Stroke Biomarkers Research Articles

Serum Dkk-1 (Dickkopf-1) Is a Potential Biomarker in the Prediction of Clinical Outcomes Among Patients With Acute Ischemic Stroke.

Objective- Serum Dkk-1 (dickkopf-1) level has been shown to be elevated in patients with ischemic stroke, but its impact on clinical outcomes of ischemic stroke remains unclear. The aim of this study is to investigate the association between serum Dkk-1 and prognosis of ischemic stroke. Approach and Results- We measured serum Dkk-1 levels in 3178 patients with ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was a combination of all-cause mortality and major disability (modified Rankin scale score, ≥3) at 1 year after stroke. Secondary outcomes were stroke recurrence and vascular events. After multivariate adjustment, elevated Dkk-1 levels were associated with an increased risk of primary outcome (odds ratio, 1.40; 95% CI, 1.03-1.89; Ptrend=0.015) when 2 extreme quartiles were compared. Each SD increase of log-transformed Dkk-1 was associated with 12% (95% CI, 1%-24%) increased risk of primary outcome. Multiple-adjusted spline regression model showed a linear association between serum Dkk-1 and risk of primary outcome ( P for linearity, 0.039). Subgroup analyses further confirmed these associations. The addition of serum Dkk-1 to conventional risk factors improved the predictive power for primary outcome (net reclassification improvement: 10.11%, P=0.029; integrated discrimination improvement: 0.21%, P=0.028). Conclusions- High serum Dkk-1 levels at baseline were associated with poor prognosis at 1 year after ischemic stroke, suggesting that serum Dkk-1 may be a potential prognostic biomarker for ischemic stroke. Further studies from other samples of patients with ischemic stroke are needed to replicate our findings and to clarify the potential mechanisms.

Evaluation of plasma levels of neopterin and soluble CD40 ligand in patients with acute ischemic stroke in upper Egypt: can they surrogate the severity and functional outcome?

Inflammation constitutes a major component of ischemic stroke pathology. The prognostic value of "neopterin" and soluble CD40 ligand (sCD40L), as a potential biomarker of ischemic stroke, has been less extensively studied. This study aims at assessing the serum levels of neopterin and sCD40L in acute ischemic stroke (AIS), to clarify its association with the severity, etiology, and risk factors of stroke, and to evaluate their relationship with the stroke functional outcome in our study sample within 90 days of follow-up. This case-control study was conducted on 100 patients with first-ever acute onset ischemic stroke and 25 control subjects. Participants were subjected to full history taking and detailed clinical and neurological examination. Brain imaging was performed after hospital admission. Blood tests were drawn for assessment of neopterin and sCD40L on the first day of admission. High levels of neopterin and sCD40L was reported. Their levels were significantly higher in relation with survival status. There was a relationship between AIS and sCD40L levels and the severity of the stroke. Within 3 months of follow-up, these biomarkers were associated significantly with poor functional outcome, within a 90-day follow-up period, and mortality. These biomarkers were highly associated in patients with small vessel occlusion as an etiology for AIS. Neopterin and sCD40L levels increased after AIS. Both biomarkers were strong and independent predictors of 90-day unfavorable clinical outcome and death in patients after AIS.

The telomere length of peripheral blood cells is associated with the risk of ischemic stroke in Han population of northern China.

Background:Telomere length is closely related to the onset and prognosis of ischemic stroke. This study was to investigate the relationship between telomere length and the incidence of ischemic stroke in Han population of northern China.Methods:In the present study, 152 patients with ischemic stroke were selected as the case group, and 152 healthy persons were used as the control group. Detection of telomere length was done by real-time polymerase chain reaction after extraction of genomic DNA from peripheral venous blood.Results:Our results showed that the telomere length of the patients in the case group was significantly lower than that of the control group (Z = −11.843, P < .0001). Further analysis found that the telomere length of the control group was inversely correlated with age (r = −0.234, P = .004), and the telomere length and homocysteine (HCY) were inversely correlated in the case group (r = −0.176, P = .03), especially in women (r = −0.357, P = .024). Multivariate regression analysis showed that telomere length was a protective factor for ischemic stroke (odds ratio [OR] 95% confidence interval [95% CI] = 0.748 [0.681–0.823], β = −0.29, P < .0001). The receiver operating characteristic curve showed that telomere length was a good diagnostic biomarker of ischemic stroke (area under the curve: 0.894, sensitivity: 84.7%, specificity: 93.4%).Conclusion:Our results indicate that shorter telomere length has some connection with the risk of ischemic stroke in the northern Chinese Han population. Telomere length might serve as a potential candidate biomarker for ischemic stroke. This requires a large sample to be further verified.

Editorial introductions

Editorial introductions

Biomarker for Ischemic Stroke Using Metabolome: A Clinician Perspective.

Finding ischemic stroke biomarker is highly desirable because it can improve diagnosis even before a patient arrives to the hospital. Metabolome is one of new technologies that help to find biomarkers. Most metabolome-related ischemic stroke studies were done in Asia and had exploratory designs. Although failed to find specific biomarkers, they discovered several important metabolite-stroke associations which belong to three pathophysiological mechanisms: Excitotoxicity with activation of glutamate, resulting in the increase of glutamate derivatives proline and pyroglutamate; Oxidative stress with production of free radicals and perturbed concentrations of uric acid, matrix metalloproteinase-9, branch-chained amino acids, sphingolipids, homocysteine, asymmetric dimethylarginine, nitric oxide and folate cycle metabolites; and Stroke mediated inflammation, affecting phospholipid metabolism with perturbed levels of lysophosphatidylethanolamine and lysophosphatidylcholine. The discovered metabolite-stroke associations need further evaluation in prospective, high-quality studies with patients matched for age, risk factors, and medications.

Direct comparison of prognostic ability of cardiac biomarkers for cardiogenic stroke and clinical outcome in patients with stroke.

Despite many recent advances in medicine, cardiogenic stroke is still a health problem with a high mortality rate. Cardiac biomarkers have been reported to be useful indicators for cardiogenic stroke and subsequent cerebrovascular events. However, there are no data directly comparing the cardiac biomarkers in stroke patients. We measured atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) levels and performed transthoracic and transesophageal echocardiography in 282 stroke patients. There were 108 cases of cardiogenic stroke and 47 cases of major adverse cardiovascular and cerebrovascular events (MACCE) during the follow-up period. Association with left atrial function and left atrial appendage function appeared somewhat stronger for BNP and NT-proBNP than ANP and hsTnT. Multivariate logistic analysis demonstrated that cardiac biomarkers excluding ANP were significantly associated with cardiogenic stroke in stroke patients, multivariate Cox's proportional hazards regression analysis demonstrated that all biomarkers were significantly associated with MACCE after adjustment for confounding risk factors. Receiver operating characteristic curve analysis showed that the C indices of BNP and NT-proBNP for cardiogenic stroke and MACCE were almost equal, but significantly greater than those of ANP and hsTnT. Both BNP and NT-proBNP levels are useful predictors of cardiogenic stroke and subsequent MACCE superior to ANP and hsTnT in stroke patients.

Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation toOutcomes in Patients With Atrial Fibrillation: Experiences From the RE - LY Trial.

BackgroundCardiac biomarkers and left ventricular hypertrophy (LVH) are related to the risk of stroke and death in patients with atrial fibrillation. We investigated the interrelationship between LVH and cardiac biomarkers and their independent associations with outcomes.Methods and ResultsPlasma samples were obtained at baseline in 5275 patients with atrial fibrillation in the RE‐LY (Randomized Evaluation of Long‐Term Anticoagulation Therapy) trial. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), cardiac troponin I and T, and growth differentiation factor‐15 were determined using high‐sensitivity (hs) assays. LVH was defined by ECG. Cox models were adjusted for baseline characteristics, LVH, and biomarkers. LVH was present in 1257 patients. During a median follow‐up of 2.0 years, 165 patients developed a stroke and 370 died. LVH was significantly (P<0.0001) associated with higher levels of all biomarkers in linear regression analyses adjusting for baseline characteristics. Geometric mean ratios (95% CIs) were as follows: NT‐proBNP, 1.32 (1.25–1.38); hs cardiac troponin I, 1.67 (1.57–1.78); hs troponin T, 1.38 (1.32–1.44); and growth differentiation factor‐15, 1.09 (1.05–1.12). For stroke, the hazard ratios (95% CIs) per 50% increase were as follows: NT‐proBNP, 1.09 (1.00–1.19); hs cardiac troponin I, 1.09 (1.03–1.15); hs troponin T, 1.14 (1.06–1.24); and growth differentiation factor‐15, 1.22 (1.08–1.38) (all P<0.05). For death, hazard ratios (95% CIs) were as follows: NT‐proBNP, 1.24 (1.17–1.31); hs cardiac troponin I, 1.13 (1.10–1.17); hs troponin T, 1.28 (1.23–1.34); and growth differentiation factor‐15, 1.31 (1.22–1.42) (all P<0.0001). LVH was not significantly associated with stroke or death after adjustment for biomarkers.ConclusionsCardiac biomarkers are significantly associated with LVH. The prognostic value of biomarkers for stroke and death is not affected by LVH. The prognostic information of LVH is attenuated in the presence of cardiac biomarkers.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Serum levels of insulin-like growth factor-1 and brain-derived neurotrophic factor as potential recovery biomarkers in stroke

ABSTRACTObjectives: Our objectives were: 1) to determine whether maximal aerobic exercise increased serum neurotrophins in chronic stroke and 2) to determine the factors that predict resting and exercise-dependent levels.Methods: We investigated the potential predictors of resting and exercise-dependent serum insulin-like growth factor-1 and brain-derived neurotrophic factor among 35 chronic stroke patients. Predictors from three domains (demographic, disease burden, and cardiometabolic) were entered into 4 separate stepwise linear regression models with outcome variables: resting insulin-like growth factor, resting brain-derived neurotrophic factor, exercise-dependent change in insulin-like growth factor, and exercise-dependent change brain-derived neurotrophic factor.Results: Insulin-like growth factor decreased after exercise (p = 0.001) while brain-derived neurotrophic factor did not change (p = 0.38). Greater lower extremity impairment predicted higher resting brain-derived neurotrophic factor (p = 0.004, r2 = 0.23). Higher fluid intelligence predicted greater brain-derived neurotrophic factor response to exercise (p = 0.01, r2 = 0.18). There were no significant predictors of resting or percent change insulin-like growth factor-1.Discussion: Biomarkers have the potential to characterize an individual’s potential for recovery from stroke. Neurotrophins such as insulin-like growth factor-1 and brain-derived neurotrophic factor are thought to be important in neurorehabilitation; however, the factors that modulate these biomarkers are not well understood. Resting brain-derived neurotrophic factor and percent change in brain-derived neurotrophic factor were related to physical and cognitive recovery in chronic stroke, albeit weakly. Insulin-like growth factor-1 was not an informative biomarker among chronic stroke patients. The novel finding that fluid intelligence positively correlated with exercise-induced change in brain-derived neurotrophic factor warrants further research.

Peripheral Blood miR-451 May Serve as a Biomarker of Ischemic Stroke.

The current study aims to investigate the correlation between the expression level of miR-451 in peripheral blood and the risk of ischemic stroke, and its feasibility as a biomarker of ischemic stroke. Three hundred and two cases of ischemic stroke diagnosed in Qianfoshan Hospital Affiliated to Shandong University from April 2017 to Dec 2017 and 302 cases matched for age and gender were selected from routine health examination subjects. Real-time quantitative PCR was used to detect the expression of microRNA in peripheral blood. Receiver operating curve (ROC) was used to analyze whether miR-451 could be used as a basis for judging ischemic stroke. The expression level of miR-451 in peripheral blood of patients with ischemic stroke was higher than that of the control group (p < 0.05). ROC analysis demonstrated that peripheral blood miR-451 could screen ischemic stroke patients from healthy controls, with the AUC of 0.912. In addition, the expression level of miR-451 was negatively correlated with the number of platelets and platelet hematocrit (p < 0.05). There is a significant correlation between the expression level of miR-451 in peripheral blood and the occurrence of ischemic stroke. miR-451 is expected to be a biomarker of ischemic stroke.

The possibility of using neuron-specific enolase as a biomarker in the acute period of stroke

The article presents a review of the literature on neuron-specific enolase (NSE) as a biomarker of stroke. It is shown that NSE does not allow differentiation of the ischemic and hemorrhagic process in stroke, but is suitable for determining the extent of brain tissue destruction both in the first hours of stroke and in the dynamics. The HSE analysis can be useful for monitoring the course of the disease, control of the dynamics of the pathological process, including when the size of the lesion increases, for evaluating the effectiveness of therapy and as a prognostic biomarker.

THE INFLUENCE OF SAMPLING TIME TO SERUM GLIAL FIBRILLARY ACIDIC PROTEIN (GFAP) LEVELS IN ACUTE STROKE

Background: Serum Glial Fibrillary Acidic Protein (GFAP) is a great potential for biomarker that is widely studied as a diagnostic biomarker of acute stroke. Sampling within 6 hours after onset is the best time window, but in Indonesia, stroke patients often arrive late more than 6 hours. Objective: To identify the difference in time of blood sampling with serum GFAP levels within 24 hours onset of ischemic stroke (IS) patients and intracerebral hemorrhage (ICH) strokes. Methods: Cross-sectional analysis with purposive sampling, sampling in IS and ICH strokes that arrive at the ER within 24-hour on-site. The serum GFAP examination was performed with ELISA. Results: In this study, 41 acute stroke patients with 24-hour onset of each stroke were grouped into group 1 (<6 hours), group 2 (6-12 hours) and group 3 (12-24 hours). One Way ANOVA and Tukey's analysis showed no significant difference in GFAP levels among the three groups in both IS and ICH. Conclusion: There was no significant difference in GFAP levels in samples <6 hours, 6-12 hours, and 12-24 hours in ischemic strokes and ICH strokes.

MiRNA-223-3p and let-7b-3p as potential blood biomarkers associated with the ischemic penumbra in rats

The present study aimed to identify commonalities in the microRNA (miRNA) expression profiles of the brain ischemic penumbra and the blood after hyperacute ischemic stroke and then to address whether the miRNA profile of blood has potential usefulness as a diagnostic biomarker of hyperacute ischemic stroke. Blood was collected from the jugular vein 4 h after permanent middle cerebral artery occlusion (pMCAO). After venous blood was collected, the rats were decapitated immediately, and brain ischemic penumbra samples were collected. Hematoxylin and eosin staining was used to observe the histopathological changes. Penumbra and blood miRNAs were measured by miRNA microarray and real-time polymerase chain reaction (PCR) analysis. MicroRNA profiles differed between hyperacute ischemic stroke and sham-operated rats. The expression of some miRNAs changed by more than 1.5-fold in the penumbra and blood 4 h after pMCAO; among those miRNAs, several were upregulated and several were downregulated. MiR-223-3p was found to be highly expressed in both the penumbra and the blood 4 h after pMCAO, and let-7b-3p was found to have low expression in both the penumbra and the blood 4 h after pMCAO. Moreover, miR-223-3p and let-7b-3p expression in blood and brain ischemic penumbra were positively correlated. The results show that select blood miRNAs may correlate with miRNA changes in the penumbra in a rat model of hyperacute ischemic stroke. Our findings suggest the potential usefulness of blood miR-223-3p and let-7b-3p as noninvasive bio markers for the diagnosis of hyperacute ischemic stroke.

Diagnostic and Prognostic Interests of Plasmatic Neuroglobin during Stroke in Adult at the Acute Phase

Introduction: Neuroglobin (Ngb) owes its name to its preferred location in the nervous system. Its plasma concentration increases during cerebral ischemia. However, the interest of its dosage in the diagnosis and the prognosis of the strokes in the adult is not defined. Objectives: To determine if plasmatic Ngb can be used as a diagnostic biomarker and prognostic for stroke in adults at the acute phase. Population and Methods: This was a prospective study in 69 people, including 39 suspected stroke (Cerebral ischemia or CI, Intracerebral hemorrhage or ICH) and 30 healthy volunteers (controls). The plasma concentration of Ngb (CmNgb in ng/ml) of the patients was determined at admission day (d1), at the third day (d3) and seventh day (d7). CmNgbtaken at d1 was compared between patients and controls. Its evolution over time, as well as its relation with the clinical parameters, including the Glasgow coma scale and the short-term mortality in stroke subjects was analyzed by the Mann and Whitney tests and the Wilcoxon test (p Results: At d1, the CmNgb of all types of stroke was 3.140 ± 2.700 ng/ml, and did not differ significantly from controls (0.303 ± 0.114 ng/ml, p = 0.070). On the other hand, it was higher in CI victims (5.800 ± 0.720 ng/ml) than in ICH (1.750 ± 0,090 ng/ml) (p = 0.030). It then decreased on d3 in CI victims (2.600 ± 0.112 ng/ml) and ICH (0.420 ± 0.211 ng/ml), returning to normal on d7 (0.420 ± 0.200 ng/ml for CI’s, p = 0.001, and 0.360 ± 0.300 ng/ml for ICH, p = 0.002). There was a relationship between CmNgb, delay of occurrence of the first symptoms of the stroke (3.140 ± 2.700 ng/ml before the 6th hour, and 0.643 ± 0.244 ng/ml after the 6th hour (p = 0.003) and the volume of the hematoma (p = 0.0027). None relationship existed between CmNgb, Glasgow coma scale (p = 0.427) and short-term mortality (CmNgb = 3.95 ng/ml in survivors versus 2.65 ng/ml in deceased p = 0.060). Conclusion: This study shows that the plasma concentration of Neuroglobin is high during stroke in humans in the acute phase. This elevation follows triphasic kinetics and appears to be more important during infarction than hemorrhage. These results suggest that CmNgb can be used as a diagnostic marker for stroke in adult at the acute phase, by differentiating ischemia from hemorrhage. However, this work needs to be confirmed on a larger sample of patients.

Multiplexed electrochemical and SERS dual-mode detection of stroke biomarkers: rapid screening with high sensitivity

In this work, a real-time assay for a highly sensitive, label-free, multiplexed electrochemical and surface-enhanced Raman spectroscopic (SERS) detection of stroke biomarkers by neuron-specific enolase (NSE) and S100-β protein was developed using lateral flow devices.

Neurofilament changes in serum and cerebrospinal fluid after acute ischemic stroke

BackgroundNeurofilament light (NFL) is a well-validated biomarker for neuronal injury and neurodegeneration. Increased cerebrospinal fluid (CSF) levels have been shown after stroke, as well as in patients with a broad range of neurodegenerative and neuroinflammatory diseases. Neurofilament heavy (NFH) belongs to the same family of structural proteins but it is less extensively studied. The potential of phosphorylated NFH (pNFH) as a stroke biomarker and for the prediction of clinical outcome is unknown. In this study, we aimed to examine the temporal pattern of NFL and pNFH concentrations in serum and CSF after acute ischemic stroke. Materials and MethodsA quantitative Enzyme-Linked ImmunoSorbent Assay (ELISA) for pNFH was developed and tested on CSF and serum samples. NFL and pNFH were analysed in serum and CSF of acute ischemic stroke patients, who were followed over time (Day 0–1, Day 2–3, Day 7–9, three weeks, and 3–5 months after stroke). ResultsNFL and pNFH concentrations in serum and CSF increased after stroke, peaked during the 3rd week, and then decreased back to almost baseline levels at 3–5 months. CSF-NFL and serum-NFL correlated to the outcome measured by Barthel Index after 3–5 months, whilst no such association was seen for pNFH. DiscussionThese findings suggest that NFL and pNFH in both CSF and serum reflect the temporal pattern of the post ischemic axonal injury and that this process does not seem to progress after 3–5 months. ConclusionNFL and pNFH in CSF and serum are promising biomarkers for axonal injury following stroke. Further studies in larger populations are needed to fully understand the progression of the neuronal damage after acute ischemic stroke and to evaluate if these biomarkers can provide additive information and how they relate to outcome.

Design of Genetic Circuit for Monitoring and Treatment of Stroke

Nowadays, stroke has become a huge threat to human health and has become the first one of the top ten causes for death in the world. In the detection and diagnosis of stroke, optimization of markers and design of corresponding gene circuits have important research and application prospects. In this paper, we propose an improved Support Vector Model (SVM) by combining Principle Component Analysis (PCA) with Mutual Information (MI) to effectively figure out the proper stroke biomarkers with high specificity and sensitivity. The design of the single-index detection circuits is implemented. And the input circuit and critical circuit of the Single-index Detection Circuit are analysed. On the basis of the single-index detection circuit, a multi-marker detection circuit is built using OR GATE and AND GATE logic circuits to achieve the detection of multi-markers.

Saliva-Omics in Plasma Cell Disorders — Proof of Concept and Potential As a Non-Invasive Tool for Monitoring Disease Burden and MRD Status

Salivaomics has exciting potential for the diagnosis and monitoring of malignancy, evidence of which has been reported in oral cancer (Sahibzada et al., 2017), head and neck malignancies (Citrin et al., 2012) and ovarian cancer (Chen et al., 1990). It has been observed that approximately 40% of cancer, stroke and cardiovascular disease biomarkers are present in whole saliva (Loo et al., 2010). Salivaomics has become an area of great interest in disease diagnosis over the last number of years, following the footsteps of the other “omics” based diagnostic tools. Saliva has been referred to as “the mirror of the body” as it gives an insight into the internal pathological state (Lee and Wong, 2009). As saliva is considered a fast, inexpensive and non-invasive method of sample collection, the future of diagnosis, early detection, monitoring and prediction of progression of disease has been thought to lie here.Monoclonal gammopathy of undetermined significance (MGUS) is characterised as a premalignant precursor tumours of MM. It has been seen that the majority of MM cases develop from MGUS (Weiss et al., 2009), leading to the need for biomarkers to monitor disease progression and explore the mechanism of malignant transformation.Serum and saliva samples were collected from 18 newly diagnosed MM patients and 8 MGUS patients, peptides were purified using the filter aided sample preparation (FASP) method and samples were prepared for label-free liquid chromatography mass spectrometry (LC-MS/MS) using an LTQ Orbitrap XL mass spectrometrer (Thermo Fisher Scientific). Proteins were analysed using the MaxQuant and Perseus software for mass-spectrometry (MS)-based proteomics data analysis, UniProtKB-Swiss Prot database and KEGG Pathway database.The abundance of proteins in saliva from MGUS compared to newly diagnosed MM was analysed using label-free mass spectrometry. A panel of 6 significant proteins was identified. Fatty Acid Binding Protein 5 (FABP5) was detected in elevated levels in saliva from MM patients compared to MGUS. The increased expression was verified using western blotting. Fatty Acid Binding Protein 5 (FABP5) is known to promote cell proliferation, survival and migration (Wang et al., 2006). FABP5 has been observed to aid in the proliferation of cancer and has been seen to be overexpressed in multiple cancer types such as breast (Levi et al., 2013), prostate (Morgan et al., 2008) and HCC (Ohata et al., 2017). FABP5 has seen to link closely with poor outcome and unfavourable clinical parameters in MM (Waheed et al., 2013).Additionally, analysis was performed on serial MM patient saliva samples during treatment. A panel of significant proteins was identified when comparing the saliva proteome during treatment the abundance of many of the detected proteins mirrored response to treatment (Table 1). For example, Transglutaminase 3 (TGM3) was observed as being decreased in abundance in saliva from patients in remission. TGM3 is expressed in brain, small intestine, mucosa and skin and has been shown to be required for the cross-linking of the structural protein trichohyalin and the keratin intermediate filaments to form a rigid structure within the inner root sheath cells (Hitomi, 2005). Overexpression of TGM3 has been observed to induce oesophageal cancer (EC) cell invasion, migration and proliferation. It has also been noted that TGM3 promotes apoptosis in EC in vitro (Li et al., 2016). TGM3 has been predicted to be a potential biomarker for disease progression in MM.This study provides proof of concept that a range of biologically significant proteins of interest can be reliably detected in the saliva of MM and MGUS patients. The observation of differential expression of FABP5 between MGUS and MM identified these as candidate proteins relevant to malignant transformation of MGUS to symptomatic MM. The demonstration of decreased abundance of FABP5 after achieving remission indicates a correlation with tumour burden. This opens the opportunity to explore candidate salivary biomarkers for use in the clinic for disease monitoring and Minimal Residual Disease (MRD) assessment. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Exploring the potential value of miR-148b-3p, miR-151b and miR-27b-3p as biomarkers in acute ischemic stroke.

Cerebrovascular disease is the main cause of death in the world. Here, we explored whether circulating serum miR-148b-3p, miR-151b and miR-27b-3p could be as potential diagnostic biomarkers for diagnosing acute ischemic stroke. Seventy-seven IS patients and forty-two healthy controls matched for age and sex were enrolled in the present study. Blood samples were drawn from IS patients within the 24 h. The correlation analysis was performed by Spearman. The ability to distinguish patients from healthy controls was determined by receiver operating characteristic (ROC) curve. The expression of circulating serum miR-148b-3p was significantly decreased, whereas miR-151b and miR-27b-3p were elevated significantly compared with controls. ROC analysis showed area under the ROC curve (AUC) of miR-148b-3p, miR-151b and miR-27b-3p to be 0.6647, 0.6852 and 0.6657, respectively. While the AUC increased to 0.8103 for the combination of miR-148b-3p and miR-27b-3p. Blood miR-151b level was negatively correlated with insulin-like growth factor-1 (IGF-1), and miR-27b-3p level was negatively correlated with IGF-1 and insulin-like growth factor binding protein-3, respectively. Our findings suggest that miR-148b-3p, miR-151b and miR-27b-3p may serve as blood-based biomarkers for diagnosing ischemic stroke patients, and the combination of miR-148b-3p and miR-27b-3p may be more powerful.

MicroRnA as a diagnostic biomarker in stroke

Acute stroke-induced damage of endothelial cells leads to impaired cerebral microcirculation and significant damage of the brain tissue. Despite recent advances in treatment approaches that improve survival after a stroke, diagnostic approaches aimed at early identification of the pathogenetic stroke subtype remain limited. MicroRNAs are promising biomarkers in stroke. The article reviews data on the relationship of stroke with changes in the levels of certain circulating microRNAs and the opportunities for their diagnostic use.

Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels as a Biomarker of Acute Intracerebral Hemorrhage

BackgroundCorrect diagnosis of cerebral stroke type, hemorrhagic or ischemic, is essential in the early stage to establish the optimum treatment. The diagnosis is mainly determined based on imaging studies. Other more available diagnostic methods are desirable, such as blood sample examination. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is very important in vascular dysfunction induced by oxidized low-density lipoprotein, including cell apoptosis. The present study evaluated LOX-1 as a biomarker for cerebral stroke. Subjects and MethodsPatients with newly diagnosed stroke were prospectively enrolled between February and July 2014. LOX-1 serum values were measured twice, within 24 hours and 2 months after the onset. ResultsA total of 16 patients were enrolled; 7 patients with intracerebral hemorrhage (ICH) and 9 patients with cerebral infarction. Median LOX-1 values of patients with ICH and infarction in the acute phase were 1825.8 and 593.9 pg/mL, respectively, significantly higher in patients with ICH than in patients with infarction (P < .0001). ConclusionLOX-1 serum level has potential as a biomarker of ICH.