RESUMO
Sepsis is life-threatening organ dysfunction due to dysregulated systemic inflammatory and immune response to infection, often leading to cognitive impairments. Growing evidence shows that artemisinin, an antimalarial drug, possesses potent anti-inflammatory and immunoregulatory activities. In this study we investigated whether artemisinin exerted protective effect against neurocognitive deficits associated with sepsis and explored the underlying mechanisms. Mice were injected with LPS (750 µg · kg-1 · d-1, ip, for 7 days) to establish an animal model of sepsis. Artemisinin (30 mg · kg-1 · d-1, ip) was administered starting 4 days prior LPS injection and lasting to the end of LPS injection. We showed that artemisinin administration significantly improved LPS-induced cognitive impairments assessed in Morris water maze and Y maze tests, attenuated neuronal damage and microglial activation in the hippocampus. In BV2 microglial cells treated with LPS (100 ng/mL), pre-application of artemisinin (40 µΜ) significantly reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-6) and suppressed microglial migration. Furthermore, we revealed that artemisinin significantly suppressed the nuclear translocation of NF-κB and the expression of proinflammatory cytokines by activating the AMPKα1 pathway; knockdown of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin in BV2 microglial cells. In conclusion, atemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect is probably mediated by activation of the AMPKα1 signaling pathway in microglia.
Assuntos
Artemisininas/uso terapêutico , Microglia/efeitos dos fármacos , Transtornos Neurocognitivos/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Sepse/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/metabolismo , Neurônios/efeitos dos fármacos , Sepse/induzido quimicamente , Sepse/complicações , Sepse/metabolismoRESUMO
Recent studies demonstrated that FoxO3 circular RNA (circFoxO3) plays an important regulatory role in tumourigenesis and cardiomyopathy. However, the role of circFoxO3 in neurodegenerative diseases remains unknown. The aim of this study was to examine the possible role of circFoxO3 in neurodegenerative diseases and the underlying mechanisms. To model human neurodegenerative conditions, hippocampus-derived neurons were treated with glutamate. Using molecular and cellular biology approaches, we found that circFoxO3 expression was significantly higher in the glutamate treatment group than that in the control group. Furthermore, silencing of circFoxO3 protected HT22 cells from glutamate-induced oxidative injury through the inhibition of the mitochondrial apoptotic pathway. Collectively, our study demonstrates that endogenous circFoxO3 plays a key role in inducing apoptosis and neuronal cell death and may act as a novel therapeutic target for neurodegenerative diseases.
Assuntos
Apoptose/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Hipocampo/metabolismo , Mitocôndrias/metabolismo , RNA Circular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteína Forkhead Box O3/genética , Ácido Glutâmico/metabolismo , Camundongos , Mitocôndrias/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Background and Purpose: Oxidative stress is involved in the development of infections. However, whether oxidative stress indicators can be used as markers of stroke-associated infection (SAI) is still unclear. The purpose of this study was to test the predictive values of superoxide dismutase (SOD) and malondialdehyde (MDA) levels for SAI incidence.Methods: A total of 45 consecutive patients with ischemic stroke who were admitted to our hospital were enrolled. A prospective study was carried out to observe the occurrence of SAI during the first 7 days after stroke. Accordingly, the patients were divided into SAI and non-SAI groups. The relationship between SOD and MDA serum levels and SAI was analyzed.Results: The patients in the SAI group had significantly higher serum SOD levels than those in the non-SAI group (41.638 ± 3.428 U/ml vs. 36.542 ± 9.114 U/ml, p = 0.033). However, there were no significant differences in MDA levels between the SAI and non-SAI group (p > 0.05). The discriminating ability of serum SOD level for SAI was measured using an ROC curve. Serum level of SOD >38.16 U/ml was useful in diagnosing SAI with a sensitivity of 88% and a specificity of 61%. Kaplan-Meier curves showed that the group with serum SOD level >38.16 U/ml had higher rates of SAI incidence (χ2 = 9.688, p = 0.002; log rank test). Furthermore, Cox regression analysis indicated that a serum SOD level >38.16 U/ml was an independent risk factor for SAI (hazard ratio = 5.836; 95% CI, 1.298-26.244; p = 0.021).Conclusions: Acute-phase serum SOD level could be a predictor of SAI.
Assuntos
Isquemia Encefálica/sangue , Infecções/sangue , Infecções/diagnóstico , Inflamação/sangue , Estresse Oxidativo , Acidente Vascular Cerebral/sangue , Superóxido Dismutase/sangue , Idoso , Biomarcadores/sangue , Isquemia Encefálica/complicações , Feminino , Humanos , Infecções/etiologia , Inflamação/etiologia , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Estudos Prospectivos , Sensibilidade e Especificidade , Acidente Vascular Cerebral/complicaçõesRESUMO
Cerebral infarction (CI) is a common clinical cerebrovascular disease, and to explore the pathophysiological mechanisms and seek effective treatment means are the hotspot and difficult point in medical research nowadays. Numerous studies have confirmed that uric acid plays an important role in CI, but the mechanism has not yet been clarified. When treating HT22 and BV-2 cells with different concentrations of uric acid, uric acid below 450 µM does not have significant effect on cell viability, but uric acid more than 500 µM can significantly inhibit cell viability. After establishing models of OGD (oxygen-glucose deprivation) with HT22 and BV-2 cells, uric acid at a low concentration (50 µM) cannot improve cell viability and apoptosis, and Reactive oxygen species (ROS) levels during OGD/reoxygenation; a suitable concentration (300 µM) of uric acid can significantly improve cell viability and apoptosis, and reduce ROS production during OGD/reoxygenation; but a high concentration (1000 µM) of uric acid can further reduce cell viability and enhance ROS production. After establishing middle cerebral artery occlusion of male rats with suture method, damage and increase of ROS production in brain tissue could be seen, and after adding suitable concentration of uric acid, the degree of brain damage and ROS production was reduced. Therefore, different concentrations of uric acid should have different effect, and suitable concentrations of uric acid have neuroprotective effect, and this finding may provide guidance for study on the clinical curative effect of uric acid.
Assuntos
Apoptose/efeitos dos fármacos , Isquemia Encefálica/patologia , Glucose/deficiência , Oxigênio/química , Traumatismo por Reperfusão/patologia , Ácido Úrico/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/patologia , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Several prior studies have linked serum prealbumin (PA) as a predictor for perioperative infection. However, whether peripheral blood PA levels can be used as an indicator of stroke-associated infection (SAI) is still unclear. In this study, we attempt to find whether serum PA is a meaningful predictor in SAI after an ischemic stroke, so as to provide theoretical basis for clinical treatment. METHODS: Consecutive patients with acute ischemic stroke who were admitted to our hospital were enrolled and serum PA was collected. A prospective study was conducted to observe the predictive value of PA in the SAI incident in ischemic stroke patients. RESULTS: Of 104 patients, 29 (27.9%) developed an SAI after 7 d of follow-up. The stroke with SAI group had significantly lower PA levels than the stroke without SAI group ( p < 0.05). The optimal cutoff value for predicting SAI was PA ≤ 191 mg/L, with sensitivity and specificity of 58.62% and 81.33%, respectively. Kaplan-Meier survival analysis showed that stroke patients with low serum PA level (PA ≤ 191 mg/L) had a higher SAI rates (log-rank test, χ2 = 16.870, p < 0.001). Cox regression analysis showed that PA ≤ 191 mg/L (hazard ratio = 3.207; 95% CI, 1.430-7.190, p = 0.005) was an independent risk factor for SAI. CONCLUSIONS: Early detection of serum PA during the acute phase of ischemic stroke may help us to identify at-risk SAI patients, and hence rapidly guide the intervention to prevent SAI.
Assuntos
Isquemia Encefálica/sangue , Infecções/sangue , Pré-Albumina/metabolismo , Acidente Vascular Cerebral/sangue , Idoso , Biomarcadores/sangue , Isquemia Encefálica/complicações , Feminino , Humanos , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND AND PURPOSE: Detecting cardioembolic stroke soon after acute cerebral ischemia has a major impact on secondary stroke prevention. Recently, the Score for the Targeting of Atrial Fibrillation (STAF) was introduced to identify stroke patients at risk of atrial fibrillation. However, whether the STAF score could be a useful approach to differentiate cardioembolic stroke from other stroke subtypes is unclear. METHODS: Consecutive patients with acute ischemic stroke that were admitted to our stroke center were enrolled. Each patient was assessed (age, baseline National Institutes of Health Stroke Scale, left atrial dilatation and absence of vascular etiology) to calculate the STAF score. A follow-up visit was conducted for each patient during hospitalization to determine the diagnosed stroke etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. RESULTS: The median and interquartile range of the STAF score was significantly higher in the cardioembolic than in the non-cardioembolic group [6 (2) vs. 2 (3), p < 0.001]. The discriminating ability of the STAF score model was good as demonstrated by the receiver operating characteristic curve. The area under the curve (AUC) of STAF score (AUC = 0.98; 95% CI, 0.96-0.99) was significantly greater than B-type natriuretic peptide (AUC = 0.87; 95% CI, 0.83-0.91) (p < 0.05). The optimal STAF cut-off value was ≥ 5, which diagnosed cardioembolic stroke with a sensitivity of 90% and specificity of 95%. CONCLUSIONS: The STAF score is a simple and accurate tool that can discriminate the cardioembolic stroke from other types during hospitalization for acute ischemic stroke.
Assuntos
Embolia Intracraniana/complicações , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos de Coortes , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNA-gene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up-regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy.
Assuntos
Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Neurônios/metabolismo , Neurônios/patologia , RNA/genética , RNA/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Camundongos , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Circular , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
OBJECTIVE: To analyze changes in magnetic resonance imaging (MRI) of spinal cord lesions in neuromyelitis optica (NMO) and the correlation between segmental length of spinal cord lesions and expanded disability status scale (EDSS) scores. METHODS: Twenty-five patients with confirmed NMO were examined from the Second Affiliated Hospital of Guangzhou Medical University, China. The information collected included their treatment, MRI, laboratory tests, and EDSS scores at different stages. RESULTS: All cases exhibited spinal cord lesions, with 23 (92%) having longitudinally extensive transverse myelitis (extending ≥3 vertebral segments). There was a positive correlation between segmental length of spinal cord lesions and EDSS scores: during the acute phase, r = 0.430 (P = 0.032); during remission, r = 0.605 (P = 0.002). Enlarged spinal cord lesions and swelling were found in 18 cases (72%) during the acute phase, and 4 cases (16%, P = 0.000) after 6 months of treatment. Lesion enhancements were found in 17 cases (68%) during the acute phase, and 8 cases (32%, P = 0.023) after 6 months of treatment. Leptomeningeal enhancement was found in three cases during the acute phase, which disappeared after treatment. Atrophy of spinal cord lesions occurred in two cases. Change in lesions was statistically significant (P = 0.006) after 12 months of treatment. CONCLUSION: Positive correlation was found between segmental length of spinal cord lesions and EDSS scores, which was more significant during remission. After 6 months of regular treatment, restorative changes compared with the acute phase were found by MRI.
Assuntos
Mielite Transversa/patologia , Neuromielite Óptica/patologia , Medula Espinal/patologia , Adulto , Atrofia/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Accumulation of glutamate damages neurons via the reactive oxygen species (ROS) injury, which was involved in the development of neurodegenerative diseases. However, the mechanism of neuronal oxidative stress damage caused by glutamate and the intervention targets still needs to be further studied. This study explored whether 5' adenosine monophosphate-activated protein kinase (AMPK)-induced glucose metabolic and mitochondrial dysfunction were related to glutamate-dependent ROS injury of the neuron. METHODS: Neuronal oxidative stress injury was induced by glutamate treatment in HT-22 cells. Western blotting was used to evaluate the phosphorylation of the AMPK. The XF24 Flux Analyzer was used to measure the effect of glutamate and Compound C (a well-known pharmacological inhibitor of AMPK phosphorylation) on the cellular oxygen consumption rate (OCR) of HT-22 cells. Glucose uptake, intracellular ROS, mitochondrial potential, apoptosis and cell viability were quantified using biochemical assays. RESULTS: Glutamate caused the phosphorylation of AMPK and subsequently promoted the glucose uptake. Furthermore, AMPK-mediated glucose uptake enhanced OCR and increased the intracellular ROS levels in neurons. The pharmacological inhibition of AMPK phosphorylation by Compound C attenuated glutamate-induced toxicity in HT22 cells by regulating the glucose uptake/mitochondrial respiration/ROS pathway. CONCLUSIONS: The AMPK phosphorylation/glucose uptake/mitochondrial respiration/ROS pathway was involved in glutamate-induced excitotoxic injury in HT22 cells. The inhibition of AMPK phosphorylation may be a potential target for the development of therapeutic agents for treating the glutamate-induced neurotoxicity.
Assuntos
Ácido Glutâmico , Fármacos Neuroprotetores , Espécies Reativas de Oxigênio/metabolismo , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Apoptose , Mitocôndrias/metabolismo , Glucose/metabolismoRESUMO
BACKGROUND: Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. METHODS: We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. RESULTS: Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. CONCLUSION: Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.
Assuntos
Encefalopatia Associada a Sepse , Camundongos , Animais , Encefalopatia Associada a Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Microglia , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismoRESUMO
Artemisinin is an anti-malarial drug that has been in use for almost half century. Recently, novel biological effects of artemisinin on cancer, inflammation-related disorders and cardiovascular disease were reported. However, neuroprotective actions of artemisinin against glutamate-induced oxidative stress have not been investigated. In the current study, we determined the effect of artemisinin against oxidative insult in HT-22 mouse hippocampal cell line. We found that pretreatment of artemisinin declined reactive oxygen species (ROS) production, attenuated the collapse of mitochondrial membrane potential induced by glutamate and rescued HT-22 cells from glutamate-induced cell death. Furthermore, our study demonstrated that artemisinin activated Akt/Bcl-2 signaling and that neuroprotective effect of artemisinin was blocked by Akt-specific inhibitor, MK2206. Taken together, our study indicated that artemisinin prevented neuronal HT-22 cell from glutamate-induced oxidative injury by activation of Akt signaling pathway.
RESUMO
Cerebral ischemia-reperfusion injury (IRI) has a complex pathogenesis, and interleukin-17 (IL-17) is a newly identified class of the cytokine family that plays an important role in ischemic inflammation. An oxygen-glucose deprivation (OGD) model showed that IL-17A expression was significantly up-regulated in microglial cells. After IL-17A siRNA transfection, the inhibition of proliferation, and the increased apoptosis in microglial cells, induced by OGD/reperfusion, was improved, and the elevation of Caspase-3, Caspase-8, Caspase-9, and poly ADP ribose polymerase (PARP) activities was inhibited. Mass spectrometry demonstrated that IL-17A functioned through a series of factors associated with oxidative stress and apoptosis and regulated Caspase-3 activity and apoptosis in microglial cells via the p53 and PI3K/Akt signaling pathways. IL-17A, HMGB1, and ROS were regulated mutually to exhibit a synergistic effect in the OGD model of microglial cells, but the down-regulation of IL-17A or HMGB1 expression did not completely inhibit the production of ROS. These findings demonstrated that ROS might be located upstream of IL-17A and HMGB1 so that ROS can regulate HMGB1/IL-17A expression to affect the p53 and PI3K/Akt signaling pathways and therefore promote the occurrence of apoptosis in microglial cells. These findings provide a novel evidence for the role of IL-17A in ischemic cerebral diseases.
RESUMO
BACKGROUND: Increasing levels of microRNA (miRNA)-21 can lead to IFN-γ deficiency, thereby suppressing immune function. Whether changes in the peripheral blood expression of miRNA-21 in patients with acute stroke are related to stroke-associated infection (SAI) remains unsettled. METHODS: MiRNA-21 and IFN-γ expression levels in peripheral blood plasma were measured in stroke patients presenting within 24h of symptom onset to assess whether these expression levels are associated with the prevalence of SAI. RESULTS: The stroke with SAI group had significantly higher miRNA-21 expression and lower IFN-γ levels than the stroke without SAI group (p<0.05). A significant negative correlation was observed between miRNA-21 expression and IFN-γ levels (r=-0.303, p=0.026). ROC curves were constructed to measure the performance of the miRNA-21 and IFN-γ to judge SAI. The areas under the ROC curve (AUC) for miRNA-21 and IFN-γ were 0.667 (95% CI, 0.525 to 0.798, p=0.028) and 0.698 (95% CI, 0.558 to 0.816, p=0.005), respectively. The optimal cutoff value was miRNA-21>0.53 and IFN-γ≤72.57pg/ml. There was a significantly different prevalence of SAI between the high miRNA-21 group and the low miRNA-21 group (p=0.008, log rank test). There was also a significant difference between the high IFN-γ group and the low IFN-γ group (p=0.003, log rank test). CONCLUSIONS: Plasma up-regulated miRNA-21 and decreased IFN-γ in acute stroke can be considered new biological predictors for SAI and thus, new therapeutic targets.
Assuntos
Infecções/sangue , Infecções/complicações , Interferon gama/sangue , MicroRNAs/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Idoso , Área Sob a Curva , Biomarcadores/sangue , Análise Química do Sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Infecções/epidemiologia , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Curva ROC , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologiaRESUMO
BACKGROUND: Previous studies have reported that statins can prevent infections, and these findings were ascribed to the anti-inflammatory and immunomodulatory properties of statins. However, the effects of statins on the risk of infection after stroke or transient ischemic attack (TIA) remain controversial. The aim of this study was to evaluate the relationship between statins and the risk of infection after stroke or TIA by means of a meta-analysis. METHODOLOGY AND FINDINGS: Studies were found by searching major electronic databases using key terms and restricting the results to studies published in English language and human studies. Pooled odds ratio (OR) for the association between infection and statins were analyzed using Stata software. A total of five studies that included 8,791 stroke or TIA patients (3,269 patients in the statin use group and 5,522 in the placebo group) were eligible and abstracted. Pooled analysis demonstrated that statins did not significantly affect the incidence of infection after stroke or TIA compared with a placebo (OR 0.819, 95% CI 0.582-1.151, I2 = 64.2%, p= 0.025). Sensitivity analyses showed that the removal of any single study did not significantly affect the pooled OR. Cumulative meta-analysis showed that the incidence of infection did not vary by publication year. No statistical evidence of publication bias was found among the studies selected, based on the results of Egger's (p = 1.000) and Begg's (p = 0.762) tests. CONCLUSIONS: This meta-analysis does not support the hypothesis that statins reduce the risk of infections in stroke or TIA patients.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infecções/tratamento farmacológico , Ataque Isquêmico Transitório/patologia , Acidente Vascular Cerebral/patologia , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Humanos , Infecções/complicações , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/metabolismo , Razão de Chances , Efeito Placebo , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismoRESUMO
BACKGROUND: Previous studies have reported that the total bilirubin (TB) level is associated with coronary artery disease, heart failure and atrial fibrillation. These heart diseases can produce cardiogenic cerebral embolism and cause cardioembolic stroke. However, whether the serum TB could be a biomarker to differentiate cardioembolic stroke from other stroke subtypes is unclear. METHODS: Our study consisted of 628 consecutive patients with ischaemic stroke. Various clinical and laboratory variables of the patients were analysed according to serum TB quartiles and stroke subtypes. RESULTS: The higher TB quartile group was associated with atrial fibrillation, larger left atrium diameter, lower left ventricular fractional shortening and cardioembolic stroke (P < 0.001, P = 0.001, P = 0.033, P < 0.001, respectively). Furthermore, serum TB was a statistically significant independent predictor of cardioembolic stroke in a multivariable setting (Continuous, per unit increase OR = 1.091, 95%CI: 1.023-1.164, P = 0.008). CONCLUSIONS: Serum TB level was independently associated with cardioembolic stroke. The combination of clinical data and serum TB may be a feasible strategy to diagnose cardioembolic stroke in the acute phase.