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1.
Medicine (Baltimore) ; 100(15): e24952, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847611

RESUMO

ABSTRACT: To explore the epidemiology of patients with spontaneous intracerebral hemorrhage (sICH) in Chengdu, China, we retrieved the data of patients with spontaneous cerebral hemorrhage admitted to the First Affiliated Hospital of Chengdu Medical College from January 2017 to December 2019. We performed a comprehensive analysis of the location of hemorrhage, demographics, factors of hemorrhage, condition of body, severity of disturbance of consciousness, treatment, length of stay (days), inpatient costs, prognosis, and mortality rate in patients with sICH. In total, data of 561 in patients with sICH were included. The hemorrhage site was primarily located in the basal ganglia and thalamus (64.71%). The mean patient age was 63.2 ±â€Š12.4 years (64.17% men, 35.83% women). Male patients (mean age 62.3 ±â€Š12.5 year) were younger than female patients (mean age 64.9 ±â€Š12.1 year). The age of sICH onset in our sample was between 40 and 79 years; this occurred in 87.70% of the included cases. There were more males than females, which may be related to more daily smoking, longer drinking years, and overweight in males than in females. Cases occurred most frequently during the winter and spring months, and the relationship between sICH visits and hospitalizations appeared as a U-shape. The median time from illness onset to hospital admission was 3.0 hours. According to the Glasgow Coma Scale (GCS) score at admission, 20.50% of sICH cases were of mild intensity, 39.93% were moderate, and 39.57% were severe. Moderate disorder is the most common sICH severity. Factors influencing the disturbance of consciousness were blood glucose level at the time of admission as well as the number of years with hypertension. The lower the degree of disturbance of consciousness and the more they smoked per day indicated they had a higher likelihood of receiving surgical treatment while in hospital. The median hospital stay was 13.0 days, while the median inpatient cost was USD 3609. The 30-day mortality rate was 18.36%. sICH is an important public health problem in Chengdu, China. A governmental initiative is urgently needed to establish a sICH monitoring system that covers the Chengdu region to develop more effective and targeted measures for sICH prevention, treatment, and rehabilitation.


Assuntos
Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Hemorragia Cerebral/mortalidade , China/epidemiologia , Feminino , Escala de Coma de Glasgow , Comportamentos Relacionados com a Saúde , Gastos em Saúde , Nível de Saúde , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estações do Ano , Fatores Sexuais , Fatores Socioeconômicos , Tempo para o Tratamento
2.
Int J Nanomedicine ; 16: 2933-2947, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33907400

RESUMO

Background: Intracerebral hemorrhage (ICH), a devastating subtype of stroke, has a poor prognosis. However, there is no effective therapy currently available due to its complex pathological progression, in which neuroinflammation plays a pivotal role in secondary brain injury. In this work, the use of statin-loaded nanomicelles to target the neuroinflammation and improve the efficacy was studied in a mouse model of ICH. Methods: Rosuvastatin-loaded nanomicelles were prepared by a co-solvent evaporation method using polyethylene glycol-poly(ε-caprolactone) (PEG-PCL) copolymer as a carrier. The prepared nanomicelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), and then in vitro and in vivo studies were performed. Results: TEM shows that the nanomicelles are spherical with a diameter of about 19.41 nm, and DLS shows that the size, zeta potential, and polymer dispersity index of the nanomicelles were 23.37 nm, -19.2 mV, and 0.221, respectively. The drug loading content is 8.28%. The in vivo study showed that the nanomicelles significantly reduced neuron degeneration, inhibited the inflammatory cell infiltration, reduced the brain edema, and improved neurological deficit. Furthermore, it was observed that the nanomicelles promoted the polarization of microglia/macrophages to M2 phenotype, and also the expression of the proinflammatory cytokines, such as IL-1ß and TNF-α, was significantly down-regulated, while the expression of the anti-inflammatory cytokine IL-10 was significantly up-regulated. The related mechanism was proposed and discussed. Conclusion: The nanomicelles treatment suppressed the neuroinflammation that might contribute to the promoted nerve functional recovery of the ICH mouse, making it potential to be applied in clinic.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Inflamação/tratamento farmacológico , Nanoestruturas/química , Rosuvastatina Cálcica/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Edema Encefálico/tratamento farmacológico , Edema Encefálico/patologia , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inflamação/patologia , Camundongos , Micelas , Microglia/efeitos dos fármacos , Microglia/patologia , Nanoestruturas/administração & dosagem , Poliésteres/química , Polietilenoglicóis/química , Células RAW 264.7 , Rosuvastatina Cálcica/administração & dosagem
3.
J Stroke Cerebrovasc Dis ; 30(6): 105765, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33813082

RESUMO

OBJECTIVES: Microglia activation, a key process in secondary injury following intracerebral hemorrhage (ICH), is divided to M1 and M2 phenotype. Protocatechuic acid (PCA) is a phenolic acid been proved neuroprotection in ICH without understanding of details. Thus, this study aimed to observe the influence of PCA on microglia activation and explore underlying mechanisms. MATERIALS AND METHODS: To assess PCA affected microglia activation in vivo, an experimental ICH mice model was established and then treated with PCA intraperitoneal injection. Immunofluorescence staining was performed in brain slices at day 3 post ICH. BV2 cells were stimulated with hemin for activation, then M1 and M2 biomarkers were analyzed using Western Blot and qPCR. At last, we detected the expression of mTOR and its downstream molecules to discuss possible mechanisms. RESULTS: At day 3 post ICH, less activated microglia gathering around hematoma after PCA treatment. Furtherly, in hemin treated BV2 cells, PCA downregulated M1 and promoted M2 biomarkers expression in both mRNA and protein level. PCA inhibited the phosphorylation of mTOR, S6K1 and 4E-BP1, while the inhibition was disappeared after supplemented with mTOR activator. CONCLUSIONS: PCA impacted microglia activation by suppressing the mTOR signaling pathway, thereby improving M1/M2 switch and attenuated neuroinflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Hemorragia Cerebral/tratamento farmacológico , Hidroxibenzoatos/farmacologia , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Fenótipo , Fosforilação , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
4.
J Stroke Cerebrovasc Dis ; 30(6): 105760, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33845422

RESUMO

Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis, neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema, and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment.


Assuntos
Barreira Hematoencefálica/metabolismo , Edema Encefálico/prevenção & controle , Hemorragia Cerebral/terapia , Proteínas da Matriz Extracelular/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Animais , Barreira Hematoencefálica/ultraestrutura , Edema Encefálico/genética , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/genética , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Ocludina/genética , Ocludina/metabolismo , RNA Interferente Pequeno/genética , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
5.
Int J Mol Sci ; 22(8)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33918041

RESUMO

Cerebral amyloid angiopathy (CAA) is characterized by accumulation of amyloid ß (Aß) in walls of leptomeningeal vessels and cortical capillaries in the brain. The loss of integrity of these vessels caused by cerebrovascular Aß deposits results in fragile vessels and lobar intracerebral hemorrhages. CAA also manifests with progressive cognitive impairment or transient focal neurological symptoms. Although development of therapeutics for CAA is urgently needed, the pathogenesis of CAA remains to be fully elucidated. In this review, we summarize the epidemiology, pathology, clinical and radiological features, and perspectives for future research directions in CAA therapeutics. Recent advances in mass spectrometric methodology combined with vascular isolation techniques have aided understanding of the cerebrovascular proteome. In this paper, we describe several potential key CAA-associated molecules that have been identified by proteomic analyses (apolipoprotein E, clusterin, SRPX1 (sushi repeat-containing protein X-linked 1), TIMP3 (tissue inhibitor of metalloproteinases 3), and HTRA1 (HtrA serine peptidase 1)), and their pivotal roles in Aß cytotoxicity, Aß fibril formation, and vessel wall remodeling. Understanding the interactions between cerebrovascular Aß deposits and molecules that accumulate with Aß may lead to discovery of effective CAA therapeutics and to the identification of biomarkers for early diagnosis.


Assuntos
Angiopatia Amiloide Cerebral/diagnóstico , Angiopatia Amiloide Cerebral/terapia , Animais , Biomarcadores , Angiopatia Amiloide Cerebral/etiologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Tomada de Decisão Clínica , Gerenciamento Clínico , Suscetibilidade a Doenças , Imunofluorescência , Humanos , Imuno-Histoquímica , Proteoma , Proteômica/métodos
6.
Eur J Endocrinol ; 184(4): 565-574, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33730688

RESUMO

Design: Cushing's disease (CD) is a rare clinical syndrome characterized by chronic exposure to hypercortisolism due to an adrenocorticotropic hormone-secreting pituitary adenoma. The adverse effects of chronic exposure to hypercortisolism on the human brain remain unclear. The purpose of this study was to assess the prevalence of cerebral microbleeds (CMBs) in CD patients and their associations with clinical characteristics. Methods: In this study, 48 active CD patients, 39 remitted CD patients, and 52 healthy control (HC) subjects underwent MRI. CD patients also underwent neuropsychological testing and clinical examinations. The number, locations, and volumes of CMBs were assessed on quantitative susceptibility mapping (QSM) images and with the Microbleed Anatomical Rating Scale. The correlation between CMBs and clinical characteristics was explored. Results: The prevalence of CMBs among active and remitted CD patients was higher than that among HCs (16.3%, 20.5%, and 3.3%, respectively). Moreover, the age of CD patients with CMBs were much younger than HCs with CMBs. Furthermore, the increased number of CMBs in active CD patients was associated with increased cerebrospinal fluid (CSF) volumes in remitted CD patients. Conclusions: Chronic exposure to hypercortisolism may be relevant to CMBs and significantly correlated with altered brain volumes in CD.


Assuntos
Encéfalo/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Imageamento por Ressonância Magnética/métodos , Hipersecreção Hipofisária de ACTH/complicações , Adulto , Idoso , Encéfalo/patologia , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/patologia , Estudos Transversais , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/patologia , Suscetibilidade a Doenças/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/epidemiologia , Hipersecreção Hipofisária de ACTH/patologia , Prevalência
7.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760209

RESUMO

With­no­lysine kinase 3 (WNK3) is a serine/threonine kinase that functions by regulating downstream signaling molecules. WNK3 mainly regulates intracellular and extracellular Na+, Cl­ and K+ levels by regulating downstream ion transporters, the disruption of which has been associated with cerebral ischemia, epilepsy, glioma and other diseases. In addition, WNK3 was demonstrated to regulate neuronal splicing factor RNA binding fox­1 homolog­1 to influence autism. Over the past 20 years, accumulating evidence has reported that dysfunctional WNK3 signaling was involved in the pathologies of various neurological disorders; therefore, WNK3 has become a promising therapeutic target for ameliorating the corresponding symptoms of such disorders. The present review aimed to provide a general overview of the expression patterns and physiological functions of WNK3 signaling and its pathophysiological roles in neurological diseases, such as epilepsy, ischemic brain injury, intracerebral hemorrhage, autism, glioma and schizophrenia.


Assuntos
Hemorragia Cerebral/genética , Transporte de Íons/genética , Doenças do Sistema Nervoso/genética , Proteínas Serina-Treonina Quinases/genética , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Hemorragia Cerebral/patologia , Epilepsia/genética , Epilepsia/patologia , Humanos , Doenças do Sistema Nervoso/patologia , Neurônios/metabolismo , Neurônios/patologia , Transdução de Sinais/genética
8.
Oxid Med Cell Longev ; 2021: 8815441, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688394

RESUMO

Oxidative stress (OS) is induced by the accumulation of reactive oxygen species (ROS) following intracerebral hemorrhage (ICH) and plays an important role in secondary brain injury caused by the inflammatory response, apoptosis, autophagy, and blood-brain barrier (BBB) disruption. This review summarizes the current state of knowledge regarding the pathogenic mechanisms of brain injury after ICH, markers for detecting OS, and therapeutic strategies that target OS to mitigate brain injury.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/patologia , Estresse Oxidativo , Animais , Biomarcadores/metabolismo , Humanos , Modelos Biológicos , Terapia de Alvo Molecular , Espécies Reativas de Oxigênio/metabolismo
9.
Oxid Med Cell Longev ; 2021: 8891373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708336

RESUMO

Background: Albumin has been regarded as a potent antioxidant with free radical scavenging activities. Oxidative stress and neuronal apoptosis are responsible for its highly damaging effects on brain injury after intracerebral hemorrhage (ICH). Here, the present study investigated the neuroprotective effect of albumin against early brain injury after ICH and the potential underlying mechanisms. Methods: Adult male Sprague-Dawley rats were subjected to intrastriatal injection of autologous blood to induce ICH. Human serum albumin was given by intravenous injection 1 h after ICH. U0126, an inhibitor of extracellular signal-regulated kinase (ERK1/2), and ML385, an inhibitor of nuclear factor-E2-related factor 2 (Nrf2), were intraperitoneally administered 1 h before ICH induction. Short- and long-term neurobehavioral tests, western blotting, immunofluorescence staining, oxidative stress evaluations, and apoptosis measurements were performed. Results: Endogenous expression of albumin (peaked at 5 days) and heme oxygenase 1 (HO-1, peaked at 24 h) was increased after ICH compared with the sham group. Albumin and HO-1 were colocalized with neurons. Compared with vehicle, albumin treatment significantly improved short- and long-term neurobehavioral deficits and reduced oxidative stress and neuronal death at 72 h after ICH. Moreover, albumin treatment significantly promoted the phosphorylation of ERK1/2; increased the expression of Nrf2, HO-1, and Bcl-2; and downregulated the expression of Romo1 and Bax. U0126 and ML385 abolished the treatment effects of albumin on behavior and protein levels after ICH. Conclusions: Albumin attenuated oxidative stress-related neuronal death may in part via the ERK/Nrf2/HO-1 signaling pathway after ICH in rats. Our study suggests that albumin may be a novel therapeutic method to ameliorate brain injury after ICH.


Assuntos
Apoptose/efeitos dos fármacos , Hemorragia Cerebral/patologia , Heme Oxigenase-1/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Albumina Sérica Humana/farmacologia , Animais , Hemorragia Cerebral/metabolismo , Humanos , Masculino , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
10.
BMC Neurol ; 21(1): 131, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743639

RESUMO

BACKGROUND: The computed tomography angiography (CTA) spot sign is a validated predictor of hematoma expansion and 30-day mortality in intracerebral hemorrhage (ICH). However, whether the spot sign predicts worse functional outcomes among ICH survivors remains unclear. This study investigated the frequency of the spot sign and its association with functional outcomes and length of hospital stay among ICH survivors. METHODS: This was a retrospective analysis of consecutive patients with primary ICH who received CTA within 24 h from presentation to admission to the emergency department of a single medical center between January 2007 and December 2017. Patients who died before discharge and those referred from other hospitals were excluded. CTAs with motion artifacts were excluded from the analysis. The presence of a spot sign was examined by an experienced neuroradiologist. Functional outcomes were determined based on the modified Rankin Scale (mRS) score and Barthel Index (BI). Severe dependency in activities of daily living (ADL) was defined as BI of ≤60 and severe disability as an mRS score of ≥4. Odds ratio (OR) and multiple linear regression were used as measures of association. RESULTS: In total, 66 patients met the inclusion criteria, of whom 9 (13.64%) were positive for a spot sign. No significant differences were observed in baseline characteristics between patients with and without a spot sign. Patients with a spot sign tended to be severely dependent in ADL at discharge (66.67% vs 41.07%; OR = 2.87; p = 0.15) and were more likely to require ICH-related surgery (66.67% vs 24.56%; OR = 6.14; p = 0.01). In multiple linear regression, patients with a higher spot sign score had a significantly longer hospital stay (coefficient = 9.57; 95% CI = 2.11-17.03; p = 0.013). CONCLUSIONS: The presence of a spot sign is a common finding and is associated with longer hospital stay and possibly worse functional outcomes in ICH survivors.


Assuntos
Angiografia Cerebral/métodos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Angiografia por Tomografia Computadorizada/métodos , Recuperação de Função Fisiológica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sobreviventes
11.
Neurology ; 96(16): e2048-e2057, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33653897

RESUMO

OBJECTIVE: Cerebral microbleeds (MBs) are a common finding in patients with cerebral small vessel disease (CSVD) and Alzheimer disease as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein. METHODS: 7-Tesla (7T) MRI was conducted and MBs were counted on quantitative susceptibility mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein. RESULTS: A total of 51 people (mean age [SD] 70.5 [8.6] years, 37% female) participated in the study: 20 had CSVD (cerebral amyloid angiopathy [CAA] with strictly lobar MBs [n = 8], hypertensive arteriopathy [HA] with strictly deep MBs [n = 5], or mixed lobar and deep MBs [n = 7], 72.4 [6.1] years, 30% female) and 31 were healthy controls (69.4 [9.9] years, 42% female). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. Patients with CAA showed the highest ratio of venous to total MBs (19%) (HA = 9%, mixed = 18%, controls = 5%). CONCLUSION: Our findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathologic studies are needed to confirm our observations.


Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Veias/diagnóstico por imagem , Veias/patologia , Idoso , Hemorragia Cerebral/etiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/patologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos
12.
Am J Forensic Med Pathol ; 42(1): 77-80, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33555675

RESUMO

ABSTRACT: Mass lesions in the brain encompass a wide range neoplastic and nonneoplastic entities. These can present as a diagnostic pitfall, with nonspecific, overlapping symptoms and similar appearances on radiology. They may cause death through varied mechanisms, either specific to the underlying pathophysiology or due to the space-occupying effect of the lesion. We report a case of fatal hemorrhagic cerebral pseudocyst, a rare mass lesion, associated with a cerebral varix, causing death in a morbidly obese individual. To the best of our knowledge, there is no previous documentation in the postmortem literature of this entity as a cause of death. This case aims to document this rare entity in the differential diagnosis of a tumor-like lesion in the brain, highlight the clinical difficulty in its assessment, and demonstrate an uncommon mechanism of death, of a mass lesion acting as a focus causing seizures, with resulting hypoxia due to effects of morbid obesity and heart failure.


Assuntos
Neoplasias Encefálicas/patologia , Cistos do Sistema Nervoso Central/patologia , Hemorragia Cerebral/patologia , Adulto , Encéfalo/irrigação sanguínea , Hemorragia Cerebral/etiologia , Feminino , Cefaleia/etiologia , Parada Cardíaca/etiologia , Humanos , Obesidade Mórbida/complicações , Lobo Parietal/patologia , Convulsões/etiologia , Varizes/patologia
13.
Int J Nanomedicine ; 16: 775-788, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33574665

RESUMO

Background: Intracerebral hemorrhage (ICH) is a common neurological crisis leading to high mortality and morbidity. Oxidative stress-induced secondary injury plays a critical role in neurological deterioration. Previously, we synthesized a porous Se@SiO2 nanocomposite and identified their therapeutic role in osteonecrosis of the femoral head. Whether this nanocomposite is neuroprotective remains to be elucidated. Methods: A porous Se@SiO2 nanocomposite was synthesized, and its biosafety was determined using a CCK-8 assay. The neuroprotective effect was evaluated by TUNEL staining, and intracellular ROS were detected with a DCFH-DA probe in SH-SY5Y cells exposed to hemin. Furthermore, the effect of the nanocomposite on cell apoptosis, brain edema and blood-brain barrier permeability were evaluated in a collagenase-induced ICH mouse model. The potential mechanism was also explored. Results: The results demonstrated that Se@SiO2 treatment significantly improved neurological function, increased glutathione peroxidase activity and downregulated malonaldehyde levels. The proportion of apoptotic cells, brain edema and blood-brain barrier permeability were reduced significantly in ICH mice treated with Se@SiO2 compared to vehicle-treated mice. In vitro, Se@SiO2 protected SH-SY5Y cells from hemin-induced apoptosis by preventing intracellular reactive oxygen species accumulation. Conclusion: These results suggested that the porous Se@SiO2 nanocomposite exerted neuroprotection by suppressing oxidative stress. Se@SiO2 may be a potential candidate for the clinical treatment of ICH and oxidative stress-related brain injuries.


Assuntos
Encéfalo/patologia , Hemorragia Cerebral/patologia , Nanocompostos/química , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Selênio/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Encéfalo/efeitos dos fármacos , Edema Encefálico/complicações , Edema Encefálico/tratamento farmacológico , Linhagem Celular Tumoral , Hemorragia Cerebral/complicações , Hemorragia Cerebral/tratamento farmacológico , Citoproteção/efeitos dos fármacos , Modelos Animais de Doenças , Hemina/toxicidade , Humanos , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Nanocompostos/toxicidade , Nanocompostos/ultraestrutura , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Selênio/uso terapêutico , Dióxido de Silício/farmacologia , Testes de Toxicidade
14.
Neurology ; 96(15): e1954-e1965, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33627495

RESUMO

OBJECTIVE: To determine whether CT-based cerebral small vessel disease (SVD) biomarkers are associated with 6-month functional outcome after intracerebral hemorrhage (ICH) and whether these biomarkers improve the performance of the preexisting ICH prediction score. METHODS: We included 864 patients with acute ICH from a multicenter, hospital-based prospective cohort study. We evaluated CT-based SVD biomarkers (white matter hypodensities [WMH], lacunes, brain atrophy, and a composite SVD burden score) and their associations with poor 6-month functional outcome (modified Rankin Scale score >2). The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test were used to assess discrimination and calibration of the ICH score with and without SVD biomarkers. RESULTS: In multivariable models (adjusted for ICH score components), WMH presence (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12-2.06), cortical atrophy presence (OR 1.80, 95% CI 1.19-2.73), deep atrophy presence (OR 1.66, 95% CI 1.17-2.34), and severe atrophy (either deep or cortical) (OR 1.94, 95% CI 1.36-2.74) were independently associated with poor functional outcome. For the revised ICH score, the AUROC was 0.71 (95% CI 0.68-0.74). Adding SVD markers did not significantly improve ICH score discrimination; for the best model (adding severe atrophy), the AUROC was 0.73 (95% CI 0.69-0.76). These results were confirmed when lobar and nonlobar ICH were considered separately. CONCLUSIONS: The ICH score has acceptable discrimination for predicting 6-month functional outcome after ICH. CT biomarkers of SVD are associated with functional outcome, but adding them does not significantly improve ICH score discrimination. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02513316.


Assuntos
Hemorragia Cerebral/complicações , Hemorragia Cerebral/patologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Recuperação de Função Fisiológica , Tomografia Computadorizada por Raios X
15.
Biomed Res Int ; 2021: 3919710, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33604373

RESUMO

Purpose: To discretely and collectively compare black hole sign (BHS) and satellite sign (SS) with recently introduced gemstone spectral imaging-based iodine sign (IS) for predicting hematoma expansion (HE) in spontaneous intracerebral hemorrhage (SICH). Methods: This retrospective study includes 90 patients from 2017 to 2019 who underwent both spectral computed tomography angiography (CTA) as well as noncontrast computed tomography (NCCT) within 6 hours of SICH onset along with subsequent follow-up NCCT scanned within 24 hours. We named the presence of any of BHS or SS as any NCCT sign. Two independent reviewers analyzed all the HE predicting signs. Receiver-operator characteristic curve analysis and logistic regression were performed to compare the predictive performance of HE. Results: A total of 61 patients had HE, out of which IS was seen in 78.7% (48/61) while BHS and SS were seen in 47.5% (29/61) and 41% (25/61), respectively. The area under the curve for BHS, SS, and IS was 63.4%, 67%, and 82.4%, respectively, while for any NCCT sign was 71.5%. There was no significant difference between IS and any NCCT sign (P = 0.108). Multivariate analysis showed IS (odds ratio 68.24; 95% CI 11.76-396.00; P < 0.001) and any NCCT sign (odds ratio 19.49; 95% CI 3.99-95.25; P < 0.001) were independent predictors of HE whereas BHS (odds ratio 0.34; 95% CI 0.01-38.50; P = 0.534) and SS (odds ratio 4.54; 95% CI 0.54-38.50; P = 0.165) had no significance. Conclusion: The predictive accuracy of any NCCT sign was better than that of sole BHS and SS. Both any NCCT sign and IS were independent predictors of HE. Although IS had higher predictive accuracy, any NCCT sign may still be regarded as a fair predictor of HE when CTA is not available.


Assuntos
Hemorragia Cerebral , Hematoma , Adulto , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/patologia , Angiografia por Tomografia Computadorizada , Meios de Contraste/uso terapêutico , Feminino , Hematoma/diagnóstico por imagem , Hematoma/epidemiologia , Hematoma/patologia , Humanos , Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
16.
Neurology ; 96(12): e1632-e1645, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33495373

RESUMO

OBJECTIVE: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we longitudinally evaluated families with dominantly inherited Alzheimer disease (DIAD). METHODS: Mutation carriers (n = 310) and noncarriers (n = 201) underwent neuroimaging, including gradient echo MRI sequences to detect CMHs, and neuropsychological and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical markers of disease. RESULTS: Three percent of noncarriers and 8% of carriers developed CMHs primarily located in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure and Hachinski ischemic scores, and more clinical, cognitive, and motor impairments than those without CMHs. APOE ε4 status was not associated with the prevalence or incidence of CMHs. Prevalent or incident CMHs predicted faster change in Clinical Dementia Rating although not composite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions. Critically, the presence of 2 or more CMHs was associated with a significant risk for development of additional CMHs over time (8.95 ± 10.04 per year). CONCLUSION: Our study highlights factors associated with the development of CMHs in individuals with DIAD. CMHs are a part of the underlying disease process in DIAD and are significantly associated with dementia. This highlights that in participants in treatment trials exposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging to separate natural incidence of CMHs from drug-related CMHs.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Hemorragia Cerebral/epidemiologia , Adulto , Encéfalo/patologia , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
17.
Stroke Vasc Neurol ; 5(4): 388-395, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33376200

RESUMO

Spontaneous intracerebral haemorrhage (ICH) is a devastating type of stroke with high mortality and morbidity and for which no effective treatments are available to date. Much experimental and clinical research have been performed to explore its mechanisms regard the subsequent inflammatory cascade and to seek the potential therapeutic strategies. The aim of this review is to discuss insights from clinical settings that have led to the development of numerous animal models of ICH. Some of the current and future challenges for clinicians to understand ICH are also surveyed.


Assuntos
Hemorragia Cerebral , Animais , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/terapia , Modelos Animais de Doenças , Progressão da Doença , /patologia , /terapia , Humanos , Prognóstico
18.
Medicine (Baltimore) ; 99(50): e23557, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327308

RESUMO

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke with higher mortality and morbidity, and it lacks effective prognostic markers. The aim of this research is to construct newly valuable prognostic nomogram incorporating red blood cell distribution width (RDW) for ICH patients.We retrospectively analyzed 953 adult patients with ICH. The impacts of RDW on short-term mortality and functional prognosis were calculated using Akaike information criterion (AIC), Bayesian information criteria (BIC) and the area under the curve (AUC) respectively, which could be used to compare with Glasgow coma scale (GCS) and ICH score. The independent factors of prognosis were identified by univariate and multivariate logistic regression analysis. A nomogram based on RDW for nerve functional prognosis was further constructed and validated. Its clinical value was subsequently explored utilizing decision curve analysis.Cumulative clinical results were retrieved for 235 inpatients from Jan 2012 to June 2017. In 30-day mortality sets, GCS and ICH score had better prognostic performance than RDW (AUC: 0.929 and 0.917 vs 0.764; AIC: 124.101 and 134.188 vs 221.372; BIC: 131.021 and 141.107 vs 228.291). In 30-day functional prognosis sets, the consequences of evaluation systems were inconsistent. GCS was the best parameter for predicting outcome using AIC (262.350 vs 276.392 and 264.756) and BIC (269.269 vs 283.311 and 271.675). However, RDW was higher than GCS and ICH score considering AUC (0.784 vs 0.759 and 0.722). Age, GCS, RDW, platelet distribution width, and surgery were independent prognostic factors by multivariate logistic regression analysis, and those coefficients were used to formulate a nomogram. This nomogram can provide accurate prediction with the concordance index of 0.880 (95% CI, 0.837-0.922) higher than Harrell's concordance index of GCS system 0.759 (95% CI, 0.698-0.819) and RDW 0.784 (95% CI, 0.721-0.847). The calibration plots showed optimal consistency between bootstrap-predicted and the actual observed values of 30-day unfavorable prognosis. Decision curve analysis showed an increased net benefit for utilizing the nomogram.High RDW values are associated with an unfavorable outcome after ICH. The established nomogram incorporating RDW should be considered for a 30-day functional prognosis.


Assuntos
Hemorragia Cerebral/diagnóstico , Índices de Eritrócitos , Eritrócitos/patologia , Nomogramas , Idoso , Biomarcadores/sangue , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/patologia , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Análise de Sobrevida
19.
Yakugaku Zasshi ; 140(11): 1323-1327, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33132267

RESUMO

Intracerebral hemorrhage (ICH) results from blood vessels rupture in the brain, forming a blood clot in the brain parenchyma. Leakage of blood constituents causes detrimental tissue damages, ensuing long-lasting neurological deficits; however, effective therapeutic approaches are not yet developed to date. In this study, leukotriene B4 (LTB4) and its receptor leukotriene B4 receptor 1 (BLT1) are proposed as novel therapeutic targets for ICH therapy. After the onset of ICH, the LTB4 content in the brain transiently elevated. Microglia are considered as the source of LTB4 production. Thrombin, a blood constituent, activated the BV-2 microglia and increased the LTB4 secretion from the BV-2 cells. Microglia-released LTB4 promoted its own microglial activation and neutrophil-like differentiated HL-60 cell migration activity. LTB4 receptors comprised of two types: BLT1 and BLT2, with BLT1 known to be a high-affinity receptor associated with chemotaxis. BLT1 knockout mice showed decreased neutrophil invasion, attenuating sensorimotor dysfunction after ICH. Furthermore, therapeutic administration of ONO-4057, an orally active LTB4 receptor antagonist, attenuated neutrophil invasion, microglial activation, axonal fragmentation, and sensorimotor deficits induced by ICH. These results suggest that LTB4 and its receptor BLT1 can be potential promising therapeutic targets that prevent tissue damages following ICH.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/genética , Descoberta de Drogas , Leucotrieno B4 , Terapia de Alvo Molecular , Fenilpropionatos/administração & dosagem , Fenilpropionatos/farmacologia , Receptores do Leucotrieno B4/antagonistas & inibidores , Administração Oral , Animais , Encéfalo/metabolismo , Movimento Celular , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Células HL-60 , Humanos , Leucotrieno B4/metabolismo , Camundongos , Microglia/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Receptores do Leucotrieno B4/metabolismo , Trombina/fisiologia
20.
J Stroke Cerebrovasc Dis ; 29(10): 105128, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912509

RESUMO

BACKGROUND: The insulin-like growth factor 2 (IGF-2) is a growth factor and anti-inflammatory cytokine that plays a crucial role in memory consolidation. However, the precise role of this factor in acute brain damage is still unclear. The present study aimed to evaluate the variations in hippocampal IGF-2 distribution on different days and investigate the effect of recombinant IGF-2 on memory cell density, and IGF-2 distribution following acute hippocampal damage resulting from intracerebral hemorrhage (ICH). METHODS: ICH was induced by injection of 100 µL of autologous blood into the left hippocampus of 72 male Sprague-Dawley rats. Recombinant IGF-2 was injected into the damaged hippocampus 30 min post-induction of ICH in the ICH-IGF-2 group. Then, on postoperative days 1, 3, 7, and 14, samples of brain tissue were collected to perform histopathological and immunohistochemical examinations. RESULTS: The stereological study indicated that the volume of the hippocampus and the number of neurons had a significant reduction, and the infarct volume had a significant increase following ICH. Following the injection of IGF-2, a significant improvement was observed in stereological studies. Immunohistochemical data showed that IGF-2 distribution increased in the hippocampus on different days after ICH, and IGF-2 injection led to a dramatic reduction in this distribution. CONCLUSIONS: In summary, the gradual increase of endogenous IGF-2 as growth and anti-inflammatory factor following hemorrhagic stroke reveals a critical role of this factor in brain recovery after injury. Moreover, the injection of IGF-2 can prevent cell death and alleviate the damage caused by the hemorrhagic stroke.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fator de Crescimento Insulin-Like II/administração & dosagem , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Animais , Morte Celular/efeitos dos fármacos , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/metabolismo , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Fatores de Tempo , Distribuição Tecidual
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