Biomarkers For Acute Stroke Research Articles

NR2 antibodies as diagnostic and prognostic stroke biomarker

Given the high percentage of disability and mortality resulting from a stroke, search of new ways to improve early diagnosis and optimize therapeutic approaches is highly relevant. The article reviews the studies of NR2 antibodies to glutamate N-methyl-D-aspartate (NMDA) receptors as a biomarker in acute stroke. The review shows that this biomarker is suitable for determining the presence of ischemic process in the brain and the degree of destruction of brain tissue, both in the first hours of stroke and at follow-up. In addition, the analysis of NR2 antibodies can be informative to predict the worsening, the increase in the locus size, which can contribute to the timely correction of treatment and will improve the effectiveness of the therapy. The prognostic potential of NR2 antibodies can be used for personalized therapeutic approach. However, currently the lack of studies of NR2 antibodies in acute stroke requires further study of this biomarker.

Abstract TP212: 24 S -Hydroxycholesterol as a Serum Biomarker for Acute Stroke

Introduction: Several serum based biomarkers for acute stroke have been identified, but the clinical values of these biomarkers have not been realized due to inadequate sensitivity and specificity in their measurements. 24 S -Hydroxycholesterol is a stable metabolite of cholesterol synthesized by neurons of the CNS, and released to the serum at a constant rate. Hypothesis: We hypothesized that serum 24 S -Hydroxycholesterol would be an ideal biomarker for acute stroke. Methods: Acute stroke patients presenting to ED were enrolled after informed consent. Serum samples were collected in ED and levels of 24 S -Hydroxycholesterol were determined by mass spectrometry. We enrolled 63 patients from October 2015 to October 2016. Of these 63 patients, 60 presented within 8 hours from onset of symptoms. Patients were categorized as no stroke, ischemic stroke, and intracerebral hemorrhage. We compared serum 24 S -Hydroxycholesterol levels in each group and the variation in 24 S -Hydroxycholesterol levels with regard to presenting NIHSS. Result: Out of the 63 patients enrolled, 22 did not have a stroke, 36 had ischemic stroke, and 5 had intracerebral hemorrhage. The mean 24 S -Hydroxycholesterol levels were 54 ng/ml, 58 ng/ml and 75 ng/ml in the no stroke group, ischemic stroke group and intracerebral hemorrhage group, respectively. No correlation was observed between NIHSS and 24 S -Hydroxycholesterol levels. Difference in 24 S -Hydroxycholesterol levels between no stroke and intracerebral hemorrhage patients was statistically significant, but was limited by the small sample size (P = 0.047). Conclusion: 24 S -Hydroxycholesterol may be a useful serum biomarker for intracerebral hemorrhage. Analyses in a larger population is needed to determine the practical importance of this biomarker.

脳卒中急性期におけるバイオマーカー：脳卒中とAGE-RAGE

脳卒中急性期におけるバイオマーカー：脳卒中とAGE-RAGE

Circulating MicroRNAs as Novel Potential Biomarkers for Early Diagnosis of Acute Stroke in Humans

Many diseases include microRNAs (miRNAs) as reported biomarkers. The significance of circulating miRNAs for early diagnosis of acute stroke in humans is unknown. We aim to determine whether circulating miRNAs potentially serve as novel biomarkers for acute stroke. We prospectively recruited patients with acute stroke and those with nonstroke disease. Patients with acute stroke were identified using magnetic resonance imaging (MRI) for early diagnosis. If the patient suffered from acute stroke that was detected with diffusion-weighted imaging, the patient was defined as an MRI(+) patient. Otherwise, it was defined as an MRI(-) patient. Circulating miRNAs were measured by miRNA microarray and real-time polymerase chain reaction (PCR) analysis. A total of 136 patients were included in the study. Testing by miRNA microarray and real-time PCR analyses showed that hsa-miR-106b-5P and hsa-miR-4306 were present with markedly high abundance in patients of acute stroke, whereas hsa-miR-320e and hsa-miR-320d were present with quite low abundance in patients compared with healthy individuals. Compared with healthy individuals, the miRNAs were increased as in patients with acute stroke as follows: hsa-miR-106b-5P, 3.63-fold in MRI(-) patients and 23.90-fold in MRI(+) patients; hsa-miR-4306, 3.19-fold in MRI(-) patients and 5.30-fold in MRI(+) patients; hsa-miR-320e, .33-fold in MRI(-) patients and .13-fold in MRI(+) patients; and hsa-miR-320d, .23-fold in MRI(-) patients and .07-fold in MRI(+) patients. Elevated hsa-miR-106b-5P and hsa-miR-4306 and decreased hsa-miR-320e and hsa-miR-320d in plasma may be novel biomarkers for the early detection of acute stroke in humans.

Elevated T2-values in MRI of stroke patients shortly after symptom onset do not predict irreversible tissue infarction

Distinct from signal alterations in diffusion-weighted images, T(2)-values are also dependent on tissue water content and known to increase with time from symptom onset in acute ischaemic stroke. The purpose of this study was to evaluate whether there is a detectable increase of T(2)-values in different regions in acute ischaemic stroke in the acute and subacute situation and to study the effect of recanalization on the evaluation of T(2)-values in the subacute phase. In addition, we sought to evaluate whether this increase in T(2)-values is reversible. For this purpose, 22 patients with acute ischaemic stroke in the territory of the middle cerebral artery underwent magnetic resonance imaging including diffusion-weighted imaging, perfusion-weighted imaging, fluid-attenuated inversion recovery to determine final infarct size, time-of-flight-angiography (acute and on day 1 or 2) and a triple echo-T(2)-sequence (calculation of T(2) maps) within 6 h after symptom onset. Images were co-registered and regions of diffusion restriction and prolonged time-to-peak as well as surviving tissue (surviving tissue = time-to-peak - final infarct size) and lesion growth (lesion growth = final infarct size-diffusion restriction) were defined and superimposed onto the quantitative T(2) map. In addition, patients were dichotomized according to recanalization information. Mean quantitative T(2)-values were derived for each patient within each region of interest. Mean T(2)-values for patients with recanalization (n = 15) in surviving tissue region of interest were 115.8 ± 7.2 ms (mean ± SD) and in the lesion growth region of interest 114.6 ± 7.0 ms. T(2)-values for patients without recanalization (n = 7) were 117.7 ± 11.4 ms in surviving tissue region of interest and 117.3 ± 12.1 ms in lesion growth region of interest. There was no significant difference between T(2)-values measured in lesion growth and surviving tissue region of interest for patients with or without recanalization. Even though it has been shown that T(2)-values increase with time from symptom onset within the infarct core, increased T(2)-values in areas of perfusion impairment do not identify irreversible damaged brain tissue and high T(2)-values are even found in tissue that is not part of the final infarct lesion and can therefore normalize. In conclusion, this study suggests that T(2)-values are not a valid imaging biomarker in acute stroke to predict tissue outcome.