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1.
Neuroradiology ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587561

RESUMO

PURPOSE: To develop and validate a prediction model based on imaging data for the prognosis of mild chronic subdural hematoma undergoing atorvastatin treatment. METHODS: We developed the prediction model utilizing data from patients diagnosed with CSDH between February 2019 and November 2021. Demographic characteristics, medical history, and hematoma characteristics in non-contrast computed tomography (NCCT) were extracted upon admission to the hospital. To reduce data dimensionality, a backward stepwise regression model was implemented to build a prognostic prediction model. We calculated the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model by a tenfold cross-validation procedure. RESULTS: Maximum thickness, volume, mean density, morphology, and kurtosis of the hematoma were identified as the most significant predictors of good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The prediction model exhibited good discrimination, with an area under the curve (AUC) of 0.82 (95% confidence interval [CI], 0.74-0.90) and good calibration (p = 0.613). The validation analysis showed the AUC of the final prognostic prediction model is 0.80 (95% CI 0.71-0.86) and it has good prediction performance. CONCLUSION: The imaging data-based prediction model has demonstrated great prediction accuracy for good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The study results emphasize the importance of imaging data evaluation in the management of CSDH patients.

2.
Front Neurosci ; 18: 1361832, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529265

RESUMO

Traumatic Brain Injury (TBI) is a prevalent form of neurological damage that may induce varying degrees of cognitive dysfunction in patients, consequently impacting their quality of life and social functioning. This article provides a mini review of the epidemiology in Chinese TBI patients and etiology of cognitive impairment. It analyzes the risk factors of cognitive impairment, discusses current management strategies for cognitive dysfunction in Chinese TBI patients, and summarizes the strengths and limitations of primary testing tools for TBI-related cognitive functions. Furthermore, the article offers a prospective analysis of future challenges and opportunities. Its objective is to contribute as a reference for the prevention and management of cognitive dysfunction in Chinese TBI patients.

3.
J Neurotrauma ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38553903

RESUMO

Traumatic brain injury (TBI)-a severe clinical problem-is compounded by a lack of effective treatments and impeded intracranial metabolic waste clearance. The glymphatic system and meningeal lymphatic vessels are instrumental in TBI pathophysiology and crucial for clearing harmful substances. Cannabidiol (CBD) has the potential to address metabolic imbalances and improve cognitive functions in neurodegenerative diseases, but its specific effect on TBI remains unclear. Using a fluid percussion injury model, we adopted a comprehensive approach that included behavioral testing, various imaging techniques, and deep cervical lymph node (dCLN) ligation to evaluate CBD's effects on neurological outcomes and lymphatic clearance in a TBI mouse model. Our results demonstrated that CBD markedly enhanced motor, memory, and cognitive functions, correlating with reduced levels of detrimental neural proteins. CBD also expedited the removal of intracranial tracers, increased cerebral blood flow, and improved tracer migration from lymphatic vessels to dCLNs. Intriguingly, CBD treatment modified aquaporin-4 polarization and diminished neuroinflammatory indicators. A key observation was that disrupting efferent lymphatic channels nullified CBD's positive effects on waste removal and cognitive enhancements, whereas its anti-inflammatory benefits continued. This finding suggests that CBD's ability to improve waste clearance may operate via the lymphatic system, thereby improving neurological outcomes in TBI patients. Therefore, our study underscores CBD's potential therapeutic role in TBI management.

4.
CNS Neurosci Ther ; 30(3): e14673, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468459

RESUMO

AIM: We aim to identify the specific CD4+ T-cell subtype influenced by brain-to-CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI). METHOD: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4+ T-cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time-of-flight analysis (CyTOF) or fluorescence-activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4+ T cells, specifically CD11b-positive CD4+ T cells, within the affected region. The population of CD4+ CD11b+ T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine-1-phosphate receptor-1 (S1PR1) on these cells. Administration of CD4+ CD11b+ T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy. CONCLUSION: The infiltration of CD4+ CD11b+ T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain-to-CLN signaling.


Assuntos
Edema Encefálico , Lesões Encefálicas Traumáticas , Vasos Linfáticos , Humanos , Animais , Edema Encefálico/patologia , Linfócitos T , Lesões Encefálicas Traumáticas/patologia , Encéfalo/patologia , Apoptose , Citocinas , Vasos Linfáticos/patologia , Linfócitos T CD4-Positivos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Modelos Animais de Doenças
5.
Sci Rep ; 14(1): 3559, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347043

RESUMO

This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone.


Assuntos
Hematoma Subdural Crônico , Humanos , Estudos Retrospectivos , Atorvastatina/uso terapêutico , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/tratamento farmacológico , Tomografia Computadorizada por Raios X , Dexametasona/uso terapêutico
6.
Theranostics ; 14(1): 304-323, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164141

RESUMO

Rationale: Meningeal lymphatic vessels (MLVs) are essential for the clearance of subdural hematoma (SDH). However, SDH impairs their drainage function, and the pathogenesis remains unclear. Herein, we aimed to understand the pathological mechanisms of MLV dysfunction following SDH and to test whether atorvastatin, an effective drug for SDH clearance, improves meningeal lymphatic drainage (MLD). Methods: We induced SDH models in rats by injecting autologous blood into the subdural space and evaluated MLD using Gadopentetate D, Evans blue, and CFSE-labeled erythrocytes. Whole-mount immunofluorescence and transmission electron microscopy were utilized to detect the morphology of MLVs. Phosphoproteomics, western blot, flow cytometry, and in vitro experiments were performed to investigate the molecular mechanisms underlying dysfunctional MLVs. Results: The basal MLVs were detected to have abundant valves and play an important role in draining subdural substances. Following SDH, these basal MLVs exhibited disrupted endothelial junctions and dilated lumen, leading to impaired MLD. Subsequent proteomics analysis of the meninges detected numerous dephosphorylated proteins, primarily enriched in the adherens junction, including significant dephosphorylation of ERK1/2 within the meningeal lymphatic endothelial cells (LECs). Subdural injection of the ERK1/2 kinase inhibitor PD98059 resulted in dilated basal MLVs and impaired MLD, resembling the dysfunctional MLVs observed in SDH. Moreover, inhibiting ERK1/2 signaling severely disrupted intercellular junctions between cultured LECs. Finally, atorvastatin was revealed to protect the structure of basal MLVs and accelerate MLD following SDH. However, these beneficial effects of atorvastatin were abolished when combined with PD98059. Conclusion: Our findings demonstrate that SDH induces ERK1/2 dephosphorylation in meningeal LECs, leading to disrupted basal MLVs and impaired MLD. Additionally, we reveal a beneficial effect of atorvastatin in improving MLD.


Assuntos
Sistema Glinfático , Vasos Linfáticos , Ratos , Animais , Atorvastatina/farmacologia , Células Endoteliais , Sistema de Sinalização das MAP Quinases , Hematoma Subdural
7.
Neurosurgery ; 94(3): 497-507, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796000

RESUMO

BACKGROUND AND OBJECTIVES: The focus on evidence-based neurosurgery has led to a considerable amount of neurosurgical evidence based on randomized controlled trials (RCTs) being published. Nevertheless, there has been no systematic appraisal of China's contribution to RCTs. Information about the changes in characteristics of Chinese neurosurgical RCTs before and during the COVID-19 pandemic is limited. This study aims to perform a detailed examination and comprehensive analysis of the characteristics of Chinese neurosurgical RCTs and to examine the differences before and during the COVID-19 pandemic. METHODS: We conducted a comprehensive database search including PubMed, Web of Science, Embase, and Cochrane Library up to March 2023, with a criterion of inclusion based on an impact factor above 0. We subsequently examined the design and quality parameters of the included RCTs and assessed the differences before and during the COVID-19 pandemic (based on follow-up ending before or after January 2020). Moreover, we investigated potential factors that may affect the quality and developmental trends of neurosurgical RCTs in China. RESULTS: The main focus of the 91 neurosurgical RCTs was vascular disease (47.3%) and trauma (18.7%). Over half of the trials used Consolidated Standards of Reporting Trial diagrams (69.2%), and the majority compared nonsurgical treatments (63.7%). Larger trials tended to have better quality scores, but those with significant efficacy were less likely to have power calculations. Over time, there was an increase in the use of Consolidated Standards of Reporting Trial diagrams and well-specified outcomes. The COVID-19 pandemic may have hindered the completion of neurosurgical RCTs in China, but it has had little impact on the design and quality so far. CONCLUSION: Chinese neurosurgeons have made significant progress in advancing neurosurgical RCTs despite challenges. However, shortcomings in sample size and power calculation need attention. Improving the rigor, rationality, and completeness of neurosurgical RCT design is crucial.


Assuntos
COVID-19 , Neurocirurgia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Neurocirúrgicos , Projetos de Pesquisa , COVID-19/epidemiologia
8.
Quant Imaging Med Surg ; 13(7): 4268-4283, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37456319

RESUMO

Background: The Tada formula has been used widely for assessing intracerebral hemorrhage (ICH) volume. However, it is only suitable for calculating regular and small volume hematomas. Therefore, we attempted to improve the formula to increase its accuracy and maintain its efficiency. Methods: Computed tomography (CT) data of 15 balls of different shapes filled with predetermined volumes of water were collected to verify the high accuracy of FireVoxel in measuring the volume. CT data from 329 patients with ICH from two different hospitals grouped by hematoma shape and volume were retrospectively reviewed. The distinctly shaped ICH volumes of 245 patients from one of the hospitals were estimated using FireVoxel and the Tada formula grouped by the hematoma shape and volume. Taking the hematoma volumes measured by FireVoxel as the reference standard, the accuracy and reliability of the Tada formula were evaluated. Polynomial fitting was employed to determine the associations of the values calculated between the Tada formula and FireVoxel. Then, a corrected Tada formula (C-Tada formula) was produced, and the limits of agreement between the C-Tada formula and Tada formula were analyzed with Bland-Altman analysis. The C-Tada formula was validated by the CT data of 84 patients from another hospital. Results: The volume measured by FireVoxel can be set as the reference standard. The ICH volume calculated by the Tada formula was significantly greater than that calculated by FireVoxel for different shapes and volumes. The percentage deviation between the volumes calculated by FireVoxel and the Tada formula was also statistically significant and influenced by ICH shape and volume. The limits of agreement between the C-Tada formula and FireVoxel were tighter than those between the Tada formula and FireVoxel. The percentage deviation of the C-Tada formula calculation from the FireVoxel estimate was greatly reduced relative to that for the Tada formula for each group. Conclusions: The C-Tada formula is more clinically valuable than the Tada formula, given its sufficient efficiency and greater accuracy and reliability in ICH volume calculation.

9.
Acta Neurol Belg ; 123(6): 2277-2286, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37269419

RESUMO

PURPOSE: To identify prognostic factors in patients with primary chronic subdural hematoma (CSDH) undergoing wait-and-watch management. METHODS: A case-control study was conducted in a single center from February 2019 to November 2021 to identify independent influencing factors of wait-and-watch management in mild CSDH patients using wait-and-watch as monotherapy. A total of 39 patients who responded to wait-and-watch management (cases) and 24 nonresponders (controls) matched for age, sex, height, weight, MGS-GCS (Markwalder grading scale and Glasgow Coma Scale), and bilateral hematoma were included. Demographics, blood cell counts, serum biochemical levels, imaging data, and relevant clinical features at baseline were collected. RESULTS: Univariate analysis revealed significant differences between cases and controls in hematoma volume, ability to urinate, maximal thickness of the hematoma, and hypodensity of the hematoma. Hypodense hematoma and hematoma volume were independently associated with the outcome in multivariate analysis. Combining these independently influencing factors revealed an area under the receiver operator characteristic curve of 0.741 (95% CI 0.609-0.874, sensitivity = 0.783, specificity = 0.667). CONCLUSIONS: The results of this study may aid in identifying patients with mild primary CSDH who could benefit from conservative management. While wait-and-watch management may be an option in some cases, clinicians need to suggest medical interventions, such as pharmacotherapy, when appropriate.


Assuntos
Hematoma Subdural Crônico , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/tratamento farmacológico , Recidiva , Escala de Coma de Glasgow
10.
CNS Neurosci Ther ; 29(12): 3876-3888, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37353947

RESUMO

AIM: We aimed to assess the effects of cerebral glucagon-like peptide-1 receptor (GLP-1R) activation on the glymphatic system and whether this effect was therapeutic for traumatic brain injury (TBI). METHODS: Immunofluorescence was employed to evaluate glymphatic system function. The blood-brain barrier (BBB) permeability, microvascular basement membrane, and tight junction expression were assessed using Evans blue extravasation, immunofluorescence, and western blot. Immunohistochemistry was performed to assess axonal damage. Neuronal apoptosis was evaluated using Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and western blot. Cognitive function was assessed using behavioral tests. RESULTS: Cerebral GLP-1R activation restored glymphatic transport following TBI, alleviating BBB disruption and neuronal apoptosis, thereby improving cognitive function following TBI. Glymphatic function suppression by treatment using aquaporin 4 inhibitor TGN-020 abolished the protective effect of the GLP-1R agonist against cognitive impairment. CONCLUSION: Cerebral GLP-1R activation can effectively ameliorate neuropathological changes and cognitive impairment following TBI; the underlying mechanism could involve the repair of the glymphatic system damaged by TBI.


Assuntos
Lesões Encefálicas Traumáticas , Sistema Glinfático , Animais , Camundongos , Apoptose/fisiologia , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Modelos Animais de Doenças , Receptor do Peptídeo Semelhante ao Glucagon 1 , Sistema Glinfático/metabolismo
12.
Front Cell Infect Microbiol ; 13: 1152512, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37180447

RESUMO

Background: Pulmonary infection caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) is a common and serious complication after brain injury. There are no definitive methods for its prediction and it is usually accompanied by a poor prognosis. This study aimed to construct and evaluate a nomogram based on patient data from the neurosurgical intensive care unit (NSICU) to predict the probability of MDR-AB pulmonary infection. Methods: In this study, we retrospectively collected patient clinical profiles, early laboratory test results, and doctors' prescriptions (66 variables). Univariate and backward stepwise regression analyses were used to screen the variables to identify predictors, and a nomogram was built in the primary cohort based on the results of a logistic regression model. Discriminatory validity, calibration validity, and clinical utility were evaluated using validation cohort 1 based on receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). For external validation based on predictors, we prospectively collected information from patients as validation cohort 2. Results: Among 2115 patients admitted to the NSICU between December 1, 2019, and December 31, 2021, 217 were eligible for the study, including 102 patients with MDR-AB infections (102 cases) and 115 patients with other bacterial infections (115 cases). We randomly categorized the patients into the primary cohort (70%, N=152) and validation cohort 1 (30%, N=65). Validation cohort 2 consisted of 24 patients admitted to the NSICU between January 1, 2022, and March 31, 2022, whose clinical information was prospectively collected according to predictors. The nomogram, consisting of only six predictors (age, NSICU stay, Glasgow Coma Scale, meropenem, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio), had significantly high sensitivity and specificity (primary cohort AUC=0.913, validation cohort 1 AUC=0.830, validation cohort 2 AUC=0.889) for early identification of infection and had great calibration (validation cohort 1,2 P=0.3801, 0.6274). DCA confirmed that the nomogram is clinically useful. Conclusion: Our nomogram could help clinicians make early predictions regarding the onset of pulmonary infection caused by MDR-AB and implement targeted interventions.


Assuntos
Acinetobacter baumannii , Pneumonia , Humanos , Estudos Retrospectivos , Nomogramas , Farmacorresistência Bacteriana Múltipla , Fatores de Risco , Unidades de Terapia Intensiva
13.
Acta Neuropathol Commun ; 11(1): 61, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37024941

RESUMO

The persistent dysregulation and accumulation of poisonous proteins from destructive neural tissues and cells activate pathological mechanisms after traumatic brain injury (TBI). The lymphatic drainage system of the brain, composed of the glymphatic system and meningeal lymphatic vessels (MLVs), plays an essential role in the clearance of toxic waste after brain injury. The neuroprotective effect of interleukin 33 (IL-33) in TBI mice has been demonstrated; however, its impact on brain lymphatic drainage is unclear. Here, we established a fluid percussion injury model to examine the IL-33 administration effects on neurological function and lymphatic drainage in the acute brain of TBI mice. We verified that exogenous IL-33 could improve the motor and memory skills of TBI mice and demonstrated that in the acute phase, it increased the exchange of cerebrospinal and interstitial fluid, reversed the dysregulation and depolarization of aquaporin-4 in the cortex and hippocampus, improved the drainage of MLVs to deep cervical lymph nodes, and reduced tau accumulation and glial activation. We speculate that the protective effect of exogenous IL-33 on TBI mice's motor and cognitive functions is related to the enhancement of brain lymphatic drainage and toxic metabolite clearance from the cortex and hippocampus in the acute stage. These data further support the notion that IL-33 therapy may be an effective treatment strategy for alleviating acute brain injury after TBI.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Interleucina-33 , Animais , Camundongos , Encéfalo/patologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Interleucina-33/farmacologia , Sistema Linfático/metabolismo
14.
Br J Neurosurg ; 37(5): 1074-1077, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33307833

RESUMO

OBJECTIVE: To evaluate the value of texture analysis of routine MRI image in peritumoral edema of differentiating diagnosis between glioblastoma (GBM) and primary brain lymphoma (PBL). METHODS: The MRI imaging data of 22 patients with glioblastoma and 21 patients with PBL who were hospitalized in our hospital from January 2010 to October 2018 were selected. All the patients were pathologically diagnosed as glioblastoma or PBL, and MRI plain scan and enhanced examination were performed before operation. FireVoxel software was used to delineate the region of interest (ROI) on the most obvious level of peritumoral edema based on T1WI enhancement. Texture parameters were extracted and compared between glioblastoma and PBL. RESULTS: In the glioblastoma group, the inhomogeneity, kurtosis and entropy texture parameters were statistically different from those in the PBL group. The entropy parameter area under the curve (AUC) (0.903) was significantly better than the kurtosis parameter AUC (0.859) and the inhomogeneity parameter AUC (0.729). When the entropy parameter Cut-off point = 3.883, the sensitivity, specificity and accuracy of glioblastoma and PBL were 85.7, 86.4 and 86.0%, respectively, by differential diagnosis. CONCLUSION: Texture analysis of tumor peritumoral edema provided quantifiable information, which might be a new method for differentiating glioblastoma from PBL.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Linfoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Linfoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Diagnóstico Diferencial , Edema/diagnóstico , Encéfalo/patologia , Estudos Retrospectivos
15.
Transl Stroke Res ; 14(5): 667-677, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35907128

RESUMO

The objective of this study is to explore whether craniocervical manual lymphatic drainage (cMLD) can promote hematoma absorption and increase the efficiency of atorvastatin-based conservative treatment in chronic subdural hematoma (CSDH) patients. All CSDH patients treated with atorvastatin-based therapy between October 2020 and February 2022 in our department were retrospectively screened for enrollment. The patients were divided into the control and cMLD groups according to whether cMLD was performed. Head CT or MR images in both groups were obtained before the treatment and 2 weeks and 4 weeks after the treatment. MR images of the deep cervical lymphatic nodes (dCLNs) in 23 patients were obtained in the cMLD group before and approximately 2 weeks after treatment. The volumes of the dCLNs and hematoma were calculated. The primary outcomes are the differences in hematoma volume reduction after 4 weeks of treatment. The secondary outcomes were (1) the differences in hematoma volume reduction between the patients in these two groups in the 2nd week, (2) the dCLN volume change in the cMLD group before and after 2 weeks of treatment, and (3) the percentage of patients who transitioned to surgery because of failure to the conservative treatment. A total of 106 consecutive patients were enrolled in this study for analysis; 54 patients received atorvastatin-based treatment (control group), and 52 were treated with both atorvastatin-based treatment and cMLD (cMLD group). At baseline, the mean hematoma volume was 76.53 ± 42.97 ml in the control group and 88.57 ± 49.01 ml in the cMLD group (p = 0.181). In the 4th week, the absolute number of hematoma reductions (20.79 ± 34.73 ml vs. 37.28 ± 28.24 ml, p = 0.009) and percentage of hematoma reductions (22.58% ± 60.01% vs. 46.43% ± 30.12%, p = 0.012) in the cMLD group were greater than those in the control group. After 2 weeks of treatment, the absolute number of hematoma reductions showed no difference in the two groups, while the percentage of hematoma reduction was higher in the cMLD group (18.18% ± 24.61% vs. 2.08% ± 25.72%, p = 0.001). One patient in cMLD and 8 patients in the control group were transitioned to receive surgical treatment. The dCLN volumes in 23 experimental patients increased significantly after 2 weeks of treatment in the cMLD group (p = 0.032). There were no severe side effects that needed to be reported. Combined with atorvastatin-based therapy, cMLD can promote hematoma absorption and decrease the surgery rate, which provides a new therapeutic strategy for CSDH.


Assuntos
Hematoma Subdural Crônico , Humanos , Atorvastatina/uso terapêutico , Atorvastatina/efeitos adversos , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/tratamento farmacológico , Hematoma Subdural Crônico/cirurgia , Estudos Retrospectivos , Drenagem Linfática Manual , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
J Clin Lab Anal ; 36(12): e24787, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36441597

RESUMO

BACKGROUND: To examine the association between low-density lipoprotein cholesterol (LDL-C) concentrations and the risk of a large hematoma volume after intracerebral hemorrhage (ICH). METHODS: Patients from the Kailuan study (Tangshan, China) who were hospitalized with ICH during 2006 and 2020 were included in this study. The concentration of lipid concentrations, hematoma volume and other clinical characteristics were retrospectively collected and analyzed. Hematoma volumes were measured on the first available brain scan using the ABC/2 method. LDL-C concentrations were obtained from the last physical examination before the occurrence of ICH. LDL-C concentration was categorized into four groups in accordance with the quartiles. Logistic regression was used to assess the association between LDL-C concentrations and the risk of a large hematoma volume of ≥30 ml. A generalized linear regression model was used to analyze the dose-response relationship between LDL-C concentration and hematoma volume. RESULTS: A total of 836 patients with ICH were evaluated. In the Multivariate logistic regression, compared to the second quartile of LDL_C, the first quartile of LDL_C had a significantly higher risk of a large hematoma volume (OR 2.49 [95% CI 1.54-4.01]), and the higher quartile of LDL_C is not associated with higher odds of large hematoma volume. In the generalized linear regression model, the adjusted ß for the association between LDL-C concentration and hematoma volume was 9.46 (95% confidence interval 2.87-16.04), whereas higher LDL-C concentration was not associated with a large hematoma volume. CONCLUSIONS: This study confirmed that low LDL-C concentrations prior to ICH are associated with a higher risk of a large hematoma volume.


Assuntos
Hemorragia Cerebral , Hematoma , Humanos , LDL-Colesterol , Estudos Retrospectivos , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/complicações , Hematoma/etiologia , Hematoma/complicações , Neuroimagem
17.
Front Neurosci ; 16: 967297, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071715

RESUMO

Intracerebral hemorrhage (ICH) is a fatal disease with high mortality and poor prognosis that triggers multiple severe brain injuries associated with an inflammatory cascade response that cannot be treated with any effective medication. Atorvastatin (ATO) suppresses inflammation, alleviates brain trauma, and eliminates subdural hematoma. Dexamethasone (DXM) also has the capacity to inhibit inflammation. Thus, we combined ATO with low-dose DXM to treat ICH mice in vivo to examine whether the combined treatment can inhibit secondary inflammation around the cerebral hemorrhage and decrease overall mortality. Compared to the monotherapy by either ATO or DXM, the combined treatment significantly improves the survivorship of the ICH mice, accelerates their recovery of impaired neurological function, and modulates the circulating cytokines, oxidative products, and apoptosis. Moreover, the benefit of ATO-DXM combination therapy was most pronounced on day 3 after dosing compared to ATO or DXM alone. Thus, early administration of ATO combined with low-dose-DXM promotes better survival of ICH and improves neurological function by reducing neuroinflammation and brain edema in their early phase.

18.
J Cereb Blood Flow Metab ; 42(12): 2287-2302, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35962479

RESUMO

The glymphatic-lymphatic fluid transport system (GLFTS) consists of glymphatic pathway and cerebrospinal fluid (CSF) lymphatic outflow routes, allowing biological liquids from the brain parenchyma to access the CSF along with perivascular space and to be cleaned out of the skull through lymphatic vessels. It is known that increased local pressure due to physical compression of tissue improves lymphatic transport in peripheral organs, but little is known about the exact relationship between increased intracranial pressure (IICP) and GLFTS. In this study, we verify our hypothesis that IICP significantly impacts GLFTS, and this effect depends on severity of the IICP. Using a previously developed inflating balloon model to induce IICP and inject fluorescent tracers into the cisterna magna, we found significant impairment of the glymphatic circulation after IICP. We further found that cerebrovascular occlusion occurred, and cerebrovascular pulsation decreased after IICP. IICP also interrupted the drainage of deep cervical lymph nodes and dorsal meningeal lymphatic function, enhancing spinal lymphatic outflow to the sacral lymph nodes. Notably, these effects were associated with the severity of IICP. Thus, our findings proved that the intensity of IICP significantly impacts GLFTS. This may have translational applications for preventing and treating related neurological disorders.


Assuntos
Sistema Glinfático , Hipertensão Intracraniana , Vasos Linfáticos , Humanos , Pressão Intracraniana , Sistema Linfático , Vasos Linfáticos/metabolismo , Hipertensão Intracraniana/líquido cefalorraquidiano , Encéfalo/metabolismo , Hemodinâmica , Líquido Cefalorraquidiano/fisiologia
19.
Front Aging Neurosci ; 13: 726592, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539386

RESUMO

Chronic subdural hematoma (CSDH) is a common form of intracranial hemorrhage in the aging population. We aimed to investigate the predictive factors for atorvastatin efficacy as a monotherapy for moderate CSDH. We retrospectively reviewed the medical records of patients who were diagnosed with moderate CSDH and received atorvastatin monotherapy between February 5, 2014, and November 7, 2015, in multiple neurosurgical departments. Univariate, multivariate and receiver operating characteristic curve analyses were performed to identify the potential significant factors indicative of the good therapeutic efficacy or poor therapeutic efficacy of atorvastatin for mild CSDH, such as age, sex, history of injury, Markwalder grading scale-Glasgow Coma Scale (MGS-GCS), Activities of Daily Life-the Barthel Index scale (ADL-BI), American Society of Anesthesiologists Physical Status classification system (ASA-PS), blood cell counts, serum levels and computed tomography findings. A total of 89 patients (75 men and 14 women) aged 24-88 years (mean age 61.95 ± 15.30 years) were followed-up for 24 weeks. Computed tomography findings at admission showed mixed-density hematoma in 22 patients, isodense hematoma in 13 patients, high-density hematoma in 26 patients, and low-density hematoma in 28 patients. In total, 3, 80, and 6 patients had MGS-GCS grades of 0, 1, and 2, respectively. The efficacy rate at 6 months was 87.6% (78/89). Eleven patients were switched to surgery due to a worsened neurological condition, of whom 8, 1, 1, and 1 had high-density, low-density, isodense and mixed-density hematomas, respectively. These patients were switched to surgery over a range of 2-27 days, with a median interval of 12 days after the medication treatment. Univariate and multivariate analyses, confirmed by ROC curves, revealed that high-density hematoma, basal cistern compression, and hematoma volume to be independent risk factors for the efficacy of atorvastatin monotherapy in patients with moderate CSDH. Atorvastatin is an effective monotherapy for the treatment of mild CSDH. High-density hematoma, basal cistern compression, and hematoma volume are independent predictors of the efficacy of atorvastatin as a non-surgical treatment. The results suggested that ADL-BI was more sensitive than the MGS-GCS and ASA-PS for determining patient outcomes in our moderate CSDH cohort.

20.
Cancer Biol Med ; 18(1): 88-104, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33628587

RESUMO

Objective: BYSL, which encodes the Bystin protein in humans, is upregulated in reactive astrocytes following brain damage and/or inflammation. We aimed to determine the role and mechanism of BYSL in glioma cell growth and survival. Methods: BYSL expression in glioma tissues was measured by quantitative real-time PCR, Western blot, and immunohistochemistry. In vitro assays were performed to assess the role of BYSL in cell proliferation and apoptosis. Protein interactions and co-localization were determined by co-immunoprecipitation and double immunofluorescence. The expression and activity of the AKT/mTOR signaling molecules were determined by Western blot analysis, and the role of BYSL in glioma growth was confirmed in an orthotopic xenograft model. Results: The BYSL mRNA and protein levels were elevated in glioma tissues. Silencing BYSL inhibited glioma cell proliferation, impeded cell cycle progression, and induced apoptosis, whereas overexpressing BYSL protein led to the opposite effects. We identified a complex consisting of BYSL, RIOK2, and mTOR, and observed co-localization and positive correlations between BYSL and RIOK2 in glioma cells and tissues. Overexpressing BYSL or RIOK2 increased the expression and activity of AKT/mTOR signaling molecules, whereas downregulation of BYSL or RIOK2 decreased the activity of AKT/mTOR signaling molecules. Silencing BYSL or RIOK2 decreased the growth of the tumors and prolonged the lifespan of the animals in an orthotopic xenograft model. Conclusions: High expression of BYSL in gliomas promoted tumor cell growth and survival both in vitro and in vivo. These effects could be attributed to the association of BYSL with RIOK2 and mTOR, and the subsequent activation of AKT signaling.


Assuntos
Neoplasias Encefálicas/genética , Moléculas de Adesão Celular/genética , Glioma/genética , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Glioma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
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