feminino , Humanos , Masculino , Espécies Reativas de Oxigênio/metabolismo
9.
Int J Med Sci ; 11(3): 282-90, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24516353

RESUMO

Quercetin has been demonstrated to play an important role in altering the progression of ischemic brain injuries and neurodegenerative diseases by protecting against oxidative stress. The effects of quercetin on brain damage after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of quercetin on oxidative stress and brain edema after experimental SAH using four equal groups (n = 16) of adult male Sprague-Dawley (SD) rats, including a sham group, an SAH + vehicle group, an SAH + quercetin10 group, and an SAH + quercetin50 group. The rat SAH model was induced by injection of 0.3 ml of non-heparinised arterial blood into the prechiasmatic cistern. In the SAH + quercetin10 and SAH + quercetin50 groups, doses of 10 mg/kg and 50 mg/kg quercetin, respectively, were directly administered by intraperitoneal injection at 30 min, 12 h, and 24 h after SAH induction. Cerebral tissue samples were extracted for enzymatic antioxidant determination, lipid peroxidation assay, caspase-3 activity and water content testing 48 h after SAH. Treatment with a high dose (50 mg/kg) of quercetin markedly enhanced the activities of copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), and treatment with this dose significantly reduced the level of malondialdehyde (MDA). Caspase-3 and brain edema was ameliorated and neurobehavioral deficits improved in rats that received the high dose of quercetin. The findings suggest that the early administration of optimal dose of quercetin may ameliorate brain damage and provide neuroprotection in the SAH model, potentially by enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation.


Assuntos
Antioxidantes/administração & dosagem , Edema Encefálico/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Quercetina/administração & dosagem , Hemorragia Subaracnóidea/tratamento farmacológico , Animais , Edema Encefálico/fisiopatologia , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/fisiopatologia , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído , Fármacos Neuroprotetores/administração & dosagem , Ratos , Hemorragia Subaracnóidea/fisiopatologia
10.
Front Oncol ; 14: 1295483, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38634059

RESUMO

The incidence of cerebral herniation caused by intratumoral hemorrhage (ITH) in cystic oligodendroglioma (COD) is exceedingly rare. This study presents a case of cerebral herniation subsequent to cystic oligodendroglioma (COD) and sudden intratumoral hemorrhage. Following initial emergency treatment and evaluation, we successfully circumvented the solid component of the tumor and proceeded with cystic puncture and external drainage to prevent the incidence of brain herniation and mitigate the severity of associated symptoms. Based on preoperative examination results, the cystic glioma was successfully resected, and the patient experienced an uneventful recovery. According to the pathological findings, the oligodendroglioma was classified as World Health Organization (WHO) grade III. The treatment efficacy was comparable to cases of the same pathological grade, in which neither intratumoral hemorrhage nor cerebral hernia was observed.

11.
Mol Cell Biochem ; 364(1-2): 209-16, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22278385

RESUMO

Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of PD. Previous studies have revealed that Astragaloside IV (AS-IV) can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative disease. In this study, we investigated whether AS-IV protect against 1-methyl-4-phenylpyridnium ion (MPP(+))-induced dopaminergic neurotoxicity in SH-SY5Y cells and determined the mechanism of AS-IV neuroprotection. We found that pretreatment with AS-IV significantly reversed the loss of cell viability, nuclear condensation, the generation of intracellular reactive oxygen species (ROS), and the increase in Bax/Bcl-2 ratio and the activity of caspase-3 induced by MPP(+). Our study suggests that the neuroprotective effect of AS-IV is related to mechanisms including ROS production and the inhibition of Bax-mediated pathway. The present study supports the notion that AS-IV may be a promising neuroprotective agent for the treatment of neurodegenerative disorders such as PD.


Assuntos
Doença de Parkinson/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacologia , Triterpenos/farmacologia , Proteína X Associada a bcl-2/metabolismo , 1-Metil-4-fenilpiridínio/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Regulação da Expressão Gênica , Humanos , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Doença de Parkinson/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética
12.
Front Neurosci ; 16: 1075885, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36570842

RESUMO

Cortical vein thrombosis (CVT) is a rare subtype of cerebral venous thrombosis. Because CVT is rare and its clinical and imaging findings are atypical, the misdiagnosis of CVT may be extremely high. We report a case of cortical venous infarction (CVI) secondary to CVT. Due to the atypical symptoms, we were perplexed about confirming the diagnosis between CVI and glioma hemorrhage. Eventually, CVT was confirmed by pathology combined with imaging.

13.
Front Oncol ; 12: 898873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600362

RESUMO

Objective: To evaluate the rate of, reasons for, and predictors of unplanned reoperation after craniotomy for glioma in a single-institution consecutive series. Methods: Patients who underwent glioma resection at our hospital from 2015 to 2021 were included (n=1563). Multivariate logistic regression was used to examine the predictors of early unplanned cranial reoperation. The predictors that were screened included patient age, sex, tumor properties, blood loss, blood pressure and antiplatelets drugs usage. Results: A total of 3.6% (56/1563) of the patients underwent an early unplanned reoperation after craniotomy for glioma. The reasons for early unplanned reoperation were brain edema (48.2%), cerebral infarction (33.9%) and hemorrhage (17.9%). The predictors of early unplanned reoperation were WHO grade III-IV, peritumoral edema ≥1 cm, subtotal resection, arterial/venous involvement and elevation in blood pressure ≥50 mmHg. Conclusions: Glioma properties and blood pressure management are decisive predictors of early unplanned reoperation for glioma resection. The authors provide a nuanced discussion regarding early unplanned reoperations and perioperative process improvement as a quality indicator for glioma patient populations.

14.
Sci Adv ; 8(39): eabq2423, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36179025

RESUMO

Blood-brain barrier (BBB) injury critically exacerbates the poor prognosis of patients with subarachnoid hemorrhage (SAH). The massively increased matrix metalloproteinases 9 (MMP-9) plays a deleterious role in BBB. However, the main source and mechanism of MMP-9 production after SAH remain unclear. We reported that the increased MMP-9 was mainly derived from reactive astrocytes after SAH. Ndrg2 knockout in astrocytes inhibited MMP-9 expression after SAH and attenuated BBB damage. Astrocytic Ndrg2 knockout decreased the phosphorylation of Smad2/3 and the transcription of MMP-9. Notably, cytoplasmic NDRG2 bound to the protein phosphatase PPM1A and restricted the dephosphorylation of Smad2/3. Accordingly, TAT-QFNP12, a novel engineered peptide that could block the NDRG2-PPM1A binding and reduce Smad2/3 dephosphorylation, decreased astrocytic MMP-9 production and BBB disruption after SAH. In conclusion, this study identified NDRG2-PPM1A signaling in reactive astrocytes as a key switch for MMP-9 production and provided a novel therapeutic avenue for BBB protection after SAH.


Assuntos
Hemorragia Subaracnóidea , Animais , Astrócitos/metabolismo , Barreira Hematoencefálica/metabolismo , Modelos Animais de Doenças , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/uso terapêutico , Proteína Fosfatase 2C/genética , Proteína Fosfatase 2C/metabolismo , Proteínas/metabolismo , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Proteínas Supressoras de Tumor/metabolismo
15.
World Neurosurg ; 149: e261-e268, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33618045

RESUMO

OBJECTIVE: The medium (2-4 cm) convexity located closer to the sinus and parasagittal meningiomas (Sindou type I-Ⅲ) without obvious invasion of the superior sagittal sinus are considered simple to operate on. However, the tumors are often accompanied by the cortical bridging vein. Because of lack of collateral vein circulation in cortical areas, the damage of peritumoral veins will subsequently lead to venous infarction. To avoid the serious complications caused by intraoperative injury of peritumoral veins, it is necessary to define the classification of the progression of peritumoral veins and tumors to guide surgical safety. METHODS: The clinical information of 57 patients with convexity and parasagittal meningiomas was collected and retrospectively analyzed. All patients underwent preoperative magnetic resonance imaging and magnetic resonance venography scanning to observe the imaging characteristics of peritumoral veins and preoperative evaluation. The actual relationship between the tumor and peritumoral vein was observed intraoperatively. Postoperative computed tomography and magnetic resonance imaging were used to determine tumor resection and the presence of venous infarction. RESULTS: According to preoperative magnetic resonance venography and intraoperative findings, we divided the peritumoral veins into 3 types: type A (n = 33, 57.9%), the vein surrounds the tumor; type B (n = 15, 26.3%), the vein is located on the ventral side of the tumor; and type C (n = 9, 15.8%), the vein is located on the dorsal side of the tumor. Peritumoral vein injury occurred in 6 cases followed by serious complications. Treatments were as follows: 4 cases underwent decompression and 2 cases were treated conservatively. The prognosis Glasgow Outcome Scale (GOS) scores were as follows: 3 cases were score 5 for injury of posterior frontal vein or middle frontal vein, 2 cases were score 3 for injury of the central vein, 1 case was score 1 for death due to injury of the central vein. All cases were followed up for 6 months. CONCLUSIONS: Attention should be paid to the peritumoral vein of special meningiomas. Injured vein in the medial third of superior sagittal sinus carries a high rate of postoperative morbidity. Understanding the type of peritumoral veins preoperatively can be used as a guide in determining the corresponding protective strategy during surgery, which can significantly decrease postoperative disability and improve quality of life.


Assuntos
Infarto Encefálico/prevenção & controle , Veias Cerebrais/diagnóstico por imagem , Complicações Intraoperatórias/prevenção & controle , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Lesões do Sistema Vascular/prevenção & controle , Adulto , Idoso , Angiografia Cerebral , Veias Cerebrais/lesões , Feminino , Escala de Resultado de Glasgow , Humanos , Angiografia por Ressonância Magnética , Masculino , Neoplasias Meníngeas/irrigação sanguínea , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/irrigação sanguínea , Meningioma/diagnóstico por imagem , Pessoa de Meia-Idade , Flebografia
16.
Brain Res ; 1729: 146600, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843625

RESUMO

N-myc downstream-regulated gene 2 (NDRG2), a newly identified astrocytic stress response gene, is involved in the regulation of astrocytic morphology and function, and has been indicated to be a potential therapeutic target for some central nervous system (CNS) diseases. However, the role of NDRG2 in intracerebral hemorrhage (ICH) remains unknown. Here, we reported that NDRG2 suppression exerted neuroprotection effect against hemorrhagic brain injury in ICH mice and in oxyhemoglobin (OxyHb)-treated cells. Ndrg2 knockout (Ndrg2-/-) mice exhibited reduced hematoma volume and neuronal apoptosis in perihematoma although Ndrg2 deficiency showed little effect on the initial hematoma volume after ICH induction by collagenase injection. Moreover, contrary to the increase in NDRG2 expression after ICH, the expression of glutamate transporter 1 (GLT1) in astrocytes was dramatically decreased in WT (Ndrg2+/+) mice, while which could be more maintained in Ndrg2 knockout mice following ICH. Furthermore, in terms of the mechanism of epigenetic regulation of GLT1 by NDRG2, the results showed that NDRG2 directly interacted with NF-κB, and inhibited the nuclear import and DNA binding activity of the NF-κB p65 subunit after OxyHb treatment in primary astrocytes, decreasing GLT1 transcription and impairing glutamate uptake. Overall, our findings indicate that NDRG2 plays a key role in the pathology of ICH by regulating astrocytic GLT1 expression; thus suppressing NDRG2 may be a potential therapeutic target for ICH.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Astrócitos/metabolismo , Hemorragia Cerebral/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Ácido Glutâmico/metabolismo , Animais , Lesões Encefálicas/metabolismo , Hemorragia Cerebral/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Transdução de Sinais/fisiologia
18.
Front Cell Dev Biol ; 8: 590903, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262986

RESUMO

There has been an increased interest for observational studies or randomized controlled trials exploring the impact of calcium intake on cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic stroke (IS). However, a direct relationship between total calcium intake and CVD has not been well established and remains controversial. Mendelian randomization (MR) studies have been performed to evaluate the causal association between serum calcium levels and CAD risk and found that increased serum calcium levels could increase the risk of CAD. However, MR analysis found no significant association between genetically higher serum calcium levels and IS as well as its subtypes. Hence, three MR studies reported inconsistent effects of serum calcium levels on CAD and IS. Here, we performed an updated MR study to investigate the association of serum calcium levels with the risk of IS using large-scale genome-wide association study (GWAS) datasets. We selected 14 independent genetic variants as the potential instrumental variables from a large-scale serum calcium GWAS dataset and extracted summary statistics corresponding to the 14 serum calcium genetic variants from the MEGASTROKE Consortium IS GWAS dataset. Interestingly, we found a significant association between serum calcium levels and IS risk using the robust inverse-variance weighted (IVW) and penalized robust IVW methods, with ß = 0.243 and P = 0.002. Importantly, the MR results from the robust MR-Egger and penalized robust MR-Egger methods further supported the causal association between serum calcium levels and IS risk, with ß = 0.256 and P = 0.005. Meanwhile, the estimates from other MR methods are also consistent with the above findings.

19.
Brain Res ; 1739: 146823, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32272097

RESUMO

Cerebral venous infarction (CVI) caused by the injury of cortical bridging veins (CBVs), is one of the most serious complications following neurosurgical craniotomy. Different from cerebral artery infarction, this CVI pathological process is more complicated, accompanied by acute venous hypertension, brain edema, cerebral ischemia and hemorrhage in the veins bridged brain area. Therefore, a reliable and stable small animal model is particularly important for the pathological study of CVI induced by surgical CBV interruption (CBVi). A mouse model established by cutting off the right CBVs from bregma to lambda with microsurgical technique is used for the assessment of the pathological process. Adult male mice underwent craniotomy after transection of the parietal skin under anesthesia. The right CBVs were exposed by removing the right skull along the right lateral edge of the sagittal sinus (forming a 4 mm × 3 mm bone window from bregma to lambda) with a drill under the operating microscope. Following the final inspection of the cerebral veins, the CBVs (30% one, 60% two, 10% none) were sacrificed using bipolar coagulation technique. Intracranial pressure (ICP) monitoring, motor function examination, brain edema assessment and brain histopathological observation after perfusion were performed at different time points (6 h, 12 h, 24 h, and 48 h) in the postoperative mice. Cerebral hemisphere swelling, midline shift and subcortical petechial hemorrhage were found on histological sections 6 h after CBVs dissection. The change of ICP was consistent with cerebral edema and peaked at 12 h after surgery, as well as the disruption of the blood-brain barrier assessed by Evans Blue staining. Tissue necrosis, nerve cell loss and monocytes infiltration were also dynamically increased in the postoperative hemispheric cortex. Behavioral tests showed obvious somato- and forelimb-motor dysfunction, and severe somatosensory disorder on the operative mice at 12 h, which were substantially recovered at 48 h. Our study provided a novel mouse model of CVI caused by surgical CBVi that was close to clinical practice, and preliminarily confirmed its pathological process. This model might become an important tool to study the clinical pathology and the molecular mechanism of nerve injury following CVI.


Assuntos
Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Veias Cerebrais/patologia , Animais , Barreira Hematoencefálica/patologia , Encéfalo/fisiopatologia , Edema Encefálico/patologia , Lesões Encefálicas/patologia , Hemorragia Cerebral/patologia , Infarto Cerebral/metabolismo , Veias Cerebrais/fisiopatologia , Veias Cerebrais/cirurgia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL
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