Diagnostic Potential of the NMDA Receptor Peptide Assay for Acute Ischemic Stroke

Background The acute assessment of patients with suspected ischemic stroke remains challenging. The use of brain biomarker assays may improve the early diagnosis of ischemic stroke. The main goal of the study was to evaluate whether the NR2 peptide, a product of the proteolytic degradation of N-methyl-D-aspartate (NMDA) receptors, can differentiate acute ischemic stroke (IS) from stroke mimics and persons with vascular risk factors/healthy controls. A possible correlation between biomarker values and lesion sizes was investigated as the secondary objective. Methods and Findings A total of 192 patients with suspected stroke who presented within 72 h of symptom onset were prospectively enrolled. The final diagnosis was determined based on clinical observations and radiological findings. Additionally gender- and age-matched healthy controls (n = 52) and persons with controlled vascular risk factors (n = 48) were recruited to compare NR2 peptide levels. Blinded plasma was assayed by rapid magnetic particles (MP) ELISA for NR2 peptide within 30 min and results for different groups compared using univariate and multivariate statistical analyses. There was a clinical diagnosis of IS in 101 of 192 (53%) and non-stroke in 91 (47%) subjects. The non-stroke group included presented with acute stroke symptoms who had no stroke (n = 71) and stroke mimics (n = 20). The highest NR2 peptide elevations where found in patients with IS that peaked at 12 h following symptom onset. When the biomarker cut off was set at 1.0 ug/L, this resulted in a sensitivity of 92% and a specificity of 96% to detect IS. A moderate correlation (rs = 0.73) between NR2 peptide values and acute ischemic cortical lesions (\u3c200 \u3emL) was found. Conclusions This study suggests that the NR2 peptide may be a brain specific biomarker to diagnose acute IS and may allow the differentiation of IS from stroke mimics and controls. Additional larger scale clinical validation studies are required

Long Lasting Local and Systemic Inflammation after Cerebral Hypoxic ischemia in Newborn Mice

Background: Hypoxic ischemia (HI) is an important cause of neonatal brain injury and subsequent inflammation affects neurological outcome. In this study we performed investigations of systemic and local activation states of inflammatory cells from innate and adaptive immunity at different time points after neonatal HI brain injury in mice. Methodology/Principal Findings: We developed a multiplex flow cytometry based method combined with immunohistochemistry to investigate cellular immune responses in the brain 24 h to 7 months after HI brain injury. In addition, functional studies of ex vivo splenocytes after cerebral hypoxic ischemia were performed. Both central and peripheral activation of CD11b + and CD11c + antigen presenting cells were seen with expression of the costimulatory molecule CD86 and MHC-II, indicating active antigen presentation in the damaged hemisphere and in the spleen. After one week, naïve CD45rb + T-lymphocytes were demonstrated in the damaged brain hemisphere. In a second phase after three months, pronounced activation of CD45rb 2 T-lymphocytes expressing CD69 and CD25 was seen in the damaged hemisphere. Brain homogenate induced proliferation in splenocytes after HI but not in controls. Conclusions/Significance: Our findings demonstrate activation of both local and systemic immune responses months after hypoxic ischemic neonatal brain injury. The long term immune activation observed is of general importance for future studies of the inflammatory response after brain injury as most previous studies have focused on the first few weeks afte

Biomarkers for Traumatic Brain Injury

Due to injuries sustained in sports and in combat, interest in TBI has never been greater. Biomarkers for Traumatic Brain Injury will fulfil a gap in our understanding of what is occurring in the brain following injury that can subsequently be detected in biological fluids and imaging. This knowledge will be useful for all researchers and clinicians interested in the biochemical and structural sequelae underpinning clinical manifestations of TBI and help guide appropriate patient management. Current and prospective biomarkers for the assessment of traumatic brain injury (TBI), particularly mild TBI, are examined using a multidisciplinary approach involving biochemistry, molecular biology, and clinical chemistry. The book incorporates presentations from outstanding researchers and clinicians in the area and describes advanced proteomic and degradomic technologies in the development of novel biomarker assays. For practical purposes, the focus of this volume is on detection of blood-based biomarkers to improve diagnostic certainty of mild TBI in conjunction with radiological and clinical findings. It represents contributions from internationally-recognized researchers at the forefront of traumatic brain injury many of whom are recipients of grants and contracts from the United States Department of Defense for research specifically on developing diagnostic tests for TBI. The book will be essential reading for scientists, pharmacologists, chemists, medical and graduate students

THE IMAGE OF THE DAUGHTER-IN-LAW IN FOLKLORE OF THE TURKIC-MONGOLIAN PEOPLES OF SIBERIA

Образ невестки в фольклоре тюрко-монгольских народов рассматривается с точки зрения ограничений и установления определенного социального статуса. Значение многочисленных свадебных, досвадебных и послесвадебных обрядов, раскрывается в образцах устного народного творчества. Семантический анализ пословиц и поговорок раскрывает значение и основные функции традиционно приписываемых невестке.The image of a daughter-in-law in the folklore of the Turkic-Mongolian peoples was considered from the point of view of restrictions and the establishment of a certain social status. The meaning of numerous wedding, pre-wedding and post-wedding rituals is revealed in examples of oral folk art. Semantic analysis of proverbs and sayings reveals the meaning and main functions traditionally attributed to the daughter-in-law

AMPAR Peptide Values in Blood of Nonathletes and Club Sport Athletes With Concussions

Objectives: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) peptide, a product of the proteolytic degradation of AMPA receptors in healthy nonathletes and athletes with concussions, is assessed. The detection of AMPAR peptide in conjunction with neuropsychological testing and neuroimaging is undertaken. Subjects: Persons (n = 124, 19–23 years) are enrolled in the pilot-blinded study according to approved Institutional Review Board protocols at Kennesaw State University and DeKalb Medical. Methods: AMPAR peptide plasma assay was performed using magnetic particles-enzyme-linked immunosorbent assay. All participants had neurocognitive tests (ImPACT); selected subjects with concussions were followed-up with magnetic resonance imaging and neurologic consultations. Results: Athletes (n = 33) with clinically defined single or multiple concussions were compared to 91 age and gender matched controls without a history of concussion. AMPAR peptide values of 0.05–0.40 ng/mL for controls and 1.0–8.5 ng/mL for concussions are found. The biomarker sensitivity of 91% and a specificity of 92% (0.4 ng/mL cut off) to assess concussions are calculated. Poorer ImPACT scores correlated with abnormal levels of the biomarker. In athletes with multiple concussions, increased AMPAR peptide values (2.0–12.0 ng/mL) were associated with minor findings on magnetic resonance imaging. Conclusion: AMPAR peptide assay combined with ImPACT and neuroimaging is a promising tool for assessment of concussions. Additional clinical validation studies are required