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Neural hypoxia

Kwan-Long Mung, Yat-Ping Tsui, Evelyn Wing-Yin Tai, Ying-Shing Chan, Daisy Kwok-Yan Shum, Graham Ka-Hon Shea
BACKGROUND: Bone marrow stromal cells (BMSCs) are attractive as a source of neural progenitors for ex vivo generation of neurons and glia. Limited numbers of this subpopulation, however, hinder translation into autologous cell-based therapy. Here, we demonstrate rapid and efficient conditioning with hypoxia to enrich for these neural progenitor cells prior to further expansion in neurosphere culture. METHOD: Adherent cultures of BMSCs (rat/human) were subjected to 1 % oxygen for 24 h and then subcultured as neurospheres with epidermal growth factor (EGF) and basic fibroblast growth factor supplementation...
October 7, 2016: Stem Cell Research & Therapy
Penha Cristina Barradas, Tiago Savignon, Alex C Manhães, Frank Tenório, Alan P da Costa, Marta C Cunha-Rodrigues, Juliana Vaillant
Hypoxic-ischemic (HI) injury is an important cause of death and disabilities. Despite all improvements in neonatal care, the number of children who suffer some kind of injury during birth has remained stable in the last decade. A great number of studies have shown alterations in neural cells and many animal models have been proposed in the last 5 decades. Robinson et al. (2005) proposed an HI model in which the uterine arteries are temporarily clamped on the 18th gestation day. The findings were quite similar to the ones observed in postmortem studies...
2016: Advances in Experimental Medicine and Biology
Ji Chen, Jinqiang Li, Qiaoqing Han, Jianzhong Lin, Tianhe Yang, Ziqian Chen, Jiaxing Zhang
BACKGROUND: Structural and functional networks can be reorganized to adjust to environmental pressures and physiologic changes in the adult brain, but such processes remain unclear in prolonged adaptation to high-altitude (HA) hypoxia. This study aimed to characterize the interhemispheric functionally and structurally coupled modifications in the brains of adult HA immigrants. METHODS: We performed resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in 16 adults who had immigrated to the Qinghai-Tibet Plateau (2300-4400 m) for 2 years and in 16 age-matched sea-level (SL) controls...
September 2016: Brain and Behavior
Andres A Urrutia, Aqeela Afzal, Jacob Nelson, Olena Davidoff, Kenneth W Gross, Volker H Haase
A classic response to systemic hypoxia is the increased production of red blood cells due to hypoxia-inducible factor (HIF)-mediated induction of erythropoietin (EPO). EPO is a glycoprotein hormone that is essential for normal erythropoiesis and is predominantly synthesized by peritubular renal interstitial fibroblast-like cells, which express cellular markers characteristic of neuronal cells and pericytes. To investigate whether the ability to synthesize EPO is a general functional feature of pericytes, we used conditional gene targeting to examine the von Hippel-Lindau (VHL) / prolyl-4-hydroxylase domain (PHD) / HIF axis in cell expressing neural glial antigen 2 (NG2), a known molecular marker of pericytes in multiple organs...
September 28, 2016: Blood
Ryan J Felling, Matthew V Covey, Paul Wolujewicz, Mona Batish, Steven W Levison
Brain injuries, such as cerebral hypoxia-ischemia (H-I), induce a regenerative response from the neural stem/progenitors (NSPs) of the subventricular zone (SVZ); however, the mechanisms that regulate this expansion have not yet been fully elucidated. The Notch- Delta-Serrate-Lag2 (DSL) signaling pathway is considered essential for the maintenance of neural stem cells, but it is not known if it is necessary for the expansion of the NSPs subsequent to perinatal H-I injury. Therefore, the aim of this study was to investigate whether this pathway contributes to NSP expansion in the SVZ after H-I and, if so, to establish whether this pathway is directly induced by H-I or regulated by paracrine factors...
December 2016: Journal of Neuroscience Research
Hadi Ansarihadipour, Mohamadreza Bayatiani
BACKGROUND: Electromagnetic fields (EMF) are associated with oxidative stress, which is in turn associated with reactive oxygen species (ROS), anemia, and hypoxia. OBJECTIVES: This study focused on the synergistic effects of lead ions and EMF on oxidative modifications in hemoglobin (Hb) and plasma proteins. PATIENTS AND METHODS: In this experimental study, the blood samples were obtained from age- and sex-matched healthy subjects at Arak University of Medical Sciences, Arak, Iran...
July 2016: Iranian Red Crescent Medical Journal
Collin M Labak, Paul Y Wang, Rishab Arora, Maheedhara R Guda, Swapna Asuthkar, Andrew J Tsung, Kiran K Velpula
GLUT1, and to a lesser extent, GLUT3, appear to be interesting targets in the treatment of glioblastoma multiforme. The current review aims to give a brief history of the scientific community's understanding of these glucose transporters and to relate their importance to the metabolic changes that occur as a result of cancer. One of the primary changes that occurs in cancer, the Warburg Effect, is characterized by an extreme shift toward glycolysis from the usual reliance on oxidative phosphorylation and is currently being investigated to target the upstream and downstream factors responsible for Warburg-induced changes...
2016: American Journal of Cancer Research
Luca Braccioli, Cobi J Heijnen, Paul J Coffer, Cora H Nijboer
BACKGROUND: Hypoxic-ischemic (HI) encephalopathy causes mortality and severe morbidity in neonates. Treatments with a therapeutic window >6 h are currently not available. Here, we explored whether delayed transplantation of allogenic neural stem cells (NSCs) at 10 d after HI could be a tool to repair HI brain injury and improve behavioral impairments. METHODS: HI was induced in 9-d-old mice. Animals received NSCs or vehicle intracranially in the hippocampus at 10 d post-HI...
October 5, 2016: Pediatric Research
Binzhi Tang, Dejian Wang, Maojun Li, Qing Wu, Qian Yang, Wei Shi, Changhui Chen
BACKGROUND: Hypoxia/ischemia (HI) brain injury is a common central nervous system insult in newborns. Studies have demonstrated bioactivity of ginsenoside Rg1 in increasing neural viability and promoting angiogenesis. However, there are few reports on roles of Rg1 in brain repair of neonatal HI, and the mechanisms involved are unclear. METHODS: a neonatal HI model was established by a modified Rice-Vannucci model (RVM) and pups received ginsenoside Rg1 or monosialotetrahexosyl ganglioside (GM1) treatment...
October 5, 2016: Pediatric Research
Kyoumi Shirai, Yuko Hamada, Nobuko Arakawa, Aiko Yamazaki, Natsuko Tohgi, Ryoichi Aki, Sumiyuki Mii, Robert M Hoffman, Yasuyuki Amoh
We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and CD34-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and spinal cord regeneration in mouse models...
September 14, 2016: Journal of Cellular Biochemistry
Mathilde Chevin, Clémence Guiraut, Caroline Maurice-Gelinas, Jessica Deslauriers, Sylvain Grignon, Guillaume Sébire
BACKGROUND: Despite the recent introduction of hypothermia as a mandatory standard of care, the incidence of neonatal encephalopathy in full-term newborns and its devastating neuro-behavioral outcomes continues to be a major individual, familial and social issue. Neonatal encephalopathy is mainly due to the compounding and interacting effects of hypoxia-ischemia and inflammation resulting from placental and other perinatal infections. It is unclear why hypothermia is effective in alleviating neonatal encephalopathy in some, but not all, full-term newborns...
September 9, 2016: International Journal of Developmental Neuroscience
J Alberto Ortega, Carissa L Sirois, Fani Memi, Nicole Glidden, Nada Zecevic
The oxygen (O2) concentration is a vital parameter for controlling the survival, proliferation, and differentiation of neural stem cells. A prenatal reduction of O2 levels (hypoxia) often leads to cognitive and behavioral defects, attributable to altered neural development. In this study, we analyzed the effects of O2 levels on human cortical progenitors, the radial glia cells (RGCs), during active neurogenesis, corresponding to the second trimester of gestation. Small changes in O2 levels profoundly affected RGC survival, proliferation, and differentiation...
September 6, 2016: Cerebral Cortex
Miguel A Zarate, Eileen I Chang, Andrew Antolic, Charles E Wood
Umbilical cord occlusion (UCO) is a hypoxic insult that has been used to model birth asphyxia and umbilical cord compression in utero. UCO triggers vigorous neural and endocrine responses that include increased plasma ACTH and cortisol concentrations, increased blood pressure (BP), and decreased heart rate (HR). We have previously reported that ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, can modify the fetal hemodynamic and ACTH responses to ventilatory hypoxia and cerebral ischemia-reperfusion...
September 2016: Physiological Reports
Patricia Ortega-Sáenz, David Macías, Konstantin L Levitsky, José A Rodríguez-Gómez, Patricia González-Rodríguez, Victoria Bonilla-Henao, Ignacio Arias-Mayenco, José López-Barneo
KEY POINTS: Biotin, a vitamin whose main role is as a coenzyme for carboxylases, accumulates at unusually large amounts within cells of the carotid body (CB). In biotin-deficient rats biotin rapidly disappears from the blood; however, it remains at relatively high levels in CB glomus cells. The CB contains high levels of mRNA for SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Animals with biotin deficiency exhibit pronounced metabolic lactic acidosis...
August 28, 2016: Journal of Physiology
Talita M Silva, Ana C Takakura, Thiago S Moreira
Catecholaminergic C1 cells reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM) and can be activated by hypoxia. These neurons regulate the hypothalamic pituitary axis via direct projections to the hypothalamic paraventricular nucleus (PVH) and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. Based on the various effects attributed to the C1 cells and what is currently known of their synaptic inputs, our hypothesis is that acute hypoxia (AH) activates RVLM projecting catecholaminergic neurons to PVH...
November 2016: Experimental Neurology
Elena Beltramo, Tatiana Lopatina, Aurora Mazzeo, Ana I Arroba, Angela M Valverde, Cristina Hernández, Rafael Simó, Massimo Porta
AIMS: Diabetic retinopathy is considered a microvascular disease, but recent evidence has underlined early involvement of the neuroretina with interactions between microvascular and neural alterations. Topical administration of somatostatin (SST), a neuroprotective molecule with antiangiogenic properties, prevents diabetes-induced retinal neurodegeneration in animals. The α2-adrenergic receptor agonist brimonidine (BRM) decreases vitreoretinal vascular endothelial growth factor and inhibits blood-retinal barrier breakdown in diabetic rats...
August 23, 2016: Acta Diabetologica
Alexandra A Calinescu, Viveka Nand Yadav, Erica Carballo, Padma Kadiyala, Dustin Tran, Daniel Zamler, Robert Doherty, Maithreyi Srikanth, Pedro R Lowenstein, Maria G Castro
PURPOSE: One likely cause of treatment failure in glioblastoma is the persistence of glioma stem-like cells (GSLCs), highly resistant to therapies currently employed. We found that CXCL12 has highest expression in glioma cells derived from neural progenitor cells (NPCs). The development and molecular signature of NPC-derived GBMs were analyzed and the therapeutic effect of blocking CXCL12 was tested. EXPERIMENTAL DESIGN: Tumors were induced by injecting DNA into the lateral ventricle of neonatal mice, using the Sleeping Beauty transposase method...
August 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Chih-Wei Zeng, Yasuhiro Kamei, Chih-Tien Wang, Huai-Jen Tsai
BACKGROUND INFORMATION: Neuron stem/progenitor cells (NSPCs) of zebrafish central nervous system (CNS) are known to thrive during oxygen recovery after hypoxia, but not all cell types have been fully characterised due to their heterogeneities. In addition, an in vivo model system is not available that can help us to identify what type-specific cell populations that are involved in neural regeneration and to track their cell fate after regeneration. To solve these issues, we employed a zebrafish transgenic line, huORFZ, which harbours an inhibitory upstream open reading frame of human chop mRNA fused downstream with GFP reporter and driven by cytomegalovirus promoter...
August 19, 2016: Biology of the Cell
Guoxiang Yuan, Ying-Jie Peng, Shakil A Khan, Jayasri Nanduri, Amritha Singh, Chirag Vasavda, Gregg L Semenza, Ganesh K Kumar, Solomon H Snyder, Nanduri R Prabhakar
Sleep apnea is a prevalent respiratory disease in which episodic cessation of breathing causes intermittent hypoxia. Patients with sleep apnea and rodents exposed to intermittent hypoxia exhibit hypertension. The carotid body senses changes in blood O2 concentrations, and an enhanced carotid body chemosensory reflex contributes to hypertension in sleep apnea patients. A rodent model of intermittent hypoxia that mimics blood O2 saturation profiles of patients with sleep apnea has shown that increased generation of reactive oxygen species (ROS) in the carotid body enhances the chemosensory reflex and triggers hypertension...
2016: Science Signaling
Jayasri Nanduri, Ying-Jie Peng, Ning Wang, Shakil A Khan, Gregg L Semenza, Ganesh K Kumar, Nanduri R Prabhakar
KEY POINTS: The effects of short-term (ST; 10 days) and long-term (LT; 30 days) intermittent hypoxia (IH) on blood pressure (BP), breathing and carotid body (CB) chemosensory reflex were examined in adult rats. ST- and LT-IH treated rats exhibited hypertension, irregular breathing with apnoea and augmented the CB chemosensory reflex, with all these responses becoming normalized during recovery from ST- but not from LT-IH. The persistent cardiorespiratory responses to LT-IH were associated with elevated reactive oxygen species (ROS) levels in the CB and adrenal medulla, which were a result of DNA methylation-dependent suppression of genes encoding anti-oxidant enzymes (AOEs)...
August 9, 2016: Journal of Physiology
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