RESUMEN
OBJECTIVE: The present research aimed to explore the dynamic change of the neutrophil-to-lymphocyte ratio (NLR) and its relationship with functional outcome following an acute ischemic stroke (AIS), whether receiving intravenous thrombolysis (IVT) or not. METHODS: We retrospectively analyzed data that were prospectively acquired from patients with AIS treated with IVT or not. For patients receiving IVT, the NLR was based on a blood test performed prior to IVT (d0) and at different time points after disease onset (d1, d3, d7). In addition, in the non-IVT group, the NLR was obtained at different time points after disease onset (d1, d3, d7). Follow-ups were performed 3 months after onset via telephone. In addition, a good outcome was defined as a modified Rankin scale (mRS) ≤1; a poor outcome means 2 ≤ mRS ≤ 6. RESULTS: A total of 204 AIS patients were included in this study. The NLR presented a dynamic change as it increased to its peak at day 1 and gradually declined to its baseline at day 7, no matter whether patients were receiving IVT or not. Patients with poor outcomes have a higher NLR at various time points. The results of multivariate logistic regression analysis demonstrated that the National Institutes of Health Stroke Scale (NIHSS), NLR d1, NLR d3, and NLR d7 were independently associated with functional outcomes. The area under the receiver operating characteristic curve of NLR in predicting outcomes was as follows: NLR d3 demonstrated robust predictive power within the IVT therapy cohort, whereas NLR d7 was predictive in the non-IVT cohort. However, the most potent predictor emerged as the combination of NIHSS and NLR. CONCLUSION: NLR has the potential to predicate diagnosis for AIS, especially when combined with the NIHSS score.
Asunto(s)
Accidente Cerebrovascular Isquémico , Linfocitos , Neutrófilos , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/diagnóstico , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Terapia Trombolítica , Valor Predictivo de las Pruebas , Anciano de 80 o más AñosRESUMEN
Hemorrhagic transformation (HT) is one of the most dangerous complications after intravenous thrombolysis in patients with acute ischemic stroke (AIS). Therefore, we want to explore the predictive effects of peripheral blood S100ß and C-Reactive Protein (CRP) levels on hemorrhagic transformation after intravenous thrombolysis in AIS patients. Ninety-two AIS patients who had been treated in Huai'an Second People's Hospital from January 2018 to December 2021 were retrospectively selected. Patients were divided into hemorrhagic transformation (HT) groups (24 cases) and no HT groups (68 cases) based on whether there was hemorrhagic transformation within 24 h after intravenous thrombolysis. General clinical data from the HT group and no HT group were compared. A multivariate logistic regression model was used to analyze the potential risk factors of HT after intravenous thrombolysis in patients with AIS. A receiver operating curve (ROC) was used to analyze the predictive value of risk factors for HT. High serum S100ß, CRP levels, and National Institutes of Health Stroke Scale (NIHSS) scores were found to be risk factors for HT after intravenous thrombolysis in patients with AIS (all P < .05). The ROC curve analysis showed that critical value of S100ß, CRP level, and NIHSS score for predicting intravenous thrombolytic HT in AIS patients were 0.335, 8.700, and 14.50, respectively, and their sensitivities were 0.750, 0.971, and 0.333 ( P < .05), respectively. High serum S100ß and CRP levels are risk factors for HT after intravenous thrombolysis in AIS patients and have predictive influence of the occurrence of HT in AIS patients.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/complicaciones , Activador de Tejido Plasminógeno/efectos adversos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Estudios Retrospectivos , Terapia Trombolítica/efectos adversosRESUMEN
DL-3-n-butylphthalide (NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke. NBP has shown recent potential as a treatment for Parkinson's disease. However, the underlying mechanism of action of NBP remains poorly understood. In this study, we established a rat model of Parkinson's disease by intraperitoneal injection of rotenone for 28 successive days, followed by intragastric injection of NBP for 14-28 days. We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson's disease, inhibited loss of dopaminergic neurons and aggregation of α-synuclein, and reduced iron deposition in the substantia nigra and iron content in serum. These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor, ferritin light chain, and transferrin 1. NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson's disease. Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition, oxidative stress, and ferroptosis in the substantia nigra.
RESUMEN
Autophagy has been implicated in stroke. Our previous study showed that the FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion (I/R). However, whether the Akt/FoxO3 signaling pathway plays a regulatory role in autophagy in cerebral I/R-induced oxidative stress injury is still unclear. The present study aims to investigate the effects of the Akt/FoxO3 signaling pathway on autophagy activation and neuronal injury in vitro and in vivo. By employing LY294002 or insulin to regulate the Akt/FoxO3 signaling pathway, we found that insulin pretreatment increased cell viability, decreased reactive oxygen species production, and enhanced the expression of antiapoptotic and autophagy-related proteins following H2O2 injury in HT22 cells. In addition, insulin significantly decreased neurological deficit scores and infarct volume and increased the expression of antiapoptotic and autophagy-related proteins following I/R injury in rats. However, LY294002 showed the opposite effects under these conditions. Altogether, these results indicate that Akt/FoxO3 signaling pathway activation inhibited oxidative stress-mediated cell death through activation of autophagy. Our study supports a critical role for the Akt/FoxO3 signaling pathway in autophagy activation in stroke.
Asunto(s)
Isquemia Encefálica , Insulinas , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Accidente Cerebrovascular , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Peróxido de Hidrógeno/farmacología , Transducción de Señal , Estrés Oxidativo , Autofagia , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/farmacología , Insulinas/metabolismo , Insulinas/farmacología , Encéfalo/metabolismo , ApoptosisRESUMEN
Nε-lysine acetylation is a reversible posttranslational modification (PTM) involved in multiple physiological functions. Genetic and animal studies have documented the critical roles of protein acetylation in brain development, functions, and various neurological disorders. However, the underlying cellular and molecular mechanism are still partially understood. Here, we profiled and characterized the mouse brain acetylome and investigated the cellular distribution of acetylated brain proteins. We identified 1,818 acetylated proteins, including 5,196 acetylation modification sites, using a modified workflow comprising filter-aided sample preparation (FSAP), acetylated peptides enrichment, and MS analysis without pre- or post-fraction. Bioinformatics analysis indicated these acetylated mouse brain proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and synapse, as well as their involvement in multiple neurological disorders. Manual annotation revealed that a set of brain-specific proteins were acetylation-modified. The acetylation of three brain-specific proteins was verified, including neurofilament light polypeptide (NEFL), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP), and neuromodulin (GAP43). Further immunofluorescence staining illustrated that acetylated proteins were mainly distributed in the nuclei of cortex neurons and axons of hippocampal neurons, sparsely distributed in the nuclei of microglia and astrocytes, and the lack of distribution in both cytoplasm and nuclei of cerebrovascular endothelial cells. Together, this study provided a comprehensive mouse brain acetylome and illustrated the cellular-specific distribution of acetylated proteins in the mouse brain. These data will contribute to understanding and deciphering the molecular and cellular mechanisms of protein acetylation in brain development and neurological disorders. Besides, we proposed some problems that need to be solved in future brain acetylome research.
RESUMEN
Small extracellular vesicles (sEVs) miRNAs are promising diagnosis and prognosis biomarkers for ischemic stroke (IS). This study aimed to determine the impact of IS on the serum sEVs miRNA profile of IS patients and a transient middle cerebral artery occlusion (tMCAO) mouse model. Small RNAseq was used to define the serum sEVs miRNA profile in IS patients and healthy controls (HC), and tMCAO mice and sham controls. Among the 1,444 and 1,373 miRNAs identified in human and mouse serum sEVs, the expression of 424 and 37 miRNAs was significantly altered in the IS patients and tMCAO mice, respectively (| Log2FC| ≥ 1, p < 0.01). Notably, five of the top 25 upregulated miRNAs in IS patients were brain-specific or enriched, including hsa-miR-9-3p, hsa-miR-124-3p, hsa-miR-143-3p, hsa-miR-98-5p, and hsa-miR-93-5p. Upregulation of these four miRNAs was further validated by qPCR. Nine of the 20 upregulated miRNAs in tMCAO mice were also brain-specific or enriched miRNAs. Temporal analysis indicated that the dynamics of mmu-miR-9-5p, mmu-miR-124-3p, mmu-miR-129-5p, and mmu-miR-433-3p were closely correlated with the evolution of ischemic brain injury, as their expression increased at 0.5 days after the onset of ischemia, peaked at day 1 or 3, and returned to normal levels at day 7 and 14. Notably, with the exceptions of mmu-miR-128-3p, the expression of the other eight miRNAs in the mouse serum sEVs was unaffected in the lipopolysaccharide (LPS)-induced neuroinflammation model. Together, in this study, we provided a comprehensive view of the influences of IS on the serum sEVs miRNA profile of IS patients and tMCAO mice and demonstrated the increment of a set of brain-specific miRNAs in serum sEVs after acute cerebral ischemia, which could be promising candidates directly reflecting the ischemic brain injury.
RESUMEN
Microglial M1 activation is detrimental to stroke outcomes. Recent studies have shown that circulating small extracellular vesicles (sEVs) can deliver miRNAs to target cells and regulate recipient cell functions. Herein, we tested the hypothesis that miRNA delivery by serum sEVs after cerebral ischemia/reperfusion (I/R) injury promote microglial M1 activation, demonstrating that serum sEVs from middle cerebral artery occlusion (MCAO) mice promoted proliferation and M1 activation of BV2 microglia. To explore the underlying mechanism of serum sEVs-mediated microglial activation in the early phase of cerebral I/R injury, we examined the effects of ischemic brain injury on the serum sEVs miRNAs profile in a mouse MCAO model using small RNAseq. Of the 1257 detected miRNA replications, the levels of 72 were significantly modulated. Bioinformatics analysis revealed that a panel of miRNAs was closely associated with inflammation, and in vitro experiments demonstrated that serum sEVs from MCAO mice could effectively transfer inflammatory miRNAs to BV2 microglia. Collectively, our data suggested that miRNAs delivered by serum sEVs after cerebral I/R injury promoted microglial M1 activation. The identification of microglial activation regulators in future studies will give rise to more effective treatments for stroke.
Asunto(s)
Isquemia Encefálica/metabolismo , Vesículas Extracelulares/metabolismo , MicroARNs/metabolismo , Microglía/metabolismo , Daño por Reperfusión/metabolismo , Animales , Isquemia Encefálica/patología , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión/patologíaRESUMEN
Mechanical thrombectomy is a highly effective but time dependent treatment for acute ischaemic stroke due to large vessel occlusion. In the UK, the national clinical guidelines for stroke and National Institute for Health and Care Excellence guidance endorses thrombectomy as an acute stroke treatment, and NHS England commissioned thrombectomy services. However, there are no UK 'real-world' data to verify the efficacy of the hub-and-spoke model in thrombectomy. There are currently 24 tertiary neuroscience centres in the UK that can provide thrombectomy treatment and many of these operate only within working hours. This study is the first to demonstrate that a hub-and-spoke thrombectomy service in routine UK 24/7 clinical practice is as effective and safe as in the setting of randomised controlled clinical trials. However, there are 9.3% of patients accepted for transfer to the thrombectomy centre who did not proceed to thrombectomy, mostly due to delays. Fifty-three per cent of thrombectomy cases were performed outside of standard working hours when transfer delays were increased. A 24/7 thrombectomy service is needed to maximise the benefit to all suitable patients. Measures, including improving workflow and optimising work forces, are needed to minimise the delays and continue to improve the service.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Inglaterra , Humanos , Medicina Estatal , Accidente Cerebrovascular/terapia , Trombectomía , Resultado del Tratamiento , Reino UnidoRESUMEN
Serum small extracellular vesicles (sEVs) have recently drawn considerable interest because of the diagnostic and therapeutic potential of their miRNAs content. However, the characteristics of human, mouse and rat serum sEVs and their differences in small RNA contents are still unknown. In this study, through nanoparticle tracking analysis and small RNA sequencing, we found that human, rat, and mouse serum sEVs exhibited distinct sizes and particle numbers as well as small RNA contents. Serum sEVs contained not only abundant miRNAs but also a large number of tRNA fragments. Most serum miRNAs existed both inside and outside of sEVs but were enriched in sEVs. Common serum sEV miRNAs (188 miRNAs) and species-specific serum sEV miRNAs (265, 58, and 159 miRNAs, respectively) were identified in humans, rats, or mice. The serum sEVs contained miRNAs from tissues and organs throughout the body, with blood cells as the main contributors. In conclusion, our findings confirmed the rationality of exploring serum sEV miRNAs as noninvasive diagnostic markers and revealed great differences in serum sEV small RNAs between humans, rats, and mice. Inadequate attention to these differences and the contribution of blood cells to serum sEV miRNAs could hinder the clinical translation of basic studies.
Asunto(s)
Exosomas/metabolismo , Vesículas Extracelulares/metabolismo , Animales , Exosomas/ultraestructura , Vesículas Extracelulares/ultraestructura , Humanos , Ratones , MicroARNs/metabolismo , Microscopía Electrónica de Transmisión , ARN de Transferencia/metabolismo , Ratas , Análisis de Secuencia de ARNRESUMEN
Histone deacetylase inhibitors (HDACi) are a promising therapeutic intervention for stroke. The involvement of the anti-inflammatory effects of HDACi in their neuroprotection has been reported, but the underlying mechanisms are still uncertain. Given the post-stroke inflammation is a time-dependent process, starting with acute and intense inflammation, and followed by a prolonged and mild one, we proposed whether target the early inflammatory response could achieve the neuroprotection of HDACi? To test this hypothesis, a single dose of suberoylanilide hydroxamic acid (SAHA) (50 mg/kg), a pan HDACi, was intraperitoneally (i.p.) injected immediately or 12 h after ischemia onset in a transient middle cerebral artery occlusion (tMCAO) mouse model. Compared with delayed injection, immediate SAHA treatment provided more protection, evidenced by smaller infarction volume, and a better outcome. This protection was accompanied by suppression of pro-inflammatory cytokines and reduction of activated microglia in the early stage of post-stroke inflammation. Moreover, SAHA treatment suppressed M1 cytokine expression (IL-6, TNF-α, and iNOS) while promoted the transcription of M2 cytokines (Arg-1 and IL-10) in LPS-challenged mouse microglia, and enhanced CD206 (M2 marker) but decreased CD86 (M1 markers) levels in microglia isolated from the ipsilateral hemisphere of MCAO mice. Collectively, our data suggested that the protection of SAHA on ischemic brain injury was closely associated with its inhibition on the early inflammatory response, and this inhibition was related to its reducing microglia activation and priming the activated microglia toward a more protective phenotype.
RESUMEN
OBJECTIVE: to evaluate whether postoperative heart rate variability (HRV) predicts short-term outcomes in patients undergoing coil embolization of ruptured aneurysms. METHODS: Consecutive patients receiving endovascular coiling to treat aneurysmal subarachnoid hemorrhage (SAH) were retrospectively reviewed between November 2011 and December 2014 in the authors' institution. Heart rate (HR) and blood pressure (BP) recorded in the initial 24 h after endovascular treatment were extracted along with other clinical data. HR variability (HRV) and BP variability (BPV) were determined as standard deviation (SD) and successive variation (SV) of every 2-h HR and BP. The correlation between HRV and clinical outcomes as assessed by Glasgow Outcome Scale (GOS) scores at discharge were analyzed statistically. RESULTS: Compared to the 310 patients with favorable outcomes (GOS 4-5), the 35 with unfavorable outcomes (GOS 1-3) had significantly higher HR, HRV, and BPV in the first postoperative day. Furthermore, HRV-SD remained to be an independent predictor of unfavorable recovery in multivariate logistic analysis (OR = 1.14; 95% CI, 1.02-1.29; P = 0.026) after adjusting for age, postoperative fever, and Glasgow Coma Scale scores on admission, which have been identified as predictors of poor prognosis. The area under the receiver operating characteristic curves for HRV-SD and BPV-SV were found to be 0.745 (95% CI, 0.658-0.833) and 0.633 (95% CI, 0.524-0.741), respectively (P < 0.05). CONCLUSIONS: Higher HRV in the first day after coil embolization was associated with unfavorable outcomes in patients with SAH. Early detection and appropriate treatment of the overactive sympathetic activity might promote functional recovery after SAH. Abbreviation: BP: Blood pressure; CI: Confidence interval; DBP: Diastolic blood pressure; GCS: Glasgow coma scale; GOS: Glasgow outcome scale; HR: Heart rate; HRV: Heart rate variability; OR: Odds ratio; ROC: Receiver operating characteristics; SD: Standard deviation; SAH: Subarachnoid hemorrhage; SV: Successive variation; SBP: Systolic blood pressure.
Asunto(s)
Embolización Terapéutica/instrumentación , Embolización Terapéutica/métodos , Frecuencia Cardíaca/fisiología , Hemorragia Subaracnoidea/fisiopatología , Hemorragia Subaracnoidea/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Femenino , Escala de Coma de Glasgow , Escala de Consecuencias de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Hemorragia Subaracnoidea/psicología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: The present study was conducted to evaluate the effect of postoperative blood pressure (BP) variability on functional outcome in patients after coil embolization of ruptured aneurysms. METHODS: The authors retrospectively reviewed their database of patients undergoing endovascular coiling to treat subarachnoid hemorrhage (SAH) between November 2011 and December 2014. BP values were recorded every 2 hours in the initial 24 hours after endovascular obliteration of ruptured aneurysms. BP variability was determined as standard deviation (SD) and successive variation (SV). Clinical outcome at discharge was assessed by the modified Rankin Scale (mRS) and Glasgow Coma Scale (GCS) Score. BP variability obtained were correlated to patient outcome and analyzed statistically. RESULTS: Favorable outcomes (mRS 0-1) achieved in 308 (83.7%) of the 368 patients. On univariate logistic analysis, postoperative systolic blood pressure variability (SBPV)-SD, SBPV-SV, diastolic blood pressure variability (DBPV)-SD and DBPV-SV were associated with clinical outcome at discharge. SBPV-SV remained to be an independent predictor for functional recovery (OR, 0.93; 95% CI, 0.88-0.98; P = 0.009) after adjusting for age, postoperative fever, and Hunt-Hess grade by multivariate analysis. Furthermore, patients with higher SBPV had lower GCS grade at discharge (P < 0.001). There was no association between clinical outcome and mean systolic BP (SBP) (P = 0.360) or mean diastolic BP (DBP) (P = 0.105) after coiling. CONCLUSION: Postoperative SBPV was a strong predictor of clinical outcome in patients undergoing coil embolization of aneurysms, independent of mean SBP or DBP and seemed to be a potential therapeutic target in aneurysmal SAH.
Asunto(s)
Aneurisma Roto/cirugía , Presión Sanguínea/fisiología , Embolización Terapéutica/métodos , Aneurisma Intracraneal/cirugía , Resultado del Tratamiento , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma Roto/complicaciones , Femenino , Escala de Coma de Glasgow , Humanos , Aneurisma Intracraneal/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Hemorragia Subaracnoidea/cirugía , Adulto JovenRESUMEN
We aimed to investigate the prevalence of stroke and related vascular risk factors in adult population aged 40 years and older in China. We conducted a prospective cross-sectional survey in nationally representative sample of 207323 individuals from all 31 Chinese provinces in 2013. Data were used to analyze the prevalence of stroke by age, sex, geographical regions and educational level. The age-standardized prevalence of stroke was significantly higher in men than in women in all age groups (P < 0.001). The age-standardized prevalence of stroke was significantly higher in rural than in urban residents among both men and women (P < 0.001). The prevalence of stroke was inversely associated with educational level. There were striking geographical variations in stroke prevalence in China with a higher prevalence of stroke in northern provinces as compared with southern provinces of the country. The age-standardized prevalence of hypertension, diabetes, dyslipidemia, atrial fibrillation and obesity in the Chinese population aged 40 years and older were 35.24%, 9.55%, 58.72%, 1.57% and 4.09%, respectively. Stroke and related vascular risk factors remains a major public threat in China and effective primary preventive strategies that aimed at reducing the burden of stroke and its risk factors are urgently needed.
Asunto(s)
Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Adulto , China/epidemiología , Diabetes Mellitus/epidemiología , Dislipidemias/complicaciones , Dislipidemias/epidemiología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Población Rural/estadística & datos numéricosRESUMEN
OBJECTIVE: Accurate identification of patients who will achieve a favorable outcome is almost impossible preoperatively or postoperatively in poor-grade (Hunt and Hess Grade IV and V) aneurysmal subarachnoid hemorrhage (SAH). Whether characteristics of blood pressure profiles during the first 24 hours after endovascular coiling could predict prognosis in poor grade patients was explored. METHODS: Data were obtained retrospectively on all patients undergoing endovascular treatment with poor-grade SAH from November 2011 to June 2016. Blood pressure during the initial 24 hours was measured at 2-hour intervals after coil embolization. Studied features of mean systolic blood pressure (MSBP) and systolic blood pressure variability (SBPV) as well as demographics, medical history, clinical characteristics, and neurologic outcomes were documented. SBPV was determined as standard deviation and successive variation of systolic blood pressure. Logistic regression analysis was used to identify predictors of favorable outcome assessed on modified Rankin Scale score of 0 to 2. RESULTS: The patients with favorable and unfavorable outcome were comparable with respect to systolic blood pressure on admission and MSBP after coiling. However, MSBP between 120 and 140 mm Hg was one of independent predictors of good outcomes at discharge (odds ratio 7.1; P = 0.002). SBPV-successive variation after embolization was associated with functional recovery (odds ratio 0.87; P = 0.011) in multivariate logistic analysis and mortality by Cox proportional hazard regression (hazard ratio, 1.10; P = 0.001) at 6-month follow-up. CONCLUSIONS: Characteristics of blood pressure profiles after coiling appeared to be simple and convenient indexes for the prognosis of patients with poor-grade SAH.
Asunto(s)
Presión Arterial/fisiología , Embolización Terapéutica , Hemorragia Subaracnoidea/fisiopatología , Hemorragia Subaracnoidea/terapia , Adulto , Anciano , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Examen Neurológico , Oportunidad Relativa , Pronóstico , Estudios Retrospectivos , Hemorragia Subaracnoidea/mortalidad , Resultado del TratamientoRESUMEN
In the last decade, although studies on exosomal microRNAs (miRNAs) derived from serum and other body fluids have increased dramatically; the contents and biological significance of serum exosomes under normal conditions remain unclear. In the present study, we profiled the small RNA content of mouse serum exosomes (mSEs) using small RNAseq and found that fragments of transfer RNAs (tRNAs) and miRNAs were the two predominant exosomal RNA species, accounting for approximately 60% and 10% of mapped reads, respectively. Moreover, 466 known and 5 novel miRNAs were identified from two independent experiments, among which the five most abundant miRNAs (miR-486a-5p, miR-22-3p, miR-16-5p, miR-10b-5p and miR-27b-3p) accounted for approximately 60% of all the aligned miRNA sequences. As inferred from the identities of the well known cell- or tissue-specific miRNAs, mSEs were primarily released by RBCs, liver and intestinal cells. Bioinformatics analysis revealed over half of the top 20 miRNAs by abundance were involved in inflammatory responses and further in vitro experiments demonstrated that mSEs potently primed macrophages towards the M2 phenotype. To the best of our knowledge, this is the first study to profile small RNAs from mSEs. In addition to providing a reference for future biomarker studies and extrapolating their origins, our data also suggest the roles of mSEs in maintaining internal homeostasis under normal conditions.
Asunto(s)
Exosomas/genética , Inflamación/genética , MicroARNs/sangre , Animales , Exosomas/metabolismo , Inflamación/sangre , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Células RAW 264.7 , Análisis de Secuencia de ARN/métodosRESUMEN
OBJECTIVE: This study aimed to evaluate the association of different stenting procedures with the procedure-related complications in stent-assisted coiling (SAC) of ruptured wide-necked aneurysms. METHODS: Consecutive patients undergoing SAC of ruptured wide-necked aneurysms were retrospectively reviewed between December 2011 and June 2016. They received 1 of the 3 stenting procedures during SAC: 1) the coiling microcatheter was "jailed" outside of the stent and the coil embolization proceeded above the stent; 2) initial stent deployment followed by the coils through the stent's strut technique; or 3) the coil-then-stent technique. The effect of different stenting procedures on clinical complications and outcomes was estimated by logistic regression models. RESULTS: Of the 93 patients enrolled in this study, 11 of them (11.8%) suffered from symptomatic thromboembolic events and 10 of them (10.8%) had hemorrhagic complications. SAC with different stenting procedures (odds ratio [OR] = 4.10, 95% confidence interval [CI]: 1.20-13.97, P = 0.024) was the only independent risk factor for symptomatic thromboembolic events. The coil-then-stent technique had a higher ischemic complications rate than the other 2 stenting procedures (P = 0.023). Serum glucose (OR = 1.48, P = 0.014) and systolic blood pressure on admission (OR = 0.97, P = 0.046) were independent predictors of hemorrhagic complications during SAC. However, different stenting procedures and stent types were correlated with neither aneurysm occlusion at the end of procedure (P = 0.498 and 0.176, respectively) nor favorable outcome at discharge (P = 0.710 and 0.928, respectively). CONCLUSION: Different stenting procedures were associated with thromboembolic but not hemorrhagic complications in SAC of ruptured wide-necked aneurysms.
Asunto(s)
Aneurisma Roto/terapia , Embolización Terapéutica/instrumentación , Embolia Intracraneal/etiología , Trombosis Intracraneal/etiología , Complicaciones Posoperatorias/etiología , Stents , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma Roto/diagnóstico por imagen , Femenino , Humanos , Embolia Intracraneal/diagnóstico por imagen , Trombosis Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Estudios Retrospectivos , Factores de Riesgo , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/etiología , VentriculostomíaRESUMEN
Several recent genome-wide association studies (GWASs) have suggested that the histone deacetylase 9 (HDAC9) gene is associated with stroke, but the reliability of these findings remains controversial, particularly for the data derived from different ethnicities and geographical locations. Therefore, we performed a meta-analysis to explore the associations between HDAC9 polymorphisms and the risk of stroke in the Chinese population. All eligible case-control studies that met the search criteria were retrieved from multiple databases, and six case-control studies with a total of 2,356 stroke patients and 3,420 healthy controls were included. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations of 3 HDAC9 gene polymorphisms with stroke risk. Our results revealed statistically significant associations of the rs2107595 (T/C) polymorphism with an increased risk of stroke in the allele, codominant and dominant models. Additionally, the rs2389995 (G/A) polymorphism was found to be significantly associated with a decreased risk of stroke in all genetic models. In conclusion, this meta-analysis suggested that the T allele of rs2107595 in HDAC9 increases the risk of stroke but that the G allele of rs2389995 decreases the risk of stroke in the Chinese population.
Asunto(s)
Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Histona Desacetilasas/genética , Polimorfismo de Nucleótido Simple , Proteínas Represoras/genética , Accidente Cerebrovascular/genética , Alelos , China/epidemiología , Genotipo , Humanos , Oportunidad Relativa , Vigilancia de la Población , Sesgo de Publicación , Accidente Cerebrovascular/epidemiologíaRESUMEN
The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain-specific miRNAs, in acute ischemic stroke (AIS) patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty-five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01). The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications.
RESUMEN
OBJECTIVE: The purpose of this study was to compare the efficacy, stability, and safety of stent-assisted coiling (SAC) and balloon-assisted coiling (BAC) in the treatment of ruptured wide-necked aneurysms in the acute period. METHODS: Consecutive patients including 65 cases treated with SAC and 32 with BAC were reviewed at the authors' institution between November 2011 and December 2014. The efficacy of these 2 approaches and the incidence of periprocedural complications were retrospectively evaluated. RESULTS: Morphologic analysis showed a lower fundus/neck ratio (1.2 vs. 1.6) in the aneurysms treated with SAC versus BAC (P < 0.001). The mean neck width of aneurysms was 4.0 mm in the patients treated with SAC versus 3.4 mm in those treated with BAC (P < 0.04). Coil protrusion into the parent vessels during embolization was an independent risk factor for cerebral ischemic events (odds ratio [OR], 4.08; 95% confidence interval [CI], 1.03-16.2). Neck width (OR, 0.65; 95% CI, 0.44-0.97) and aneurysm perforation during procedure (OR, 6.24; 95% CI, 1.21-32.3) were independent predictors of complete occlusion (Raymond 1) by immediate postembolization angiography. There was no statistical difference between the 2 techniques regarding the rate of aneurysm occlusion at the end of procedure, periprocedural complications, and favorable outcome at discharge and follow-up. CONCLUSIONS: These findings suggested that SAC was more appropriate than BAC for ruptured wide-necked aneurysms with lower fundus/neck ratio or wider neck size. However, periprocedural complications, occlusion rates, and favorable outcomes did not differ between the 2 techniques.