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Brain blood markers for injury

Lutz Menzel, Lisa Kleber, Carina Friedrich, Regina Hummel, Larissa Dangel, Jennifer Winter, Katja Schmitz, Irmgard Tegeder, Michael K E Schäfer
In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn(-/-) ) 24 h and 5 days after experimental TBI...
October 25, 2016: Glia
Alexander N Shikov, Olga N Pozharitskaya, Valery G Makarov
PURPOSE: Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen syn. A. mandshurica Rupr. & Maxim is evaluated for its medicinal application. The aim of this study is to analyze pharmacological studies on A. elata var. mandshurica published until December 2015. METHODS: The information regarding the chemistry, safety, effectiveness, and pharmacological and clinical effects of A. elata was systematically collected from the scientific literature through library catalogs; online services such as E-library...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
William Peacock
Dear Editor I read with great interest the manuscript titled "A New Panel of Blood Biomarkers for the Diagnosis of Mild Traumatic Brain Injury/Concussion in Adults" by Shan R, et al, published in the January issue of the Journal. (1) I do have some questions. The key to marker discovery studies is a precise and accurate description of how the population was identified, including controls. I have significant concerns about the control population in the manuscript. In the presentation the characteristics of the control group are unclear, described only as "not patients in the ED" and with the same exclusion criteria of the other cohorts...
October 18, 2016: Journal of Neurotrauma
Suman Pradhan, Christine Pellino, Kayleigh MacMaster, Dennis Coyle, Alison A Weiss
Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing E. coli, and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed...
2016: Frontiers in Cellular and Infection Microbiology
Hui Shi, Kuang Zheng, Zulu Su, Hai Su, Ming Zhong, Xuenong He, Changlong Zhou, Hao Chen, Qijiang Xiong, Yi Zhang
Microglia polarization plays a vital role in brain inflammatory injury following intracerebral hemorrhage (ICH). Previous studies have shown that sinomenine possesses potential immunoregulatory capabilities. However, microglia polarization's exact mechanisms in ICH remain uncertain. Therefore, we examined the role of sinomenine on microglia polarization and brain inflammation following ICH. For the experiment, autologous blood models were constructed in C57/BL6 mice. Markers of classically activated (M1) and alternatively activated (M2) microglia were detected by real-time polymerase chain reaction, immunofluorescence, and flow cytometry...
October 15, 2016: Journal of Neuroimmunology
Alison Halstrom, Ellen MacDonald, Claire Neil, Glenn Arendts, Daniel Fatovich, Melinda Fitzgerald
Traumatic brain injury (TBI) encompasses a broad range of injury mechanisms and severity. A detailed determination of TBI severity can be a complex challenge, with current clinical tools sometimes insufficient to tailor a clinical response to a spectrum of patient needs. Blood biomarkers of TBI may supplement clinical assessments but currently available biomarkers have limited sensitivity and specificity. While oxidative stress is known to feature in damage mechanisms following TBI, investigation of blood biomarkers of oxidative stress has been limited...
September 30, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Matej Orešič, Jussi P Posti, Maja H Kamstrup-Nielsen, Riikka S K Takala, Hester F Lingsma, Ismo Mattila, Sirkku Jäntti, Ari J Katila, Keri L H Carpenter, Henna Ala-Seppälä, Anna Kyllönen, Henna-Riikka Maanpää, Jussi Tallus, Jonathan P Coles, Iiro Heino, Janek Frantzén, Peter J Hutchinson, David K Menon, Olli Tenovuo, Tuulia Hyötyläinen
Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n=22), moderate (moTBI; n=14) or mild TBI (mTBI; n=108) according to Glasgow Coma Scale...
July 15, 2016: EBioMedicine
Moon-Sook Woo, Jiwon Yang, Cesar Beltran, Sunghee Cho
Infiltrating monocyte-derived macrophages (M-Mφ) influence stroke-induced brain injury. While the inflammatory nature of M-Mφ in acute stroke has been well documented, their role during the resolution phase of stroke is less clear. With emerging evidence for the involvement of scavenger receptors in innate immunity, this current study addresses a M-Mφ CD36 role in mediating phagocytosis during the recovery phase of stroke. Stroke increases CD36 and TSP-1/2 mRNA levels in ipsilateral hemisphere at acute (3d) and recovery (7d) periods...
September 19, 2016: Journal of Biological Chemistry
Christos Lazaridis, Claudia S Robertson
This article reviews the role of modalities that directly monitor brain parenchyma in patients with severe traumatic brain injury. The physiology monitored involves compartmental and perfusion pressures, tissue oxygenation and metabolism, quantitative blood flow, pressure autoregulation, and electrophysiology. There are several proposed roles for this multimodality monitoring, such as to track, prevent, and treat the cascade of secondary brain injury; monitor the neurologically injured patient; integrate various data into a composite, patient-specific, and dynamic picture; apply protocolized, pathophysiology-driven intensive care; use as a prognostic marker; and understand pathophysiologic mechanisms involved in secondary brain injury to develop preventive and abortive therapies, and to inform future clinical trials...
October 2016: Neurosurgery Clinics of North America
Henrik Zetterberg, Kaj Blennow
Diagnostic and prognostic biomarkers for mild traumatic brain injury (TBI), also known as concussion, remain a major unmet clinical need. Moderate to severe TBI can be diagnosed definitively by clinical assessment and standard neuroimaging techniques that detect the gross damage to the brain parenchyma. Diagnostic tools for mild TBI are lacking and, currently, the diagnosis has to be made on clinical grounds alone, because most patients show no gross pathological changes on CT. Most patients with mild TBI recover quickly, but about 15% develop an ill-defined condition called postconcussive syndrome (PCS)...
October 2016: Nature Reviews. Neurology
P M Abdul-Muneer, Adriano Andrea Conte, Debanjan Haldar, Mathew Long, Rachel Patel, Vijayalakshmi Santhakumar, Christopher M Overall, Bryan J Pfister
Traumatic brain injury (TBI), even at mild levels, can activate matrix metalloproteinases (MMPs) and the induction of neuroinflammation that can result in blood brain barrier breakdown and neurodegeneration. MMP2 has a significant role in neuroinflammation and neurodegeneration by modulating the chemokine CXCL12 (stromal cell derived factor SDF-1α) signaling pathway and the induction of apoptosis. SDF-1α is responsible for cell proliferation and differentiation throughout the nervous system and is also implicated in various neurodegenerative illnesses...
September 7, 2016: Brain, Behavior, and Immunity
Ling Guo, Hongyan Zhang, Yinglong Hou, Tianshu Wei, Ju Liu
Endothelial subcellular structures, including caveolae, fenestrae and transendothelial channels, are crucial for regulating microvascular function. Plasmalemma vesicle-associated protein (PLVAP) is an endothelial cell-specific protein that forms the stomatal and fenestral diaphragms of blood vessels and regulates basal permeability, leukocyte migration and angiogenesis. Loss of PLVAP in mice leads to premature mortality due to disrupted homeostasis. Evidence from previous studies suggested that PLVAP is involved in cancer, traumatic spinal cord injury, acute ischemic brain disease, transplant glomerulopathy, Norrie disease and diabetic retinopathy...
September 2016: Experimental and Therapeutic Medicine
Joon Ha Park, Ki-Yeon Yoo, In Hye Kim, Jeong-Hwi Cho, Jae-Chul Lee, Ji Hyeon Ahn, Hyun Jin Tae, Bing Chun Yan, Dae Won Kim, Ok Kyu Park, Seung-Hae Kwon, Song Her, Jin Su Kim, Jung Hoon Choi, Choong Hyun Lee, In Koo Hwang, Jae Youl Cho, Jun Hwi Cho, Young-Guen Kwon, Sungwoo Ryoo, Young-Myeong Kim, Moo-Ho Won, Il Jun Kang
Hydroquinone (HQ), a major benzene metabolite, occurs naturally in various plants and is manufactured for commercial use. Although HQ displays various biological effects, its neuroprotective effects following ischemic insults have not been investigated. In this study, we first examined neuroprotective effects of HQ in a rat model of transient focal cerebral ischemia. Animals were subjected to transient middle cerebral artery occlusion for 120 min. HQ (50 or 100 mg/kg) or vehicle was intraperitoneally administered once at 30 min after ischemia-reperfusion...
August 31, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Xian-Yue Wang, Wen-Peng Dong, Guang Tong, Sheng-Hui Bi, Ben Zhang, Hua Lu, Xiao-Wu Wang, Wei-da Zhang
OBJECTIVE: To investigate the protective effects of high-dose ulinastatin on the vital organs in patients undergoing total arch replacement for type A aortic dissection. METHODS: Between September 2014 and March 2016, 66 patients with type A aortic dissection underwent total arch replacement at our center. Thirty-six of the patients received ulinastatin treatment at 300 000 U/8 h from admission to 3 days postoperatively and at 300 000 U/2 h during cardiopulmonary bypass surgery (UTI group), and the other 30 patients did not receive perioperative ulinastatin treatment (control group)...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Evelyn M R Lake, Paolo Bazzigaluppi, Bojana Stefanovic
Ischaemic stroke is the leading cause of adult disability worldwide. Effective rehabilitation is hindered by uncertainty surrounding the underlying mechanisms that govern long-term ischaemic injury progression. Despite its potential as a sensitive non-invasive in vivo marker of brain function that may aid in the development of new treatments, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has found limited application in the clinical research on chronic stage stroke progression...
October 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Oiva Arvola, Henri Haapanen, Johanna Herajärvi, Tuomas Anttila, Ulla Puistola, Peeter Karihtala, Hannu Tuominen, Vesa Anttila, Tatu Juvonen
Remote ischemic precondition has become prominent as one of the most promising methods to mitigate neurological damage following ischemic insult. The purpose of this study was to investigate whether the effects of remote ischemic preconditioning can be seen in the markers of oxidative stress or in redox-regulating enzymes in a porcine model. A total of 12 female piglets were randomly assigned to 2 groups. The study group underwent an intervention of 4 cycles of 5-minute ischemic preconditioning on the right hind leg...
2016: Seminars in Thoracic and Cardiovascular Surgery
Nadine Legros, Stefanie Dusny, Hans-Ulrich Humpf, Gottfried Pohlentz, Helge Karch, Johannes Müthing
Shiga toxin (Stx)-mediated injury to microvascular endothelial cells in the brain significantly contributes to the pathogenesis of the hemolytic-uremic syndrome caused by enterohemorrhagic Escherichia coli (EHEC). Stxs are AB5 toxins and the B-pentamers of the two major Stx subtypes Stx1a and Stx2a preferentially bind to the glycosphingolipid (GSL) globotriaosylceramide (Gb3Cer) expressed by human endothelial cells. Here we report on comprehensive structural analysis of the different lipoforms of Gb3Cer (Galα4Galβ4Glcβ1Cer) and globotetraosylceramide (Gb4Cer, GalNAcβ3Galα4Galβ4Glcβ1Cer, the less effective Stx receptor) of primary human brain microvascular endothelial cells and their association with lipid rafts...
August 24, 2016: Glycobiology
Johan Ljungqvist, Henrik Zetterberg, Marios Mitsis, Kaj Blennow, Thomas Skoglund
Diffuse axonal injury (DAI) is an important cause of morbidity in patients with traumatic brain injury (TBI). There is currently no simple and reliable technique for early identification of patients with DAI, or to prognosticate long-term outcome in this patient group. In the present study, we examined acute serum concentrations of neurofilament light (NFL) in nine patients with severe TBI and DAI using a novel ultrasensitive single molecule array (Simoa) assay. The relationships between the NFL concentrations and MRI in the acute stage as well as clinical outcome and magnetic resonance diffusion tensor imaging (MR-DTI) parameters at 12 months were analyzed...
October 13, 2016: Journal of Neurotrauma
Yuek Ling Chai, Saima Hilal, Jenny P C Chong, Yan Xia Ng, Oi Wah Liew, Xin Xu, Mohammad Kamran Ikram, Narayanaswamy Venketasubramanian, A Mark Richards, Mitchell K P Lai, Christopher P Chen
Vascular pathology plays an important role in the development of cognitive decline and dementia. In this context, growth differentiation factor-15 (GDF-15) has been suggested to be a biomarker due to its regulatory roles in inflammatory and trophic responses during tissue injury. However, limited data exist on the associations of GDF-15 with either cerebrovascular disease (CeVD) burden or the spectrum of cognitive impairment. Therefore, we aimed to study peripheral levels of GDF-15 incognitive impairment no dementia (CIND) or Alzheimer disease (AD) subjects assessed for CeVD using a case-control cohort design, with cases recruited from memory clinics and controls from memory clinics and the community...
August 2016: Medicine (Baltimore)
Elham Abbasloo, Fatemeh Dehghan, Mohammad Khaksari, Hamid Najafipour, Reza Vahidi, Shahriar Dabiri, Gholamreza Sepehri, Golamreza Asadikaram
Traumatic brain injury (TBI) is a major health concern affecting the general public as well as military personnel. However, there is no FDA-approved therapy for the treatment of TBIs. In this work, we investigated the neurotherapeutic effects of the well-known natural Iranian medicine Satureja Khuzistanica Jamzad (SKJ) essential oil (SKEO) on the outcomes of diffused experimental TBI, with particular attention paid to its anti-inflammatory and anti-apoptotic effects. Male Wistar rats were treated with doses of 50, 100 and 200 (mg/kg, i...
2016: Scientific Reports
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