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hypoxia ischemic stress

Håvard Tetlie Garberg, Marianne U Huun, Lars O Baumbusch, Monica Åsegg-Atneosen, Rønnaug Solberg, Ola Didrik Saugstad
BACKGROUND: There is a lack of reliable biomarkers that can identify and grade acute hypoxic-ischemic encephalopathy in newborns. MicroRNAs (miRNA) are short, non-coding strands of RNA that are released into the circulation in response to tissue stress and injury. Some miRNAs are highly tissue specific and thus may potentially be non-invasive biomarkers of neonatal hypoxic-ischemic brain injury. OBJECTIVE: The aim of this study was to characterize the temporal expression of selected circulating miRNAs in a clinically relevant piglet model of neonatal hypoxia-ischemia (HI)...
October 18, 2016: Neonatology
Wating Su, Yuan Zhang, Qiongxia Zhang, Jinjin Xu, Liying Zhan, Qiqi Zhu, Qingquan Lian, Huimin Liu, Zhong-Yuan Xia, Zhengyuan Xia, Shaoqing Lei
BACKGROUND: Patients with diabetes are prone to develop cardiac hypertrophy and more susceptible to myocardial ischemia-reperfusion (I/R) injury, which are concomitant with hyperglycemia-induced oxidative stress and impaired endothelial nitric oxide (NO) synthase (eNOS)/NO signaling. Caveolae are critical in the transduction of eNOS/NO signaling in cardiovascular system. Caveolin (Cav)-3, the cardiomyocytes-specific caveolae structural protein, is decreased in the diabetic heart in which production of reactive oxygen species are increased...
October 12, 2016: Cardiovascular Diabetology
Shyanne Page, Alli Munsell, Abraham J Al-Ahmad
BACKGROUND: Cerebral hypoxia/ischemia (H/I) is an important stress factor involved in the disruption of the blood-brain barrier (BBB) following stroke injury, yet the cellular and molecular mechanisms on how the human BBB responds to such injury remains unclear. In this study, we investigated the cellular response of the human BBB to chemical and environmental H/I in vitro. METHODS: In this study, we used immortalized hCMEC/D3 and IMR90 stem-cell derived human brain microvascular endothelial cell lines (IMR90-derived BMECs)...
October 11, 2016: Fluids and Barriers of the CNS
Yong-Seok Han, Jun Hee Lee, Yeo Min Yoon, Chul Won Yun, Hyunjin Noh, Sang Hun Lee
Mesenchymal stem cells (MSCs) are 'adult' multipotent cells that promote regeneration of injured tissues in vivo. However, differences in oxygenation levels between normoxic culture conditions (21% oxygen) and both the MSC niche (2-8% oxygen) and ischemic injury-induced oxidative stress conditions in vivo have resulted in low efficacy of MSC therapies in both pre-clinical and clinical studies. To address this issue, we examined the effectiveness of hypoxia preconditioning (2% oxygen) for enhancing the bioactivity and tissue-regenerative potential of adipose-derived MSCs...
October 6, 2016: Cell Death & Disease
Hai-Feng Pei, Juan-Ni Hou, Fei-Peng Wei, Qiang Xue, Fan Zhang, Cheng-Fei Peng, Yi Yang, Yue Tian, Juan Feng, Jin Du, Lei He, Xiu-Chuan Li, Er-He Gao, De Li, Yong-Jian Yang
Mitochondrial dysfunction leads to reactive oxygen species (ROS) overload, exacerbating injury in myocardial infarction (MI). As a receptor for translocases in the outer mitochondrial membrane (Tom) complex, Tom70 has an unknown function in MI, including in melatonin-induced protection against MI injury. We delivered specific small interfering RNAs against Tom70 or lentivirus vectors carrying Tom70a sequences into the left ventricles of mice or to cultured neonatal murine ventricular myocytes (NMVMs). At 48 h post-transfection, the left anterior descending coronary arteries of mice were permanently ligated, while the NMVMs underwent continuous hypoxia...
October 5, 2016: Journal of Pineal Research
Attila Szabo, Attila Kovacs, Jordi Riba, Srdjan Djurovic, Eva Rajnavolgyi, Ede Frecska
N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins...
2016: Frontiers in Neuroscience
So Y Cheon, Kyoung J Cho, So Y Kim, Eun H Kam, Jong E Lee, Bon-Nyeo Koo
Conditions of increased oxidative stress including cerebral ischemia can lead to blood-brain barrier dysfunction via matrix metalloproteinase (MMP). It is known that MMP-9 in particular is released from brain endothelial cells is involved in the neuronal cell death that occurs after cerebral ischemia. In the intracellular signaling network, apoptosis signal-regulating kinase 1 (ASK1) is the main activator of the oxidative stress that is part of the pathogenesis of cerebral ischemia. ASK1 also promotes apoptotic cell death and brain infarction after ischemia and is associated with vascular permeability and the formation of brain edema...
2016: Frontiers in Cellular Neuroscience
De-An Zhao, Ling-Yun Bi, Qian Huang, Fang-Min Zhang, Zi-Ming Han
BACKGROUND AND OBJECTIVES: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism...
September 13, 2016: Revista Brasileira de Anestesiologia
Jennifer K Lee, Bing Wang, Michael Reyes, Jillian S Armstrong, Ewa Kulikowicz, Polan T Santos, Jeong-Hoo Lee, Raymond C Koehler, Lee J Martin
Therapeutic hypothermia provides incomplete neuroprotection after hypoxia-ischemia (HI)-induced brain injury in neonates. We previously showed that cortical neuron and white matter apoptosis are promoted by hypothermia and early rewarming in a piglet model of HI. The unfolded protein response (UPR) may be one of the potential mediators of this cell death. Here, neonatal piglets underwent HI or sham surgery followed by 29 h of normothermia, 2 h of normothermia + 27 h of hypothermia or 18 h of hypothermia + rewarming...
September 14, 2016: Developmental Neuroscience
Jun Zhang, Peter A McCullough
Hypoxia, reactive oxygen species (ROS) and oxidative stress contribute to contrast-induced acute kidney injury (CI-AKI) and ischemic reperfusion injury (IRI) in the kidney and heart. Imbalance between the increased formation of ROS by hypoxia in the cardiac and renal tissue and the low availability of endogenous antioxidants is a common cause of cellular and tissue damage. Therefore, a strategy to inhibit ROS generation or to scavenger free radicals becomes an important intervention to prevent CI-AKI and myocardial IRI...
September 8, 2016: Nephron
P P Tregub, V P Kulikov, Yu G Motin, M E Nagibaeva, A S Zabrodina
We studied the expression of chaperone GRP-78 and transcription factor NF-kB during the development of ischemic tolerance of the brain after combined and isolated exposure to hypoxia and hypercapnia. Combined exposure to hypoxia and hypercapnia maximally increased the expression of chaperone GRP-78 and transcription factor NF-kB, while the formation of ischemia-induced tolerance under conditions of hypercapnic hypoxia can be associated with activation of adaptive stress mechanisms in the endoplasmic reticulum...
August 2016: Bulletin of Experimental Biology and Medicine
Brett R Ely, Andrew T Lovering, Michal Horowitz, Christopher T Minson
Recent research has suggested a potential for some of the physiological and cellular responses to heat acclimation to carry over to improved tolerance of the novel stresses of another environment. This cross-tolerance is evident in heat-acclimated animals that exhibit enhanced tolerance to either hypoxic or ischemic stress, and is primarily attributed to shared cellular stress response pathways. These pathways include Hypoxia-Inducible Factor-1 (HIF-1) and Heat Shock Proteins (HSP). Whether these shared cellular stress response pathways translate to systemic cross-tolerance (improved exercise tolerance, reduced risk of environment-associated illness) has not been clearly shown, particularly in humans...
July 2014: Temperature: Multidisciplinary Biomedical Journal
Xiaoxia Sun, Hong Zuo, Chunmei Liu, Yafeng Yang
The kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling axis plays an important role in regulating oxidative stress in ischemic cardiomyocytes. Targeting Keap1 in order to promote Nrf2 activation is considered a potential method for protecting cardiomyocytes against ischemic injury. In recent years, microRNAs (miRNAs or miRs) have emerged as powerful tools for controlling gene expression. The present study aimed to determine whether Keap1-Nrf2 was regulated by specific miRNAs in cardiomyocytes under hypoxic conditions...
October 2016: International Journal of Molecular Medicine
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
David Kitzenberg, Sean P Colgan, Louise E Glover
The creatine/phosphocreatine pathway plays a conserved and central role in energy metabolism. Compartmentalization of specific creatine kinase enzymes permits buffering of local high energy phosphates in a thermodynamically favorable manner, enabling both rapid energy storage and energy transfer within the cell. Augmentation of this metabolic pathway by nutritional creatine supplementation has been shown to elicit beneficial effects in a number of diverse pathologies, particularly those that incur tissue ischemia, hypoxia or oxidative stress...
December 2016: Clinical and Translational Medicine
Xudan Shi, Desislava Met Doycheva, Liang Xu, Jiping Tang, Min Yan, John H Zhang
OBJECTIVE: Hypoxic ischemic (HI) encephalopathy remains the leading cause of perinatal brain injury resulting in long term disabilities. Stabilization of blood brain barrier (BBB) after HI is an important target, therefore, in this study we aim to determine the role of sestrin2, a stress inducible protein which is elevated after various insults, on BBB stabilization after moderate and severe HI injuries. METHODS: Rat pups underwent common carotid artery ligation followed by either 150min (severe model) or 100min (moderate model) of hypoxia...
November 2016: Neurobiology of Disease
Xudan Shi, Liang Xu, Desislava Met Doycheva, Jiping Tang, Min Yan, John H Zhang
Hypoxic-ischemic encephalopathy is a condition caused by reduced oxygen and cerebral blood flow to the brain resulting in neurological impairments. Effective therapeutic treatments to ameliorate these disabilities are still lacking. We sought to investigate the role of sestrin2, a highly conserved stress-inducible protein, in a neonatal rat hypoxic-ischemic encephalopathy model. Ten-day-old rat pups underwent right common carotid artery ligation followed by 2.5 h hypoxia. At 1 h post hypoxic-ischemic encephalopathy, rats were intranasally administered with recombinant human sestrin2 and sacrificed for brain infarct area measurement, Fluoro-Jade C, immunofluorescence staining, Western blot, and neurological function testing...
July 5, 2016: Journal of Cerebral Blood Flow and Metabolism
Eridan Rocha-Ferreira, Brogan Rudge, Michael P Hughes, Ahad A Rahim, Mariya Hristova, Nicola J Robertson
Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention that could be administered as an alternative to cooling in cases of perinatal hypoxia-ischemia (HI). In the current study we hypothesized that RIPostC in the piglet model of birth asphyxia confers protection by reducing nitrosative stress and subsequent nitrotyrosine formation, as well as having an effect on glial immunoreactivity. Postnatal day 1 (P1) piglets underwent HI brain injury and were randomised to HI (control) or HI + RIPostC...
2016: Oxidative Medicine and Cellular Longevity
John O Onukwufor, Don Stevens, Collins Kamunde
The mitochondrial ATP-sensitive K(+) (mitoKATP) channel plays a significant role in mitochondrial physiology and protects against ischemic reperfusion injury in mammals. Although fish frequently face oxygen fluctuations in their environment, the role of the mitoKATP channel in regulating the responses to oxygen stress is rarely investigated in this class of animals. To elucidate whether and how the mitoKATP channel protects against hypoxia-reoxygenation (H-R)-induced mitochondrial dysfunction in fish, we first determined the mitochondrial bioenergetic effects of two key modulators of the channel, diazoxide and 5-hydroxydecanoate (5-HD), using a wide range of doses...
September 1, 2016: Journal of Experimental Biology
Rachel Speer, Rajiv R Ratan
Homeostasis is the process by which cells adapt to stress and prevent or repair injury. Unique programs have evolved to sense and activate these homeostatic mechanisms and as such, homeostatic sensors may be potent therapeutic targets. The hypoxic response mediated by hypoxia inducible factor (HIF) downstream of oxygen sensing by HIF prolyl 4-hydroxylases (PHDs) has been well-studied, revealing cell-type specific regulation of HIF stability, activity, and transcriptional targets. HIF's paradoxical roles in nervous system development, physiology, and pathology arise from its complex roles in hypoxic adaptation and normoxic biology...
2016: Advances in Experimental Medicine and Biology
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