Stroke Biomarkers Research Articles

Routine serum C-reactive protein and stroke outcome after intravenous thrombolysis

The clinical usefulness of blood biomarkers in acute stroke is not yet fully established, especially after thrombolytic therapy. Our aim was to investigate the association between routine serum C-reactive protein (CRP) measured within 24h after admission and outcome in ischaemic stroke patients treated with intravenous thrombolysis, adjusting for a history of recent infection. We analysed the data of consecutive stroke patients who received intravenous alteplase in our centre between October 2003 and December 2011, collected in a detailed prospective registry. Routine serum CRP was measured within 24h from admission; concentration >5ng/ml was considered elevated. Serum CRP was measured in 341 of 406 stroke patients treated with alteplase. Patients with elevated CRP (135/341, 42.5%) compared to those with normal CRP values, were significantly older, more frequently presented with a preexisting disability, comorbidities and suffered more severe strokes. They had a higher proportion of symptomatic intracranial haemorrhage according to ECASS II definition (7.2% vs 1.6%, P=0.010), higher 3-month mortality (25.6% vs 11.3%, P=0.001), and were less frequently alive and independent after 3months (45.9% vs 63.7%, P=0.002). However, those associations were not confirmed after adjustment for age, stroke severity, diabetes, congestive heart failure, lack of prestroke disability and signs of recent infection. According to our findings, elevated routine serum CRP measured within 24h after admission does not seem to independently affect the outcome in patients receiving intravenous thrombolysis for stroke. However, further studies of blood samples taken directly before the treatment are needed.

Stroke care in West Bohemia – personalised medicine approach

Cerebrovascular disease is the third main cause of death and the leading cause of disablement in the Czech Republic. The incidence of stroke is higher than in Western European countries and is one of causes of lower average age in this country. The data of 15880 stroke patients who entered into the IKTA stroke register from 13 Czech stroke centres in the year 2010 and 2011 indicates higher proportion of stroke recurrence and unfavourable patient risk profile than in other Western European countries. Three major risk factors well–defined are arterial hypertension (identified in 86.2% of patients), dyslipidemia (58.2%) and diabetes mellitus (34.9% of stroke patients). Three or more risk factors were found in 80.7% of stroke patients. The incidence of vascular risk factors in stroke patients is significantly higher than stated in the literature and this unfavourable risk profile may be the main cause of the high incidence of stroke and its recurrence in Czech Republic. Stroke is a typical heterogeneous entity. In April 2010 the Ministry of Health published a document “Cerebrovascular Care in the Czech Republic, Constitution of Stroke Centres”. 11 Complex Cerebrovascular Centres and 23 Cerebrovascular Centres covering the whole area of the Czech Republic were constituted with intension to admit, diagnose and, if necessary, treat all new stroke patients, who had been formerly treated in the departments of internal medicine of any hospitals in the country. The aim is to provide complex, optimal and personalised care in acute phase of stroke, provide early rehabilitation and provide or propose optimal second prevention. Faculty Hospital Pilsen incorporates a long-term experience with stroke care and is one of two hospitals where patients with ischaemic stroke were first treated with intravenous thrombolysis in our country. The stroke care is coordinated by the Department of Neurology with its Stroke Unit and Stroke Team. The cooperation with neuroradiology, neurosurgery, cardiology, biochemical and immunoanalytic laboratories, pathology, genetics and some other specialities in Faculty Hospital and in Faculty of Medicine in Pilsen of Charles University in Prague is well established as well as the cooperation with Emergency Medical Service. Due to these facts West Bohemia region with 589 thousands of habitants has only one Complex Cerebrovascular Centre and no one or two smaller Cerebrovascular Centres as is usual in other regions. The advantage of this situation is the concentration of all stroke patients into the best equipped facility. Due to this fact stroke patients in West Bohemia are well diagnosed and treated. Exact data (numbers of thrombolytic, neurosurgical therapy, neuroradiological interventions and their proportion to all stroke patients) are presented. Special research project “Study of Variety Stroke Biomarkers in Acute Stroke Patients in the Context of Personalised Medicine“, supported by Czech Ministry of Health is being solved in our centre from the year 2011. Its main goal is to test the effectiveness of variety of stroke biomarkers and implement them into the personalised stroke care. Supported by Ministry of Health, Czech Republic - conceptual development of research organization (Faculty Hospital Pilsen - FNPl, 00669806) and by the project ED2.1.00/03.0076 from European Regional Development Fund.

Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke.

In 1995, the NINDS (National Institute of Neurological Disorders and Stroke) tPA (tissue plasminogen activator) Stroke Study Group published the results of a large multicenter clinical trial demonstrating efficacy of intravenous tPA by revealing a 30% relative risk reduction (absolute risk reduction 11%–15%) compared with placebo at 90 days in the likelihood of having minimal or no disability. Since approval in 1996, tPA remains the only drug treatment for acute ischemic stroke approved by the US Food and Drug Administration. Over the years, an abundance of research and clinical data has supported the safe and efficacious use of intravenous tPA in all eligible patients. Despite such supporting data, it remains substantially underutilized. Challenges to the utilization of tPA include narrow eligibility and treatment windows, risk of symptomatic intracerebral hemorrhage, perceived lack of efficacy in certain high-risk subgroups, and a limited pool of neurological and stroke expertise in the community. With recent US census data suggesting annual stroke incidence will more than double by 2050, better education and consensus among both the medical and lay public are necessary to optimize the use of tPA for all eligible stroke patients. Ongoing and future research should continue to improve upon the efficacy of tPA through more rapid stroke diagnosis and treatment, refinement of advanced neuroimaging and stroke biomarkers, and successful demonstration of alternative means of reperfusion.

Abstract W MP39: Basic Fibroblast Growth Factor after Ischemic Stroke in Diabetic Patients - Research for Biomarkers in Ischemic Stroke (REBIOS)

Background: In patients with diabetes mellitus (DM), functional outcome after ischemic stroke is poor. However, the precise mechanisms remain unclear. We hypothesized that basic fibroblast growth factor (bFGF), a neurotrophic/growth factor, does not function after ischemic stroke in DM patients compared with in non-DM ones. Methods and Results: We recruited 171 patients with ischemic stroke from the Fukuoka Stroke Registry, a prospective multi-centered study for acute stroke in Japan, and age- and sex- matched healthy subjects. Blood samples were obtained at five time points after the onset, day 0 (within 24 hours), 3, 7, 14 and 90. Plasma bFGF values were measured by Human MAP® v1.6, a multiplexed immunoassay (Myriad RBM, Inc.). Plasma bFGF was significantly higher in stroke patients at day 0 than in the controls (162.1 ± 21.0 vs. 91.0 ± 8.1 pg/ml, p = 0.001). The concentration of bFGF remained high during 90 days after onset. Unexpectedly, bFGF was significantly higher in patients with DM than in those without DM (180.8 ± 19.5 vs. 127.5 ± 13.1 pg/ml, p = 0.033), while the presence of DM did not associate with bFGF levels in healthy controls. Plasma bFGF was correlated positively with HbA1c ( p = 0.037), causal plasma glucose ( p = 0.048), and ICAM-1 ( p = 0.032) / VCAM-1 ( p = 0.086), representative adhesion molecules expressed in endothelial cells. In a mouse middle cerebral artery occlusion (MCAO) stroke model, bFGF expression in streptpzotocin-induced diabetic mice was significantly greater in ischemic hemisphere than in contralateral hemisphere. Immunohistochemical examination demonstrated that bFGF was expressed highly in vWF + endothelial cells, desmin + pericytes, and MAP2 + neurons, in peri-infarct areas after MCAO. Conclusion: Plasma bFGF was increased after ischemic stroke, which was prominent in DM patients. The presence of hyperglycemia in acute ischemic stroke may affect the expression of bFGF in various cell types in peri-infarct areas, which in turn may be associated with endothelial function, including the expression of adhesion molecules.

Abstract W P143: Race-specific Effects of Inflammatory and Vascular Remodeling Biomarkers in Ischemic Stroke

Background: Blacks have a higher risk of stroke than whites; inflammatory and vascular remodeling (VR) biomarkers may mediate this risk. We aimed to determine associations between inflammatory and VR biomarkers and ischemic stroke in a bi-racial sample of the Atherosclerosis Risk In Communities (ARIC) cohort. Methods: In a case-control pilot study, 133 participants from Forsyth and Jackson Field Centers were identified: 32 blacks and 33 whites with first ischemic stroke after visit 2, and 33 black and 35 white stroke-free controls. We assayed IL-8, IL-10, IL-1 receptor antagonist (IL-1ra), IL-1β, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) with Quantikine ELISA. We calculated IL-1β/IL-1ra ratio, representing the IL-1 pathway. Biomarkers were covariates in race-specific logistic regression models; if significant, biomarker-by-race interactions were explored. Results: Cases were older (mean age 60y vs 56y; p<0.0001); more had hypertension (52% vs 35%; p=0.043), and diabetes (35% vs 13%; p=0.0034). There were no differences in biomarkers between blacks and whites (cases and controls). In blacks, there was a trend toward a reduced risk of stroke with increasing levels of IL-1ra after adjustment (p=0.074). In whites, stroke was associated with higher levels of TIMP-1 (p=0.011; interaction p=0.079) and with higher levels of IL-8 (p=0.011; interaction p=0.11) in the unadjusted, but not adjusted model (Table). Conclusion: We identified race-specific associations between biomarkers and incident stroke. VR biomarkers (TIMP-1) may be associated with stroke in whites, and there was a trend towards lower levels of IL-1ra (counter-inflammatory) and risk of stroke in blacks. Larger studies are warranted to confirm these findings and determine if these markers will explain differences in stroke risk in blacks vs whites.

Abstract T P32: Computer Aided Detection of Asymptomatic Cerebral Microbleeds on Magnetic Resonance Images

Purpose: Manual rating of Cerebral microbleeds (CMBs) is time-consuming and inconsistent. Since the presence and number of CMBs have become a potential diagnostic and prognostic biomarker of stroke, an automatic identification method is required. We proposed a computer aided diagnosis (CAD) system for the detection of the CMBs on the magnetic resonance (MR) images automatically. Methods: Eighty-one patients were recruited in this study. CMBs on the MR T2* weighted images were manually rated according to the Microbleed Anatomic Rating Scale (MARS) criteria. Our automated method consisted of two steps: i) Pre-processing: After skull stripping, isolated islands of points were removed while holes were restored to avoid over segmentation. Local threshold segmentation was applied for the initial candidate selection. ii) Identification model: Seven features were extracted from each candidate: area, roundness, intensity, average of the boundary, contrast, shape-intensity and location-mark (according to the probability density templates calculated from the location information of the CMBs). For further identification of each candidate, Random Forest (RF) model was used to distinguish CMBs from the mimics. Results: A total of 337 CMBs in the 81 patients were studied. Comparing with the counting from the experienced doctors, high sensitivity of 92% (310/337) was achieved after pre-processing. The RF model eliminated most of the false-positives while maintaining a reliable sensitivity of 94% (291/310) and specificity of 96% (4272/4450). The area under the Receiver operating characteristic curve was 0.98 ± 0.02 for the detection model. In summary, this CAD system had an overall sensitivity of 86% (291/337) and specificity of 96% (4272/4450), producing only 2.2 false-positives per subject. Conclusion: This presented strategy is technically effective. The results indicate that it has the potential to be used for clinical detection of CMBs.

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.

Circulating MicroRNAs as Biomarkers of Acute Stroke

MicroRNAs have been identified as key regulators of gene expression and thus their potential in disease diagnostics, prognosis and therapy is being actively pursued. Deregulation of microRNAs in cerebral pathogenesis has been reported to a limited extent in both animal models and human. Due to the complexity of the pathology, identifying stroke specific microRNAs has been a challenge. This study shows that microRNA profiles reflect not only the temporal progression of stroke but also the specific etiologies. A panel of 32 microRNAs, which could differentiate stroke etiologies during acute phase was identified and verified using a customized TaqMan Low Density Array (TLDA). Furthermore we also found 5 microRNAs, miR-125b-2*, -27a*, -422a, -488 and -627 to be consistently altered in acute stroke irrespective of age or severity or confounding metabolic complications. Differential expression of these 5 microRNAs was also observed in rat stroke models. Hence, their specificity to the stroke pathology emphasizes the possibility of developing these microRNAs into accurate and useful tools for diagnosis of stroke.

Risk factors and biomarkers of ischemic stroke in cancer patients.

Background and PurposeStroke is common among cancer patients. However, risk factors and biomarkers of stroke in cancer patients are not well established. This study aimed to investigate risk factors and biomarkers as well as etiology of ischemic stroke in cancer patients.MethodsA retrospective review was conducted in cancer patients with ischemic stroke who were admitted to a general hospital in Busan, Korea, between January 2003 and December 2012. The risk factors and biomarkers for stroke and stroke subtypes in cancer patients were compared with age- and sex-matched noncancer patients with ischemic stroke who were admitted to the same hospital during the same period.ResultsOne hundred fifty-six cancer patients with ischemic stroke were identified. Cancer patients with ischemic stroke were found to have a significantly lower proportion of hypertension, atrial fibrillation, hyperlipidemia, and ischemic heart disease than noncancer patients with ischemic stroke. However, stroke biomarkers, such as erythrocyte sedimentation rate and high-sensitivity C-reactive protein, fibrinogen, pro-brain natriuretic peptide, and D-dimer levels, were significantly increased in cancer patients with ischemic stroke than in noncancer patients. Large-artery atherosclerosis and stroke of undetermined cause were more common in cancer patients with ischemic stroke than in noncancer patients with ischemic stroke.ConclusionsCancer patients with ischemic stroke showed different risk factors, stroke biomarkers, and stroke etiology compared with noncancer patients with ischemic stroke.

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.

Circulating miR-30a, miR-126 and let-7b as biomarker for ischemic stroke in humans

BackgroundRecently, plasma miRNAs have been reported as biomarkers for various diseases. However, the knowledge on the association of plasma miRNAs with ischemic stroke is still lacking. In this study, we investigated whether plasma concentrations of miR-30a, miR-126 and let-7b may be biomarkers for ischemic stroke in humans.MethodsOne hundred ninety seven patients with ischemic stroke were recruited and their blood samples were collected at 24 h, 1 week, 4 weeks, 24 weeks and 48 weeks after symptoms onset, and fifty healthy volunteers were selected as control. Levels of miRNA were quantified by quantitative real-time PCR. Relative expression level of miRNA was calculated using 2-ΔΔct method. The ability to distinguish the ischemic stroke group from control group was characterized by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was calculated.ResultsCirculating miR-30a and miR-126 levels were markedly down-regulated in all patients with ischemic stroke until 24 weeks. However, circulating let-7b was lower in patients with large-vessel atherosclerosis than healthy volunteers, whereas circulating let-7b had higher level in patients with other kinds of ischemic stroke until 24 weeks. Among all patients, circulating miRNAs levels returned to normal 48 weeks after symptom onset. Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUC) of plasma miR-30a were 0.91, 0.91, 0.92 and 0.93, the miR-126 were 0.92, 0.94, 0.93 and 0.92, and let-7b were 0.93, 0.92, 0.92 and 0.91 at 24 h, 1 w, 4 w and 24 w, respectively.ConclusionsThese data suggest that miR-30a, miR-126 and let-7b might be useful biomarkers for ischemic stroke in humans.

The association between routine serum C-reactive protein and outcome in ischemic stroke patients treated with intravenous alteplase

The association between routine serum C-reactive protein and outcome in ischemic stroke patients treated with intravenous alteplase

MicroRNA: Not Far from Clinical Application in Ischemic Stroke

Ischemic stroke predominates in all types of stroke and none neuroprotective agents success in the clinical trial. MicroRNAs are small endogenous noncoding RNA molecules that act as negative or positive regulators of gene expressions by binding completely or partially to complementary target sequences in the mRNAs. The genes which could be modulated by microRNAs play a role in the etiology and pathophysiology ischemic stroke. Therefore, microRNAs may have function on ischemic stroke. A lot of previous studies have investigated the roles of microRNAs in the ischemic stroke. This mini review would highlight the recent progress of microRNAs on the ischemic stroke. Accumulating evidence demonstrated that microRNAs contributed to the etiology of ischemic stroke and modulated the pathophysiological process such as brain edema, local inflammation, and apoptosis in the brain tissues after stroke. And we also discussed the potential application of microRNAs in ischemic stroke such as a biomarker of stroke and drug target. In conclusion, microRNAs play an important role in stroke etiology, pathophysiology, diagnosis, and therapy for ischemic stroke. It needs further research to investigate the biological function in ischemic stroke before it enters the clinical practice.

Serum microRNA-21 and microRNA-221 as Potential Biomarkers for Cerebrovascular Disease

Background/Aims: MicroRNA miR-21, miR-221 and miR-145 have been implicated in the cardiovascular system. We aimed to compare the serum levels of the three microRNAs (miRNAs) in different severities of cerebrovascular diseases and evaluate the feasibility of using these miRNAs as biomarkers for stroke. Methods: We enrolled 167 subjects with ischemic stroke, 66 atherosclerosis subjects with any carotid plaque score and 157 healthy controls. These three types of subjects represent three levels of severity in cerebrovascular diseases. Analysis of covariance was used to evaluate the relationship between miRNAs and disease severity with adjustment for conventional risk factors. To test the prediction for stroke, we built regression models containing the serum miRNA levels and risk factors. Prediction capabilities were compared by the receiver operating characteristic curves. Results: Stroke patients and atherosclerosis subjects had significantly higher miR-21 and lower miR-221 serum levels than healthy controls, while the miR-145 expression was too low to provide useful information in this regard. The best model showed that miR-21 and miR-221 were independent predictors. There was a 6.2-fold increase for stroke risk when miR-21 levels increase by log₁₀2^-ΔCt = 1, while a 10.4-fold increase was observed as miR-221 decreases by log₁₀2^-ΔCt = 1. Conclusions: Serum miR-145 was not detected in over 50% of the patients and it may not be an ideal marker to predict stroke. MiR-21 and miR-221 are novel biomarkers for atherosclerosis and stroke.

Decreased Leukocyte Telomere Length (LTL) Is Associated with Stroke but Unlikely to Be Causative

AimsInterindividual variability in telomere length is highly heritable. Leukocyte telomere length (LTL) shortening has been shown to be associated with the process of atherosclerosis. But whether the inheritance of LTL is related to stroke is still unclear. The aim of this study was to test if telomere shortening was associated with stroke and whether this association was mainly due to inheritance or acquired cardiovascular risk factors.MethodsOur study was focused on stroke in patients and their siblings. 450 subjects were recruited into this study: 150 patients with ischemic stroke as case group, 150 siblings of patients free of stroke (sibling group) and 150 healthy people as normal control. LTL was measured by real-time Polymerase Chain Reactions. The association between LTL and the cardiovascular risk factors was also determined.ResultsA significant decrease of LTL was found in case group when comparing with sibling (0.92±0.77 vs 1.68±1.24, p<0.001) and normal groups (0.92±0.77 vs 1.95±1.07, p<0.001), but no significant difference was found between sibling group and healthy control (p = 0.330). Shorter telomere length was independently associated with hypertension (p = 0.029, OR = 2.189, 95%CI:1.084–4.421), recent social pressure (p = 0.001, OR = 3.121, 95%CI:1.597–6.101), age (p = 0.004, OR = 1.055, 95%CI:1.017–1.093), HDL (p = 0.022, OR = 0.227, 95%CI:0.064–0.810) and diabetes (p = 0.018, OR = 3.174, 95%CI:1.221–8.252). Additionally, shortened length of telomere (p = 0.017, OR = 3.996, 95%CI:1.283–12.774) was an independent risk biomarker for stroke among case and sibling groups.ConclusionThe present study has demonstrated that decreased LTL might be associated with ischemic stroke but unlikely to be causative.

Capillary-based enzyme-linked immunosorbent assay for highly sensitive detection of thrombin-cleaved osteopontin in plasma

In this study, a highly sensitive capillary-based enzyme-linked immunosorbent assay (ELISA) has been developed for the analysis of picomolar levels of thrombin-cleaved osteopontin (trOPN), a potential biomarker for ischemic stroke, in human plasma. Using a square capillary coated with 8.5μg/ml anti-human trOPN capture antibody for ELISA, the linear range obtained was 2 to 16pM trOPN antigen. This concentration range was in the detection window of trOPN antigen in plasma samples. Compared with the conventional microplate-based ELISA, the current capillary technique significantly reduced the amounts of reagent from milliliter to microliter, reduced the analysis time from 8 to 3h, and had a better sensitivity and detection limit performance from approximately 50pM down to 2pM of trOPN antigen. These results indicate that this capillary-based immunoassay is a potential tool for biomarker detection and may be useful in clinical trials and medical diagnostic applications.

RNA-based blood genomics as an investigative tool and prospective biomarker for ischemic stroke

Stroke is a leading cause of death and disability, and considerable effort is being expended to investigation of its pathological mechanisms, as well as the identification of clinically relevant biomarkers that could assist in diagnosis. RNA-based analysis of gene expression in blood represents a new field of study addressing both paradigms. A number of recent animal and human studies using microarray technology demonstrate rapidly-induced, measurable changes in gene expression in response to ischemic trauma, and distinct expression 'profiles' specific to the injury subtype. The incorporation of newer technologies for a more detailed transcriptome analysis holds great promise for further improving our knowledge of stroke at the molecular level, and potentially enhancing standards of diagnosis.

Whole Genome Expression of Cellular Response to Stroke

Many attempts have been made at developing biomarkers for stroke. Although successful to some degree,1–3 none have been sufficiently robust to be used in clinical practice. Thus, there is still a great need for more in-depth studies of the biology of human stroke to understand its pathogenesis better. This should make it possible to develop blood tests for stroke and transient ischemic attacks (TIAs) to guide treatment and ultimately improve outcomes. The traditional approach to develop stroke biomarkers has been to select candidate markers based on known pathobiology. The majority of markers that have been evaluated are proteins that are measured in patients at various times before or after stroke. The rationale for this approach is that brain injury releases molecules into blood that can be measured as evidence of brain injury; or that other cells and organs release molecules that either cause or contribute to a stroke, or are a response to the stroke. These approaches have been handicapped because they require a guess at the most reliable biomarker. Our group took a different approach to the problem by assessing the immune system after stroke.4,5 The rationale for this approach is shown in Figure 1. The expression of genes in leukocytes is influenced by many factors associated with ischemic stroke. Leukocytes interact with blood clots, platelets, atherosclerotic plaque, and injured brain endothelial cells via adhesion molecules.5 In addition, leukocytes detect circulating cytokines, chemokines, and hormones. Each has the potential to modulate RNA expression in leukocytes. Figure 1. Schematic of interactions between circulating leukocytes and factors involved in ischemic stroke, including blood clots, platelets, atherosclerotic plaque, and damaged endothelial cells. Each factor can influence expression of leukocyte RNA. This figure is reproduced from an article by Sharp et al.5 To provide proof-of-principle that …

A preliminary method development study to identify potential stroke biomarkers in plasma using multiple chromatographies with nanoLC-ESIMS detection

Stroke is the leading cause of disability in the USA. Rapid, reliable diagnosis via a point-of-care blood test may facilitate earlier treatment to reduce disability. We have recently reported detailed methods of chromatographic separations of plasma samples coupled with nanoESI-ion trap a list of proteins which are viable candidates for further investigation as stroke biomarkers.

Exploring molecular mechanism underlying Chinese medicine syndrome: A study on correlation between Chinese medicine syndrome and biomarkers for ischemic stroke

To investigate whether Chinese medicine (CM) syndrome is associated with particular molecular mechanism, we explored the correlation between CM syndrome and changes of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase 9 (MMP-9) and heat shock protein 70 (HSP70) in patients with ischemic stroke, which were reported to play an important role in the inflammatory and apoptosis cascade. CM syndrome factors of 175 patients with ischemic stroke were assessed using Ischemic Stroke CM Syndrome Factor Diagnostic Scale (ISTSFDS). The patients were grouped according to the main syndrome factor combinations at different time points based on distribution probability of syndrome factor combinations. Blood levels of ICAM-1, MMP-9 and HSP70 were quantified by enzyme-linked immunosorbent assay. ICAM-1 expression was significantly higher in the internal-wind+phlegm-dampness+blood-stasis, phlegmdampness+ blood-stasis, internal-fire+phlegm-dampness+blood-stasis group than that in the blood-stasis+qideficiency group within 72 h from stroke onset (P <0.05); HSP70 expression was significantly lower in the phlegm-dampness+blood-stasis, internal-fire+phlegm-dampness+blood-stasis, blood-stasis group than that in the phlegm-dampness+blood-stasis+qi-deficiency group on the 7th day from stroke onset (P<0.05). Phlegm-dampness and blood-stasis exist through the whole process of ischemic stroke. An increased level of ICAM-1 and a reduced level of HSP70 reflect the pathological state of phlegm-stasis mutual binding. These results suggest that inflammation and apoptosis induced by cerebral vascular injury in the pathological processes of ischemic stroke are more prominent in the excess syndrome state like phlegm-dampness and blood-stasis.