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Ekaterina Turlova, Zhong-Ping Feng, Hong-Shuo Sun
Stroke is one of the major causes of mortality and morbidity worldwide, yet novel therapeutic treatments for this condition are lacking. This review focuses on the roles of the transient receptor potential melastatin 2 (TRPM2) ion channels in cellular damage following hypoxia-ischemia and their potential as a future therapeutic target for stroke. Here, we highlight the complex molecular signaling that takes place in neurons, glial cells and the blood-brain barrier following ischemic insult. We also describe the evidence of TRPM2 involvement in these processes, as shown from numerous in vitro and in vivo studies that utilize genetic and pharmacological approaches...
March 15, 2018: Acta Pharmacologica Sinica
Yang Yuan, Shan-Shan Pan
BACKGROUND: Late exercise preconditioning (LEP) is confirmed to have a protective effect on acute cardiovascular stress. However, the mechanisms by which mitophagy participates in EP-induced cardioprotection remain unclear. LEP may involve mitophagy mediated by the receptors PARK2 gene-encoded E3 ubiquitin ligase (Parkin) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) to scavenge damaged mitochondria. METHODS: Our exercise preconditioning (EP) protocol involved four 10-minute periods of running, separated by 10-minute recovery intervals, plus a period of exhaustive running at 24 hours after EP...
March 9, 2018: Journal of Cardiovascular Pharmacology
Luna Samanta, Ashok Agarwal, Nirlipta Swain, Rakesh Sharma, Banu Gopalan, Sandro C Esteves, Damayanthi Durairajanayagam, Edmund Sabanegh
PURPOSE: Varicocele may disrupt testicular microcirculation and induce hypoxia-ischemia related degenerative changes in testicular cells and spermatozoa. Superoxide production at low oxygen concentrations exacerbates oxidative stress in men with varicocele. Therefore, the present study was designed to study the role of mitochondrial redox regulation and its possible involvement in sperm dysfunction in varicocele-associated infertility. MATERIALS AND METHODS: Differentially expressed mitochondrial proteins were identified in 50 infertile men with varicocele and ten fertile controls by secondary LC-MS/MS data-driven in silico analysis...
March 9, 2018: Journal of Urology
Tina Markus, David Ley, Stefan R Hansson, Tadeusz Wieloch, Karsten Ruscher
BACKGROUND: Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The beta1-adrenergic agonist dobutamine protects against hypoxia/aglycemia induced neuronal damage. We aimed to identify the associated protective biological processes involved. RESULTS: Hippocampal slices from 6 days old mice showed significant changes of gene expression comparing slices with or without dobutamine (50 mM) in the following two experimental paradigms: (1) control conditions versus lipopolysacharide (LPS) stimulation and (2) oxygen-glucose deprivation (OGD), versus combined LPS/OGD...
March 9, 2018: BMC Neuroscience
Xiangyun Yin, Jixiu Zhao, Hong Jiang, Liangliang Li, Jian Jiang, Hongmin Xi, Xiangli Peng, Xiaohang Yin, Xiaotong Shi, Lulu Zhang
BACKGROUND: Premature birth is a significant health care burden. Xenon (Xe) is a general anesthetic with neuroprotective effects. OBJECTIVES: Here, we investigate the neuroprotective role of Xe in a lipopolysaccharide (LPS)- and hypoxia-ischemia (HI)-induced white matter damage (WMD) model. METHODS: Three-day-old Sprague-Dawley rats were randomly divided into a sham group (group A, n = 24), an LPS + HI group (group B, n = 24), and an LPS + HI + Xe group (group C, n = 72)...
March 8, 2018: Neonatology
Tao Xiong, Yi Qu, Huiqin Wang, Hongju Chen, Jianghu Zhu, Fengyan Zhao, Rong Zou, Li Zhang, Dezhi Mu
Glycogen synthase kinase 3 beta (GSK-3β) plays an important role in neurological outcomes after brain injury. However, its roles and mechanisms in hypoxia-ischemia (HI) are unclear. Activation of mTOR complex 1 (mTORC1) has been proven to induce the synthesis of proteins associated with regeneration. We hypothesized that GSK-3β inhibition could activate the mTORC1 signaling pathway, which may reduce axonal injury and induce synaptic protein synthesis and functional recovery of synapses after HI. By analyzing a P7 rat model of cerebral HI and an in vitro ischemic (oxygen glucose deprivation) model, we found that GSK-3β inhibitors (GSK-3β siRNA or lithium chloride) activated mTORC1 signaling, leading to increased expression of synaptic proteins, including synapsin 1, PSD95, and GluR1, and the microtubule-associated protein Tau and decreased expression of the axonal injury-associated protein amyloid precursor protein...
February 28, 2018: Journal of Neuropathology and Experimental Neurology
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
Kate E Hawkins, Michelangelo Corcelli, Kate Dowding, Anna M Ranzoni, Filipa Vlahova, Kwan-Leong Hau, Avina Hunjan, Donald Peebles, Pierre Gressens, Henrik Hagberg, Paolo de Coppi, Mariya Hristova, Pascale V Guillot
Human mesenchymal stem cells (MSCs) have huge potential for regenerative medicine. In particular, the use of pluripotent stem cell-derived mesenchymal stem cells (PSC-MSCs) overcomes the hurdle of replicative senescence associated with the in vitro expansion of primary cells and has increased therapeutic benefits in comparison to the use of various adult sources of MSCs in a wide range of animal disease models. On the other hand, fetal MSCs exhibit faster growth kinetics and possess longer telomeres and a wider differentiation potential than adult MSCs...
February 28, 2018: Stem Cells Translational Medicine
Ningbo Xu, Yixin Zhang, Desislava Met Doycheva, Yan Ding, Yiting Zhang, Jiping Tang, Hongbo Guo, John H Zhang
Adiponectin is an important adipocyte-derived plasma protein that has beneficial effects on cardio- and cerebrovascular diseases. A low level of plasma Adiponectin is associated with increased mortality post ischemic stroke; however, little is known about the causal role of Adiponectin as well as its molecular mechanisms in neonatal hypoxia ischemia (HI). In the present study, ten-day-old rat pups were subjected to right common carotid artery ligation followed by 2.5 h hypoxia. Recombinant human Adiponectin (rh-Adiponectin) was administered intranasally 1 h post HI...
February 24, 2018: Neuropharmacology
Mohammed Alotaibi
During labour, the uterus itself is vulnerable to hypoxia/ischemia that can occur with each strong contraction and this may ultimately cause dysfunctional labour in some women. Periods of Intermittent re-oxygenations are beneficial to tissues subjected to hypoxia to wash out metabolic by-products that have been accumulated during hypoxic stresses which may affect the tissue viability. We proposed that short intermittent hypoxic episodes may protect the uterus from subsequent sustained long hypoxia. To investigate this, two sets of experiments were performed on term-pregnant and nonpregnant rat uterine tissues...
February 12, 2018: Theriogenology
Byong Sop Lee, Dong-Cheol Woo, Chul-Woong Woo, Ki-Soo Kim
β-Hydroxybutyrate (BHB) is a representative ketone body that may play a role in the mitigation of neonatal hypoxic-ischemic encephalopathy by altering energy metabolism. This study aimed to investigate the neuroprotective efficacy of exogenous BHB administration in a suckling rat model after hypoxia-ischemia (HI). Thirteen-day-old (P13) rat pups were subjected to 120 min of hypoxia according to the Rice-Vannucci model. BHB (5.0 mmol/kg, HI-BHB) or vehicle (0.9% saline, HI-Veh) was administered 0, 2, 4, and 6 h after HI induction...
February 21, 2018: Developmental Neuroscience
Yi-Chao Lee, Ying-Chao Chang, Chia-Ching Wu, Chao-Ching Huang
Therapy targeting the neurovascular unit may provide effective neuroprotection against neonatal hypoxia-ischemia (HI). We hypothesized that the peripheral injection of hypoxia-preconditioned human umbilical vein endothelial cells (HUVECs) following HI protects against neurovascular damage and provides long-term neuroprotection in a postpartum (P) day-7 rat pup model. Compared with normoxic HUVECs, hypoxic HUVECs showed enhanced migration and angiogenesis in vitro and had augmented migration effects into the brain when administered intraperitoneally in vivo after HI...
February 19, 2018: Molecular Neurobiology
Josephine Herz, Christian Köster, Barbara S Reinboth, Mark Dzietko, Wiebke Hansen, Hemmen Sabir, Cindy van Velthoven, Ivo Bendix, Ursula Felderhoff-Müser
Acute hypothermia treatment (HT) is the only clinically established intervention following neonatal hypoxic-ischemic brain injury. However, almost half of all cooled infants still die or suffer from long-lasting neurological impairments. Regenerative therapies, such as mesenchymal stem cells (MSC) appear promising as adjuvant therapy. In the present study, we hypothesized that HT combined with delayed MSC therapy results in augmented protection, improving long-term neurological outcome. Postnatal day 9 (P9) C57BL/6 mice were exposed to hypoxia-ischemia followed by 4 hours HT...
February 14, 2018: Brain, Behavior, and Immunity
Zhen Zheng, Li Zhang, Yi Qu, Guoguang Xiao, Shiping Li, Shan Bao, Q Richard Lu, Dezhi Mu
Hypoxic-ischemic encephalopathy (HIE) is a serious disease for neonates. However, present therapeutic strategies are not effective enough for treating HIE. Previous study showed that mesenchymal stem cells (MSCs) can exert neuroprotective effects for brain damage, but its mechanism remains elusive. Using in vitro coculture of rat cortical primary neurons and MSCs in HI conditions, we demonstrated that MSCs help increase brain derived neurotrophic factor (BDNF) and autophagy markers (LC3II and Beclin1) in the cultures and decrease cells death (lactate dehydrogenase levels)...
February 16, 2018: Stem Cells
Lin Qiao, Jianhua Fu, Xindong Xue, Yongyan Shi, Li Yao, Wanjie Huang, Jun Li, Dan Zhang, Na Liu, Xin Tong, Yanna Du, Yuqing Pan
As research into periventricular leukomalacia (PVL) gradually increases, concerns are emerging about long‑term neuron injury. The present study aimed to investigate neuronal injury and the relevant alterations in apoptosis and autophagy in a PVL model established previously. A rat model of hypoxia‑ischemia‑induced PVL was established. In the model group, Sprague‑Dawley (SD) rats [postnatal day 3 (P3)] were subjected to right common carotid artery ligation followed by suturing and exposed to 6‑8% oxygen for 2 h; in the control group, SD rats (P3) were subjected to right common carotid artery dissection followed by suturing, without ligation and hypoxic exposure...
February 7, 2018: Molecular Medicine Reports
Dan Wu, Lee J Martin, Frances J Northington, Jiangyang Zhang
The recently developed oscillating-gradient diffusion MRI (OG-dMRI) technique extends our ability to examine brain structures at different spatial scales. In this study, we investigated the sensitivity of OG-dMRI in detecting cellular and subcellular structural changes in a mouse model of neonatal hypoxia ischemia (HI). Neonatal mice received unilateral HI injury or sham injury at postnatal day 10, followed by in vivo T 2 -weighted and diffusion MRI of the brains at 3-6 h and 24 h after HI. Apparent diffusion coefficient (ADC) maps were acquired using conventional pulsed-gradient dMRI (PG-dMRI) and OG-dMRI with oscillating frequencies from 50 to 200 Hz...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Hannah C Glass
PURPOSE OF REVIEW: Neonatal encephalopathy is the most common condition in neonates encountered by child neurologists. The etiology is most often global hypoxia-ischemia due to failure of cerebral perfusion to the fetus caused by uterine, placental, or umbilical cord compromise prior to or during delivery. Other etiologies of neonatal encephalopathy include ischemic stroke and intracranial hemorrhage, infection, developmental anomalies, and inborn errors of metabolism. RECENT FINDINGS: Therapeutic hypothermia is standard of care for the treatment of neonatal encephalopathy presumed to be caused by hypoxia-ischemia...
February 2018: Continuum: Lifelong Learning in Neurology
Clémence Delteil, David Meyronet, Andre Maues de Paula, Anne Jouvet, Marie-Dominique Piercecchi-Marti
According to the French High Authority for Health, sudden unexpected death in infants (SUDI) is defined as "a sudden death that occurs in an infant, whereas nothing in its known history could have predicted it". This is an exclusion diagnosis. There are great interregional disparities despite the professional recommendations established in February 2007. For the examination of the brain, instructions are not adapted to current and research practice. The role of the pathologist, like anyone involved in SUDI, is to eliminate an abuse head trauma and to determine the cause of death...
February 8, 2018: Annales de Pathologie
Rui-Bin Zhao, Li-Hua Zhu, Jia-Ping Shu, Li-Xing Qiao, Zheng-Kun Xia
Hypoxic/ischemic brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. However, the molecular mechanism of HIBD in the neonatal infant is still elusive. Long non-coding RNAs are shown as important regulators of brain development and many neurological diseases. Here, we determined the role of long noncoding RNA-GAS5 in HIBD. GAS5 expression was significantly up-regulated in hypoxic/ischemic-injured neonatal brain and hippocampal neurons. GAS5 knockdown protected against hypoxic/ischemic-induced brain injury in vivo and primary hippocampal neuron injury in vitro...
February 8, 2018: Biochemical and Biophysical Research Communications
Ayako Tateishi, Satoshi Ohira, Yoichiro Yamamoto, Hiroyuki Kanno
The placental tissues of pregnancy-induced hypertension (PIH) patients exhibit multiple infarctions, acute atherosis, distal villous hypoplasia, and increased syncytial knots. However, these findings are not observed in all cases of PIH; thus, the significance of these changes in PIH is still unclear. We studied the frequency of histopathological changes of placental tissue in the subgroups of PIH, such as mild and severe PIH and early-onset (< 34 weeks) and late-onset (≥ 34 weeks) PIH. One hundred seven cases of PIH diagnosed at the Shinshu University Hospital, Matsumoto, Japan, between 2008 and 2014 were collected...
February 9, 2018: Virchows Archiv: An International Journal of Pathology
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