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1.
Biomed Pharmacother ; 133: 111048, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378955

RESUMO

Subarachnoid hemorrhage (SAH) is an acute and severe disease with high disability and mortality. Inflammatory reactions have been proven to occur throughout SAH. Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) have shown broad potential for the treatment of brain dysfunction and neuroprotective effects through neurogenesis and angiogenesis after stroke. However, the mechanisms of EVs in neuroinflammation during the acute phase of SAH are not well known. Our present study was designed to investigate the effects of MSCs-EVs on neuroinflammation and the polarization regulation of microglia to the M2 phenotype and related signaling pathways after SAH in rats. The SAH model was induced by an improved method of intravascular perforation, and MSCs-EVs were injected via the tail vein. Post-SAH assessments included neurobehavioral tests as well as brain water content, immunohistochemistry, PCR and Western blot analyses. Our results showed that MSCs-EVs alleviated the expression of inflammatory cytokines in the parietal cortex and hippocampus 24 h and 48 h after SAH and that MSCs-EVs inhibited NF-κB and activated AMPK to reduce inflammation after SAH. Furthermore, MSC-EVs regulated the polarization of microglia toward the M2 phenotype by downregulating interleukin-1ß, cluster of differentiation 16, cluster of differentiation 11b, and inducible nitric oxide synthase and upregulating the expression of cluster of differentiation 206 and arginase-1. Additionally, MSCs-EVs inhibited the neuroinflammatory response and had neuroprotective effects in the brain tissues of rats after SAH. This study may support their use as a potential treatment strategy for early SAH in the future.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Encéfalo/enzimologia , Vesículas Extracelulares/transplante , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Microglia/enzimologia , NF-kappa B/metabolismo , Hemorragia Subaracnóidea/cirurgia , Animais , Encéfalo/patologia , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Vesículas Extracelulares/enzimologia , Masculino , Células-Tronco Mesenquimais/enzimologia , Microglia/patologia , Fenótipo , Fosforilação , Ratos Sprague-Dawley , Transdução de Sinais , Hemorragia Subaracnóidea/enzimologia , Hemorragia Subaracnóidea/patologia
2.
J Stroke Cerebrovasc Dis ; 29(9): 105054, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807460

RESUMO

BACKGROUND: Phospholipids and sphingolipids are cell membrane components, that participate in signaling events and regulate a wide variety of vital cellular processes. Sphingolipids are involved in ischemic stroke pathophysiology. Throughout cleavage of membrane sphingomyelin by sphingomyelinase in stroke patients, it results in increased Ceramide (Cer) levels in brain tissue. Different studies showed the evidence that sphingomyelinase with Cer production induces expression of interleukin (IL)-6 and have vasoconstrictive proprieties. With this study, we intend to evaluate cerebrospinal fluid (CSF) lipid profile changes in a rabbit closed cranium subarachnoid hemorrhage (SAH) model. METHODS: A total of 14 New Zealand white rabbits were randomly allocated either to SAH or sham group. In the first group SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cisterna magna. Intracranial pressure (ICP) and arterial blood pressure were continuously monitored. Digital subtraction angiography of the basilar artery, CSF and blood samples were performed at day 0 pre SAH and on day 3 post SAH. The amount of IL-6 and various lipids in CSF were quantified using ELISA and Liquid Chromatography-Mass Spectrometry respectively. Cell death was detected in bilateral basal cortex, hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: SAH Induction led to acute increase of ICP and increased delayed cerebral vasospasm (DCVS). At follow up CSF IL-6 levels showed a significant increase compared to baseline. Between baseline and follow up there were no significant differences in any of the measured CSF Lipids irrespective of subgroups. No relevant correlation was found between IL-6 and any of the sphingolipids. We found a correlation between baseline and follow up for the phospholipids phosphatidylethanolamine and phosphatidylcholine. CONCLUSIONS: Neuronal apoptosis, DCVS and IL-6 seems not to be related to changes in CSF lipid profiles except for PEA and PC in a rabbit closed cranium SAH model.


Assuntos
Artéria Basilar/fisiopatologia , Interleucina-6/líquido cefalorraquidiano , Lipídeos/líquido cefalorraquidiano , Neurônios/metabolismo , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Vasoconstrição , Vasoespasmo Intracraniano/líquido cefalorraquidiano , Animais , Apoptose , Artéria Basilar/diagnóstico por imagem , Biomarcadores/líquido cefalorraquidiano , Modelos Animais de Doenças , Interleucina-6/biossíntese , Pressão Intracraniana , Neurônios/patologia , Fosfatidilcolinas/líquido cefalorraquidiano , Fosfatidiletanolaminas/líquido cefalorraquidiano , Projetos Piloto , Coelhos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/fisiopatologia , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/patologia , Vasoespasmo Intracraniano/fisiopatologia
3.
J Neurovirol ; 26(5): 802-804, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32797352
4.
Leg Med (Tokyo) ; 47: 101742, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32653857

RESUMO

The fatal rupture of a saccular aneurysm at the junction between the left anterior cerebral artery and anterior communicating artery affected by fibromuscular dysplasia (FMD) is a rare condition. Here is reported the case of a subject involved in a road traffic accident a few minutes before the death, which opened the debate on the real cause of death in a forensic setting. By autopsy, the examination of the brain revealed subarachnoid haemorrhage with flooding of the ventricles due to the breached saccular aneurysm of the junction between the left anterior cerebral artery and anterior communicating artery, in FMD mainly affecting the circle of Willis arteries. A spontaneous aneurysmal rupture was excluded on the basis of probabilistic analysis, in the presence of alternative hypotheses that could explain the facts. The passenger's delayed loss of consciousness may be explained as much by a hypertension-linked rupture of the aneurysm triggered by the emotional stress experienced, as by the traumatic shaking/impact of the aneurysm against the bony skull structures, in a subject predisposed to aneurysm frailty due to FMD. Overall, the concausal role of both the road traffic accident, typified by high kinetic energy, and the presence of a pre-existing aneurysmatic weakness due to FMD is fully recognized. The identification of anatomical variants, jointly with uncommon diseases at the examination of the brain base arteries in any case of isolated basal subarachnoid haemorrhage, may avoid wrong legal consequences even when the cause of death seems to be obviously of simple traumatic origin.


Assuntos
Acidentes de Trânsito , Aneurisma Roto/etiologia , Círculo Arterial do Cérebro , Displasia Fibromuscular/complicações , Displasia Fibromuscular/diagnóstico , Medicina Legal , Aneurisma Intracraniano/etiologia , Ferimentos e Lesões/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/patologia , Autopsia , Feminino , Displasia Fibromuscular/patologia , Humanos , Hipertensão/complicações , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/patologia , Adulto Jovem
5.
Stroke ; 51(7): 2249-2254, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32539672

RESUMO

BACKGROUND AND PURPOSE: Delayed neurological deficits are a devastating consequence of subarachnoid hemorrhage (SAH), which affects about 30% of surviving patients. Although a very serious concern, delayed deficits are understudied in experimental SAH models; it is not known whether rodents recapitulate the delayed clinical decline seen in SAH patients. We hypothesized that mice with SAH develop delayed functional deficits and that microthrombi and infarction correlate with delayed decline. METHODS: Adult C57BL/6J mice of both sexes were subjected to endovascular perforation to induce SAH. Mice were allowed to survive for up to 1 week post-ictus and behavioral performance was assessed daily. Postmortem microthrombi, large artery diameters (to assess vasospasm), and infarct volume were measured. These measures were analyzed for differences between SAH mice that developed delayed deficits and SAH mice that did not get delayed deficits. Correlation analyses were performed to identify which measures correlated with delayed neurological deficits, sex, and infarction. RESULTS: Twenty-three percent of males and 47% of females developed delayed deficits 3 to 6 days post-SAH. Female mice subjected to SAH had a significantly higher incidence of delayed deficits than male mice with SAH. Mice that developed delayed deficits had significantly more microthrombi and larger infarct volumes than SAH mice that did not get delayed deficits. Microthrombi positively correlated with infarct volume, and both microthrombi and infarction correlated with delayed functional deficits. Vasospasm did not correlate with either infarction delayed functional deficits. CONCLUSIONS: We discovered that delayed functional deficits occur in mice following SAH. Sex differences were seen in the prevalence of delayed deficits. The mechanism by which microthrombi cause delayed deficits may be via formation of infarcts.


Assuntos
Comportamento Animal , Infarto Cerebral/etiologia , Trombose Intracraniana/etiologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/patologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
6.
Nat Commun ; 11(1): 3159, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32572022

RESUMO

Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been reported to drain macromolecules and immune cells from CSF into cervical lymph nodes (CLNs). However, whether meningeal lymphatics are involved in clearing extravasated erythrocytes in CSF after SAH remains unclear. Here we show that a markedly higher number of erythrocytes are accumulated in the lymphatics of CLNs and meningeal lymphatics after SAH. When the meningeal lymphatics are depleted in a mouse model of SAH, the degree of erythrocyte aggregation in CLNs is significantly lower, while the associated neuroinflammation and the neurologic deficits are dramatically exacerbated. In addition, during SAH lymph flow is increased but without significant lymphangiogenesis and lymphangiectasia. Taken together, this work demonstrates that the meningeal lymphatics drain extravasated erythrocytes from CSF into CLNs after SAH, while suggesting that modulating this draining may offer therapeutic approaches to alleviate SAH severity.


Assuntos
Sistema Linfático/patologia , Meninges/patologia , Hemorragia Subaracnóidea/patologia , Animais , Lesões Encefálicas , Eritrócitos , Linfonodos/fisiopatologia , Linfangiogênese , Vasos Linfáticos/fisiopatologia , Masculino , Meningite/etiologia , Meningite/patologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Pescoço , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
7.
AJNR Am J Neuroradiol ; 41(6): 1015-1021, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32409315

RESUMO

BACKGROUND AND PURPOSE: In patients with SAH, the amount of blood is strongly associated with clinical outcome. However, it is commonly estimated with a coarse grading scale, potentially limiting its predictive value. Therefore, we aimed to develop and externally validate prediction models for clinical outcome, including quantified blood volumes, as candidate predictors. MATERIALS AND METHODS: Clinical and radiologic candidate predictors were included in a logistic regression model. Unfavorable outcome was defined as a modified Rankin Scale score of 4-6. An automatic hemorrhage-quantification algorithm calculated the total blood volume. Blood was manually classified as cisternal, intraventricular, or intraparenchymal. The model was selected with bootstrapped backward selection and validated with the R 2, C-statistic, and calibration plots. If total blood volume remained in the final model, its performance was compared with models including location-specific blood volumes or the modified Fisher scale. RESULTS: The total blood volume, neurologic condition, age, aneurysm size, and history of cardiovascular disease remained in the final models after selection. The externally validated predictive accuracy and discriminative power were high (R 2 = 56% ± 1.8%; mean C-statistic = 0.89 ± 0.01). The location-specific volume models showed a similar performance (R 2 = 56% ± 1%, P = .8; mean C-statistic = 0.89 ± 0.00, P = .4). The modified Fisher models were significantly less accurate (R 2 = 45% ± 3%, P < .001; mean C-statistic = 0.85 ± 0.01, P = .03). CONCLUSIONS: The total blood volume-based prediction model for clinical outcome in patients with SAH showed a high predictive accuracy, higher than a prediction model including the commonly used modified Fisher scale.


Assuntos
Algoritmos , Volume Sanguíneo , Hemorragia Subaracnóidea/patologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Estudos Retrospectivos
8.
Neurochirurgie ; 66(3): 155-161, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32387429

RESUMO

BACKGROUND: The neuropathological mechanism of heart rhythm disorders, following spinal cord pathologies, to our knowledge, has not yet been adequately investigated. In this study, the effect of the ischemic neurodegeneration of the thoracic sympathetic nuclei (TSN) on the heart rate (HR) was examined following a spinal subarachnoid hemorrhage (SSAH). METHODS: This study was conducted on 22 rabbits. Five rabbits were used as a control group, five as SHAM, and twelve as a study group. The animals' HRs were recorded via monitoring devices on the first day, and those results were accepted as baseline values. The HRs were remeasured after injecting 0.5 cc of isotonic saline for SHAM and 0.5 cc of autolog arterial blood into the thoracic spinal subarachnoid space at T4-T5 for the study group. After a three-week follow-up with continuous monitoring of their HRs, the rabbit's thoracic spinal cords and stellate ganglia were extracted. The specimens were evaluated by histopathological methods. The densities of degenerated neurons in the TSN and stellate ganglia were compared with the HRs. RESULTS: The mean HRs and mean degenerated neuron density of the TSN and stellate ganglia in control group were 251±18/min, 5±2/mm3, and 3±1/mm3, respectively. The mean HRs and the mean degenerated neuron density of the TSN and stellate ganglia were detected as 242±13/min, 6±2/mm3, and 4±2/mm3 in SHAM (P>0.05 vs. control); 176±19/min, 94±12/mm3, and 28±6/mm3 in the study group (P<0.0001 vs. control and P<0.005 vs. SHAM), respectively. CONCLUSIONS: SAH induced TSN neurodegeneration may have been responsible for low HRs following SSAH. To date this has not been mentioned in the literature.


Assuntos
Gânglios Simpáticos/irrigação sanguínea , Gânglios Simpáticos/fisiopatologia , Frequência Cardíaca , Hemorragia Subaracnóidea/fisiopatologia , Animais , Apoptose , Isquemia , Masculino , Degeneração Neural/patologia , Neurônios/patologia , Coelhos , Medula Espinal/patologia , Gânglio Estrelado/patologia , Hemorragia Subaracnóidea/patologia
9.
World Neurosurg ; 138: e913-e921, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32247799

RESUMO

OBJECTIVE: To analyze angiographic characteristics of cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH) and their potential impact on secondary infarction and functional outcome. METHODS: Demographic, clinical, and imaging data of sSAH patients with angiographic CVS admitted over a 6-year period were retrospectively analyzed. RESULTS: A total of 85 patients were included in the final analysis. A total of 311 arterial territories in 85 angiographies demonstrated angiographic CVS. The anterior cerebral artery (ACA) was the most common site of angiographic CVS (42.1%), followed by the middle cerebral artery (MCA) (26.7%). In 29 angiographies (34%) CVS was found in more than 3 vessels and a bilateral pattern was identified in 53 cases (62%). Older age (OR 3.24 [95% CI 1.30-8.07], P = 0.012) was identified as the only significant risk factor for CVS-related infarction (OR 22.67, P = 0.015). Unfavorable outcome was associated with older age (OR 3.24, P = 0.023) and poor World Federation of Neurosurgical Societies grade (OR 3.64, P = 0.015). Analyses of angiographic characteristics did not reveal any risk factors for unfavorable outcome. We identified distal CVS as a significant risk factor for CVS-related infarction (OR 2.89, P = 0.026). CONCLUSIONS: Angiographic CVS after sSAH shows a specific distribution pattern in favor of ACA and MCA and in most cases 2-3 affected vessels are affected, often bilaterally. Patients exhibiting distal CVS have a higher risk for CVS-related infarction and should be observed closely. Nonetheless, the majority of angiographic characteristics did not allow conclusions about functional outcome nor the occurrence of CVS-related infarction in sSAH patients.


Assuntos
Hemorragia Subaracnóidea/diagnóstico por imagem , Vasoespasmo Intracraniano/diagnóstico por imagem , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/patologia , Resultado do Tratamento , Vasoespasmo Intracraniano/complicações , Vasoespasmo Intracraniano/patologia
10.
BMC Neurol ; 20(1): 70, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32113481

RESUMO

BACKGROUND: In aneurysmal subarachnoid hemorrhage (SAH) and multiple intracranial aneurysms (MIAs) identification of the bleeding source cannot always be assessed according to the hemorrhage pattern. Therefore, we developed a statistical model for the prediction of the ruptured aneurysm in patients with SAH and multiple potential bleeding sources at the time of ictus. METHODS: Between 2012 and 2015, 252 patients harboring 619 aneurysms were admitted to the authors' institution. Patients were followed prospectively. Aneurysm and patient characteristics, as well as radiological findings were entered into a computerized database. Gradient boosting techniques were used to derive the statistical model for the prediction of the ruptured aneurysm. Based on the statistical prediction model, a scoring system was produced for the use in the clinical setting. The aneurysm with the highest score poses the highest possibility of being the bleeding source. The prediction score was then prospectively applied to 34 patients suffering from SAH and harboring MIAs. RESULTS: According to the statistical prediction model the main factors affecting the rupture in patients harboring multiple aneurysms were: 1) aneurysm size, 2) aneurysm location and 3) aneurysm shape. The prediction score identified correctly the ruptured aneurysm in all the patients that were used in the prospective validation. Even in the five most debatable and challenging cases assessed in the period of prospective validation, for which the score was designed for, the ruptured aneurysm was predicted correctly. CONCLUSIONS: This new and simple prediction score might provide additional support for neurovascular teams for treatment decision in SAH patients harboring multiple aneurysms. In a small prospective sample, the prediction score performed with high accuracy but larger cohorts for external validation are warranted.


Assuntos
Aneurisma Roto/patologia , Aneurisma Intracraniano/patologia , Modelos Estatísticos , Hemorragia Subaracnóidea/patologia , Adulto , Idoso , Aneurisma Roto/complicações , Feminino , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Neuroimagem , Estudos Prospectivos , Hemorragia Subaracnóidea/etiologia
11.
World Neurosurg ; 138: e579-e590, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32165343

RESUMO

BACKGROUND: The interhemispheric approach (IHA) provides an excellent surgical corridor for clipping anterior communicating artery aneurysms (AcoAAs). However, an important disadvantage of the approach is obtaining proximal control at A1 in the last stage of dissection, especially in anterior or superior projecting AcoAAs and ruptured cases. We describe and evaluate the microsurgical clipping of AcoAAs using the IHA with early A1 exposure. METHODS: This was a retrospective descriptive study in patients with AcoAA who received microsurgical clipping through the IHA with early A1 exposure between April 2016 and May 2019. Aneurysm morphology, projection, completeness of clipping, surgical complications, and outcomes were collected from medical records. RESULTS: Twenty-five patients with AcoAA received microsurgical clipping via the IHA with early A1 exposure. Twenty-three patients (92%) presented with subarachnoid hemorrhage. Intraoperative rupture while dissecting the interhemispheric fissure occurred in 2 cases, for which proximal control via subfrontal route was effectively performed. Of the patients, 100% achieved complete obliteration of their aneurysms. Postoperative anosmia was detected in 22.7%. In ruptured cases, 16 (88.9%) of the good grade patients achieved a good outcome (Glasgow Outcome Scale scores of 4 and 5) at 3 months after the operation. CONCLUSIONS: The IHA with early A1 is safe and effective for clipping AcoAAs.


Assuntos
Artéria Cerebral Anterior/cirurgia , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/patologia , Aneurisma Roto/cirurgia , Artéria Cerebral Anterior/patologia , Craniotomia , Dura-Máter/cirurgia , Feminino , Escala de Resultado de Glasgow , Humanos , Aneurisma Intracraniano/patologia , Complicações Intraoperatórias/cirurgia , Masculino , Microcirurgia , Pessoa de Meia-Idade , Transtornos do Olfato/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento
12.
World Neurosurg ; 138: e736-e742, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32200016

RESUMO

OBJECTIVE: Caffeic acid phenethyl ester (CAPE), a phenolic compound, besides being 1 of the biologically active components of propolis, is a compound with antioxidant, antiinflammatory, antiviral, reperfusion damage prevention, immune stimulant, and carcinostatic, anticancer properties. The aim of this study was to investigate the possible effects of CAPE on cerebral vasospasm and early brain injury, which were experimentally administered intraperitoneally in rats with subarachnoid hemorrhage. METHODS: Thirty-two Wistar Albino rats weighing 200 to 300 g were used in our study. The rats divided into 3 groups: the control group (n = 10), subarachnoid hemorrhage group (n = 11), and subarachnoid hemorrhage + CAPE group (n = 11). These groups were evaluated according to the Ischemia index in hippocampal CA3 regions and the morphometric analysis of basilar artery diameter after being sacrificed at the end of 72nd hour. RESULTS: A significant difference was found between group 1 and group 2 for the CA-3 region, it was concluded that early brain damage occurred after subarachnoid hemorrhage. When the neuronal damage in CA-3 region was evaluated between group 2 and group 3, a statistically significant difference was found between the groups. There was a statistically significant difference between group 1 and group 3 in terms of ischemia detection. CONCLUSIONS: It was shown that CAPE has a preventive effect on early brain injury after subarachnoid hemorrhage and has a positive effect on reducing cerebral vasospasm. Our study is the first study in the literature showing that CAPE inhibits ischemic brain injury following subarachnoid hemorrhage.


Assuntos
Região CA3 Hipocampal/efeitos dos fármacos , Ácidos Cafeicos/administração & dosagem , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Álcool Feniletílico/análogos & derivados , Hemorragia Subaracnóidea/patologia , Vasoespasmo Intracraniano/patologia , Animais , Região CA3 Hipocampal/patologia , Modelos Animais de Doenças , Neurônios/patologia , Álcool Feniletílico/administração & dosagem , Própole , Ratos Wistar
13.
PLoS One ; 15(2): e0227349, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32097426

RESUMO

OBJECTIVE: The amount of extravasated blood is an established surrogate marker for subarachnoid hemorrhage (SAH) severity, which varies in different experimental SAH (eSAH) models. A comprehensive eSAH grading system would allow a more reliable correlation of outcome parameters with SAH severity. The aim of this study was to define a severity score for eSAH related to the Fisher-Score in humans. MATERIAL AND METHODS: SAH was induced in 135 male rats using the modified double hemorrhage model. A sham group included 8 rats, in which saline solution instead of blood was injected. Histological analysis with HE(hematoxylin-eosin)-staining for the visualization of blood was performed in all rats on day 5. The amount and distribution of blood within the subarachnoid space and ventricles (IVH) was analyzed. RESULTS: The mortality rate was 49.6% (71/143). In all except five SAH rats, blood was visible within the subarachnoid space. As expected, no blood was detected in the sham group. The following eSAH severity score was established (ESAS-score): grade I: no SAH visible; grade II: local or diffuse thin SAH, no IVH; grade III: diffuse / thick layers of blood, no IVH; grade IV: additional IVH. Grade I was seen in five rats (7.9%), grade II in 28.6% (18/63), grade III in 41.3% (26/63) and grade IV in 22.2% (14/63) of the rats with eSAH. CONCLUSION: The double hemorrhage model allows the induction of a high grade SAH in more than 60% of the rats, making it suitable for the evaluation of outcome parameters in severe SAH.


Assuntos
Ventrículos Cerebrais/patologia , Hemorragia Subaracnóidea/patologia , Espaço Subaracnóideo/patologia , Animais , Modelos Animais de Doenças , Masculino , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/sangue
14.
Neurology ; 94(12): e1281-e1293, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32107323

RESUMO

OBJECTIVE: To determine if CSF and plasma levels of soluble vascular endothelial (sVE)-cadherin are associated with functional outcome after subarachnoid hemorrhage (SAH) and to investigate sVE-cadherin effects on microglia. METHODS: Serial CSF and plasma were collected from prospectively enrolled patients with nontraumatic SAH from a ruptured aneurysm in the anterior circulation and who required an external ventricular drain for clinical indications. Patients with normal-pressure hydrocephalus without SAH served as controls. For prospective assessment of long-term outcomes at 3 and 6 months after SAH, modified Rankin Scale scores (mRS) were obtained and dichotomized into good (mRS ≤ 2) vs poor (mRS > 2) outcome groups. For SAH severity, Hunt and Hess grade was assessed. Association of CSF sVE-cadherin levels with long-term outcomes, HH grade, and CSF tumor necrosis factor (TNF)-α levels were evaluated. sVE-cadherin effects on microglia were also studied. RESULTS: sVE-cadherin levels in CSF, but not in plasma, were higher in patients with SAH and were associated with higher clinical severity and higher CSF TNF-α levels. Patients with SAH with higher CSF sVE-cadherin levels over time were more likely to develop worse functional outcome at 3 months after SAH. Incubation of cultured microglia with sVE-cadherin resulted in increased inducible nitric oxide synthase, interleukin-1ß, reactive oxygen species, cell soma size, and metabolic activity, consistent with microglia activation. Microinjection of sVE-cadherin fragments into mouse brain results in an increased number of microglia surrounding the injection site, compared to injection of denatured vascular endothelial-cadherin fragments. CONCLUSIONS: These results support the existence of a novel pathway by which sVE-cadherin, released from injured endothelium after SAH, can shift microglia into a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in SAH.


Assuntos
Antígenos CD/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Caderinas/líquido cefalorraquidiano , Microglia/metabolismo , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/farmacologia , Caderinas/farmacologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Pessoa de Meia-Idade , Prognóstico , Recuperação de Função Fisiológica/fisiologia , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/patologia , Adulto Jovem
15.
World Neurosurg ; 138: e251-e259, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32105867

RESUMO

BACKGROUND: Intracranial bypass to treat ruptured aneurysms has been well described in the literature but is largely deferred in patients with higher Hunt and Hess (H & H) grades due to complexity and length of surgery, risk of inducing vasospasm, and poor prognosis. However, there is a paucity of data and no direct comparison with more traditional open surgical techniques. This study investigated outcomes in patients with H & H grade 3-5 aneurysmal subarachnoid hemorrhage (aSAH) unfavorable for stand-alone endovascular treatment managed with bypass compared with direct surgical clipping. METHODS: A prospective database of patients treated for aSAH with H & H grade 3-5 between 2013 and 2018 was retrospectively analyzed. Complications and functional status at discharge and latest follow-up were compared between patients who underwent bypass surgery versus direct clipping. RESULTS: Twenty-three patients underwent revascularization, and 60 underwent clipping alone. There were no significant differences in all-cause 30-day mortality (15% vs. 16%; P = 0.97) or Glasgow Outcome Scale and modified Rankin Scale at discharge or median 8-month follow-up (P > 0.67). There was a higher overall stroke rate with revascularization (P = 0.004), specifically endovascular treatment-related stroke (P = 0.049), with no difference in surgical (P = 0.47) or vasospasm-related stroke (P = 0.53). There were no differences in overall complications, medical complications, seizures, reruptures, hydrocephalus, or perioperative death (P > 0.05). CONCLUSIONS: Bypass is a viable option for patients presenting with higher H & H grade aSAH deemed unfavorable for stand-alone endovascular therapy. Despite obvious differences in aneurysm complexity and a higher risk of stroke, functional outcomes with revascularization can be comparable with clipping in this high-risk patient cohort.


Assuntos
Revascularização Cerebral/métodos , Procedimentos Endovasculares/métodos , Hemorragia Subaracnóidea/cirurgia , Adulto , Idoso , Revascularização Cerebral/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Hemorragia Subaracnóidea/patologia , Instrumentos Cirúrgicos , Resultado do Tratamento
16.
Acta Neurochir (Wien) ; 162(3): 545-552, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31915942

RESUMO

BACKGROUND: Myelin basic protein (MBP) is the second most abundant protein in central nervous system myelin. Since the 1980s, it has been regarded as a marker of brain tissue injury in both trauma and disease. There have been no recent reports regarding MBP in aneurysmal subarachnoid haemorrhage (SAH). METHODS: One hundred four SAH patients with ruptured aneurysms underwent endovascular treatment within 24 h of rupture, and 156 blood samples were collected: 104 on days 0-3, 32 on days 4-6 and 20 on days 9-12 post-SAH. MBP levels were assayed using ELISA and compared with the clinical status on admission, laboratory results, imaging findings and treatment outcome at 3 months. RESULTS: MBP levels on days 0-3 post-SAH were significantly higher among poor outcome patients (p < 0.001), non-survivors (p = 0.005), patients who underwent intracranial intervention (p < 0.001) and patients with intracerebral haemorrhage (ICH; p < 0.001). On days 4-6 post-SAH, significantly higher levels were found following intracranial intervention (p = 0.009) and ICH (p = 0.039). There was clinically relevant correlation between MBP levels on days 0-3 post-SAH and 3-month Glasgow Outcome Scale (cc = - 0.42) and also ICH volume (cc = 0.48). All patients who made a full recovery had MBP levels below detection limit on days 0-3 post-SAH. Following endovascular aneurysm occlusion, there was no increase in MBP in 86 of the 104 patients investigated (83%). CONCLUSIONS: The concentration of MBP in peripheral blood after intracranial aneurysm rupture reflects the severity of the brain tissue injury (due to surgery or ICH) and correlates with the treatment outcome. Endovascular aneurysm occlusion was not followed by a rise in MBP in most cases, suggesting the safety of this technique.


Assuntos
Aneurisma Roto/sangue , Encéfalo/patologia , Proteína Básica da Mielina/sangue , Hemorragia Subaracnóidea/sangue , Adulto , Idoso , Aneurisma Roto/patologia , Aneurisma Roto/cirurgia , Biomarcadores/sangue , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Feminino , Escala de Resultado de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/cirurgia
17.
Am J Trop Med Hyg ; 102(3): 574-577, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31933459

RESUMO

Human infection with the trematode Fasciola occurs with a worldwide prevalence of up to 17 million. Sheep and cattle are the normal host. Infection typically results in hepatobiliary disease, but extrahepatic manifestations are occasionally reported. Here, we present the case of a previously healthy 31-year-old Kurdish woman, admitted to hospital with a subarachnoid hemorrhage, eosinophilic meningitis, and lung and liver disease. A diagnosis of Fasciola infection was made based on strongly positive serology in blood and cerebrospinal fluid. The patient improved following treatment with triclabendazole and prednisolone.


Assuntos
Fasciolíase/complicações , Fasciolíase/patologia , Meningite/parasitologia , Hemorragia Subaracnóidea/parasitologia , Adulto , Anticorpos Anti-Helmínticos/sangue , Fasciolíase/tratamento farmacológico , Feminino , Humanos , Imunoglobulina G/sangue , Meningite/diagnóstico , Meningite/patologia , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/patologia , Triclabendazol/uso terapêutico
18.
J Neuroinflammation ; 17(1): 16, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31926558

RESUMO

OBJECTIVE: The potential roles and mechanisms of pericytes in maintaining blood-brain barrier (BBB) integrity, which would be helpful for the development of therapeutic strategies for subarachnoid hemorrhage (SAH), remain unclear. We sought to provide evidence on the potential role of pericytes in BBB disruption and possible involvement and mechanism of CypA signaling in both cultured pericytes and SAH models. METHODS: Three hundred fifty-three adult male C57B6J mice weighing 22 to 30 g, 29 CypA-/- mice, 30 CypA+/+ (flox/flox) mice, and 30 male neonatal C57B6J mice were used to investigate the time course of CypA expression in pericytes after SAH, the intrinsic function and mechanism of CypA in pericytes, and whether the known receptor CD147 mediates these effects. RESULTS: Our data demonstrated both intracellular CypA and CypA secretion increased after SAH and could activate CD147 receptor and downstream NF-κB pathway to induce MMP9 expression and proteolytic functions for degradation of endothelium tight junction proteins and basal membranes. CypA served as autocrine or paracrine ligand for its receptor, CD147. Although CypA could be endocytosed by pericytes, specific endocytosis inhibitor chlorpromazine did not have any effect on MMP9 activation. However, specific knockdown of CD147 could reverse the harmful effects of CypA expression in pericytes on the BBB integrity after SAH. CONCLUSIONS: This study demonstrated for the first time that CypA mediated the harmful effects of pericytes on BBB disruption after SAH, which potentially mediated by CD147/NF-κB/MMP9 signal, and junction protein degradation in the brain. By targeting CypA and pericytes, this study may provide new insights on the management of SAH patients.


Assuntos
Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Ciclofilina A/metabolismo , Pericitos/metabolismo , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/patologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/fisiologia
19.
Cerebrovasc Dis ; 49(1): 79-87, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940632

RESUMO

BACKGROUND: Emerging evidence indicates a beneficial effect of mesenchymal stem cell (MSC) transplantation in subarachnoid hemorrhage (SAH). Chronic hydrocephalus is a common complication after SAH, which is associated with subarachnoid fibrosis promoted by transforming growth factor-ß1 (TGF-ß1). This study investigated the effect of human umbilical cord derived MSCs (hUC-MSCs) with TGF-ß1 knockdown on chronic hydrocephalus after SAH. METHODS: About 0.5 mL autologous blood was injected into the cerebellomedullaris cistern of 6-week SD rats to establish SAH model. hUC-MSCs or hUC-MSCs carrying TGF-ß1 knockdown (1 × 105 cells) were intraventricularly transplanted at 1 day before surgery and at P10. Neurological behavior score and water maze test were performed to assess neurological functions. Hydrocephalus was evaluated by Nissl staining. Concentrations of proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. The levels of TGF-ß1, p-Smad2/3, and Smad2/3 were measured using western blotting. RESULTS: Intraventricular hUC-MSCs transplantation significantly attenuated SAH-induced chronic hydrocephalus, upregulation of inflammatory cytokines, and behavioral impairment. Knockdown of TGF-ß1 in hUC-MSCs enhanced these effects. hUC-MSCs also reduced the upregulation of TGF-ß1 levels and Smad2/3 phosphorylation after SAH, and this effect was also enhanced by TGF-ß1 knockdown. CONCLUSION: Transplantation of hUC-MSCs exerts beneficial effect after SAH, possibly be through inhibiting TGF-ß1/Smad2/3 signaling pathway. Knockdown of TGF-ß1 in hUC-MSCs enhanced these effects.


Assuntos
Encéfalo/cirurgia , Hidrocefalia/prevenção & controle , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Hemorragia Subaracnóidea/cirurgia , Fator de Crescimento Transformador beta1/metabolismo , Cordão Umbilical/citologia , Animais , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Células Cultivadas , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Hidrocefalia/metabolismo , Hidrocefalia/patologia , Hidrocefalia/fisiopatologia , Masculino , Atividade Motora , Fosforilação , Ratos Sprague-Dawley , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/fisiopatologia , Fator de Crescimento Transformador beta1/genética
20.
Acta Neurochir (Wien) ; 162(3): 533-544, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31980948

RESUMO

BACKGROUND: Outcome of early, aggressive management of aneurysmal subarachnoid hemorrhage (aSAH) in patients with Hunt and Hess grade V is hitherto limited, and we therefore present our results. METHODS: Retrospective study analyzing the medical data of 228 aSAH patients in Glasgow Coma Score 3-5 admitted to our hospital during the years 2002-2012. Background and treatment variables were registered. Outcome was evaluated after 3 and 12 months. RESULTS: We intended to treat 176 (77.2%) patients, but only 146 went on to aneurysm repair. Of 52 patients managed conservatively, 27 had abolished cerebral circulation around arrival and 25 were deemed unsalvageable. One-year overall mortality was 65.8% and most (84.7%) of the fatalities occurred within 30 days. One-year mortality was higher in patients > 70 years. Without aneurysm repair, mortality was 100%. After 1 year, 21.9% of all patients lived independently and 4.8% lived permanently in an institution. Outcome in the 78 survivors (34.2%) was favorable in 64.1% in terms of modified Rankin Scale score 0-2, and 85.9% of survivors were able to live at home. Return to work was low for all 228 patients with 14.0% of those employed prior to the hemorrhage having returned to paid work, and respectively, 26.3% in the subgroup of survivors. CONCLUSIONS: Even with aggressive, early treatment, 1-year mortality is high in comatose aSAH patients with 65.8%. A substantial portion of the survivors have a favorable outcome at 1 year (64.1%, corresponding to 21.9% of all patients admitted) and 85.9% of the survivors could live at home alone or aided.


Assuntos
Aneurisma Intracraniano/mortalidade , Hemorragia Subaracnóidea/mortalidade , Adulto , Idoso , Feminino , Escala de Coma de Glasgow , Humanos , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/cirurgia , Análise de Sobrevida , Resultado do Tratamento
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