Increased interleukin-6 levels in neuron-derived plasma small extracellular vesicles in patients with aneurysmal subarachnoid hemorrhage

2020 ◽  
Author(s):  
Niansheng Lai ◽  
Yang Yao ◽  
Feiyun Qin ◽  
Tao Yu ◽  
Dayong Xia ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Extracellular Vesicles ◽  
Interleukin 6 ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multivariate Logistic Regression Analysis ◽  
Distinct Pattern ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Sequential Precipitation ◽  
First Time

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke characterized by high rates of mortality and disability. Identifying circulating biomarkers is helpful to improve prognosis. In this study, for the first time, we identify circulating interleukin-6 (IL-6) levels in neuron-derived small extracellular vesicles (NDSEVs) as potential biomarkers in prognosis of aSAH.Methods We extracted small extracellular vesicles from the plasma of aSAH patients and healthy controls and enriched them using sequential precipitation and anti-L1CAM antibody immunoabsorption. Subsequently, we determined IL-6 levels using an enzyme-linked immunosorbent assay (ELISA).Results Plasma IL-6 NDSEVs showed distinct pattern differences between aSAH patients and healthy controls. There were significant correlations of IL-6concentrations in plasma with severity in aSAH. The AUCs of IL-6 for distinguishing the severe aSAH patients from mild aSAH patients were 0.961. After multivariate logistic regression analysis, only age, acute hydrocephalus,and the levels of IL-6 NDSEVs enabled prediction of neurological outcome at 1 year. The IL-6 NDSEVs levels were greater and positively associated with disease and prognosis of aSAH patients.Conclusions These data suggest a neuroinflammatory cascade in aSAH patients. IL-6 NDSEVs may be a biomarkers to monitor the progression of aSAH.

scholarly journals Increased Interleukin-6 Levels in Neuron-Derived Plasma Small Extracellular Vesicles of Subarachnoid Haemorrhage Patients

2020 ◽  
Author(s):  
Niansheng Lai ◽  
Yang Yao ◽  
Tao Yu ◽  
Dayong Xia ◽  
Xintong Zhao ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Interleukin 6 ◽  
Distinct Pattern ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Monitoring ◽  
Healthy Controls ◽  
Circulating Biomarkers ◽  
Sequential Precipitation ◽  
Near Future ◽  
First Time

Abstract Background: Aneurismal subarachnoid hemorrhage (aSAH) is a serious type of stroke with high mortality and disability. Identifying circulating biomarkers is helpful to improve theranostics of aSAH. In this study, we are for the first time to report circulating interleukin-6(IL-6) in neuron-derived small extracellular vesicles(NDSEVs) were identified to be the potential biomarkers in prognosis of aSAH. Methods: We extracted small extracellular vesicles from the plasma of aSAH patients and healthy controls and were enriched by sequential precipitation and anti-L1CAM antibody immunoabsorption. Subsequently,we determined IL-6 levels by an enzyme-linked immunosorbent assay (ELISA). Result: Plasma IL-6 NDSEVs showed distinct pattern differences between aSAH patients and healthy controls. The IL-6NDSEVs levels were increased and positively associated with disease monitoring and prognosis of aSAH patients. These data suggest an elevated neuroinflammatory cascade in aSAH patients.Conclusion: The IL-6NDSEVs maybe prospective biomarkers to indicate its progression, and thus may own great potential in applications such as prognostic evaluation of aSAH in the near future.

scholarly journals Increased interleukin-6 levels in neuron-derived plasma small extracellular vesicles of subarachnoid haemorrhage patients

2020 ◽  
Author(s):  
Niansheng Lai ◽  
Yang Yao ◽  
Tao Yu ◽  
Dayong Xia ◽  
Xintong Zhao ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Interleukin 6 ◽  
Distinct Pattern ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Circulating Biomarkers ◽  
Sequential Precipitation ◽  
Near Future ◽  
First Time ◽  
Elisa Result

Abstract Background: Aneurismal subarachnoid hemorrhage (aSAH) is a serious type of stroke with high mortality and disability. Identifying circulating biomarkers is helpful to improve theranostics of aSAH. In this study, we are for the first time to report circulating interleukin-6(IL-6) in neuron-derived small extracellular vesicles(NDSEVs) were identified to be the potential biomarkers in prognosis of aSAH. Methods: We extracted small extracellular vesicles from the plasma of aSAH patients and healthy controls and were enriched by sequential precipitation and anti-L1CAM antibody immunoabsorption. Subsequently,we determined IL-6 levels by an enzyme-linked immunosorbent assay (ELISA). Result: Plasma IL-6 NDSEVs showed distinct pattern differences between aSAH patients and healthy controls. The IL-6 NDSEVs levels were increased and positively associated with disease monitoring and prognosis of aSAH patients. These data suggest an elevated neuroinflammatory cascade in aSAH patients. Conclusion: The IL-6 NDSEVs maybe prospective biomarkers to indicate its progression, and thus may own great potential in applications such as prognostic evaluation of aSAH in the near future.

Evidence for a conditioning effect of inhalational anesthetics on angiographic vasospasm after aneurysmal subarachnoid hemorrhage

2020 ◽  
Vol 133 (1) ◽  
pp. 152-158 ◽  
Author(s):  
Umeshkumar Athiraman ◽  
Diane Aum ◽  
Ananth K. Vellimana ◽  
Joshua W. Osbun ◽  
Rajat Dhar ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multivariate Logistic Regression Analysis ◽  
Secondary Brain Injury ◽  
Large Artery ◽  
Inhalational Anesthetics ◽  
Angiographic Vasospasm ◽  
Inhalational Anesthetic

OBJECTIVEDelayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numerous studies. Recently, several animal studies have identified a strong protective role for inhalational anesthetics against secondary brain injury after SAH including DCI—a phenomenon referred to as anesthetic conditioning. The aim of the present study was to assess the potential role of inhalational anesthetics against cerebral vasospasm and DCI in patients suffering from an SAH.METHODSAfter IRB approval, data were collected retrospectively for all SAH patients admitted to the authors’ hospital between January 1, 2010, and December 31, 2013, who received general anesthesia with either inhalational anesthetics only (sevoflurane or desflurane) or combined inhalational (sevoflurane or desflurane) and intravenous (propofol) anesthetics during aneurysm treatment. The primary outcomes were development of angiographic vasospasm and development of DCI during hospitalization. Univariate and logistic regression analyses were performed to identify independent predictors of these endpoints.RESULTSThe cohort included 157 SAH patients whose mean age was 56 ± 14 (± SD). An inhalational anesthetic–only technique was employed in 119 patients (76%), while a combination of inhalational and intravenous anesthetics was employed in 34 patients (22%). As expected, patients in the inhalational anesthetic–only group were exposed to significantly more inhalational agent than patients in the combination anesthetic group (p < 0.05). Multivariate logistic regression analysis identified inhalational anesthetic–only technique (OR 0.35, 95% CI 0.14–0.89), Hunt and Hess grade (OR 1.51, 95% CI 1.03–2.22), and diabetes (OR 0.19, 95% CI 0.06–0.55) as significant predictors of angiographic vasospasm. In contradistinction, the inhalational anesthetic–only technique had no significant impact on the incidence of DCI or functional outcome at discharge, though greater exposure to desflurane (as measured by end-tidal concentration) was associated with a lower incidence of DCI.CONCLUSIONSThese data represent the first evidence in humans that inhalational anesthetics may exert a conditioning protective effect against angiographic vasospasm in SAH patients. Future studies will be needed to determine whether optimized inhalational anesthetic paradigms produce definitive protection against angiographic vasospasm; whether they protect against other events leading to secondary brain injury after SAH, including microvascular thrombi, autoregulatory dysfunction, blood-brain barrier breakdown, neuroinflammation, and neuronal cell death; and, if so, whether this protection ultimately improves patient outcome.

scholarly journals Associations between endothelin polymorphisms and aneurysmal subarachnoid hemorrhage, clinical vasospasm, delayed cerebral ischemia, and functional outcome

2018 ◽  
Vol 128 (5) ◽  
pp. 1311-1317 ◽  
Author(s):  
Christoph J. Griessenauer ◽  
Robert M. Starke ◽  
Paul M. Foreman ◽  
Philipp Hendrix ◽  
Mark R. Harrigan ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Multivariate Logistic Regression Analysis ◽  
Renin Angiotensin System ◽  
Nucleotide Polymorphisms ◽  
Endothelin 1 ◽  
Potent Vasoconstrictor

OBJECTIVEEndothelin-1, a potent vasoconstrictor, and its receptors may be involved in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), clinical vasospasm, delayed cerebral ischemia (DCI), and functional outcome following aSAH. In the present study, common endothelin single nucleotide polymorphisms (SNPs) and their relation to aSAH were evaluated.METHODSBlood samples from all patients enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study were used for genetic evaluation. The CARAS study prospectively enrolled patients with aSAH at 2 academic institutions in the US from 2012 to 2015. Common endothelin SNPs were detected using 5′ exonnuclease (TaqMan) genotyping assays. Analysis of associations between endothelin SNPs and aSAH and its clinical sequelae was performed.RESULTSSamples from 149 patients with aSAH and 50 controls were available for analysis. In multivariate logistic regression analysis, the TG (odds ratio [OR] 2.102, 95% confidence interval [CI] 1.048–4.218, p = 0.036) and TT genotypes (OR 7.884, 95% CI 1.003–61.995, p = 0.05) of the endothelin-1 T/G SNP (rs1800541) were significantly associated with aSAH. There was a dominant effect of the G allele (CG/GG genotypes; OR 4.617, 95% CI 1.311–16.262, p = 0.017) of the endothelin receptor A G/C SNP (rs5335) on clinical vasospasm. Endothelin SNPs were not associated with DCI or functional outcome.CONCLUSIONSCommon endothelin SNPs were found to be associated with presentation with aSAH and clinical vasospasm. Further studies are required to elucidate the relevant pathophysiology and its potential implications in the treatment of patients with aSAH.

scholarly journals Early serum miR-1297 is an indicator of poor neurological outcome in patients with aSAH

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Bin Sheng ◽  
Nian-sheng Lai ◽  
Yang Yao ◽  
Jin Dong ◽  
Zhen-bao Li ◽  
...  
Keyword(s):  
Neurological Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multivariate Logistic Regression Analysis ◽  
Endovascular Coiling ◽  
World Federation ◽  
Healthy Controls ◽  
Fisher Score ◽  
Independent Predictive Factor ◽  
Time Points ◽  
Poor Outcome

Objective: MiRNAs are important regulators of translation and have been described as biomarkers of a number of cardiovascular diseases, including stroke. The purpose of the study was to determine expression levels of serum miR-1297 in patients with aneurysmal subarachnoid hemorrhage (aSAH), and to assess whether miR-1297 was the prognostic indicator of aSAH. Methods: We treated 128 aSAH patients with endovascular coiling. The World Federation of Neurological Surgeons (WFNS) grades, Hunt–Hess grades, and modified Fisher scores were used to assess aSAH severity. Neurologic outcome was assessed using the Modified Rankin Scale (mRS) at 1-year post-aSAH. Serum was taken at various time points (24, 72, and 168 h, and 14 days). Serum samples from aSAH patients and healthy controls were subjected to reverse transcription (RT) quantitative real-time PCR (RT-qPCR). Results: A poor outcome at 1 year was associated with significantly higher levels of miR-1297 value at the four time points, higher WFNS grade, higher Hunt–Hess grade, and higher Fisher score. Serum miR-1297 levels were significantly higher in patients, compared with healthy controls. There were significant correlations of miR-1297 concentrations in serum with severity in aSAH. The AUCs of miR-1297 at the four time points for distinguishing the aSAH patients from healthy controls were 0.80, 0.94, 0.77, and 0.59, respectively. After multivariate logistic regression analysis, only miR-1297 at 24 and 72 h enabled prediction of neurological outcome at 1 year. Conclusion: Serum was an independent predictive factor of poor outcome at 1 year following aSAH. This result supports the use of miR-1297 in aSAH to aid determination of prognosis.

scholarly journals Predictors of the development of takotsubo cardiomyopathy in aneurysmal subarachnoid hemorrhage and outcomes in patients with intra-aortic balloon pumps

2020 ◽  
pp. 1-6
Author(s):  
Joshua S. Catapano ◽  
Andrew F. Ducruet ◽  
Fabio A. Frisoli ◽  
Candice L. Nguyen ◽  
Christopher E. Louie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Subarachnoid Hemorrhage ◽  
Takotsubo Cardiomyopathy ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multivariate Logistic Regression Analysis ◽  
High Morbidity ◽  
Female Patients ◽  
Neurological Outcomes ◽  
Poor Outcomes

OBJECTIVETakotsubo cardiomyopathy (TC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Previous studies have shown that female patients presenting with a poor clinical grade are at the greatest risk for developing TC. Intra-aortic balloon pumps (IABPs) are known to support cardiac function in severe cases of TC, and they may aid in the treatment of vasospasm in these patients. In this study, the authors investigated risk factors for developing TC in the setting of aSAH and outcomes among patients requiring IABPs.METHODSThe authors retrospectively reviewed the records of 1096 patients who had presented to their institution with aSAH. Four hundred five of these patients were originally enrolled in the Barrow Ruptured Aneurysm Trial, and an additional 691 patients from a subsequent prospectively maintained aSAH database were analyzed. Medical records were reviewed for the presence of TC according to the modified Mayo Clinic criteria. Outcomes were determined at the last follow-up, with a poor outcome defined as a modified Rankin Scale (mRS) score > 2.RESULTSTC was identified in 26 patients with aSAH. Stepwise multivariate logistic regression analysis identified female sex (OR 8.2, p = 0.005), Hunt and Hess grade > III (OR 7.6, p < 0.001), aneurysm size > 7 mm (OR 3, p = 0.011), and clinical vasospasm (OR 2.9, p = 0.037) as risk factors for developing TC in the setting of aSAH. TC patients, even with IABP placement, had higher rates of poor outcomes (77% vs 47% with an mRS score > 2, p = 0.004) and mortality at the last follow-up (27% vs 11%, p = 0.018) than the non-TC patients. However, aggressive intra-arterial endovascular treatment for vasospasm was associated with good outcomes in the TC patients versus nonaggressive treatment (100% with mRS ≤ 2 at last follow-up vs 53% with mRS > 2, p = 0.040).CONCLUSIONSTC after aSAH tends to occur in female patients with large aneurysms, poor clinical grades, and clinical vasospasm. These patients have significantly higher rates of poor neurological outcomes, even with the placement of an IABP. However, aggressive intra-arterial endovascular therapy in select patients with vasospasm may improve outcome.

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