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Hypoxic ischemic

Carlos Menendez-Castro, Dörte Nitz, Nada Cordasic, Jutta Jordan, Tobias Bäuerle, Fabian B Fahlbusch, Wolfgang Rascher, Karl F Hilgers, Andrea Hartner
Neonatal nephron loss may follow hypoxic-ischemic events or nephrotoxic medications. Its long-term effects on the kidney are still unclear. Unlike term infants, preterm neonates less than 36 weeks gestational age show ongoing nephrogenesis. We hypothesized that nephron loss during nephrogenesis leads to more severe renal sequelae than nephron loss shortly after the completion of nephrogenesis. Rats show nephrogenesis until day 10 of life resembling the situation of preterm infants. Animals were uninephrectomized at day 1 (UNX d1) resulting in nephron reduction during nephrogenesis and at day 14 of life (UNX d14) inducing nephron loss after the completion of nephrogenesis...
March 14, 2018: Scientific Reports
Anna Maria Fratta Pasini, Chiara Stranieri, Anna Maria Rigoni, Sergio De Marchi, Denise Peserico, Chiara Mozzini, Luciano Cominacini, Ulisse Garbin
AIM: Ischemia-reperfusion (I-R) produces reactive oxygen species (ROS) that damage cells and favour cytotoxicity and apoptosis in peripheral artery disease (PAD) patients. Since brief episodes of I-R (ischemic conditioning) protect cells against ischemic harms, we evaluated whether a short-course of supervised treadmill training, characterized by repeated episodes of I-R, makes peripheral blood mononuclear cells (PBMCs) from PAD patients with intermittent claudication more resistant to I-R injuries by reducing oxidative stress and by inducing an adaptative response of unfolded protein response (UPR) and nuclear factor-E2-related factor (Nrf2) pathway expression...
March 13, 2018: Journal of Atherosclerosis and Thrombosis
Wei Jiang, Min Guo, Min Gong, Li Chen, Yang Bi, Yun Zhang, Yuan Shi, Ping Qu, Youxue Liu, Jie Chen, Tingyu Li
Our previous studies demonstrated that vitamin A deficiency (VAD) can impair the postnatal cognitive function of rats by damaging the hippocampus. The present study examined the effects of retinoic acid (RA) on apoptosis induced by hypoxic-ischemic damage in vivo and in vitro, and investigated the possible signaling pathway involved in the neuroprotective anti-apoptotic effects of RA. Flow cytometry, immunofluorescence staining and behavioral tests were used to evaluate the neuroprotective and anti-apoptotic effects of RA...
March 13, 2018: Molecular Brain
Juan Zhang, Lorelei Donovan Tucker, DongYan, Yujiao Lu, Luodan Yang, Chongyun Wu, Yong Li, Quanguang Zhang
Hypoxic-ischemic (HI) encephalopathy is a leading cause of dire mortality and morbidity in neonates. Unfortunately, no effective therapies have been developed as of yet. Oxidative stress plays a critical role in pathogenesis and progression of neonatal HI. Previously, as a Nrf2 activator, tert-butylhydroquinone (TBHQ) has been demonstrated to exert neuroprotection on brain trauma and ischemic stroke models, as well as oxidative stress-induced cytotoxicity in neurons. It is, however, still unknown whether TBHQ administration can protect against oxidative stress in neonatal HI brain injury...
March 9, 2018: Neurochemistry International
James A Roberts, Karl J Friston, Michael Breakspear
Brain activity derives from intrinsic dynamics (due to neurophysiology and anatomical connectivity) in concert with stochastic effects that arise from sensory fluctuations, brainstem discharges, and random microscopic states such as thermal noise. The dynamic evolution of systems composed of both dynamic and random fluctuations can be studied with stochastic dynamic models (SDMs). This article, Part II of a two-part series, reviews applications of SDMs to large-scale neural systems in health and disease. Stochastic models have already elucidated a number of pathophysiological phenomena, such as epilepsy and hypoxic ischemic encephalopathy, although their use in biological psychiatry remains rather nascent...
April 2017: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Francesca Felice, Anna Maria Piras, Silvia Rocchiccioli, Maria Chiara Barsotti, Tatiana Santoni, Angela Pucci, Silvia Burchielli, Federica Chiellini, Nadia Ucciferri, Roberto Solaro, Angelina Altomare, Antonella Cecchettini, Rossella Di Stefano
Endothelial progenitor cells (EPCs) contribute to ischemic tissue repair by paracrine secretion up-regulated by hypoxia. In this study we use novel nanoparticles (NPs) as carriers for a controlled release of EPC secretome (CM) to improve their angiogenic properties. Thein vivo effect in ischemic hindlimb rat model was evaluated, comparing hypoxic EPC-CM-NPs with hypoxic EPC-CM alone. A proteomic characterization of hypoxic CM and the in vitro effect on endothelial cells (HUVECs) were also performed. Up to 647 protein, 17 of which with angiogenic properties, were upregulated by hypoxia...
March 8, 2018: International Journal of Pharmaceutics
Xu Chen, Xuan Li, Wenyan Zhang, Jie He, Bo Xu, Bin Lei, Zhenhua Wang, Courtney Cates, Thomas Rousselle, Ji Li
BACKGROUND: AMP-activated Protein Kinase (AMPK) is a stress-activated kinase that protects against cardiomyocyte injury during ischemia and reperfusion. c-Jun N-terminal kinase (JNK), a mitogen activated protein kinase, is activated by ischemia and reperfusion. NF-κB is an important transcription factor involved in ischemia and reperfusion injury. METHODS AND RESULTS: The intrinsic activation of AMPK attenuates the inflammation which occurred during ischemia/reperfusion through the modulation of the JNK mediated NF-κB signaling pathway...
March 8, 2018: Metabolism: Clinical and Experimental
Heather Campbell, Rathinaswamy B Govindan, Srinivas Kota, Tareq Al-Shargabi, Marina Metzler, Nickie Andescavage, Taeun Chang, Gilbert Vezina, Adre du Plessis, An N Massaro
OBJECTIVE: To evaluate whether infants with hypoxic-ischemic encephalopathy and evidence of autonomic dysfunction have aberrant physiological responses to care events that could contribute to evolving brain injury. STUDY DESIGN: Continuous tracings of heart rate (HR), blood pressure (BP), cerebral near infrared spectroscopy, and video electroencephalogram data were recorded from newborn infants with hypoxic-ischemic encephalopathy who were treated with hypothermia...
March 6, 2018: Journal of Pediatrics
Robert Carlsson, Ilknur Özen, Marco Barbariga, Abderahim Gaceb, Michaela Roth, Gesine Paul
Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown and may be of importance for future therapeutic targets. Here we evaluate the transcriptional responses in in vitro cultured human brain pericytes after oxygen and/or glucose deprivation...
2018: PloS One
Daigo Ochiai, Hirotaka Masuda, Yushi Abe, Toshimitsu Otani, Marie Fukutake, Tadashi Matsumoto, Kei Miyakoshi, Mamoru Tanaka
Mesenchymal stem cells (MSCs) have generated great interest in the fields of regenerative medicine and immunotherapy because of their unique biological properties. Among MSCs, amniotic fluid stem cells (AFS) have a number of characteristics that make them attractive candidates for tissue engineering and cell replacement strategies, particularly for perinatal medicine. If various neonatal conditions, including birth asphyxia, preterm birth, and congenital abnormalities, which result in long-lasting severe impairments, could be predicted during pregnancy, it would allow collection of small samples of amniotic fluid cells by amniocentesis...
March 6, 2018: Keio Journal of Medicine
Sandra E Juul, Bryan A Comstock, Patrick J Heagerty, Dennis E Mayock, Amy M Goodman, Stephanie Hauge, Fernando Gonzalez, Yvonne W Wu
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of neonatal death and frequently leads to significant long-term disability in survivors. Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Adjunctive therapies are needed, and erythropoietin (Epo) has the potential to provide additional neuroprotection. OBJECTIVES: The aim of this study was to review the current incidence, mechanism of injury, and sequelae of HIE, and to describe a new phase III randomized, placebo-controlled trial of Epo neuroprotection in term and near-term infants with moderate to severe HIE treated with therapeutic hypothermia...
March 7, 2018: Neonatology
Lilly L Chang, James L Wynn, Marisa J Pacella, Candace C Rossignol, Felix Banadera, Neil Alviedo, Alfonso Vargas, Jeffrey Bennett, Melissa Huene, Nicole Copenhaver, Livia Sura, Kimberly Barnette, Jayne Solomon, Nikolay A Bliznyuk, Josef Neu, Michael D Weiss
BACKGROUND: Withholding enteral feedings during hypothermia lacks supporting evidence. OBJECTIVES: We aimed to determine if minimal enteral nutrition (MEN) during hypothermia in patients with hypoxic-ischemic encephalopathy was associated with a reduced duration of parenteral nutrition, time to full oral feeds, and length of stay, but would not be associated with increased systemic inflammation or feeding complications. METHODS: We performed a pilot, retrospective, matched case-control study within the Florida Neonatal Neurologic Network from December 2012 to May 2016 of patients who received MEN during hypothermia (n = 17) versus those who were not fed (n = 17)...
March 6, 2018: Neonatology
Lina Chalak, Samantha Latremouille, Imran Mir, Pablo J Sánchez, Guilherme Sant'Anna
A review of the conundrum called mild hypoxic-ischemic encephalopathy (HIE) is provided. During the past decades, the definition of HIE has evolved to accommodate the short window of time required for the initiation of therapeutic hypothermia. Also, neurological evaluations have changed with the use of simpler staging systems that can be applied within the first 6 h of life. In this review, we discuss the challenges in the identification of newborns with "mild HIE" within 6 h after birth, the limitations in the existing early biomarkers of brain injury, and the current knowledge gaps in the long term neurodevelopmental outcomes of infants diagnosed with mild HIE...
March 2, 2018: Early Human Development
Renato S Procianoy, Andrea Lucia A Corso, Maria Gabriela Longo, Leonardo Vedolin, Rita C Silveira
OBJECTIVE: To determine the neurodevelopment outcomes after Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy (HIE) and identify the neonatal Magnetic Resonance Imaging (MRI) findings associated with neurological outcome in a middle-income country. STUDY DESIGN: All infants born after 35 completed weeks' gestation with signs of moderate to severe encephalopathy and evidence of perinatal asphyxia before 6 hours of life were submitted to whole-body hypothermia and were imaged at 18 ± 8...
March 4, 2018: Journal of Maternal-fetal & Neonatal Medicine
Rahul Badheka, Narendra Kumar Barad, Charulata Savant Sankhla
Pediatric movement disorders are commonly encountered clinical entities in the pediatric outpatient department. These disorders are a heterogenous group of disorders and may represent an underlying genetic disorder, a metabolic disorder or a hypoxic-ischemic insult during the perinatal period. Hyperkinetic movement disorders are more common as compared to hypokinetic disorders. This is unlike the situation in adult movement disorders where hypokinetic disorders are more often seen. A child's nervous system is more prone to hypoxic-ischemic insults due to its higher metabolic demands and the presence of an immature blood-brain barrier...
March 2018: Neurology India
Satyan Lakshminrusimha, Seetha Shankaran, Abbot Laptook, Scott McDonald, Martin Keszler, Krisa Van Meurs, Ronnie Guillet, Sanjay Chawla, Beena G Sood, Sonia Bonifacio, Abhik Das, Rosemary D Higgins
OBJECTIVE: To determine the characteristics of term infants with persistent pulmonary hypertension of the newborn (PPHN) associated with moderate or severe hypoxic ischemic encephalopathy (HIE). METHODS: We compared infants with and without PPHN enrolled in 2 randomized trials of therapeutic hypothermia: the induced hypothermia trial of cooling to 33.5°C for 72 hours vs normothermia, and the "usual-care" arm (33.5°C for 72 hours) of the optimizing cooling trial...
March 1, 2018: Journal of Pediatrics
Fred Rincon
Evidence from animal models indicates that lowering temperature by a few degrees can produce substantial neuroprotection. In humans, hypothermia has been found to be neuroprotective with a significant impact on mortality and long-term functional outcome only in cardiac arrest and neonatal hypoxic-ischemic encephalopathy. Clinical trials have explored the potential role of maintaining normothermia and treating fever in critically ill brain injured patients. This review concentrates on basic concepts to understand the physiologic interactions of thermoregulation, effects of thermal modulation in critically ill patients, proposed mechanisms of action of temperature modulation, and practical aspects of targeted temperature management...
April 2018: Neurosurgery Clinics of North America
Qingyi Ma, Lubo Zhang
Neonatal hypoxia-ischemia (HI) is the most common cause of brain injury in neonates, which leads to high neonatal mortality and severe neurological morbidity in later life (Vannucci, 2000; Volpe, 2001). Yet the molecular mechanisms of neuronal death and brain damage induced by neonatal HI remain largely elusive. Herein, using both in vivo and in vitro models, we determine an endogenous neuroprotectant role of c-type natriuretic peptide (CNP) in preserving neuronal survival after HI brain injury in mouse pups...
March 5, 2018: Experimental Neurology
Maria J Perez-Alvarez, Mario Villa Gonzalez, Irene Benito-Cuesta, Francisco G Wandosell
Intense efforts are being undertaken to understand the pathophysiological mechanisms triggered after brain ischemia and to develop effective pharmacological treatments. However, the underlying molecular mechanisms are complex and not completely understood. One of the main problems is the fact that the ischemic damage is time-dependent and ranges from negligible to massive, involving different cell types such as neurons, astrocytes, microglia, endothelial cells, and some blood-derived cells (neutrophils, lymphocytes, etc...
2018: Frontiers in Neuroscience
Ying Xie, Daofang Jiang, Jing Xiao, Chensheng Fu, Zhenxing Zhang, Zhibin Ye, Xiaoli Zhang
Ischemic preconditioning (IPC) has a strong renoprotective effect during renal ischemia/reperfusion (I/R) injury that is thought to relate to autophagy. However, the role of autophagy during IPC-afforded renoprotection and the precise mechanisms involved are unknown. In this study, an in vitro hypoxia/reoxygenation (H/R) model was established in which oxygen and glucose deprivation (OGD) was applied to renal cells for 15 h followed by reoxygenation under normal conditions for 30 min, 2 h or 6 h; transient OGD and subsequent reoxygenation were implemented before prolonged H/R injury to achieve hypoxic preconditioning (HPC)...
March 1, 2018: Cell Death & Disease
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