Biomarkers For Acute Ischemic Stroke Research Articles

Potential Biomarkers in Stroke and Current Therapeutics

Stroke is a brain injury where a sudden interruption of the blood supply in brain part and the brain does not receive the enough blood flow due to which there is a lack of oxygen and glucose and without blood supply the brain cells begin to die (cerebral infarction) and cause brain damage. So there is a need to understand the pathophysiology and to effective biomarkers in acute ischemic stroke and may help to enhance the current clinical outcome of stroke. Various biomarkers are associated with the pathophysiologic mechanism and they may help in stroke assessment, diagnosis, prognosis or treatment. There is a higher rate of morbidity and mortality in stroke. Hence a better pharmacological management is desired for the fast recovery and treatment from stroke. Thrombolytics, antihypertensive, anti-platelet therapy, antioxidants, rehabilitation technique and their combinations e.g. Aspirin and clopidogrel, Aspirin and dipyridamole, ramipril and telmisartan, IgGglial cell-lined derived neurotropic factor (GDNF) and IgG – tumor necrosis factor receptor(TNFR) etc. and various surgical treatment such as carotid endarterectomy, stereotactic radiosurgery, hypothermia, revascularization of the blood supply, endovascular treatment of aneurysms and angioplasty and stenting of vessels in the neck and brain are also required for the beneficial outcomes in future. Key-wordsStroke, Biomarker, Pathophysiology, Combinational therapy, Surgical treatment -------------------------------------------------IJLSSR----------------------------------------------INTRODUCTION Stroke is a neurological disease which cause of disability and death (1). The blood supply of brain in stroke is obstructed because of ischemia and hemorrhage which causes the brain dysfunctioning. Ischemia caused by blockage in blood vessels via thrombosis and arterial embolism vasoconstriction. In ischemia reduction in sufficient blood flow to alter the normal cellular function (2). Stroke has two major categories of brain ischemia one is global-ischemia and other one is focal ischemia. In focal ischemia models, the middle cerebral artery is occluded, either temporarily (vessels are blocked up to 3 hrs) or permanently (vessels) are blocked usually for one or more days) to allow the reperfusion (3-4). Access this article online Quick Response Code: Website: www.ijlssr.com

Analysis of Potential Amino Acid Biomarkers in Brain Tissue and the Effect of Galangin on Cerebral Ischemia.

Galangin, a potent scavenger of free radicals, has been used as an herbal medicine for various ailments for centuries in Asia. With complex pathophysiology, ischemic stroke is one of the most frequent causes of death and disability worldwide. We have reported that galangin provides direct protection against ischemic injury as a potential neuroprotective agent and has potential therapeutic effects on the changes of serum amino acids in ischemic stroke; however, the mechanism of the changes of amino acids in the ischemic brain tissue has not yet been clarified. In this paper, we explored brain tissue amino acid biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. Finally, we identified that glutamic acid, alanine and aspartic acid showed significant changes (p < 0.05 or p < 0.01) in galangin-treated groups compared with vehicle-treated rats and the four enzymes associated with these three AAs’ metabolic pathways; GLUD1, SLC16A10, SLC1A1 and GPT were identified by multiplex interactions with the three amino acids. By metabolite-protein network analysis and molecular docking, six of 28 proteins were identified and might become potential galangin biomarkers for acute ischemic stroke. The data in our study provides thoughts for exploring the mechanism of disease, discovering new targets for drug candidates and elucidating the related regulatory signal network.

Apolipoprotein A1-Unique Peptide as a Diagnostic Biomarker for Acute Ischemic Stroke.

Clinically-informative biomarkers of ischemic stroke are needed for rapid diagnosis and timely treatment. In the present study, APOA1 unique peptide (APOA1-UP), a novel peptide biomarker, was identified and quantified by multiple reaction monitoring (MRM) using labeled reference peptide (LRP). Serum samples of 94 patients in the ischemic stroke group and 37 patients in the non-stroke group were analyzed for the levels of total APOA1-UP, low density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC). Median ratio of total APOA1-UP/LRP was 2.14 (interquartile range, 0.40) in the non-stroke group and 1.32 (0.44) in the ischemic stroke group (p < 0.0001). The serum level of total APOA1-UP was independently correlated with the presence of ischemic stroke by multivariate logistic regression analysis (p < 0.0001). From the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9750 and the optimal cutoff value of the serum APOA1-UP level was 1.80, which yielded a sensitivity of 90.63% and a specificity of 97.14%. The diagnostic efficiency of HDL-C was lower, with an AUC of 0.7488. Therefore, the serum level of APOA1-UP is a diagnostic biomarker candidate for ischemic stroke in the early stage.

Diagnostic and Prognostic Significance of Blood Biomarkers in Acute Ischemic Stroke

Diagnostic and Prognostic Significance of Blood Biomarkers in Acute Ischemic Stroke

Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke.

Aim:We investigated to study the prognostic importance of brain natriuretic peptide (BNP) in ischemic stroke.Materials and Methods:We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score on admission and functional disability by Barthel Index (BI) at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP). Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A P = 0.05 was considered as significant.Results:Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI) 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml) was very high as compared to controls (<60 ng/ml) (P < 0.001). There was a positive correlation between age and BNP (R2 = 0.34; P < 0.00); NIHSS and BNP (R2 = 0.255; P < 0.01), negative correlation between BI and BNP (R2 = −0.064; P < 0.01). Mean BNP levels across the OCSP showed higher values in TACI (F = 4.609 P = 0.005). Regression analysis showed that BNP can predict BI which was statistically significant.Conclusion:Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients.

Serum IL-33 Is a Novel Diagnostic and Prognostic Biomarker in Acute Ischemic Stroke.

Interleukin-33 (IL-33), a newly recognized IL-1 family member, is expressed in various tissues and cells, and involved in pathogenesis of many human diseases. For example, IL-33 plays a protective role in cardiovascular diseases. However, the role of IL-33 in acute ischemic stroke (AIS) remains unclear. This study aims to investigate whether IL-33 level in AIS patient serum can be used as a potential diagnostic and prognostic marker. The study included two hundred and six patients with first-ever ischemic stroke, who were admitted within 72 hours after stroke onset. The serum level of IL-33 was measured with ELISA and the severity of AIS patients on admission was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score. The functional outcome at 3 months was determined using the Barthel index (BI). We found that serum IL-33 was significantly higher (P < 0.001) in patients with AIS [57.68 ng/L (IQR, 44.95-76.73)] compared with healthy controls [47.48 ng/L (IQR, 38.67-53.78)]. IL-33 was an independent diagnostic biomarker for AIS with an OR of 1.051 (95%Cl, 1.018-1.085; P=0.002). Serum IL-33 was higher (P < 0.05) in the stroke patients with small cerebral infarction volume compared to AIS patients with large cerebral infarction. In addition, serum IL-33 was also significantly higher (P = 0.001) in the patients with mild stroke, compared to the patients with severe stroke. Furthermore, serum IL-33 level in AIS patients with a worse outcome was higher (P < 0.001) compared to AIS patients with a better outcome. IL-33 was also an independent predictor for the functional outcome with an adjusted OR of 0.932 (95% CI, 0.882-0.986). Our results suggest that the lower level of serum IL-33 is associated with large infarction volume and greater stroke severity in AIS patients. Thus, IL-33 can be used as a novel and independent diagnostic and predicting prognostic marker in AIS.

Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126.

Emerging data suggest that exosomal microRNA (miRNA) may provide potential biomarkers in acute ischemic stroke. However, the effects of ischemia-reperfusion on total versus exosomal miRNA responses in circulating blood remain to be fully defined. Here, we quantified levels of miR-126 in whole serum versus exosomes extracted from serum and compared these temporal profiles against reperfusion and outcomes in a rat model of acute focal cerebral ischemia. First, in vitro experiments confirmed the vascular origin and changes in miR-126 in brain endothelial cultures subjected to oxygen-glucose deprivation. Then in vivo experiments were performed by inducing permanent or transient focal cerebral ischemia in rats, and total serum and exosomal miR-126 levels were quantified, along with measurements of infarction and neurological outcomes. Exosomal levels of miR-126 showed a transient reduction at 3 h post-ischemia that appeared to normalize back close to pre-ischemic baselines after 24 h. There were no detectable differences in exosomal miR-126 responses in permanent or transient ischemia. Serum miR-126 levels appeared to differ in permanent versus transient ischemia. Significant reductions in serum miR-126 were detected at 3 h after permanent ischemia but not transient ischemia. By 24 h, serum miR-126 levels were back close to baseline in both permanent and transient ischemia. Overall, there were no correlations between serum miR-126 and exosomal miR-126. This proof-of-concept study suggests that changes in serum miR-126 may be able to distinguish severe permanent ischemia from milder injury after transient ischemia.

Identification of Site-Specific Stroke Biomarker Candidates by Laser Capture Microdissection and Labeled Reference Peptide.

The search to date for accurate protein biomarkers in acute ischemic stroke has taken into consideration the stage and/or the size of infarction, but has not accounted for the site of stroke. In the present study, multiple reaction monitoring using labeled reference peptide (LRP) following laser capture microdissection (LCM) is used to identify site-specific protein biomarker candidates. In middle cerebral artery occlusion (MCAO) rat models, both intact and infarcted brain tissue was collected by LCM, followed by on-film digestion and semi-quantification using triple-quadrupole mass spectrometry. Thirty-four unique peptides were detected for the verification of 12 proteins in both tissue homogenates and LCM-captured samples. Six insoluble proteins, including neurofilament light polypeptide (NEFL), alpha-internexin (INA), microtubule-associated protein 2 (MAP2), myelin basic protein (MBP), myelin proteolipid protein (PLP) and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP), were found to be site-specific. Soluble proteins, such as neuron-specific enolase (NSE) and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), and some insoluble proteins, including neurofilament heavy polypeptide (NEFH), glial fibrillary acidic protein (GFAP), microtubule-associated protein tau (MAPT) and tubulin β-3 chain (TUBB3), were found to be evenly distributed in the brain. Therefore, we conclude that some insoluble protein biomarkers for stroke are site-specific, and would make excellent candidates for the design and analysis of relevant clinical studies in the future.

Abstract T P32: Infarct Volume as a Potential Prognostic Biomarker for Acute Ischemic Stroke after Intravenous Recombinant Tissue-Type Plasminogen Activator Therapy

Background: Pretreatment infarct volume has been known as a predictor of outcome in patients with acute ischemic stroke after intravenous recombinant tissue-type plasminogen activator (IV rt-PA) therapy. To confirm the importance of infarct volume in patients with undergoing IV rt-PA therapy, we sought to characterize the relationship between final infarct volume and long-term outcome. Method: We retrospectively reviewed outcomes of acute ischemic stroke patients who had treated with IV rt-PA. Patients underwent magnetic resonance imaging at baseline and 7 days after IV rt-PA. Baseline characteristics, stroke features, time from onset to treatment, initial National Institutes of Health Stroke Scale (NIHSS) score, the presence of major artery occlusion, and laboratory findings were recorded. Outcomes included complete independence (mRS of 0 to 1), unfavorable outcome (mRS of 4 to 6) at 90-day, and mortality within 90-day. Multivariate regression analysis was used to identify predictors of the outcomes. Results: Of 116 patients, 47 (41%) patients achieved complete independence. At univariate analysis, they were younger (median age, 71 versus 77, p=0.008), had a lower prevalence of diabetes mellitus (23% versus 43%, p=0.040), had a lower initial NIHSS score (median, 8 versus 16, p&lt;0.001), had a lower prevalence of internal carotid artery occlusion (9 versus 29%, p=0.010), had no occlusion (36 versus 10%, p=0.001), had a lower prevalence of parenchymal hemorrhage (2 versus 20%, p=0.004), had smaller diffusion-weighted imaging lesion volume at baseline (median, 2.6 versus 8.0ml, p=0.008) and final infarct volume at 7-day (median, 3.8 versus 42.2ml, p&lt;0.001). Age (Odds ratio [OR], 0.943, 95% confidence interval [CI], 0.896 to 0.992; p=0.024) and final infarct volume (OR, 0.952; 95%CI, 0.992 to 0.982; p=0.002) were identified as independent predictors of complete independence. They also predicted unfavorable outcome (p=0.036 and p&lt;0.001) and mortality (p=0.036 and p=0.035). Conclusion: Among patients with acute stroke patients who undergo IV rt-PA therapy, final infarct volume is a critical determinant of 90-day functional outcome and mortality.

The Role of D-Dimer, Fibrinogen and C-Reactive Protein as Plasma Biomarkers in Acute Ischemic Stroke

Background: Previous studies on pathophysiology suggest a role of inflammation in atherothrombotic stroke and intracardiac thrombosis in cardioembolic stroke. We explored the magnitude of D-dimer, fibrinogen and C-reactive protein (CRP) as biomarkers in acute ischemic cerebral stroke and their relation to ischemic stroke subtypes and their impact on stroke outcome after 30 days. Methods: The study was performed on 100 patients, admitted to Neurology Department, Menoufiya University, within 24 hours of acute ischemic stroke. Patients were subjected to clinical data collection, general and neurological examination, laboratory assessment (routine and biomarkers), brain computerized tomography (CT), magnetic resonance imaging (MRI), MRA, carotid and vertebrobasilar duplex and cardiac assessment. The patients were classified according to Trial of ORG 10172 in acute stroke treatment (TOAST) classification. Severity and disability were assessed by Scandinavian stroke scale and modified Rankin scale at admission and at 30 days. Results: We found that D-dimer, fibrinogen and CRP were significantly higher in patients than in controls (P < 0.001). D-dimer and fibrinogen were higher in cardioembolic stroke while CRP was higher in atherothrombotic subtype. The biomarkers were correlated significantly with the severity and disability of stroke at onset and 30 days. Conclusions: These three biomarkers in acute ischemic stroke can be considered as non-invasive tools which add important information regarding etiology and outcome. J Neurol Res. 2015;5(6):277-282 doi: http://dx.doi.org/10.14740/jnr362w

The Role of D-Dimer, Fibrinogen and C-Reactive Protein as Plasma Biomarkers in Acute Ischemic Stroke

The Role of D-Dimer, Fibrinogen and C-Reactive Protein as Plasma Biomarkers in Acute Ischemic Stroke

Diagnostic Significance of Ischemia-Modified Albumin, S100b, and Neuron-Specific Enolase in Acute Ischemic Stroke

Objective: Use of biochemical markers of cerebral ischemia is a newly favored approach for early diagnosis of ischemic stroke. Our aim was to establish the sensitivity and specificity of ischemia-modified albumin (IMA) in acute ischemic stroke and to compare it with S100b and neuron-specific enolase (NSE). We also intended to investigate the usefulness of a panel composed of these three biomarkers in acute ischemic stroke. Material and Methods: Consecutive adult patients who were admitted to the emergency department with focal neurological deficits were enrolled. Serum samples were obtained at the initial examination, and IMA, S100b, and NSE were measured. Receiver operating characteristics (ROC) curve analysis was used to determine the cut-off values of the biomarker and biomarker groups. Results: Serum IMA, NSE, and S100b levels were significantly higher in ischemic stroke patients (p<0.001, p=0.005, p=0.001, respectively). The optimum diag nostic cutoff point for IMA was 0.31 ABSU with 90% sensitivity and 57% specificity; 18 µg/L for NSE with 61% sensitivity and 53% specificity; and 65 pcg/l for S100b with 87% sensitivity and 72% specificity. With a combination of IMA with either S100b or NSE, instead of IMA alone, the best results were obtained with IMA and S100b, at 97% sensitivity and 37% specificity. Conclusion: This study indicates that IMA was a sensitive diagnostic biomarker in the acute phase of ischemic stroke, although its specificity is low. The combi nation of IMA with S100b and NSE did not add any beneficial effect to the specificity of IMA alone. (JAEM 2014; 13: 112-7)

Supplementation of folic acid and vitamin B12 reduces plasma levels of asymmetric dimethylarginine in patients with acute ischemic stroke

Increased levels of asymmetric dimethylarginine (ADMA) have been observed in patients with acute ischemic stroke. We aimed to investigate the correlation between ADMA and ischemic stroke, and evaluate the effect of supplementation of folic acid and vitamin B12 on concentrations of ADMA. Patients were randomized into intervention and non-intervention groups within 3days after symptom onset. Intervention group patients were treated with folic acid (5mg daily) and vitamin B12 (500μg twice daily) for 12weeks. ADMA and homocysteine (Hcy) concentrations were measured before treatment (baseline) and 2 and 12weeks after treatment. The laboratory measures were also collected from healthy controls. Eighty five subjects were enrolled in this study, from whom 72 with complete baseline and follow-up laboratory data were included in the present analysis. Thirty four patients were assigned to the intervention group and 38 patients to the non-intervention group. Sixty people were enrolled as healthy controls. Levels of ADMA and Hcy were raised (p<0.05) in patients with acute ischemic stroke. With supplementation of both folic acid and vitamin B12, the levels of ADMA and Hcy decreased significantly at 2 and 12weeks (p<0.05). The present study reconfirmed that ADMA can be regarded as a risk biomarker for acute ischemic stroke. We observed that with supplementation of folic acid and vitamin B12, levels of ADMA were decreased in patients with acute ischemic stroke.

Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review

Stroke is one of the major causes of death and disability, including ischemic stroke, which accounts for 85 - 87 % of cases. Currently, there are few treatment options available for minimizing tissue death following a stroke. Emerging data suggest that biomarkers may help improve current clinical outcome of stroke. As such, there is a pressing need to understand the pathophysiology and to explore effective biomarkers following an ischemic brain event. The pathophysiology of ischemic stroke is complex, and majorly involves excitotoxicity, oxidative stress, inflammation, blood-brain barrier dysfunction, apoptosis, etc. Several of the biomarkers are related to these pathophysiologic mechanisms and they may have applications in stroke prediction, diagnosis, assessment, prognosis or treatment. In this review, we summarized the pathophysiology of ischemic stroke and some related biomarkers are examined.

Correlative study of serum cystatin C levels with severity of acute ischemic stroke.

Background: The attractiveness of cystatin C as a biomarker for acute ischemic stroke is obvious, in the background of accumulating evidence indicating a link between vascular disease of the kidney and brain. We investigated the association of serum cystatin C levels with first onset acute ischemic stroke and the correlation of serum cystatin C levels with severity of acute ischemic stroke as assessed by NIH stroke scale. Methods: A total of 50 patients with first onset of acute ischemic stroke, aged more than 45 years, presenting within 72 hours after onset, by interview, history, clinical examination, neuroimaging and other investigations. Serum Cystatin C was measured by means of a particle-enhanced immunenephelometric assay (N Latex Cystatin C) with a nephelometer (Siemens BN Prospec). Results: Serum cystatin C levels were significantly raised in 62% (n=31) patients of acute ischemic stroke compared with controls 14% (n=7), with a p < 0.001. Compared with controls, the mean serum cystatin C level was significantly higher in stroke patients (1.33±0.71 versus 0.83±0.24 mg / L, p < 0.001). The diagnostic accuracy of serum cystatin C as a marker of acute ischemic stroke evaluated using Receiver Operating Characteristic (ROC) curve analysis, showed a sensitivity of 66.00 and specificity of 84.00 with an area under curve of 0.80 (and 95 % CI (0.71 - 0.87)). Conclusion: Serum cystatin C was a better marker for acute ischemic stroke and indicator of severe neurological impairment. Key words: Acute ischemic stroke, Cystatin C, NIH Stroke scale.

MRI Biomarkers in Acute Ischemic Stroke: A Conceptual Framework and Historical Analysis

Over the past 2 decades, advanced multimodal imaging has offered much promise for stroke investigators and clinicians, particularly those interested in using imaging to optimize and extend the time window for acute ischemic stroke therapies. Multimodal imaging has many potential applications in the acute stroke setting, such as the following: (1) to confirm the diagnosis of acute cerebral ischemia and exclude contraindications to treatment (eg, acute blood because of hemorrhagic transformation [HT]; (2) to select patients likely to benefit or not benefit from therapies (eg, by characterizing the extent of core irreversibly injured tissue, salvageable penumbra, or markers of high risk for HT); and (3) to serve as a surrogate or auxiliary outcome measure to test putative treatments. However, the promise of advanced multimodal imaging as a selection modality to optimize efficacy and safety of new treatments for stroke and also as a surrogate end point to test interventions has yet to be fully realized. Both of these applications use neuroimaging as a biomarker. A critical analysis of both the successes and missteps of studies performed to date, including translation of animal models to human studies, can provide valuable lessons that can be applied to the design of future studies. Applying current definitions and criteria for biomarkers to stroke neuroimaging research helps provide a conceptual framework for this analysis. The National Institutes of Health Biomarkers Definitions Working Group defines a biomarker as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.1 Biomarkers (Table 1 shows types, definitions, and examples) can be used as a diagnostic tool, a prognostic tool, a predictive tool (for predicting response to an intervention), or a substitute for a clinical outcome to measure the response to an intervention (surrogate end …

Study of Hemostatic Biomarkers in Acute Ischemic Stroke by Clinical Subtype

We studied the usefulness of hemostatic biomarkers in assessing the pathology of thrombus formation, subtype diagnosis, prognosis in the acute phase of cerebral infarction, and differences between various hemostatic biomarkers. Our study included 69 patients with acute cerebral infarction who had been hospitalized within 2 days of stroke onset. Fibrin monomer complex (FMC), soluble fibrin (SF), D-dimer, thrombin-antithrombin III complex, fibrinogen, antithrombin III, and fibrin/fibrinogen degradation products (FDPs) were assayed as hemostatic biomarkers on days 1, 2, 3, and 7 of hospitalization. In the cardioembolic (CE) stroke group, FMC and SF levels were significantly higher on days 1 and 2 of hospitalization, and D-dimer levels were significantly higher on day 1 of hospitalization, compared to the noncardioembolic (non-CE) stroke group. FDP levels were significantly higher at all times in the CE group compared to the non-CE group. Neither the National Institute of Health Stroke Scale (NIHSS) used during hospitalization nor the modified Rankin Scale (mRS) used at discharge found any significant correlations to hemostatic biomarkers, but the NIHSS score during hospitalization was significantly higher in the CE group than in the non-CE group. Measurements of hemostatic biomarkers, such as FMC, SF, and D-dimer on the early stage of cerebral infarction are useful for distinguishing between CE and non-CE stroke.

Endogenous granulocyte colony-stimulating factor: a biomarker in acute ischemic stroke

Granulocyte colony-stimulating factor (G-CSF) may protect ischemic brain injury either in animal or human. No studies have reported that endogenous G-CSF (enG-CSF) level is related to the severity of ischemic stroke. This study was designed to assess the severity of ischemic patients correlated with the alteration of enG-CSF on the 1st day after an ischemic event. Patient’s plasma enG-CSF and scoring of National Institute of Health Stroke Scale were measured on the 1st day after ischemic stroke. The acute ischemic stroke could significantly induce enG-GCF secretion as compared with healthy control group (16.77 vs. 22.86 μg/L, p = 0.001). Elevated enG-CSF concentration was positively correlated with the severity of stroke patients on day 1 after the event (p = 0.006; Spearman correlation coefficient = 0.268). The enG-CSF is a good biomarker for prediction of severity of acute ischemic stroke.

Discriminative Capacity of Biomarkers for Acute Stroke in the Emergency Department

Acute ischemic stroke remains largely a clinical diagnosis. To assess the potential of several biomarkers to distinguish acute ischemic stroke from mimics in the emergency department (ED). In this prospective study, 63 patients with suspected acute stroke were enrolled. Blood samples were collected at ED presentation and assayed for B-type natriuretic peptide, C-reactive protein (CRP), matrix metalloproteinase 9 (MMP-9), D-dimer, and protein S100B. Final diagnosis of stroke was rendered by blinded independent stroke experts after review of all clinical, imaging, and conventional laboratory data during admission. Logistic regression and bootstrapping models were used to evaluate the association between biomarker values and acute stroke. Thirty-four patients had a final diagnosis of stroke and 29 with mimics. The initial ED values of CRP, MMP-9, and S100B (C-indices of 0.808, 0.811, and 0.719, respectively) and the National Institutes of Health Stroke Scale (NIHSS) (C-index 0.887) predicted acute cerebral ischemia. CRP levels added discriminative value over clinical variables alone in the diagnosis of stroke. When the levels of CRP were added to the NIHSS, the combination was highly predictive of stroke (bootstrap mean C-index 0.951, 90% Confidence Interval 0.903-0.991, likelihood test p = 0.004). Biomarker testing with CRP and potentially MMP-9 and S100B, may add valuable and time-sensitive diagnostic information in the early evaluation of patients with suspected stroke in the ED. Future prospective evaluations are necessary to validate the diagnostic capability of these biomarkers for acute ischemic stroke in the ED before they should be considered for use in clinical practice.

Serum free hemoglobin as a novel potential biomarker for acute ischemic stroke

Currently, no practical biomarker is available for the diagnosis of acute ischemic stroke. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has being applied extensively to analyze large biomolecules such as proteins. The technique is likely to be of remarkable value as indicators of systemic processes such as atherosclerosis and stroke. The aim of this study is to identify potential protein biomarkers for ischemic stroke diagnosis utilizing MALDI-TOF MS. Serum samples obtained from acute ischemic stroke patients (n = 47) and controls (n = 34) were analyzed by MALDI-TOF MS. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS), subtype by the Trial of Org 10172 in Acute Stroke Treatment (TOAST), functional outcome by the modified Rankin Scale (mRS) and infarct volume by the diffusion-weighted images. Risk factors and routine laboratory data of the stroke patients were registered prospectively. The peaks of hemoglobin (Hb) alpha-chain and beta-chain were differentially expressed between stroke patients and controls (p < 0.0001). Hb ions were detected in the samples collected from 33 (70.2%) stroke patients and 5 (14.7%) controls. The sensitivity is 70.2% and the specificity is 85.3%. Among stroke patients, there is no significant correlation (p > 0.05) between Hb peaks and the NIHSS, TOAST, mRS, stroke risk factors, infarct volume, infarct location and laboratory data. Serum free Hb may serve as a novel potential biomarker for the diagnosis of acute ischemic stroke. The clinical value of this potential biomarker may be clarified by further studies quantifying serum free Hb levels.