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Sample records for neonatal hypoxic-ischemic injury

  1. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

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    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  2. Neuroinflammation and MMPs: potential therapeutic targets in neonatal hypoxic-ischemic injury

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    Pennypacker Keith R; Leonardo Christopher C

    2009-01-01

    Abstract Exposure to hypoxic-ischemic insults during the neonatal or perinatal developmental periods produces various forms of pathology. Injuries that occur in response to these events often manifest as severe cognitive and/or motor disturbances over time. Due to difficulties regarding the early diagnosis and treatment of hypoxic-ischemic injury, there is a growing need for effective therapies that can be delivered at delayed time points. Much of the research into mechanisms of neural injury...

  3. Marine Compound Xyloketal B Reduces Neonatal Hypoxic-Ischemic Brain Injury

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    Ai-Jiao Xiao

    2014-12-01

    Full Text Available Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508 with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury.

  4. Neuroprotective effects of volume-regulated anion channel blocker DCPIB on neonatal hypoxic-ischemic injury

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    Ammar ALIBRAHIM; Li-yan ZHAO; Christine You-jin BAE; Andrew BARSZCZYK; Christopher LF SUN; Guan-lei WANG; Hong-shuo SUN

    2013-01-01

    Aim:To evaluate the role of swelling-induced activation of volume-regulated anion channels (VRACs) in a neonatal hypoxic-ischemic injury model using the selective VRAC blocker 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on5-yl) oxobutyric acid (DCPIB).Methods:Cerebral hypoxic-ischemic injury was induced in 7-day-old mouse pups with Rice-Vannucci method.Prior to the onset of ischemia,the animals were ip administered DCPIB (10 mg/kg).The animals were sacrificed 24 h afterwards,coronal sections of the brains were cut and the areas of infarct were examined using TTC staining and an image-analysis system.Cultured PC12 cells were subjected to oxygen-glucose deprivation (OGD) for 4 h.The cellular viability was assessed using Cell Counting Kit 8.Intracellular chloride concentration [Clˉ]i was measured using 6-methoxy-N-ethylquinolinium iodide.Results:DCPIB-treated mice showed a significant reduction in hemispheric corrected infarct volume (26.65%+2.23%) compared to that in vehicle-treated mice (45.52%+1.45%,P<O.O01).DCPIB-treated mice also showed better functional recovery as they were more active than vehicle-treated mice at 4 and 24 h post injury.In cultured PC12 cells,DCPIB (10 μmol/L) significantly reduced OGD-induced cell death.Moreover,DCPIB (20 μmol/L) blocked hypotonic-induced decrease in [Clˉ]i in PC12 cells of both control and OGD groups.Conclusion:The results further support the pathophysiological role of VRACs in ischemic brain injury,and suggest DCPIB as a potential,easily administrable agent targeting VRACs in the context of perinatal and neonatal hypoxic-ischemic brain injury.

  5. Role of Antioxidants in Neonatal Hypoxic-Ischemic Brain Injury: New Therapeutic Approaches.

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    Arteaga, Olatz; Álvarez, Antonia; Revuelta, Miren; Santaolalla, Francisco; Urtasun, Andoni; Hilario, Enrique

    2017-01-28

    Hypoxic-ischemic brain damage is an alarming health and economic problem in spite of the advances in neonatal care. It can cause mortality or detrimental neurological disorders such as cerebral palsy, motor impairment and cognitive deficits in neonates. When hypoxia-ischemia occurs, a multi-faceted cascade of events starts out, which can eventually cause cell death. Lower levels of oxygen due to reduced blood supply increase the production of reactive oxygen species, which leads to oxidative stress, a higher concentration of free cytosolic calcium and impaired mitochondrial function, triggering the activation of apoptotic pathways, DNA fragmentation and cell death. The high incidence of this type of lesion in newborns can be partly attributed to the fact that the developing brain is particularly vulnerable to oxidative stress. Since antioxidants can safely interact with free radicals and terminate that chain reaction before vital molecules are damaged, exogenous antioxidant therapy may have the potential to diminish cellular damage caused by hypoxia-ischemia. In this review, we focus on the neuroprotective effects of antioxidant treatments against perinatal hypoxic-ischemic brain injury, in the light of the most recent advances.

  6. Changes in cerebral oxidative metabolism during neonatal seizures following hypoxic ischemic brain injury

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    Subhabrata Mitra

    2016-08-01

    Full Text Available Seizures are common following hypoxic ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain, however the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system we measured the concentration changes in the oxidation state of cerebral cytochrome-c-oxidase (Δ[oxCCO] and hemodynamics during recurrent neonatal seizures following hypoxic ischemic encephalopathy in a newborn infant. A rapid increase in Δ[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude integrated electro-encephalogram (aEEG. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Δ[oxCCO] during seizures correlated with changes in mean EEG voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Δ[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism.

  7. Role of Antioxidants in Neonatal Hypoxic?Ischemic Brain Injury: New Therapeutic Approaches

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    Arteaga, Olatz; ?lvarez, Antonia; Revuelta, Miren; Santaolalla, Francisco; Urtasun, Andoni; Hilario, Enrique

    2017-01-01

    Hypoxic?ischemic brain damage is an alarming health and economic problem in spite of the advances in neonatal care. It can cause mortality or detrimental neurological disorders such as cerebral palsy, motor impairment and cognitive deficits in neonates. When hypoxia?ischemia occurs, a multi-faceted cascade of events starts out, which can eventually cause cell death. Lower levels of oxygen due to reduced blood supply increase the production of reactive oxygen species, which leads to oxidative ...

  8. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

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    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  9. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

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    Huang, Yuejun; Lai, Huihong; Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Chen, Yunbin; Ma, Lian

    2013-01-01

    In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  10. Inhibition of miRNA-210 reverses nicotine-induced brain hypoxic-ischemic injury in neonatal rats

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    Wang, Lei; Ke, Jun; Li, Yong; Ma, Qinyi; Dasgupta, Chiranjib; Huang, Xiaohui; Zhang, Lubo; Xiao, DaLiao

    2017-01-01

    Maternal tobacco use in pregnancy increases the risk of neurodevelopmental disorders and neurobehavioral deficits in postnatal life. The present study tested the hypothesis that perinatal nicotine exposure exacerbated brain vulnerability to hypoxic-ischemic (HI) injury in neonatal rats through up-regulation of miR-210 expression in the developing brain. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps. Experiments of HI brain injury were performed in 10-day-old pups. Perinatal nicotine treatment significantly decreased neonatal body and brain weights, but increased the brain to body weight ratio. Perinatal nicotine exposure caused a significant increase in HI brain infarct size in the neonates. In addition, nicotine enhanced miR-210 expression and significantly attenuated brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase isoform B (TrkB) protein abundance in the brain. Of importance, intracerebroventricular administration of a miR-210 inhibitor (miR-210-LNA) significantly decreased HI-induced brain infarct size and reversed the nicotine-increased vulnerability to brain HI injury in the neonate. Furthermore, miR-210-LNA treatment also reversed nicotine-mediated down-regulation of BDNF and TrkB protein expression in the neonatal brains. These findings provide novel evidence that the increased miR-210 plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the brain. It represents a potential novel therapeutic approach for treatment of brain hypoxic-ischemic encephalopathy in the neonate-induced by fetal stress. PMID:28123348

  11. An Isolation Method for Assessment of Brain Mitochondria Function in Neonatal Mice with Hypoxic-Ischemic Brain Injury

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    Caspersen, Casper S.; Sosunov, Alexander; Utkina-Sosunova, Irina; Ratner, Veniamin I.; Starkov, Anatoly A.; Ten, Vadim S.

    2010-01-01

    This work was undertaken to develop a method for the isolation of mitochondria from a single cerebral hemisphere in neonatal mice. Mitochondria from the normal mouse brain hemisphere isolated by the proposed method exhibited a good respiratory control ratio of 6.39 ± 0.53 during glutamate-malate-induced phosphorylating respiration. Electron microscopy showed intact mitochondria. The applicability of this method was tested on mitochondria isolated from naïve mice and their littermates subjected to hypoxic-ischemic insult. Hypoxic-ischemic insult prior to reperfusion resulted in a significant (p < 0.01) inhibition of phosphorylating respiration compared to naïve littermates. This was associated with a profound depletion of the ATP content in the ischemic hemisphere. The expression for Mn superoxide dismutase and cytochrome C (markers for the integrity of the mitochondrial matrix and outer membrane) was determined by Western blot to control for mitochondrial integrity and quantity in the compared samples. Thus, we have developed a method for the isolation of the cerebral mitochondria from a single hemisphere adapted to neonatal mice. This method may serve as a valuable tool to study mitochondrial function in a mouse model of immature brain injury. In addition, the suggested method enables us to examine the mitochondrial functional phenotype in immature mice with a targeted genetic alteration. PMID:18349523

  12. Complement component c1q mediates mitochondria-driven oxidative stress in neonatal hypoxic-ischemic brain injury.

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    Ten, Vadim S; Yao, Jun; Ratner, Veniamin; Sosunov, Sergey; Fraser, Deborah A; Botto, Marina; Sivasankar, Baalasubramanian; Morgan, B Paul; Silverstein, Samuel; Stark, Raymond; Polin, Richard; Vannucci, Susan J; Pinsky, David; Starkov, Anatoly A

    2010-02-10

    Hypoxic-ischemic (HI) brain injury in infants is a leading cause of lifelong disability. We report a novel pathway mediating oxidative brain injury after hypoxia-ischemia in which C1q plays a central role. Neonatal mice incapable of classical or terminal complement activation because of C1q or C6 deficiency or pharmacologically inhibited assembly of membrane attack complex were subjected to hypoxia-ischemia. Only C1q(-/-) mice exhibited neuroprotection coupled with attenuated oxidative brain injury. This was associated with reduced production of reactive oxygen species (ROS) in C1q(-/-) brain mitochondria and preserved activity of the respiratory chain. Compared with C1q(+/+) neurons, cortical C1q(-/-) neurons exhibited resistance to oxygen-glucose deprivation. However, postischemic exposure to exogenous C1q increased both mitochondrial ROS production and mortality of C1q(-/-) neurons. This C1q toxicity was abolished by coexposure to antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). Thus, the C1q component of complement, accelerating mitochondrial ROS emission, exacerbates oxidative injury in the developing HI brain. The terminal complement complex is activated in the HI neonatal brain but appeared to be nonpathogenic. These findings have important implications for design of the proper therapeutic interventions against HI neonatal brain injury by highlighting a pathogenic priority of C1q-mediated mitochondrial oxidative stress over the C1q deposition-triggered terminal complement activation.

  13. Radioiodinated tracers for the evaluation of dopamine receptors in the neonatal rat brain after hypoxic-ischemic injury

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    Zouakia, A. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Chalon, S. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Kung, H.F. (Hospital of the Univ. of Pennsylvania, Dept. of Radiology, Philadelphia, PA (United States)); Dognon, A.M. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Saliba, E. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Besnard, J.C. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Guilloteau, D. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France))

    1994-06-01

    In order to evaluate in vivo SPET for assessing cerebral function after hypoxic-ischemic injury in human neonates, we studied D[sub 1] and D[sub 2] dopamine receptors in a rat model. Seven-day-old rats underwent permanent unilateral common carotid ligation followed by exposure to 8% O[sub 2]. Two weeks later, in brains with no visible loss of hemispheric volume, striatal dopaminergic receptors were studied, with [[sup 125]I]TISCH and [[sup 125]I]IBZM for the D[sub 1] and D[sub 2] dopamine receptors, respectively. Using [[sup 125]I]TISCH, we observed no modifications of D[sub 1] receptors, but in contrast, ex vivo and in vitro autoradiographic experiments showed a 40% decrease in the striatal binding of [[sup 125]I]IBZM on both the ipsilateral and the contralateral side to the carotid ligation. These alterations were detected with IBZM, a D[sub 2] dopamine receptor ligand usable for SPET imaging. (orig./MG)

  14. The pentose phosphate pathway and pyruvate carboxylation after neonatal hypoxic-ischemic brain injury.

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    Brekke, Eva M F; Morken, Tora S; Widerøe, Marius; Håberg, Asta K; Brubakk, Ann-Mari; Sonnewald, Ursula

    2014-04-01

    The neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance to limit the injury. Furthermore, in the neonatal brain, neurons depend on de novo synthesis of neurotransmitters via pyruvate carboxylase (PC) in astrocytes to increase neurotransmitter pools. In the adult brain, PPP activity increases in response to various injuries while pyruvate carboxylation is reduced after ischemia. However, little is known about the response of these pathways after neonatal hypoxia-ischemia (HI). To this end, 7-day-old rats were subjected to unilateral carotid artery ligation followed by hypoxia. Animals were injected with [1,2-(13)C]glucose during the recovery phase and extracts of cerebral hemispheres ipsi- and contralateral to the operation were analyzed using (1)H- and (13)C-NMR (nuclear magnetic resonance) spectroscopy and high-performance liquid chromatography (HPLC). After HI, glucose levels were increased and there was evidence of mitochondrial hypometabolism in both hemispheres. Moreover, metabolism via PPP was reduced bilaterally. Ipsilateral glucose metabolism via PC was reduced, but PC activity was relatively preserved compared with glucose metabolism via pyruvate dehydrogenase. The observed reduction in PPP activity after HI may contribute to the increased susceptibility of the neonatal brain to oxidative stress.

  15. Nelfinavir inhibits intra-mitochondrial calcium influx and protects brain against hypoxic-ischemic injury in neonatal mice.

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    Irina V Utkina-Sosunova

    Full Text Available Nelfinavir (NLF, an antiretroviral agent, preserves mitochondrial membranes integrity and protects mature brain against ischemic injury in rodents. Our study demonstrates that in neonatal mice NLF significantly limits mitochondrial calcium influx, the event associated with protection of the brain against hypoxic-ischemic insult (HI. Compared to the vehicle-treated mice, cerebral mitochondria from NLF-treated mice exhibited a significantly greater tolerance to the Ca(2+-induced membrane permeabilization, greater ADP-phosphorylating activity and reduced cytochrome C release during reperfusion. Pre-treatment with NLF or Ruthenium red (RuR significantly improved viability of murine hippocampal HT-22 cells, reduced Ca(2+ content and preserved membrane potential (Ψm in mitochondria following oxygen-glucose deprivation (OGD. Following histamine-stimulated Ca(2+ release from endoplasmic reticulum, in contrast to the vehicle-treated cells, the cells treated with NLF or RuR also demonstrated reduced Ca(2+ content in their mitochondria, the event associated with preserved Ψm. Because RuR inhibits mitochondrial Ca(2+ uniporter, we tested whether the NLF acts via the mechanism similar to the RuR. However, in contrast to the RuR, in the experiment with direct interaction of these agents with mitochondria isolated from naïve mice, the NLF did not alter mitochondrial Ca(2+ influx, and did not prevent Ca(2+ induced collapse of the Ψm. These data strongly argues against interaction of NLF and mitochondrial Ca(2+ uniporter. Although the exact mechanism remains unclear, our study is the first to show that NLF inhibits intramitochondrial Ca(2+ flux and protects developing brain against HI-reperfusion injury. This novel action of NLF has important clinical implication, because it targets a fundamental mechanism of post-ischemic cell death: intramitochondrial Ca(2+ overload → mitochondrial membrane permeabilization → secondary energy failure.

  16. Sex Differences in Behavioral Outcomes Following Temperature Modulation During Induced Neonatal Hypoxic Ischemic Injury in Rats

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    Amanda L. Smith

    2015-05-01

    Full Text Available Neonatal hypoxia ischemia (HI; reduced oxygen and/or blood flow to the brain can cause various degrees of tissue damage, as well as subsequent cognitive/behavioral deficits such as motor, learning/memory, and auditory impairments. These outcomes frequently result from cardiovascular and/or respiratory events observed in premature infants. Data suggests that there is a sex difference in HI outcome, with males being more adversely affected relative to comparably injured females. Brain/body temperature may play a role in modulating the severity of an HI insult, with hypothermia during an insult yielding more favorable anatomical and behavioral outcomes. The current study utilized a postnatal day (P 7 rodent model of HI injury to assess the effect of temperature modulation during injury in each sex. We hypothesized that female P7 rats would benefit more from lowered body temperatures as compared to male P7 rats. We assessed all subjects on rota-rod, auditory discrimination, and spatial/non-spatial maze tasks. Our results revealed a significant benefit of temperature reduction in HI females as measured by most of the employed behavioral tasks. However, HI males benefitted from temperature reduction as measured on auditory and non-spatial tasks. Our data suggest that temperature reduction protects both sexes from the deleterious effects of HI injury, but task and sex specific patterns of relative efficacy are seen.

  17. Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury.

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    Daadi, Marcel M; Davis, Alexis S; Arac, Ahmet; Li, Zongjin; Maag, Anne-Lise; Bhatnagar, Rishi; Jiang, Kewen; Sun, Guohua; Wu, Joseph C; Steinberg, Gary K

    2010-03-01

    Hypoxic-ischemic (HI) brain injury in newborn infants represents a major cause of cerebral palsy, development delay, and epilepsy. Stem cell-based therapy has the potential to rescue and replace the ischemic tissue caused by HI and to restore function. However, the mechanisms by which stem cell transplants induce functional recovery are yet to be elucidated. In the present study, we sought to investigate the efficacy of human neural stem cells derived from human embryonic stem cells in a rat model of neonatal HI and the mechanisms enhancing brain repair. The human neural stem cells were genetically engineered for in vivo molecular imaging and for postmortem histological tracking. Twenty-four hours after the induction of HI, animals were grafted with human neural stem cells into the forebrain. Motor behavioral tests were performed the fourth week after transplantation. We used immunocytochemistry and neuroanatomical tracing to analyze neural differentiation, axonal sprouting, and microglia response. Treatment-induced changes in gene expression were investigated by microarray and quantitative polymerase chain reaction. Bioluminescence imaging permitted real time longitudinal tracking of grafted human neural stem cells. HI transplanted animals significantly improved in their use of the contralateral impeded forelimb and in the Rotorod test. The grafts showed good survival, dispersion, and differentiation. We observed an increase of uniformly distributed microglia cells in the grafted side. Anterograde neuroanatomical tracing demonstrated significant contralesional sprouting. Microarray analysis revealed upregulation of genes involved in neurogenesis, gliogenesis, and neurotrophic support. These results suggest that human neural stem cell transplants enhance endogenous brain repair through multiple modalities in response to HI.

  18. Magnetic resonance imaging (MRI) and prognostication in neonatal hypoxic-ischemic injury: a vignette-based study of Canadian specialty physicians.

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    Bell, Emily; Rasmussen, Lisa Anne; Mazer, Barbara; Shevell, Michael; Miller, Steven P; Synnes, Anne; Yager, Jerome Y; Majnemer, Annette; Muhajarine, Nazeem; Chouinard, Isabelle; Racine, Eric

    2015-02-01

    Magnetic resonance imaging (MRI) could improve prognostication in neonatal brain injury; however, factors beyond technical or scientific refinement may impact its use and interpretation. We surveyed Canadian neonatologists and pediatric neurologists using general and vignette-based questions about the use of MRI for prognostication in neonates with hypoxic-ischemic injury. There was inter- and intra-vignette variability in prognosis and in ratings about the usefulness of MRI. Severity of predicted outcome correlated with certainty about the outcome. A majority of physicians endorsed using MRI results in discussing prognosis with families, and most suggested that MRI results contribute to end-of-life decisions. Participating neonatologists, when compared to participating pediatric neurologists, had significantly less confidence in the interpretation of MRI by colleagues in neurology and radiology. Further investigation is needed to understand the complexity of MRI and of its application. Potential gaps relative to our understanding of the ethical importance of these findings should be addressed.

  19. Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic- ischemic brain injury

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    Lara-Celador, I.; Go(n)i-de-Cerio, F.; Antonia Alvarez; Enrique Hilario

    2013-01-01

    One of the most important causes of brain injury in the neonatal period is a perinatal hypoxic- ischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death. Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes. Among them, the endocannabinoid system emerges as a natural system of neuroprotection. The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant. The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.

  20. Neonatal seizures and therapeutic hypothermia for hypoxic-ischemic encephalopathy

    OpenAIRE

    2014-01-01

    Neonatal seizures are associated with morbidity and mortality. Hypoxic-ischemic encephalopathy (HIE) is the most common cause of seizures in newborns. Neonatal animal models suggest that therapeutic hypothermia can reduce seizures and epileptiform activity in the setting of hypoxia-ischemia, however data from human studies have conflicting results. In this research highlight, we will discuss the findings of our recent study that demonstrated a decreased seizure burden in term newborns with mo...

  1. Shear Stress Induces Differentiation of Endothelial Lineage Cells to Protect Neonatal Brain from Hypoxic-Ischemic Injury through NRP1 and VEGFR2 Signaling

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    Chia-Wei Huang

    2015-01-01

    Full Text Available Neonatal hypoxic-ischemic (HI brain injuries disrupt the integrity of neurovascular structure and lead to lifelong neurological deficit. The devastating damage can be ameliorated by preserving the endothelial network, but the source for therapeutic cells is limited. We aim to evaluate the beneficial effect of mechanical shear stress in the differentiation of endothelial lineage cells (ELCs from adipose-derived stem cells (ASCs and the possible intracellular signals to protect HI injury using cell-based therapy in the neonatal rats. The ASCs expressed early endothelial markers after biochemical stimulation of endothelial growth medium. The ELCs with full endothelial characteristics were accomplished after a subsequential shear stress application for 24 hours. When comparing the therapeutic potential of ASCs and ELCs, the ELCs treatment significantly reduced the infarction area and preserved neurovascular architecture in HI injured brain. The transplanted ELCs can migrate and engraft into the brain tissue, especially in vessels, where they promoted the angiogenesis. The activation of Akt by neuropilin 1 (NRP1 and vascular endothelial growth factor receptor 2 (VEGFR2 was important for ELC migration and following in vivo therapeutic outcomes. Therefore, the current study demonstrated importance of mechanical factor in stem cell differentiation and showed promising protection of brain from HI injury using ELCs treatment.

  2. The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12 expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury

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    Walker Aisha L

    2005-10-01

    Full Text Available Abstract Background Stromal cell-derived factor 1 (SDF-1 or CXCL12 is chemotaxic for CXCR4 expressing bone marrow-derived cells. It functions in brain embryonic development and in response to ischemic injury in helping guide neuroblast migration and vasculogenesis. In experimental adult stroke models SDF-1 is expressed perivascularly in the injured region up to 30 days after the injury, suggesting it could be a therapeutic target for tissue repair strategies. We hypothesized that SDF-1 would be expressed in similar temporal and spatial patterns following hypoxic-ischemic (HI injury in neonatal brain. Results Twenty-five 7-day-old C57BL/J mice underwent HI injury. SDF-1 expression was up regulated up to 7 days after the injury but not at the later time points. The chief sites of SDF-1 up regulation were astrocytes, their foot processes along blood vessels and endothelial cells. Conclusion The localization of SDF-1 along blood vessels in the HI injury zone suggests that these perivascular areas are where chemotaxic signaling for cellular recruitment originates and that reactive astrocytes are major mediators of this process. The associated endothelium is likely to be the site for vascular attachment and diapedesis of CXCR4 receptor expressing cells to enter the injured tissue. Here we show that, relative to adults, neonates have a significantly smaller window of opportunity for SDF-1 based vascular chemotaxic recruitment of bone marrow-derived cells. Therefore, without modification, following neonatal HI injury there is only a narrow period of time for endogenous SDF-1 mediated chemotaxis and recruitment of reparative cells, including exogenously administered stem/progenitor cells.

  3. A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy.

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    Kyng, Kasper J; Skajaa, Torjus; Kerrn-Jespersen, Sigrid; Andreassen, Christer S; Bennedsgaard, Kristine; Henriksen, Tine B

    2015-05-16

    Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world's 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of xenon and melatonin have led to clinical phase I and II trials(1,2). The piglet HIE model is further used for neonatal resuscitation- and hemodynamic studies as well as in investigations of cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (< 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global hypoxia-ischemia is induced by lowering the inspiratory oxygen fraction to achieve global hypoxia, ischemia through hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure. Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.

  4. Hypoxic-Ischemic Neonatal Encephalopathy: Animal Experiments for Neuroprotective Therapies

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    Hiroshi Sameshima

    2013-01-01

    Full Text Available Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult.

  5. Endogenous hypothermic response to hypoxia reduces brain injury: Implications for modeling hypoxic-ischemic encephalopathy and therapeutic hypothermia in neonatal mice.

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    Reinboth, Barbara S; Köster, Christian; Abberger, Hanna; Prager, Sebastian; Bendix, Ivo; Felderhoff-Müser, Ursula; Herz, Josephine

    2016-09-01

    Hypothermia treatment (HT) is the only formally endorsed treatment recommended for hypoxic-ischemic encephalopathy (HIE). However, its success in protecting against brain injury is limited with a number to treat of 7-8. The identification of the target mechanisms of HIE in combination with HT will help to explain ineffective therapy outcomes but also requires stable experimental models in order to establish further neuroprotective therapies. Despite clinical and experimental indications for an endogenous thermoregulatory response to HIE, the potential effects on HIE-induced brain injury have largely been neglected in pre-clinical studies. In the present study we analyzed gray and white matter injury and neurobehavioral outcome in neonatal mice considering the endogenous thermoregulatory response during HIE combined with HT. HIE was induced in postnatal day (PND) 9 C57BL/6 mice through occlusion of the right common carotid artery followed by one hour of hypoxia. Hypoxia was performed at 8% or 10% oxygen (O2) at two different temperatures based on the nesting body core temperature. Using the model which mimics the clinical situation most closely, i.e. through maintenance of the nesting temperature during hypoxia we compared two mild HT protocols (rectal temperature difference 3°C for 4h), initiated either immediately after HIE or with delay of 2h. Injury was determined by histology, immunohistochemistry and western blot analyses at PND 16 and PND 51. Functional outcome was evaluated by Rota Rod, Elevated Plus Maze, Open Field and Novel Object Recognition testing at PND 30-PND 36 and PND 44-PND 50. We show that HIE modeling in neonatal mice is associated with a significant endogenous drop in body core temperature by 2°C resulting in profound neuroprotection, expressed by reduced neuropathological injury scores, reduced loss of neurons, axonal structures, myelin and decreased astrogliosis. Immediately applied post-hypoxic HT revealed slight advantages over a delayed

  6. Temporal characterization of microglia/macrophage phenotypes in a mouse model of neonatal hypoxic-ischemic brain injury

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    Nina Hellström Erkenstam

    2016-12-01

    Full Text Available Immune cells display a high degree of phenotypic plasticity, which may facilitate their participation in both the progression and resolution of injury-induced inflammation. The purpose of this study was to investigate the temporal expression of genes associated with classical and alternative polarization phenotypes described for macrophages and to identify related cell populations in the brain following neonatal hypoxia-ischemia (HI. HI was induced in 9-day old mice and brain tissue was collected up to 7 d post-insult to investigate expression of genes associated with macrophage activation. Using cell-markers, CD86 (classic activa-tion and CD206 (alternative activation, we assessed temporal changes of CD11b+ cell populations in the brain and studied the protein expression of the immunomodulatory factor galectin-3 in these cells. HI induced a rapid regulation (6h of genes associated with both classical and alternative polarization phenotypes in the injured hemisphere. FACS analysis showed a marked increase in the number of CD11+CD86+ positive cells at 24 h after HI (+3,667 %, which was coupled with a relative suppression of CD11+CD206+ cells and cells that did not express either CD86 or CD206. The CD11+CD206+ popula-tion was mixed with some cells also expressing CD86. Confocal microscopy confirmed that a subset of cells expressed both CD86 and CD206, particularly in injured grey and white matter. Protein con-centration of galectin-3 was markedly increased mainly in the cell population lacking CD86 or CD206 in the injured hemisphere. These cells were predominantly resident microglia as very few galectin-3 positive cells co-localized with infiltrating myeloid cells in Lys-EGFP-ki mice after HI.In summary, HI was characterized by an early mixed gene response, but with a large expansion of mainly the CD86 positive population during the first day. However, the injured hemisphere also con-tained a subset of cells expressing both CD86 and CD206 and a

  7. Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications

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    Amanda L. Smith

    2014-04-01

    Full Text Available Hypoxia-ischemia (HI; reduction in blood/oxygen supply is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA. Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P7, an age comparable to a term (GA 36–38 human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD—a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are

  8. Therapeutic Effect of Caffeine Treatment Immediately Following Neonatal Hypoxic-Ischemic Injury on Spatial Memory in Male Rats

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    R. Holly Fitch

    2013-03-01

    Full Text Available Hypoxia Ischemia (HI refers to the disruption of blood and/or oxygen delivery to the brain. Term infants suffering perinatal complications that result in decreased blood flow and/or oxygen delivery to the brain are at risk for HI. Among a variety of developmental delays in this population, HI injured infants demonstrate subsequent memory deficits. The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes. Caffeine is an adenosine receptor antagonist that has recently shown promising results as a therapeutic agent following HI injury. The current study sought to investigate the therapeutic benefit of caffeine following early HI injury in male rats. On post-natal day (P 7, HI injury was induced (cauterization of the right common carotid artery, followed by two hours of 8% oxygen. Male sham animals received only a midline incision with no manipulation of the artery followed by room air exposure for two hours. Subsets of HI and sham animals then received either an intraperitoneal (i.p. injection of caffeine (10 mg/kg, or vehicle (sterile saline immediately following hypoxia. All animals later underwent testing on the Morris Water Maze (MWM from P90 to P95. Results show that HI injured animals (with no caffeine treatment displayed significant deficits on the MWM task relative to shams. These deficits were attenuated by caffeine treatment when given immediately following the induction of HI. We also found a reduction in right cortical volume (ipsilateral to injury in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate. These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

  9. Attenuation of reactive gliosis does not affect infarct volume in neonatal hypoxic-ischemic brain injury in mice.

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    Katarina Järlestedt

    Full Text Available BACKGROUND: Astroglial cells are activated following injury and up-regulate the expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP and vimentin. Adult mice lacking the intermediate filament proteins GFAP and vimentin (GFAP(-/-Vim(-/- show attenuated reactive gliosis, reduced glial scar formation and improved regeneration of neuronal synapses after neurotrauma. GFAP(-/-Vim(-/- mice exhibit larger brain infarcts after middle cerebral artery occlusion suggesting protective role of reactive gliosis after adult focal brain ischemia. However, the role of astrocyte activation and reactive gliosis in the injured developing brain is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We subjected GFAP(-/-Vim(-/- and wild-type mice to unilateral hypoxia-ischemia (HI at postnatal day 9 (P9. Bromodeoxyuridine (BrdU; 25 mg/kg was injected intraperitoneally twice daily from P9 to P12. On P12 and P31, the animals were perfused intracardially. Immunohistochemistry with MAP-2, BrdU, NeuN, and S100 antibodies was performed on coronal sections. We found no difference in the hemisphere or infarct volume between GFAP(-/-Vim(-/- and wild-type mice at P12 and P31, i.e. 3 and 22 days after HI. At P31, the number of NeuN(+ neurons in the ischemic and contralateral hemisphere was comparable between GFAP(-/-Vim(-/- and wild-type mice. In wild-type mice, the number of S100(+ astrocytes was lower in the ipsilateral compared to contralateral hemisphere (65.0+/-50.1 vs. 85.6+/-34.0, p<0.05. In the GFAP(-/-Vim(-/- mice, the number of S100(+ astrocytes did not differ between the ischemic and contralateral hemisphere at P31. At P31, GFAP(-/-Vim(-/- mice showed an increase in NeuN(+BrdU(+ (surviving newly born neurons in the ischemic cortex compared to wild-type mice (6.7+/-7.7; n = 29 versus 2.9+/-3.6; n = 28, respectively, p<0.05, but a comparable number of S100(+BrdU(+ (surviving newly born astrocytes. CONCLUSIONS/SIGNIFICANCE: Our results suggest that

  10. Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy

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    Gabriel eGonzales-Portillo

    2014-08-01

    Full Text Available Treatments for neonatal hypoxic ischemic encephalopathy (HIE have been limited. The aim of this paper is to offer translational research guidance on stem cell therapy for neonatal HIE by examining clinically relevant animal models, practical stem cell sources, safety and efficacy of endpoint assays, as well as a general understanding of modes of action of this cellular therapy. In order to do so, we discuss the clinical manifestations of HIE, highlighting its overlapping pathologies with stroke providing insights on the potential of cell therapy, currently investigated in stroke, for HIE. To this end, we draw guidance from recommendations outlined in Stem cell Therapeutics as an Emerging Paradigm for Stroke or STEPS, which have been recently modified to Baby STEPS to cater for the neonatal symptoms of HIE. These guidelines recognized that neonatal HIE exhibits distinct disease symptoms from adult stroke in need of an innovative translational approach that facilitates the entry of cell therapy in the clinic. Finally, new information about recent clinical trials, and insights into combination therapy are provided with the vision that stem cell therapy may benefit from available treatments, such as hypothermia, already being tested in children diagnosed with HIE.

  11. A Qualitative Study of Physician Perspectives on Prognostication in Neonatal Hypoxic Ischemic Encephalopathy.

    Science.gov (United States)

    Rasmussen, Lisa Anne; Bell, Emily; Racine, Eric

    2016-10-01

    Hypoxic ischemic encephalopathy is the most frequent cause of neonatal encephalopathy and yields a great degree of morbidity and mortality. From an ethical and clinical standpoint, neurological prognosis is fundamental in the care of neonates with hypoxic ischemic encephalopathy. This qualitative study explores physician perspectives about neurological prognosis in neonatal hypoxic ischemic encephalopathy. This study aimed, through semistructured interviews with neonatologists and pediatric neurologists, to understand the practice of prognostication. Qualitative thematic content analysis was used for data analysis. The authors report 2 main findings: (1) neurological prognosis remains fundamental to quality-of-life predictions and considerations of best interest, and (2) magnetic resonance imaging is presented to parents with a greater degree of certainty than actually exists. Further research is needed to explore both the parental perspective and, prospectively, the impact of different clinical approaches and styles to prognostication for neonatal hypoxic ischemic encephalopathy.

  12. Perinatal Hypoxic-Ischemic brain injury; MR findings

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    Park, Dong Woo; Seo, Chang Hye [Inje University Pusan Paik Hospital, Pusan (Korea, Republic of)

    1994-09-15

    To characterize the MR findings of hypoxic-ischemic brain injury and to assess the value of the MR imaging. SE T1-, T2-weighted, and IR brain MR images of 44 infants and children with the past history of perinatal hypoxic insults were reviewed. Abnormal brain MR findings of 8 patients with birth history of prematurity and 36 patients with birth history of full-term/posterm including 7 with severe anoxic insult history, were compared in regard to the location and the character of the lesions. MRI demonstrated the followings; (1)abnormal signal intensity lesions of subcortical and/or deep cerebral white matter, cortex, and deep gray matter, (2)atrophy of the cerebral white matter, cortex and corpus callosum, with/without ventriculomegaly, and (3)delay in myelination. Periventricular and deep white matter lesions were demonstrated in the prematurity, the deep white matter lesions and/ or subcortical white matter lesions in the term/post-term, and deep gray matter lesions in the 7 patients with severe anoxic insults history. MR imaging was useful in the diagnosis of the hypoxic-ischemic brain injury, and the white and gray matter lesions were correlated with the time of the injury and the severity of hypoxic insult.

  13. Use of estetrol with other steroids for attenuation of neonatal hypoxic-Ischemic brain injury: to combine or not to combine?

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    Tskitishvili, Ekaterine; Pequeux, Christel; Munaut, Carine; Viellevoye, Renaud; Nisolle, Michelle; Noël, Agnes; Foidart, Jean-Michel

    2016-01-01

    Estetrol (E4), estradiol (E2) and progesterone (P4) have important antioxidative and neuroprotective effects in neuronal system. We aimed to study the consequence of combined steroid therapy in neonatal hypoxic-ischemic encephalopathy (HIE). In vitro the effect of E4 combined with other steroids on oxidative stress and the cell viability in primary hippocampal cultures was evaluated by lactate dehydrogenase and cell survival assays. In vivo neuroprotective and therapeutic efficacy of E4 combined with other steroids was studied in HIE model of immature rats. The rat pups rectal temperature, body and brain weights were evaluated. The hippocampus and the cortex were investigated by histo/immunohistochemistry: intact cell number counting, expressions of markers for early gray matter lose, neuro- and angiogenesis were studied. Glial fibrillary acidic protein was evaluated by ELISA in blood samples. In vitro E4 and combinations of high doses of E4 with P4 and/or E2 significantly diminished the LDH activity and upregulated the cell survival.In vivopretreatment or treatment by different combinations of E4 with other steroids had unalike effects on body and brain weight, neuro- and angiogenesis, and GFAP expression in blood. The combined use of E4 with other steroids has no benefit over the single use of E4. PMID:27231853

  14. Use of estetrol with other steroids for attenuation of neonatal hypoxic-ischemic brain injury: to combine or not to combine?

    Science.gov (United States)

    Tskitishvili, Ekaterine; Pequeux, Christel; Munaut, Carine; Viellevoye, Renaud; Nisolle, Michelle; Noël, Agnes; Foidart, Jean-Michel

    2016-06-07

    Estetrol (E4), estradiol (E2) and progesterone (P4) have important antioxidative and neuroprotective effects in neuronal system. We aimed to study the consequence of combined steroid therapy in neonatal hypoxic-ischemic encephalopathy (HIE). In vitro the effect of E4 combined with other steroids on oxidative stress and the cell viability in primary hippocampal cultures was evaluated by lactate dehydrogenase and cell survival assays. In vivo neuroprotective and therapeutic efficacy of E4 combined with other steroids was studied in HIE model of immature rats. The rat pups rectal temperature, body and brain weights were evaluated.The hippocampus and the cortex were investigated by histo/immunohistochemistry: intact cell number counting, expressions of markers for early gray matter lose, neuro- and angiogenesis were studied. Glial fibrillary acidic protein was evaluated by ELISA in blood samples. In vitro E4 and combinations of high doses of E4 with P4 and/or E2 significantly diminished the LDH activity and upregulated the cell survival.In vivopretreatment or treatment by different combinations of E4 with other steroids had unalike effects on body and brain weight, neuro- and angiogenesis, and GFAP expression in blood. The combined use of E4 with other steroids has no benefit over the single use of E4.

  15. Effects of Graded Hypothermia on Hypoxic-ischemic Brain Damage in the Neonatal Rat

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan Xia; Yi-xin Xia

    2011-01-01

    Objective To investigate the effect of graded hypothermia on neuropathologic alteratiors of neonatal rat brain after exposed to hypoxic-ischemic insult at 37℃, 33℃, 31℃, and 28℃, respectively, and to observe the effect of hypothermia on 72-kDa heat shock protein (HSP72) expression after hypoxic-ischemic insult. Methods Seven days old Wistar rats were subjected to unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 2 hours at 37℃, 33℃, 31℃, and 28℃, respectively. The brain temperature was monitored indirectly by inserting a mini-thermocouple probe into the temporal muscle during hypoxia. After hypoxia-ischemia their mortality was assessed. Neuronal damage was assessed with HE staining 72 hours after hypoxia. HSP72 expression at 0.5, 24, and 72 hours of recovery was immunohistochemically assessed using a monoclonal antibody to HSP72. Results Hypoxia-ischemia caused 10.5% (2/19) of mortality in rat of 37℃ group, but no death occurred in 33℃, 31℃ or 28℃ groups. HE staining showed neuropathologic damage was extensive in rats exposed to hypoxia-ischemia at 37℃ (more than 80.0%). The incidence of severe brain damage was significantly decreased in 33℃ (53.3%) and 31℃ groups (44.4%), and no histologic injury was seen in the 28℃ group of rats. Expression of HSP72 was manifest and persistent in the rat brain of 37℃ group, but minimum in the rat brain of 28℃ group. Conclusion Mild and moderate hypothermia might prevent cerebral visible neuropathologic damage associated with hypoxic-ischemic injury by decreasing stress response.

  16. Estrogen inhibits lipid peroxidation after hypoxic-ischemic brain damage in neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Hui Zhu; Xiao Han; Dafeng Ji; Guangming Lv; Meiyu Xu

    2012-01-01

    Sprague-Dawley neonatal rats within 7 days after birth were used in this study. The left common carotid artery was occluded and rats were housed in an 8% O2 environment for 2 hours to establish a hypoxic-ischemic brain damage model. 17β-estradiol (1 × 10-5 M) was injected into the rat abdominal cavity after the model was successfully established. The left hemisphere was obtained at 12, 24, 48, 72 hours after operation. Results showed that malondialdehyde content in the left brain of neonatal rats gradually increased as modeling time prolonged, while malondialdehyde content of 17β-estrodial-treated rats significantly declined by 24 hours, reached lowest levels at 48 hours, and then peaked at 72 hours after injury. Nicotinamide-adenine dinucleotide phosphate histochemical staining showed the nitric oxide synthase-positive cells and fibers dyed blue/violet and were mainly distributed in the cortex, hippocampus and medial septal nuclei. The number of nitric oxide synthase-positive cells peaked at 48 hours and significantly decreased after 17β-estrodial treatment. Our experimental findings indicate that estrogen plays a protective role following hypoxic-ischemic brain damage by alleviating lipid peroxidation through reducing the expression of nitric oxide synthase and the content of malondialdehyde.

  17. Apparent diffusion coefficient histogram analysis of neonatal hypoxic-ischemic encephalopathy

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    Cauley, Keith A. [University of Massachusetts Medical School, Department of Radiology, Worcester, MA (United States); New York Presbyterian Hospital, Columbia University Medical Center, Department of Radiology, New York, NY (United States); Filippi, Christopher G. [New York Presbyterian Hospital, Columbia University Medical Center, Department of Radiology, New York, NY (United States)

    2014-06-15

    Diffusion-weighted imaging is a valuable tool in the assessment of the neonatal brain, and changes in diffusion are seen in normal development as well as in pathological states such as hypoxic-ischemic encephalopathy (HIE). Various methods of quantitative assessment of diffusion values have been reported. Global ischemic injury occurring during the time of rapid developmental changes in brain myelination can complicate the imaging diagnosis of neonatal HIE. To compare a quantitative method of histographic analysis of brain apparent coefficient (ADC) maps to the qualitative interpretation of routine brain MR imaging studies. We correlate changes in diffusion values with gestational age in radiographically normal neonates, and we investigate the sensitivity of the method as a quantitative measure of hypoxic-ischemic encephalopathy. We reviewed all brain MRI studies from the neonatal intensive care unit (NICU) at our university medical center over a 4-year period to identify cases that were radiographically normal (23 cases) and those with diffuse, global hypoxic-ischemic encephalopathy (12 cases). We histographically displayed ADC values of a single brain slice at the level of the basal ganglia and correlated peak (s-sD{sub av}) and lowest histogram values (s-sD{sub lowest}) with gestational age. Normative s-sD{sub av} values correlated significantly with gestational age and declined linearly through the neonatal period (r {sup 2} = 0.477, P < 0.01). Six of 12 cases of known HIE demonstrated significantly lower s-sD{sub av} and s-sD{sub lowest} ADC values than were reflected in the normative distribution; several cases of HIE fell within a 95% confidence interval for normative studies, and one case demonstrated higher-than-normal s-sD{sub av}. Single-slice histographic display of ADC values is a rapid and clinically feasible method of quantitative analysis of diffusion. In this study normative values derived from consecutive neonates without radiographic evidence of

  18. CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological correlations

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    Gutierrez, Leonardo Guilhermino; Portela, Luiz Antonio Pezzi [Hospital Alemao Oswaldo Cruz and Hospital do Coracao, Diagnostic Imaging Division, Sao Paulo (Brazil); Rovira, Alex [University Hospital Vall d' Hebron, MR Unit, Department of Radiology, Barcelona (Spain); Costa Leite, Claudia da [Clinics Hospital of the University of Sao Paulo, School of Medicine, Department of Radiology, Sao Paulo (Brazil); Lucato, Leandro Tavares [Hospital Alemao Oswaldo Cruz and Hospital do Coracao, Diagnostic Imaging Division, Sao Paulo (Brazil); Clinics Hospital of the University of Sao Paulo, School of Medicine, Department of Radiology, Sao Paulo (Brazil)

    2010-11-15

    Non-neonatal hypoxic-ischemic encephalopathy is a clinical condition often related to cardiopulmonary arrest that demands critical management and treatment decisions. Management depends mainly on the degree of neurological impairment and prognostic considerations. Computed tomography (CT) is often used to exclude associated or mimicking pathology. If any, only nonspecific signs such as cerebral edema, sulci effacement, and decreased gray matter (GM)/white matter (WM) differentiation are evident. Pseudosubarachnoid hemorrhage, a GM/WM attenuation ratio <1.18, and inverted GM attenuation are associated with a poor prognosis. Magnetic resonance (MR) imaging is more sensitive than CT in assessing brain damage in hypoxic-ischemic encephalopathy. Some MR findings have similarities to those seen pathologically, based on spatial distribution and time scale, such as lesions distributed in watershed regions and selective injury to GM structures. In the acute phase, lesions are better depicted using diffusion-weighted imaging (DWI) because of the presence of cytotoxic edema, which, on T2-weighted images, only become apparent later in the early subacute phase. In the late subacute phase, postanoxic leukoencephalopathy and contrast enhancement could be observed. In the chronic phase, atrophic changes predominate over tissue signal changes. MR can be useful for estimating prognosis when other tests are inconclusive. Some findings, such as the extent of lesions on DWI and presence of a lactate peak and depleted N-acetyl aspartate peak on MR spectroscopy, seem to have prognostic value. (orig.)

  19. Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE)

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    Harding, Benjamin; Conception, Katherine; Li, Yong; Zhang, Lubo

    2016-01-01

    Hypoxic-ischemic encephalopathy (HIE) resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis) and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI) insult in neonatal rats via intracerebroventricular (ICV) injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS) sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional inflammatory injury, such

  20. Frequency of Hypoxic-Ischemic Encephalopathy Among Hospitalized Neonates in West Iran

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    Fatemeh Eghbalian

    2010-06-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is brain damage from a shortage of oxygen or blood flow to the tissues[1,2] and is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia[1-6]. It is a major contributor to neonatal death and morbidity[4-6]. 15%-20% of HIE cases die during the neonatal period and 30% of those who survive suffer from neurodevelopmental disorders[1,3,6].An estimated 23% of the 4 million neonatal deaths and 8% of all deaths at <5 years of age throughout the world each year are associated with signs of asphyxia at birth[1,4]. Even at referral centers in developed countries, death or moderate to severe disability occurs for 53% to 61% of infants diagnosed as having moderate to severe HIE[1,4,6]. Children with moderate/severe neonatal encephalopathy are at risk for reduced school performance, whereas those with mild encephalopathy have school performance scores similar to those of their peers[1,6]. HIE is one of the most common causes of cerebral palsy and other severe neurologic deficits in children occurring in two to nine of every 1000 live births [1-6]. The incidence of HIE reported in different studies varies widely[2-6], which may be explained by the selection criteria for studies of HIE during the neonatal period[3,4].The aim of the present study was to evaluate the frequency of hypoxic-ischemic encephalo-pathy in hospitalized neonates with seizure in Hamedan (west Iran in a two year period.This is a retrospective cross sectional study on 34 neonates from 2004 to 2006.Inclusion criteria were: all neonates with seizures due to HIE asphyxia having pH below 7, 5th minute Apgar score between 0 and 3, decreased muscle tone and consciousness, cortical atrophy in brain CT scan and multiple organ involvement (eg, kidney, lungs, liver, heart, intestines. Neonates with jitteriness were excluded from the study.The study was based on the recorded files of the patients. CT scan findings, blood

  1. Comparison of early and late MRI in neonatal hypoxic-ischemic encephalopathy using three assessment methods

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    Charon, Valerie; Proisy, Maia; Bruneau, Bertrand; Treguier, Catherine; Rozel, Celine [University Hospital, Department of Imaging, Hopital Sud, Rennes, Cedex 2 (France); Ferre, Jean-Christophe [University Hospital, Department of Neuroradiology, Hopital Pontchaillou, Rennes (France); Beuchee, Alain [University Hospital, Department of Neonatology, Hopital Sud, Rennes (France); Chauvel, Jennifer [Saint Brieuc Hospital, Department of Neonatology, Saint-Brieuc (France)

    2015-12-15

    There is no consensus on the optimum timing of MRI in neonates with hypoxic-ischemic encephalopathy treated with hypothermia. Reliable early imaging assessment might help managing treatment. To assess non-random differences between early and late MRI that might influence intensive-care decisions. This single-center retrospective study included all asphyxiated term neonates eligible for hypothermia treatment November 2009-July 2012. MRI scans were systematically performed at day 4 (early MRI) and day 11 of life as part of routine protocol. Two experienced pediatric radiologists reviewed both scans according to three assessment methods: a pattern classification, a scoring system and a simplified classification. Agreement between early and late imaging findings was assessed using Cohen's kappa coefficients. Thirty-three neonates were included. Interobserver agreement was excellent. Early MRI detected all severe injuries. Agreement between early and late MRI was excellent for the simplified classification (κ = 0.82), good for the pattern classification (κ = 0.64), and good to excellent for 3 scores out of 4 in the scoring system (κ = 0.70-0.89). Early MRI may provide valuable information about brain injury to help parents and neonatologists in intensive-care decisions at the end of hypothermia treatment. (orig.)

  2. Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage.

    Science.gov (United States)

    Feng, Zhichun; Liu, Jing; Ju, Rong

    2013-05-05

    Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

  3. Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Zhichun Feng; Jing Liu; Rong Ju

    2013-01-01

    Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2′-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2′- deoxyuridine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

  4. Mild hypoxemia during initial reperfusion alleviates the severity of secondary energy failure and protects brain in neonatal mice with hypoxic-ischemic injury.

    Science.gov (United States)

    Niatsetskaya, Zoya V; Charlagorla, Pradeep; Matsukevich, Dzmitry A; Sosunov, Sergey A; Mayurasakorn, Korapat; Ratner, Veniamin I; Polin, Richard A; Starkov, Anatoly A; Ten, Vadim S

    2012-02-01

    Reperfusion triggers an oxidative stress. We hypothesized that mild hypoxemia in reperfusion attenuates oxidative brain injury following hypoxia-ischemia (HI). In neonatal HI-mice, the reperfusion was initiated by reoxygenation with room air (RA) followed by the exposure to 100%, 21%, 18%, 15% oxygen for 60 minutes. Systemic oxygen saturation (SaO(2)), cerebral blood flow (CBF), brain mitochondrial respiration and permeability transition pore (mPTP) opening, markers of oxidative injury, and cerebral infarcts were assessed. Compared with RA-littermates, HI-mice exposed to 18% oxygen exhibited significantly decreased infarct volume, oxidative injury in the brain mitochondria and tissue. This was coupled with improved mitochondrial tolerance to mPTP opening. Oxygen saturation maintained during reperfusion at 85% to 95% was associated (r=0.57) with the best neurologic outcome. Exposure to 100% or 15% oxygen significantly exacerbated brain injury and oxidative stress. Compared with RA-mice, hyperoxia dramatically increased reperfusion CBF, but exposure to 15% oxygen significantly reduced CBF to values observed during the HI-insult. Mild hypoxemia during initial reperfusion alleviates the severity of HI-brain injury by limiting the reperfusion-driven oxidative stress to the mitochondria and mPTP opening. This suggests that at the initial stage of reperfusion, a slightly decreased systemic oxygenation (SaO(2) 85% to 95%) may be beneficial for infants with birth asphyxia.

  5. The Relationship between Plasma Endothelin and Hypoxic- Ischemic Encephalopathy in 70 Tibetan Neonates of Plateau Area

    Institute of Scientific and Technical Information of China (English)

    DEJI Meiduo; ZHAO Rong; ZHAO Min; WU Sulan

    2002-01-01

    Objective To discuss the dynamic changing characteristics of plasma endothelin in Tibetan neonates of plateau area with hypoxic - ischemic encephalopathy. Methods Plasma ET level has been determined for 10 days 72 hours after birth by radioimmunoassay in 70 tibetan neonates with HIE.The control group consisted of 20 healthy neonates. Results During acute stage, plasma ET levels of mild, moderate and severe groups were significantly higher that of control group (P < 0.001 ). During acute stage, plasma ET level was closely related with the severity of HIE. Severer HIE was, higher ET level. Conclusion ET was involved in the regulation of HIE.

  6. Pharmacological Neuroprotection after Perinatal Hypoxic-Ischemic Brain Injury

    NARCIS (Netherlands)

    Fan, Xiyong; Kavelaars, Annemieke; Heijnen, Cobi J.; Groenendaal, Floris; van Bel, Frank

    2010-01-01

    Perinatal hypoxia-ischemia (HI) is an important cause of neonatal brain injury. Recent progress in the search for neuroprotective compounds has provided us with several promising drugs to reduce perinatal HI-induced brain injury. In the early stage (first 6 hours after birth) therapies are concentra

  7. Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of nuclear factor (erythroid-derived 2)-like 2

    Science.gov (United States)

    Zhao, Hailin; Mitchell, Sian; Ciechanowicz, Sarah; Savage, Sinead; Wang, Tianlong; Ji, Xunming; Ma, Daqing

    2016-01-01

    Perinatal hypoxic ischaemic encephalopathy (HIE) has a high mortality rate with neuropsychological impairment. This study investigated the neuroprotective effects of argon against neonatal hypoxic-ischaemic brain injury. In vitro cortical neuronal cell cultures derived from rat foetuses were subjected to an oxygen and glucose deprivation (OGD) challenge for 90 minutes and then exposed to 70% argon or nitrogen with 5% carbon dioxide and balanced with oxygen for 2 hours. In vivo, seven-day-old rats were subjected to unilateral common carotid artery ligation followed by hypoxic (8% oxygen balanced with nitrogen) insult for 90 minutes. They were exposed to 70% argon or nitrogen balanced with oxygen for 2 hours. In vitro, argon treatment of cortical neuronal cultures resulted in a significant increase of p-mTOR and Nuclear factor (erythroid-derived 2)-like 2(Nrf2) and protection against OGD challenge. Inhibition of m-TOR through Rapamycin or Nrf2 through siRNA abolished argon-mediated cyto-protection. In vivo, argon exposure significantly enhanced Nrf2 and its down-stream effector NAD(P)H Dehydrogenase, Quinone 1(NQO1) and superoxide dismutase 1(SOD1). Oxidative stress, neuroinflammation and neuronal cell death were significantly decreased and brain infarction was markedly reduced. Blocking PI-3K through wortmannin or ERK1/2 through U0126 attenuated argon-mediated neuroprotection. These data provide a new molecular mechanism for the potential application of argon as a neuroprotectant in HIE. PMID:27016422

  8. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gang, QiangQiang, E-mail: rousikang@163.com; Zhang, Jianing, E-mail: 1325916060@qq.com; Hao, Peng, E-mail: 1043600590@qq.com; Xu, Yikai, E-mail: yikaivip@163.com

    2013-11-01

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy.

  9. IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Aly, Hany; Khashaba, Mohamed T; El-Ayouty, Mostafa; El-Sayed, Osman; Hasanein, Bothina M

    2006-04-01

    The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates is not fully defined. We hypothesize that interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) correlate with the severity of brain injury and can predict neurological deficits in infants who suffered from hypoxic ischemic encephalopathy (HIE). A prospective study was conducted on 24 term infants diagnosed with HIE and 13 controls. HIE was clinically classified into mild, moderate and severe according to Sarnat and Sarnat grading. Blood and CSF samples were obtained from all infants in the first 24h of life as part of routine investigations for suspected meningitis and/or sepsis. Neurological examination and Denver Developmental Screening Test II (DDST II) were performed at 6 and 12 months of life. IL-1beta, IL-6 and TNF-alpha were all significantly increased in HIE infants when compared to control. IL-1beta in the CSF correlated with the severity of HIE (r=0.61, P=0.001) more than IL-6 (r=0.45, P=0.004) or TNF-alpha (r=0.47, P=0.003). IL-1beta exhibited the highest CSF/serum ratio among the three studied cytokines suggesting its local release in the brain after the initial hypoxic injury. Abnormal neurological findings and/or abnormal DDST II at 6 and 12 months were best predicted by IL-1beta in the CSF (sensitivity=88% and specificity=80%). This study confirms the role of IL-1beta in the ongoing neuronal injury that occurs in the latent phase following the original HIE insult.

  10. Therapeutic administration of plasminogen activator inhibitor-1 prevents hypoxic-ischemic brain injury in newborns.

    Science.gov (United States)

    Yang, Dianer; Nemkul, Niza; Shereen, Ahmed; Jone, Alice; Dunn, R Scott; Lawrence, Daniel A; Lindquist, Diana; Kuan, Chia-Yi

    2009-07-08

    Disruption of the integrity of the blood-brain barrier (BBB) is an important mechanism of cerebrovascular diseases, including neonatal cerebral hypoxia-ischemia (HI). Although both tissue-type plasminogen activator (tPA) and matrix metalloproteinase-9 (MMP-9) can produce BBB damage, their relationship in neonatal cerebral HI is unclear. Here we use a rodent model to test whether the plasminogen activator (PA) system is critical for MMP-9 activation and HI-induced brain injury in newborns. To test this hypothesis, we examined the therapeutic effect of intracerebroventricular injection of plasminogen activator inhibitor-1 (PAI-1) in rat pups subjected to unilateral carotid artery occlusion and systemic hypoxia. We found that the injection of PAI-1 greatly reduced the activity of both tPA and urokinase-type plasminogen activator after HI. It also blocked HI-induced MMP-9 activation and BBB permeability at 24 h of recovery. Furthermore, magnetic resonance imaging and histological analysis showed the PAI-1 treatment reduced brain edema, axonal degeneration, and cortical cell death at 24-48 h of recovery. Finally, the PAI-1 therapy provided a dose-dependent decrease of brain tissue loss at 7 d of recovery, with the therapeutic window at 4 h after the HI insult. Together, these results suggest that the brain PA system plays a pivotal role in neonatal cerebral HI and may be a promising therapeutic target in infants suffering hypoxic-ischemic encephalopathy.

  11. Intranasal administration of aTf protects and repairs the neonatal white matter after a cerebral hypoxic-ischemic event.

    Science.gov (United States)

    Guardia Clausi, Mariano; Paez, Pablo M; Campagnoni, Anthony T; Pasquini, Laura A; Pasquini, Juana M

    2012-10-01

    Our previous studies showed that the intracerebral injection of apotransferrin (aTf) attenuates white matter damage and accelerates the remyelination process in a neonatal rat model of cerebral hypoxia-ischemia (HI) injury. However, the intracerebral injection of aTf might not be practical for clinical treatments. Therefore, the development of less invasive techniques capable of delivering aTf to the central nervous system would clearly aid in its effective clinical use. In this work, we have determined whether intranasal (iN) administration of human aTf provides neuroprotection to the neonatal mouse brain following a cerebral hypoxic-ischemic event. Apotransferrin was infused into the naris of neonatal mice and the HI insult was induced by right common carotid artery ligation followed by exposure to low oxygen concentration. Our results showed that aTf was successfully delivered into the neonatal HI brain and detected in the olfactory bulb, forebrain and posterior brain 30 min after inhalation. This treatment successfully reduced white matter damage, neuronal loss and astrogliosis in different brain regions and enhanced the proliferation and survival of oligodendroglial progenitor cells (OPCs) in the subventricular zone and corpus callosum (CC). Additionally, using an in vitro hypoxic model, we demonstrated that aTf prevents oligodendrocyte progenitor cell death by promoting their differentiation. In summary, these data suggest that iN administration of aTf has the potential to be used for clinical treatment to protect myelin and to induce remyelination in demyelinating hypoxic-ischemic events in the neonatal brain. Copyright © 2012 Wiley Periodicals, Inc.

  12. Thioperamide treats neonatal hypoxic-ischemic encephalopathy by postsynaptic H1 receptors*

    Institute of Scientific and Technical Information of China (English)

    Feiyong Jia; Lin Du; Yunpeng Hao; Shicheng Liu; Ning Li; Huiyi Jiang

    2013-01-01

    Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of thioperamide during brain edema in a rat model of neonatal hypoxic- is-chemic encephalopathy. Our results showed that thioperamide significantly decreased brain water content and malondialdehyde levels, while significantly increased histamine levels and superoxide dismutase activity in the hippocampus. This evidence demonstrates that thioperamide could pre-vent oxidative damage and attenuate brain edema fol owing neonatal hypoxic-ischemic encepha-lopathy. We further observed that changes in the above indexes occurred after combined treatment of thioperamide with the H1 receptor antagonist, pyrilamine, and the H2 receptor antagonist, ci-metidine. Experimental findings indicated that pyrilamine reversed the effects of thioperamide;however, cimetidine had no significant influence on the effects of thioperamide. Our present findings suggest that thioperamide can increase brain histamine content and attenuate brain edema and oxidative damage by acting in combination with postsynaptic H1 receptors in a rat model of neo-natal hypoxic-ischemic encephalopathy.

  13. Spatiotemporal Characteristics of Freezing of Gait in Patients After Hypoxic-Ischemic Brain Injury

    OpenAIRE

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Yong Wook

    2016-01-01

    Abstract The objective of this study was to investigate spatiotemporal characteristics with gait variability in patients with freezing of gait (FOG) after hypoxic-ischemic brain injury (HIBI). Eleven patients showing FOG after HIBI and 15 normal controls were consecutively enrolled. We performed gait analysis using a computerized gait system (VICON MX-T10 Motion Analysis System) and compared spatiotemporal characteristics and gait variability in both groups. Additionally, we performed correla...

  14. Preterm Hypoxic Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Krishna G Gopagondanahalli

    2016-10-01

    Full Text Available Hypoxic ischemic encephalopathy (HIE is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic ischemic episode before or during birth. However, in the preterm infant, defining hypoxic ischemic injury, its clinical course, monitoring and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic ischemic insult in preterm infants is probably higher than recognized, and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies.

  15. Evolution of the Therapeutic Effects of Induced Local Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    B. Basiri

    2011-04-01

    Full Text Available Introduction & Objective: Hypoxic-ischemic encephalopathy is one of the most important causes of permanent damage to brain tissue that redound to mortality and/or late sequelae such as cerebral palsy or delayed neural development. 15-20 percent of Hypoxic-ischemic encephalopathy (HIE cases die during neonatal period and 25-30 percent of those who survive suffer from neural development problems such as cerebral palsy and mental retardation. Hypothermia or lowering temperature of brain or total body is a new and promising treatment. The present study was done to assess therapeutic effects of induced local hypothermia in hypoxic-ischemic encephalopathy (HIE among neonates admitted to Fatemieh and Beset hospitals of Hamadan city.Materials & Method: The present study was performed as a randomized clinical trial upon 36 neonates who had inclusion criteria to be imported into the study. In the first 6 hours after birth, the neonates were randomly classified into two 18 person groups. In the control group the neonates were managed with routine treatments consisted of preservative measures and anti-convulsive treatments, if necessary. In the case group the neonates received induced local hypothermia for 6 hours in addition to routine therapeutic managements. The data were analyzed using SPSS Version 13.Results: 72.7% of the neonates of the case and control groups were male. There was no significant difference between the case and control groups in sex, birth weight, gestational age and perinatal obstetric complications. The mean duration of admission was 7.72±4.23 days in the case group and 10.06±5.99 days in the control group with no significant difference between the two groups (P=0.199. The mean time of starting oral feeding was 3.44±3.11 days and 4.53±2.74 days in the control and case groups respectively and this difference was not statistically significant either (P=0.737.The mean time of regaining consciousness was 3.72±3.19 days in the case

  16. Arterial spin-labelling perfusion MRI and outcome in neonates with hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Vis, Jill B. de; Hendrikse, Jeroen [University Medical Center Utrecht, Department of Radiology, HP E 01.132, P.O. Box 85500, Utrecht (Netherlands); Petersen, Esben T. [University Medical Center Utrecht, Department of Radiology, HP E 01.132, P.O. Box 85500, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiotherapy, Utrecht (Netherlands); Vries, Linda S. de; Bel, Frank van; Alderliesten, Thomas; Negro, Simona; Groenendaal, Floris; Benders, Manon J.N.L. [Wilhelmina Children' s Hospital/University Medical Center Utrecht, Department of Neonatology, Utrecht (Netherlands)

    2015-01-15

    Hyperperfusion may be related to outcome in neonates with hypoxic-ischemic encephalopathy (HIE). The purpose of this study was to evaluate whether arterial spin labelling (ASL) perfusion is associated with outcome in neonates with HIE and to compare the predictive value of ASL MRI to known MRI predictive markers. Twenty-eight neonates diagnosed with HIE and assessed with MR imaging (conventional MRI, diffusion-weighted MRI, MR spectroscopy [MRS], and ASL MRI) were included. Perfusion in the basal ganglia and thalami was measured. Outcome at 9 or 18 months of age was scored as either adverse (death or cerebral palsy) or favourable. The median (range) perfusion in the basal ganglia and thalami (BGT) was 63 (28-108) ml/100 g/min in the neonates with adverse outcome and 28 (12-51) ml/100 g/min in the infants with favourable outcome (p < 0.01). The area-under-the-curve was 0.92 for ASL MRI, 0.97 for MRI score, 0.96 for Lac/NAA and 0.92 for ADC in the BGT. The combination of Lac/NAA and ASL MRI results was the best predictor of outcome (r {sup 2} = 0.86, p < 0.001). Higher ASL perfusion values in neonates with HIE are associated with a worse neurodevelopmental outcome. A combination of the MRS and ASL MRI information is the best predictor of outcome. (orig.)

  17. Critical role of neuronal pentraxin 1 in mitochondria-mediated hypoxic-ischemic neuronal injury.

    Science.gov (United States)

    Al Rahim, Md; Thatipamula, Shabarish; Hossain, Mir Ahamed

    2013-02-01

    Developing brain is highly susceptible to hypoxic-ischemic (HI) injury leading to severe neurological disabilities in surviving infants and children. Previously, we have reported induction of neuronal pentraxin 1 (NP1), a novel neuronal protein of long-pentraxin family, following HI neuronal injury. Here, we investigated how this specific signal is propagated to cause the HI neuronal death. We used wild-type (WT) and NP1 knockout (NP1-KO) mouse hippocampal cultures, modeled in vitro following exposure to oxygen glucose deprivation (OGD), and in vivo neonatal (P9-10) mouse model of HI brain injury. Our results show induction of NP1 in primary hippocampal neurons following OGD exposure (4-8 h) and in the ipsilateral hippocampal CA1 and CA3 regions at 24-48 h post-HI compared to the contralateral side. We also found increased PTEN activity concurrent with OGD time-dependent (4-8 h) dephosphorylation of Akt (Ser473) and GSK-3β (Ser9). OGD also caused a time-dependent decrease in the phosphorylation of Bad (Ser136), and Bax protein levels. Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3. NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential (ΔΨ(m)). This NP1 induction preceded the increased mitochondrial release of cytochrome C (Cyt C) into the cytosol, activation of caspase-3 and OGD time-dependent cell death in WT primary hippocampal neurons. In contrast, in NP1-KO neurons there was no translocation of Bad and Bax from cytosol to the mitochondria, and no evidence of ΔΨ(m) loss, increased Cyt C release and caspase-3 activation following OGD; which resulted in

  18. Animal models of hypoxic-ischemic brain injury%缺血缺氧性脑损伤动物模型

    Institute of Scientific and Technical Information of China (English)

    冷军; 刘慧娟; 王磊; 曹忠; 王敏

    2010-01-01

    The animal models of hypoxic-ischemic brain injury have been established inmany animals, such as monkeys, dogs, rats, mice, rabbits, and pigs. These models have provideda great deal of important information for neonatal hypoxic-ischemic brain injury. Howerver, thedifferent species vary in their susceptibility to the various types of ischemic insults. This articlereviews the animal models of hypoxic-ischemic brain injury in different species.%已在许多动物,如猴、狗、大鼠、小鼠、兔、猪等建立缺血缺氧性脑损伤动物模型.这些模型为新生儿缺血缺氧性脑损伤的研究提供了大量重要信息.但是,不同种属对各种类型缺血性损伤的易感性存在差异.文章对利用不同种属动物制作的缺血缺氧性脑损伤模型做了综述.

  19. White matter apoptosis is increased by delayed hypothermia and rewarming in a neonatal piglet model of hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Wang, B; Armstrong, J S; Reyes, M; Kulikowicz, E; Lee, J-H; Spicer, D; Bhalala, U; Yang, Z-J; Koehler, R C; Martin, L J; Lee, J K

    2016-03-01

    Therapeutic hypothermia is widely used to treat neonatal hypoxic ischemic (HI) brain injuries. However, potentially deleterious effects of delaying the induction of hypothermia and of rewarming on white matter injury remain unclear. We used a piglet model of HI to assess the effects of delayed hypothermia and rewarming on white matter apoptosis. Piglets underwent HI injury or sham surgery followed by normothermic or hypothermic recovery at 2h. Hypothermic groups were divided into those with no rewarming, slow rewarming at 0.5°C/h, or rapid rewarming at 4°C/h. Apoptotic cells in the subcortical white matter of the motor gyrus, corpus callosum, lateral olfactory tract, and internal capsule at 29h were identified morphologically and counted by hematoxylin & eosin staining. Cell death was verified by terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay. White matter neurons were also counted, and apoptotic cells were immunophenotyped with the oligodendrocyte marker 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). Hypothermia, slow rewarming, and rapid rewarming increased apoptosis in the subcortical white matter relative to normothermia (ppiglets had more apoptosis in the lateral olfactory tract than those that were rewarmed (ppiglets had more apoptosis than shams after normothermia, slow rewarming, and rapid rewarming (ppiglet model of HI; in some regions these temperature effects are independent of HI. Vulnerable cells include myelinating oligodendrocytes. This study identifies a deleterious effect of therapeutic hypothermia in the developing brain.

  20. Differentiation between peritrigonal terminal zones and hypoxic-ischemic white matter injury on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Liauw, Lishya [Department of Radiology, C3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: l.liauw@rad.umcn.nl; Grond, Jeroen van der [Department of Radiology, C3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: j.van_der_grond@lumc.nl; Slooff, Valerie [Emma Children' s Hospital AMC, University of Amsterdam, P.O. Box 22700, 1100 DD Amsterdam (Netherlands)], E-mail: v.d.slooff@amc.uva.nl; Wiggers-de Bruine, Francisca [Department of Radiology, C3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: f.t.wiggers-de_bruine@lumc.nl; Laan, Laura [Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: l.a.e.m.laan@lumc.nl; Cessie, Saskia le [Department of Medical Statistics and Bio-Informatics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden (Netherlands)], E-mail: c.le_cessie@lumc.nl; Buchem, Mark van [Department of Radiology, C3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: m.a.van_buchem@lumc.nl; Wezel-Meijler, Gerda van [Department of Neonatology, J6S-201, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: g.van_wezel-meijler@lumc.nl

    2008-03-15

    The differentiation between terminal zones and pathological signal intensity changes on MRI of children and young adults is of diagnostic importance. We assessed the diagnostic value of several morphological features on MRI to differentiate between terminal zones and hypoxic-ischemic white matter injury. We selected all brain MRI examinations performed in subjects up to 20 years of age showing increased signal intensity on T2-weighted images in the peritrigonal areas. 75 individuals were assigned to a patient group (n = 28) if there was evidence of hypoxia-ischemia during the perinatal period or a control group (n = 47). Aspect, location, extent, shape, and borders of signal intensity changes in the peritrigonal areas were studied. Signal intensity of the peritrigonal areas was related to signal intensity of surrounding white matter. Presence of Virchow Robin spaces, hypoxic-ischemic abnormalities, and local atrophy were also recorded. Chi-squared tests assessed whether presence or absence of morphological characteristics differed between patients and controls. Logistic regression analysis studied which characteristics were best to discriminate between the two groups. Very high signal intensity of the peritrigonal areas on FLAIR (Odds Ratio 25) and presence of local atrophy (Odds Ratio 14.3) were best predictors to discriminate between the two groups.

  1. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-08-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders.

  2. Emodin prevents hypoxic-ischemic neuronal injury Involvement of the activin A pathway

    Institute of Scientific and Technical Information of China (English)

    Hongliang Guo; Xiaoran Shen; Ye Xu; Junliang Yuan; Dongming Zhao; Wenli Hu

    2013-01-01

    Emodin, an extract of dried rhizomes and the root of the Rhizoma Polygoni Cuspidati, can protect neurons from hypoxic-ischemic brain damage. This study aimed to verify the underlying mechanism. After PC12 cells had differentiated into neuron-like cells under the induction of mouse nerve growth factor, cells were subjected to oxygen-glucose deprivation and treated with emodin. Results showed that the viability of neuron-like cells cultured under an ischemia-hypoxia environment decreased, while the expression of activin A and caspase-3 in cells increased. Emodin raised the survival rate of oxygen-glucose deprived neuron-like cells, increased activin A expression, and decreased caspase-3 expression. Experimental findings indicate that emodin can inhibit neuronal apoptosis and alleviate the injury of nerve cells after oxygen-glucose deprivation through the activin A pathway.

  3. Early application of nerve growth factor affects serum inflammatory cytokine levels in neonatal hypoxic ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: It has been demonstrated that there are changes of various cytokines, chemokines and adhesion factors in neonatal hypoxic ischemic encephalopathy (HIE). What are the changes of interleukin-6 and interleukin-18 in serum of HIE neonates.OBJECTIVE: To observe the dynamic changes of interleukin-6 and interleukin-18 in peripheral serum at different time after HIE in neonates, and analyze the possible therapeutic efficacy of early application of NGF.DESIGN: A non-randomized controlled observation synchronically.SETTING: Department of Neonatology, Sun Yat-sen Hospital affiliated to Sun Yat-sen University.PARTICIPANTS: Sixty neonates with HIE were selected from the Department of Neonatology, Sun Yat-sen Hospital affiliated to Sun Yat-sen University from January 2004 to October 2006, including 32 boys and 28 girls, who were all accorded with the diagnostic standards for moderate to severe HIE. The neonates were divided into two groups NGF-treated group (n =30), HIE group (n =30). The HIE neonates in the NGF-treated group were given routine treatment and intramuscular injection of NGF within 24 hours after birth. Those in the HIE group were given routine treatments. Meanwhile, 30 apneic normal neonates (17 boys and 13 girls) at the same period were selected as the control group. The gestational age was 37 - 42 weeks in all the three groups, the body mass at birth was 2 500 - 4 000 g. Informed contents were obtained from the relatives of all the enrolled neonates.METHODS: The HIE neonates in the NGF-treated group were given routine treatment and intramuscular injection of NGF (2 000 U) within 24 hours after birth, once a day, 10 days as a course. Those in the HIE group were given routine treatments. Blood samples (3 mL) were drawn from femoral vein in all the neonates 1, 3 and 7 days after birth. The levels of interleukin-6 and interleukin-18 in serum were detected with enzyme-linked immunoabsorbent assay (ELISA).MAIN OUTCOME MEASURES: Serum levels of interlenkin

  4. Combination treatment of hypothermia and mesenchymal stromal cells amplifies neuroprotection in primary rat neurons exposed to hypoxic-ischemic-like injury in vitro: role of the opioid system.

    Directory of Open Access Journals (Sweden)

    Yuji Kaneko

    Full Text Available This study was designed to reveal the therapeutic regimen and mechanism of action underlying hypothermia treatment in combination with stem cell transplantation for ameliorating neonatal hypoxic-ischemic-like injury. Primary rat neurons were exposed to oxygen-glucose deprivation (OGD, which produced hypoxic-ischemic-like injury in vitro, then incubated at 25°C (severe hypothermia, 34°C (moderate hypothermia, and 37°C (normothermia with or without subsequent co-culture with mesenchymal stromal cells (MSCs. Combination treatment of moderate hypothermia and MSCs significantly improved cell survival and mitochondrial activity after OGD exposure. The exposure of delta opioid human embryonic kidney cells (HEK293 to moderate hypothermia attenuated OGD-mediated cell alterations, which were much more pronounced in HEK293 cells overexpressing the delta opioid receptor. Further, the addition of delta opioid peptide to 34°C hypothermia and stem cell treatment in primary rat neurons showed synergistic neuroprotective effects against OGD which were significantly more robust than the dual combination of moderate hypothermia and MSCs, and were significantly reduced, but not completely abolished, by the opioid receptor antagonist naltrexone altogether implicating a ligand-receptor mechanism of neuroprotection. Further investigations into non-opioid therapeutic signaling pathways revealed growth factor mediation and anti-apoptotic function accompanying the observed therapeutic benefits. These results support combination therapy of hypothermia and stem cells for hypoxic-ischemic-like injury in vitro, which may have a direct impact on current clinical trials using stand-alone hypothermia or stem cells for treating neonatal encephalopathy.

  5. Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns.

    Science.gov (United States)

    Yang, Dianer; Sun, Yu-Yo; Bhaumik, Siddhartha Kumar; Li, Yikun; Baumann, Jessica M; Lin, Xiaoyi; Zhang, Yujin; Lin, Shang-Hsuan; Dunn, R Scott; Liu, Chia-Yang; Shie, Feng-Shiun; Lee, Yi-Hsuan; Wills-Karp, Marsha; Chougnet, Claire A; Kallapur, Suhas G; Lewkowich, Ian P; Lindquist, Diana M; Murali-Krishna, Kaja; Kuan, Chia-Yi

    2014-12-03

    Intrauterine infection (chorioamnionitis) aggravates neonatal hypoxic-ischemic (HI) brain injury, but the mechanisms linking systemic inflammation to the CNS damage remain uncertain. Here we report evidence for brain influx of T-helper 17 (TH17)-like lymphocytes to coordinate neuroinflammatory responses in lipopolysaccharide (LPS)-sensitized HI injury in neonates. We found that both infants with histological chorioamnionitis and rat pups challenged by LPS/HI have elevated expression of the interleukin-23 (IL-23) receptor, a marker of early TH17 lymphocytes, in the peripheral blood mononuclear cells. Post-LPS/HI administration of FTY720 (fingolimod), a sphingosine-1-phosphate receptor agonist that blocks lymphocyte trafficking, mitigated the influx of leukocytes through the choroid plexus and acute induction of nuclear factor-κB signaling in the brain. Subsequently, the FTY720 treatment led to attenuated blood-brain barrier damage, fewer cluster of differentiation 4-positive, IL-17A-positive T-cells in the brain, less proinflammatory cytokine, and better preservation of growth and white matter functions. The FTY720 treatment also provided dose-dependent reduction of brain atrophy, rescuing >90% of LPS/HI-induced brain tissue loss. Interestingly, FTY720 neither opposed pure-HI brain injury nor directly inhibited microglia in both in vivo and in vitro models, highlighting its unique mechanism against inflammation-sensitized HI injury. Together, these results suggest that the dual hit of systemic inflammation and neonatal HI injury triggers early onset of the TH17/IL-17-mediated immunity, which causes severe brain destruction but responds remarkably to the therapeutic blockade of lymphocyte trafficking.

  6. Sex-dependent mitochondrial respiratory impairment and oxidative stress in a rat model of neonatal hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Demarest, Tyler G; Schuh, Rosemary A; Waddell, Jaylyn; McKenna, Mary C; Fiskum, Gary

    2016-06-01

    Increased male susceptibility to long-term cognitive deficits is well described in clinical and experimental studies of neonatal hypoxic-ischemic encephalopathy. While cell death signaling pathways are known to be sexually dimorphic, a sex-dependent pathophysiological mechanism preceding the majority of secondary cell death has yet to be described. Mitochondrial dysfunction contributes to cell death following cerebral hypoxic-ischemia (HI). Several lines of evidence suggest that there are sex differences in the mitochondrial metabolism of adult mammals. Therefore, this study tested the hypothesis that brain mitochondrial respiratory impairment and associated oxidative stress is more severe in males than females following HI. Maximal brain mitochondrial respiration during oxidative phosphorylation was two-fold more impaired in males following HI. The endogenous antioxidant glutathione was 30% higher in the brain of sham females compared to males. Females also exhibited increased glutathione peroxidase (GPx) activity following HI injury. Conversely, males displayed a reduction in mitochondrial GPx4 protein levels and mitochondrial GPx activity. Moreover, a 3-4-fold increase in oxidative protein carbonylation was observed in the cortex, perirhinal cortex, and hippocampus of injured males, but not females. These data provide the first evidence for sex-dependent mitochondrial respiratory dysfunction and oxidative damage, which may contribute to the relative male susceptibility to adverse long-term outcomes following HI. Lower basal GSH levels, lower post-hypoxic mitochondrial glutathione peroxidase (mtGPx) activity, and mitochondrial glutathione peroxidase 4 (mtGPx4) protein levels may contribute to the susceptibility of the male brain to oxidative damage and mitochondrial dysfunction following neonatal hypoxic-ischemia (HI). Treatment of male pups with acetyl-L-carnitine (ALCAR) protects against the loss of mtGPx activity, mtGPx4 protein, and increases in protein

  7. Mapping the Knowledge Structure of Neonatal Hypoxic-Ischemic Encephalopathy Over the Past Decade: A Co-word Analysis Based on Keywords.

    Science.gov (United States)

    Huang, Jichong; Tang, Jun; Qu, Yi; Zhang, Li; Zhou, Yan; Bao, Shan; Mu, Dezhi

    2016-05-01

    The aim of this study was to analyze the knowledge structure and report the evolution of hypoxic-ischemic encephalopathy research over the past decade based on co-word analysis. Scientific publications focusing on neonatal hypoxic-ischemic encephalopathy were searched from the Web of Science database (January 2005 to December 2014). The keywords from these articles were extracted, and a knowledge network based on these keywords was built using Ucinet6.212 and NetDraw2.084 software. A total of 1892 papers were included, and 39 high-frequency keywords were defined. "HIE" and "neonate" located at the center of the knowledge network. Etiology and pathogenesis, clinical manifestation, and therapy were researched more widely in the network than other aspects of hypoxic-ischemic encephalopathy. This co-word analysis provides an overview of neonatal hypoxic-ischemic encephalopathy research and suggests that the etiology, clinical manifestation, and therapy of hypoxic-ischemic encephalopathy have become research cores over the past decade.

  8. Mesenchymal stem cells protect neurons against hypoxic-ischemic injury via inhibiting parthanatos, necroptosis, and apoptosis, but not autophagy.

    Science.gov (United States)

    Kong, Deyan; Zhu, Juehua; Liu, Qian; Jiang, Yongjun; Xu, Lily; Luo, Ning; Zhao, Zhenqiang; Zhai, Qijin; Zhang, Hao; Zhu, Mingyue; Liu, Xinfeng

    2017-03-01

    Cellular therapy with mesenchymal stem cells (MSCs) protects cortical neurons against hypoxic-ischemic injury of stroke. Although sorts of efforts have been made to confirm the neuroprotective effect of MSCs on neurons against hypoxic-ischemic injury, the mechanism is until now far away from clear. Here in this study, oxygen-glucose deprivation (OGD)-injured neuron model was applied to mimic the neuronal hypoxic-ischemic injury in vitro. Co-culturing with MSCs in a transwell co-culture system, the OGD injured neurons were rescued by 75.0 %. Further data demonstrated that co-culturing with MSCs protected the cortical neurons from the OGD-induced parthanatos by alleviating apoptosis-inducing factor (AIF) nuclear translocation; attenuated the neuronal necroptosis by down-regulating the expression of the two essential kinases in necroptosis, receptor interacting protein kinase1 (RIP1) and 3 (RIP3); rescued the neurons from apoptosis by deactivating caspase-3; whilst performed no significant influence on OGD-induced neuronal autophagy, according to its failed regulation on Beclin1. In conclusion, MSCs potentially protect the cortical neurons from OGD-injury in vitro, through rescuing neurons from the cell death of parthanatos, necroptosis, and apoptosis, but not autophagy, which could provide some evidence to the mechanism explanation on stem cell treatment for ischemic stroke.

  9. Gastrodin protects neonatal rat brain against hypoxic-ischemic encephalopathy Acute therapeutic drug effects

    Institute of Scientific and Technical Information of China (English)

    Yanjun Niu; Zhengyong Jin

    2008-01-01

    BACKGROUND:Pharmacological experiments have demonstrated that gastrodin has a protective effect on neonatal rat brain subjected to hypoxia-ischemia; however,the underlying mechanism has not been fully elucidated. OBJECTIVE:The aim of this study was to investigate the acute therapeutic effects of gastrodin by observing prostaglandin B2 and 6-keto-prostaglandin F 1 a in brain issue of neonatal rats that received gastrodin injections immediately after hypoxia-ischemia.DESIGN:Single-factor design.SETTING:Department of Pediatrics,Affiliated Hospital of Yanbian University. MATERIALS:This study was performed in the Laboratory of the Department of Pediatrics,Affiliated Hospital of Yanbian University(key laboratory of provincial Health Department)from April to December 2003.Fifty-five Wistar rats of either gender,aged 7 days,were provided by the Laboratory Animal Center of Affiliated Hospital of Yanbian University.The rats were randomly divided into normal control(n=10), model(n=15),gastrodin-treated(n=15),and Danshen-treated(n=15)groups.The protocol was performed in accordance with guidelines from the Institute of Health Sciences for the use and care of animals.The following reagents were.used:Gastrodin(Sancai Medicine Group Co.,Ltd.,Zhongshan,Guangdong Province,China;component:gastrodin),Danshen(Conba Stock Company,Jinhua,Zhengjiang Province,China; component:salvia miltiorrhiza),and reagent kits for 125I-prostaglandin B2 and 125I-6-prostaglandin F 1 a (Research and Development Center for Science and Technology,General Hospital of Chinese PLA). METHODS:Rats in the normal control group received no treatment.Rats in the remaining 3 groups were anesthetized,followed by ligation of the left common carotid artery.One hour later,the rats were placed in a closed hypoxic box and allowed to inhale 8% oxygen-air(2.0-3.0 L/min)for 2 hours to develop hypoxic-ischemic encephalopathy.Immediately after lesion,rats in the gastrodin and Danshen-treated groups were intraperitoneally

  10. Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-01-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

  11. Effect of NGF combined with citicoline + cerebroprotein hydrolysate on neurobehavioral development and serum indexes in neonatal hypoxic ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Jian-Ning Zhang

    2016-01-01

    Objective:To analyze the effect of NGF combined with citicoline + cerebroprotein hydrolysate on neurobehavioral development and serum indexes in neonatal hypoxic ischemic encephalopathy.Methods: A total of 68 children with neonatal hypoxic ischemic encephalopathy (HIE) were randomly divided into observation group and control group, control group received supportive treatment + NGF combined with citicoline therapy, observation group received supportive treatment + NGF combined with citicoline and cerebroprotein hydrolysate treatment, and then differences in the levels of neurobehavioral development, creatine kinase and brain band, illness-related indexes,etc. were compared between two groups. Results: Serum nerve indexes NSE and S100B levels as well as myocardial enzyme spectrum-related parameters CK, CK-BB and CK-MB levels of observation group after treatment were lower than those of control group (P<0.05); serum MBP, ET-1, NO and CO levels were lower than those of control group, and FN level was higher than that of control group (P<0.05). Conclusions: NGF combined with citicoline + cerebroprotein hydrolysate therapy for children with HIE can reduce brain tissue damage and optimize physical status, and it is of positive clinical significance.

  12. Blood carbon dioxide levels and adverse outcome in neonatal hypoxic-ischemic encephalopathy.

    LENUS (Irish Health Repository)

    Nadeem, Montasser

    2012-01-31

    We investigated pCO(2) patterns and the relationship between pCO(2) levels and neurodevelopmental outcome in term infants with hypoxic-ischemic encephalopathy. Blood gases during the first 72 hours of life were collected from 52 infants with hypoxic-ischemic encephalopathy. Moderate hypocapnia (pCO(2) <3.3 kPa), severe hypocapnia (pCO(2) <2.6 kPa), and hypercapnia (pCO(2) >6.6 kPa) were correlated to neurodevelopmental outcome at 24 months. Normocapnia was documented in 416\\/551 (75.5%) of samples and was present during the entire 72 hours in only 6 out of 52 infants. Mean (standard deviation) pCO(2) values did not differ between infants with normal and abnormal outcomes: 5.43 (2.4) and 5.41 (2.03), respectively. There was no significant association between moderate hypocapnia, severe hypocapnia, or hypercapnia and adverse outcome (odds ratio [OR] = 1.84, 95% confidence interval [CI] = 0.49 to 6.89; OR = 3.16, CI = 0.14 to 28.45; and OR = 1.07, CI = 0.24 to 5.45, respectively). In conclusion, only one in nine newborns had normocapnia throughout the first 72 hours. Severe hypocapnia was rare and occurred only in ventilated babies. Hypercapnia and hypocapnia in infants with hypoxic-ischemic encephalopathy during the first 72 hours of life were not associated with adverse outcome.

  13. Maternal Cigarette Smoke Exposure Worsens Neurological Outcomes in Adolescent Offspring with Hypoxic-Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Yik L. Chan

    2017-09-01

    Full Text Available Hypoxic-ischemic (HI encephalopathy occurs in approximately 6 per 1000 term newborns leading to devastating neurological consequences, such as cerebral palsy and seizures. Maternal smoking is one of the prominent risk factors contributing to HI injury. Mitochondrial integrity plays a critical role in neural injury and repair during HI. We previously showed that maternal cigarette smoke exposure (SE can reduce brain mitochondrial fission and autophagosome markers in male offspring. This was accompanied by increased brain cell apoptosis (active caspase-3 and DNA fragmentation (TUNEL staining. Here, we aimed to investigate whether maternal SE leads to more severe neurological damage after HI brain injury in male offspring. Female BALB/c mice (8 weeks were exposed to cigarette smoke prior to mating, during gestation, and lactation. At postnatal day 10, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen. At postnatal day 40–44, maternal SE reduced grip strength in grip traction and foot fault tests, which were also reduced by HI injury to similar levels regardless of the maternal group. Limb coordination was impaired by maternal SE which was not worsened by HI injury. Maternal SE increased anxiety level in the offspring, which was normalized by HI injury. Apoptosis markers were increased in different brain regions by maternal SE, with the cortex having further increased TUNEL by HI injury, along with increased markers of inflammation and mitophagy. We conclude that maternal SE can worsen HI-induced cellular damage in male offspring well into adolescence.

  14. Neuroprotective Role of Nerve Growth Factor in Hypoxic-Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Antonio Chiaretti

    2013-06-01

    Full Text Available Hypoxic-ischemic brain injuries (HIBI in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF, Brain-Derived Neurotrophic Factor (BDNF, and Glial Derived Neurotrophic Factor (GDNF, play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG and cerebral perfusion at single-photon emission computed tomography (SPECT. The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

  15. Spatiotemporal Characteristics of Freezing of Gait in Patients After Hypoxic-Ischemic Brain Injury

    Science.gov (United States)

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Yong Wook

    2016-01-01

    Abstract The objective of this study was to investigate spatiotemporal characteristics with gait variability in patients with freezing of gait (FOG) after hypoxic-ischemic brain injury (HIBI). Eleven patients showing FOG after HIBI and 15 normal controls were consecutively enrolled. We performed gait analysis using a computerized gait system (VICON MX-T10 Motion Analysis System) and compared spatiotemporal characteristics and gait variability in both groups. Additionally, we performed correlation analysis to identify the gait parameters associated with severity of freezing, which we measured based on unified Parkinson disease Rating Scale subscore. Spatiotemporal characteristic of FOG patients showed increased stance time and double support phase and decreased swing time, single support phase, stride length, step length, and gait velocity compared with normal controls (P step length asymmetry were significantly increased in HIBI patients with FOG (P step length, and gait velocity variability in HIBI patients with FOG compared with normal controls (P step length, and single support phase to be spatiotemporal parameters related to FOG severity (P < 0.05). Our findings suggest that bilateral gait coordination deterioration plays a considerable role for pathophysiology of FOG in HIBI patients. Additional studies with a larger number of subjects are needed to further investigate the neural mechanism of FOG after HIBI. PMID:27175696

  16. Blood immunological parameters upon hypoxic-ischemic injuries of central nervous system in newborns and infants

    Directory of Open Access Journals (Sweden)

    Gulomjan Khalimbetov

    2012-05-01

    Full Text Available The paper studies interrelation between immune system condition and circulating concentrations of neuropeptides and neuron-specific enolase (NSE upon perinatal pathology in newborns and infants. Reactivity of cytokine and interleukin links of immune systems was found varying in newborns and infants with CNS hypoxic-ischemic pathology, accompanied by psychomotor retardation, a psycho-speech disorder, emotional and behavioral disorders (EBD and paroxysmal syndrome. At admission irrespectively of a syndrome type in the patients with CNS hypoxic-ischemic pathology, as compared with the patients in the control group, circulating TNF-α and IL-1 were found increased by 3.4-4.1 and 6.4-7.9 times, respectively. Release of S100 protein and NSE seems to be the underlying mechanism for enhancement of synthesis and/or release of TNF-α and IL-1 into circulation of patients with CNS hypoxic-ischemic pathology.

  17. Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2012-11-01

    Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

  18. Cortical region-specific engraftment of embryonic stem cell-derived neural progenitor cells restores axonal sprouting to a subcortical target and achieves motor functional recovery in a mouse model of neonatal hypoxic-ischemic brain injury.

    Science.gov (United States)

    Shinoyama, Mizuya; Ideguchi, Makoto; Kida, Hiroyuki; Kajiwara, Koji; Kagawa, Yoshiteru; Maeda, Yoshihiko; Nomura, Sadahiro; Suzuki, Michiyasu

    2013-01-01

    Hypoxic-ischemic encephalopathy (HIE) at birth could cause cerebral palsy (CP), mental retardation, and epilepsy, which last throughout the individual's lifetime. However, few restorative treatments for ischemic tissue are currently available. Cell replacement therapy offers the potential to rescue brain damage caused by HI and to restore motor function. In the present study, we evaluated the ability of embryonic stem cell-derived neural progenitor cells (ES-NPCs) to become cortical deep layer neurons, to restore the neural network, and to repair brain damage in an HIE mouse model. ES cells stably expressing the reporter gene GFP are induced to a neural precursor state by stromal cell co-culture. Forty-hours after the induction of HIE, animals were grafted with ES-NPCs targeting the deep layer of the motor cortex in the ischemic brain. Motor function was evaluated 3 weeks after transplantation. Immunohistochemistry and neuroanatomical tracing with GFP were used to analyze neuronal differentiation and axonal sprouting. ES-NPCs could differentiate to cortical neurons with pyramidal morphology and expressed the deep layer-specific marker, Ctip2. The graft showed good survival and an appropriate innervation pattern via axonal sprouting from engrafted cells in the ischemic brain. The motor functions of the transplanted HIE mice also improved significantly compared to the sham-transplanted group. These findings suggest that cortical region specific engraftment of preconditioned cortical precursor cells could support motor functional recovery in the HIE model. It is not clear whether this is a direct effect of the engrafted cells or due to neurotrophic factors produced by these cells. These results suggest that cortical region-specific NPC engraftment is a promising therapeutic approach for brain repair.

  19. Effects of isoflurane postconditioning on mitochondrial permeability transition pore in brain tissues of neonatal rats with hypoxic-ischemic brain injury%异氟醚后处理对缺血缺氧性脑损伤新生大鼠脑组织线粒体通透性转换孔的影响

    Institute of Scientific and Technical Information of China (English)

    纪国余; 薛杭; 于威威; 季海音; 杨雅婷; 赵平

    2014-01-01

    Objective To evaluate the effects of isoflurane postconditioning on mitochondrial permeability transition pore (mPTP) in brain tissues of neonatal rats with hypoxic-ischemic brain injury.Methods One hundred and twenty 7-day-old Sprague-Dawley rats,weighing 12-16 g,were randomly divided into 4 groups (n =30 each) using a random number table:sham operation group (group S),isoflurane group (group I),hypoxicischemic brain injury group (group HIBI),and hypoxic-ischemic brain injury + isoflurane postconditioning group (group HI).To establish hypoxic-ischemic brain injury model in the neonatal rats,the left common carotid artery ligation was carried out,and then the rats were exposed to 8% O2 + 92% N2 at 37 ℃ for 2 h in HIBI and HI groups.The rats inhaled 1.5 % isoflurane for 30 min after the model was established in group HI.The rats only inhaled 1.5% isoflurane for 30 min in group I.At 24 h after the model was established,10 rats taken out randomly in each group were sacrificed and brains were removed to detect mPTP opening.At 7 days after the model was established,the survival rate was recorded in the rest rats.The rats were then sacrificed and brains were removed and the right and left cerebral hemispheres were weighed separately,and the ratio between left/right cerebral hemispheres was calculated.The density of normal neurons in ventral posterior inferior thalamic nucleus and hippocampal CA3 region in the left and right cerebral hemispheres were measured and the ratios of the density of normal neurons in the left to right cerebral hemisphere were calculated.Results There was no significant difference in the survival rate between the four groups (P > 0.05).Compared with group S,the ratios of the density of normal neurons in the left to right cerebral hemisphere,weight of left cerebral hemisphere,and ratio between left/right cerebral hemispheres were significantly decreased,and mPTP opening was increased in group HIBI (P < 0.05),and no significant changes

  20. Dedifferentiated Fat Cells as a Novel Source for Cell Therapy to Target Neonatal Hypoxic-Ischemic Encephalopathy.

    Science.gov (United States)

    Mikrogeorgiou, Alkisti; Sato, Yoshiaki; Kondo, Taiki; Hattori, Tetsuo; Sugiyama, Yuichiro; Ito, Miharu; Saito, Akiko; Nakanishi, Keiko; Tsuji, Masahiro; Kazama, Tomohiko; Kano, Koichiro; Matsumoto, Taro; Hayakawa, Masahiro

    2017-03-09

    Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) remains a major cause of mortality and persistent neurological disabilities in affected individuals. At present, hypothermia is considered to be the only applicable treatment option, although growing evidence suggests that cell-based therapy might achieve better outcomes. Dedifferentiated fat (DFAT) cells are derived from mature adipocytes via a dedifferentiation strategy called ceiling culture. Their abundance and ready availability might make them an ideal therapeutic tool for the treatment of HIE. In the present study, we aimed to determine whether the outcome of HIE can be improved by DFAT cell treatment. HI injury was achieved by ligating the left common carotid artery in 7-day-old rat pups, followed by 1-h exposure to 8% O2. Subsequently, the severity of damage was assessed by diffusion-weighted magnetic resonance imaging to assign animals to equivalent groups. 24 h after hypoxia, DFAT cells were injected at 105 cells/pup into the right external jugular vein. To evaluate brain damage in the acute phase, a group of animals was sacrificed 48 h after the insult, and paraffin sections of the brain were stained to assess several acute injury markers. In the chronic phase, the behavioral outcome was measured by performing a series of behavioral tests. From the 24th day of age, the sensorimotor function was examined by evaluating the initial forepaw placement on a cylinder wall and the latency to falling from a rotarod treadmill. The cognitive function was tested with the novel object recognition (NOR) test. In vitro conditioned medium (CM) prepared from cultured DFAT cells was added at various concentrations to neuronal cell cultures, which were then exposed to oxygen-glucose deprivation (OGD). The number of cells that stained positive for the apoptosis marker active caspase-3 decreased by 73 and 52% in the hippocampus and temporal cortex areas of the brain, respectively, in the DFAT-treated pups. Similarly, the

  1. Can induced hypothermia be assured during brain MRI in neonates with hypoxic-ischemic encephalopathy?

    Energy Technology Data Exchange (ETDEWEB)

    Wintermark, Pia [Children' s Hospital Boston, Division of Newborn Medicine, Boston, MA (United States); Children' s Hospital Boston, Department of Radiology, Boston, MA (United States); Montreal Children' s Hospital, Division of Newborn Medicine, Montreal, QC (Canada); Labrecque, Michelle; Hansen, Anne [Children' s Hospital Boston, Division of Newborn Medicine, Boston, MA (United States); Warfield, Simon K.; DeHart, Stephanie [Children' s Hospital Boston, Department of Radiology, Boston, MA (United States)

    2010-12-15

    Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1 C (range: -0.8 to 0.8 C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. (orig.)

  2. Unilateral hypoxic-ischemic injury in young children from abusive head trauma, lacking craniocervical vascular dissection or cord injury

    Energy Technology Data Exchange (ETDEWEB)

    McKinney, Alexander M.; Thompson, Linda R.; Truwit, Charles L.; Velders, Scott; Karagulle, Ayse; Kiragu, Andrew [University of Minnesota Medical School, Department of Radiology, Hennepin County Medical Center, Minneapolis, MN (United States)

    2008-02-15

    Abusive head trauma (AHT) in young children usually has a severe outcome when associated with hypoxic-ischemic encephalopathy (HIE), which is best characterized by MRI in the acute or subacute phase utilizing diffusion-weighted imaging (DWI). HIE in this setting has been hypothesized to result from stretching of the spinal cord, brainstem, or vasculature. To provide clinical correlation in patients with unilateral HIE and to postulate a mechanism in the setting of suspected AHT. IRB approval was obtained. Over a 5-year period, the medical records and images were reviewed of the 53 children {<=}3 years of age who presented with acute head trauma according to the hospital registry. The children were subselected in order to determine how many suffered either HIE or AHT, and to detect those with unilateral HIE. In 11 of the 53 children, the etiology of the head trauma was highly suspicious for abuse. In 38 the head trauma was accidental and in 4 the trauma was of unknown etiology and at the time of this report was unresolved legally. Of the 53, 4 suffered HIE confirmed by CT or MRI. In three of these four with HIE the trauma was considered highly suspicious for AHT. Two of these three were the only patients with unilateral HIE, and both (7 months and 14 months of age) presented with early subacute phase HIE seen on DW MRI (range 4-7 days) and are described in detail with clinical correlation. The third child with AHT and HIE had bilateral findings. In the fourth patient the HIE was bilateral and was considered accidental. The work-up for both patients with unilateral HIE included head CT, craniocervical MRI, and craniocervical MR angiography (MRA). In both, there was mostly unilateral, deep white matter restricted diffusion, with subdural hematomas that were small compared to the extent of hypoxic-ischemic insult, and no skull fracture. Craniocervical MRA and axial thin-section fat-saturation images were negative for dissection, brainstem, or cord injury. Legal

  3. Flaxseed mitigates brain mass loss, improving motor hyperactivity and spatial memory, in a rodent model of neonatal hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Mucci, Daniela de Barros; Fernandes, Flávia Spreafico; Souza, Amanda Dos Santos; Sardinha, Fátima Lúcia de Carvalho; Soares-Mota, Márcia; Tavares do Carmo, Maria das Graças

    2015-06-01

    Neonatal hypoxic-ischemic (HI) encephalopathy is a major cause of perinatal morbimortality. There is growing evidence that n-3 polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), attenuate brain injury. This study aimed to investigate the possible neuroprotective effect of maternal intake of flaxseed, rich in DHA׳s precursor α-linolenic acid, in the young male offspring subjected to perinatal HI. Wistar rats were divided in six groups, according to maternal diet and offspring treatment at day 7: Control HI (CHI) and Flaxseed HI (FHI); Control Sham and Flaxseed Sham; Control Control and Flaxseed Control. Flaxseed diet increased offspring׳s hippocampal DHA content and lowered depressive behavior. CHI pups presented brain mass loss, motor hyperactivity and poor spatial memory, which were improved in FHI rats. Maternal flaxseed intake may prevent depressive symptoms in the offspring and promote neuroprotective effects, in the context of perinatal HI, improving brain injury and its cognitive and behavioral impairments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Hyperbaric oxygen suppresses hypoxic-ischemic brain damage in newborn rats.

    Science.gov (United States)

    Zhu, Min; Lu, Mengru; Li, Qing-Jie; Zhang, Zhuo; Wu, Zheng-Zheng; Li, Jie; Qian, Lai; Xu, Yun; Wang, Zhong-Yuan

    2015-01-01

    The optimal therapeutic time-window and protective mechanism of hyperbaric oxygen in hypoxic-ischemic brain damage remain unclear. This study aimed to determine the neuroprotective effects of hyperbaric oxygen. Following hypoxic-ischemic brain damage modeling in neonatal rats, hyperbaric oxygen was administered at 6, 24, 48, and 72 hours and 1 week after hypoxia, respectively, once daily for 1 week. Fourteen days after hypoxic-ischemic brain damage, cell density and apoptosis rate, number of Fas-L+, caspase-8+, and caspase-3+ neuronal cells, levels of nitric oxide, malondialdehyde, and superoxide dismutase in hippocampus were examined. Morris water maze test was conducted 28 days after insult. Significant improvements were found in cell density, rate of apoptosis, oxidative stress markers, FasL, and caspases in rats treated with hyperbaric oxygen within 72 hours compared to hypoxic-ischemic injury. Similarly, time-dependent behavioral amelioration was observed in pups treated with hyperbaric oxygen. Our findings suggest that hyperbaric oxygen protects against hypoxic-ischemic brain damage by inhibiting oxidative stress and FasL-induced apoptosis, and optimal therapeutic time window is within 72 hours after hypoxic-ischemic brain damage.

  5. Semi-quantitative Assessment of Brain Maturation by Conventional Magnetic Resonance Imaging in Neonates with Clinically Mild Hypoxic-ischemic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Jie Gao; Qin-Li Sun; Yu-Miao Zhang; Yan-Yan Li; Huan Li; Xin Hou; Bo-Lang Yu

    2015-01-01

    Background:Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases.The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI).Methods:Totally,45 neonates with clinically mild HIE and 45 matched control neonates were enrolled.Gestated age,birth weight,age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups.According to MR findings,mild HIE neonates were divided into three subgroups:Pattern Ⅰ,neonates with normal MR appearance; Pattern Ⅱ,preterm neonates with abnormal MR appearance; Pattern Ⅲ,full-term neonates with abnormal MR appearance.TMS and its parameters,progressive myelination (M),cortical infolding (C),involution of germinal matrix tissue (G),and glial cell migration bands (B),were employed to assess brain maturation and compare difference between HIE and control groups.Results:The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs.12.36 ± 1.26,P < 0.001).In four parameters of TMS scores,the M and C scores were significantly lower in mild HIE group.Of the three patterns of mild HIE,Pattern Ⅰ (10 cases) showed no significant difference of TMS compared with control neonates,while Pattern Ⅱ (22 cases),Ⅲ (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs.11.48 ± 0.55,P < 0.05; 12.59 ± 1.28 vs.13.25 ± 1.29,P < 0.05).It was M,C,and GM scores that significantly decreased in Pattern Ⅱ,while for Pattern Ⅲ,only C score significantly decreased.Conclusions:The TMS system,based on conventional MRI,is an effective method to detect delayed brain maturation in clinically mild HIE.The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of

  6. Apparent diffusion coefficient in quantitative analysis of brain injury in term neonates with hypoxic-ischemic encephalopathy%应用表观弥散系数定量分析缺血缺氧性脑病新生儿的脑损伤

    Institute of Scientific and Technical Information of China (English)

    赵博; 张雪宁; 徐国萍; 孟华伟

    2014-01-01

    Objective Applying diffusion weighted image (DWI) and apparent diffusion coefficient (ADC) to analyze brain injury caused by hypoxic-ischemic encephalopathy (HIE) in term neonates.Methods From June 1,2010 to January 5,2011,thirty-eight full term neonates with HIE were hospitalized in the Second Hospital of Tianjin Medical University.Those with nervous system diseases were excluded.The 38 cases were divided to mild HIE group (n=24) and moderate-to-severe HIE group (n=14).The control group included 10 normal full term neonates without history of asphyxia.All babies were scanned by magnetic resonance imaging (MRI).Spin echo-echo planar imaging sequence was used for DWI images.ADC values of nine regions (frontal lobe gray matter,frontal white matter,parietal gray matter,parietal white matter,corona radiata,caudate nucleus,putamen,posterior limb of the internal capsule and thalamus) were measured.MRI and DWI images were compared.ADC values were compared by analysis of variance and Student-Newman-Keuls test.Results ADC values of the nine indicated regions (frontal lobe gray matter,frontal white matter,parietal gray matter,parietal white matter,corona radiata,caudate nucleus,putamen,posterior limb of the internal capsule and thalamus) were (1.37±0.07),(1.81±0.12),(1.35±0.10),(1.84±0.09),(1.23±0.11),(1.28±0.09),(1.18±0.08),(1.05±0.07) and (1.15±0.08) ×10-3 mm2/s in control group,(1.28±0.11),(1.60±0.15),(1.27±0.09),(1.59±0.20),(1.19±0.15),(1.19±0.13),(1.11±0.09),(0.97±0.11) and (1.06±0.12) ×10-3 mm2/s in mild HIE group,and (1.18±0.14),(1.51±0.22),(1.19±0.09),(1.56±0.19),(1.03±0.16),(1.08±0.07),(1.02±0.07),(0.87±0.09) and (0.96±0.12) × 10-3 mm2/s in moderate-to-severe HIE group.ADC values among the three groups had statistical difference (F=3.89,3.21,4.05,3.30,3.28,3.27,4.12,4.75and 4.72,all P<0.05).ADC values of frontal lobe gray matter,frontal white matter,parietal gray matter,parietal white matter,putamen,posterior limb of the internal

  7. MODEST HYPOTHERMIA PROVENTS APOPTOSIS IN A NEONATAL RAT MODEL OF HYPOXIC-ISCHEMIC BRAINDAMAGE

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective Recent studies in neonatal animals have shown that even slightly decreasing in brain or core temperature could ameliorate the damage resulting from hypoxic-ischemia insults. But the influence of hypothermia which had been used after the end of hypoxia-ischemia of the model hypoxia-ischemia brain damage(HIBD)was unknown. This research wanted to investigate whether hypothermia of defferent begin time after HIBD still could protect the brain in neonatal rats. Methods Pericranial temperatures were adjusted to 31 C in neonatal rats immediately or 2h after the end of hypoxia-ischemia(HI),the number of apoptosis cells in HIBD rats' brain had been counted,rat pups' storing food ability had been observed. Results Apoptosis increased obviously when rat pups were 8 days old, while hypothermia reduced apoptosis ,and postponed apoptosis expression in group that 31 C hypothermia was used immediately or 1h after the end of HI,and hypothermia improved the rat pups' storing food ability. This effect was more obviously in the group that hypothermia was used immediately after the HI than in the group that hypothermia was used 1h after the HI. But the protective effect was not clear in the group that hypothermia was used 2 h after the HI. Conclusion Hypothermia which was used within 1h after the end of HI could protect the HIBD neonatal rat pups brain, this effect was more obviously in the hypothermia be used early after the end of HI group than in the hypothermia be used late after the end of HI group.

  8. Fetal heart rate patterns in neonatal hypoxic-ischemic encephalopathy: relationship with early cerebral activity and neurodevelopmental outcome.

    LENUS (Irish Health Repository)

    Murray, Deirdre M

    2009-09-01

    Despite widespread use of fetal heart rate monitoring, the timing of injury in hypoxic-ischemic encephalopathy (HIE) remains unclear. Our aim was to examine fetal heart rate patterns during labor in infants with clinical and electroencephalographic (EEG) evidence of HIE and to relate these findings to neurodevelopmental outcome. Timing of onset of pathological cardiotocographs (CTGs) was determined in each case by two blinded reviewers and related to EEG grade at birth and neurological outcome at 24 months. CTGs were available in 35 infants with HIE (17 mild, 12 moderate, 6 severe on EEG). Admission CTGs were normal in 24\\/35 (69%), suspicious in 8\\/35 (23%), and pathological in 3\\/35 (8%). All CTGs developed nonreassuring features prior to delivery. Three patterns of fetal heart rate abnormalities were seen: group 1, abnormal CTGs on admission in 11\\/35 (31%); group 2, normal CTGs on admission with gradual deterioration to pathological in 20\\/35 cases (57%); and group 3, normal CTGs on admission with acute sentinel events in 4\\/35 (11.5%). The median (interquartile range) duration between the development of pathological CTGs and delivery was 145 (81, 221) minutes in group 2 and 22 (12, 28) minutes in group 3. There was no correlation between duration of pathological CTG trace and grade of encephalopathy (R = 0.09, P = 0.63) or neurological outcome (P = 0.75). However, the grade of encephalopathy was significantly worse in group 3 (P = 0.001), with a trend to worse outcomes. The majority of infants with HIE have normal CTG traces on admission but develop pathological CTG patterns within hours of delivery. More severe encephalopathy was associated with normal admission CTG and acute sentinel events shortly before delivery.

  9. Fetal heart rate patterns in neonatal hypoxic-ischemic encephalopathy: relationship with early cerebral activity and neurodevelopmental outcome.

    LENUS (Irish Health Repository)

    Murray, Deirdre M

    2012-01-31

    Despite widespread use of fetal heart rate monitoring, the timing of injury in hypoxic-ischemic encephalopathy (HIE) remains unclear. Our aim was to examine fetal heart rate patterns during labor in infants with clinical and electroencephalographic (EEG) evidence of HIE and to relate these findings to neurodevelopmental outcome. Timing of onset of pathological cardiotocographs (CTGs) was determined in each case by two blinded reviewers and related to EEG grade at birth and neurological outcome at 24 months. CTGs were available in 35 infants with HIE (17 mild, 12 moderate, 6 severe on EEG). Admission CTGs were normal in 24\\/35 (69%), suspicious in 8\\/35 (23%), and pathological in 3\\/35 (8%). All CTGs developed nonreassuring features prior to delivery. Three patterns of fetal heart rate abnormalities were seen: group 1, abnormal CTGs on admission in 11\\/35 (31%); group 2, normal CTGs on admission with gradual deterioration to pathological in 20\\/35 cases (57%); and group 3, normal CTGs on admission with acute sentinel events in 4\\/35 (11.5%). The median (interquartile range) duration between the development of pathological CTGs and delivery was 145 (81, 221) minutes in group 2 and 22 (12, 28) minutes in group 3. There was no correlation between duration of pathological CTG trace and grade of encephalopathy (R = 0.09, P = 0.63) or neurological outcome (P = 0.75). However, the grade of encephalopathy was significantly worse in group 3 (P = 0.001), with a trend to worse outcomes. The majority of infants with HIE have normal CTG traces on admission but develop pathological CTG patterns within hours of delivery. More severe encephalopathy was associated with normal admission CTG and acute sentinel events shortly before delivery.

  10. Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    Sergey A Sosunov

    Full Text Available This study demonstrates that in mice subjected to hypoxia-ischemia (HI brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting a recovery of complex-I dependent mitochondrial respiration. This significantly attenuates an oxidative stress and reduces the extent of HI brain injury. Neonatal mice were subjected to HI, and at the initiation of reperfusion were exposed to isoflurane with or without mechanical ventilation. At the end of HI and isoflurane exposure cerebral mitochondrial respiration, H2O2 emission rates were measured followed by an assessment of cerebral oxidative damage and infarct volumes. At 8 weeks after HI navigational memory and brain atrophy were assessed. In vitro, direct effect of isoflurane on mitochondrial H2O2 emission was compared to that of complex-I inhibitor, rotenone. Compared to controls, 15 minutes of isoflurane anesthesia inhibited recovery of the compex I-dependent mitochondrial respiration and decreased H2O2 production in mitochondria supported with succinate. This was associated with reduced oxidative brain injury, superior navigational memory and decreased cerebral atrophy compared to the vehicle-treated HI-mice. Extended isoflurane anesthesia was associated with sluggish recovery of cerebral blood flow (CBF and the neuroprotection was lost. However, when isoflurane anesthesia was supported with mechanical ventilation the CBF recovery improved, the event associated with further reduction of infarct volume compared to HI-mice exposed to isoflurane without respiratory support. Thus, in neonatal mice brief isoflurane anesthesia initiated at the onset of reperfusion limits mitochondrial release of oxidative radicals and attenuates an oxidative stress. This novel mechanism contributes to neuroprotective action of isoflurane. The use of mechanical ventilation during isoflurane anesthesia counterbalances negative effect of isoflurane anesthesia on

  11. Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cell transplantation improves hypoxic-ischemic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dengna Zhu; Yanjie Jia; Jun Wang; Boai Zhang; Guohui Niu; Yazhen Fan

    2011-01-01

    Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cells were transplanted into a hypoxic-ischemic neonatal rat model via the tail vein.BrdU-positive cells at day 7post-transplantation,as well as nestin-and neuron specific enolase-positive cells at day 14 wereincreased compared with those of the single neural stem cell transplantation group.In addition,theproportion of neuronal differentiation was enhanced.The genetically modified cell-transplanted ratsexhibited enhanced performance in correctly crossing a Y-maze and climbing an angled slope compared with those of the single neural stem cell transplantation group.These results showed that human insulin-like growth factor 1-transfected neural stem cell transplantation promotes therecovery of the learning,memory and motor functions in hypoxic-ischemic rats.

  12. Synergy of endothelial and neural progenitor cells from adipose-derived stem cells to preserve neurovascular structures in rat hypoxic-ischemic brain injury.

    Science.gov (United States)

    Hsueh, Yuan-Yu; Chang, Ya-Ju; Huang, Chia-Wei; Handayani, Fitri; Chiang, Yi-Lun; Fan, Shih-Chen; Ho, Chien-Jung; Kuo, Yu-Min; Yang, Shang-Hsun; Chen, Yuh-Ling; Lin, Sheng-Che; Huang, Chao-Ching; Wu, Chia-Ching

    2015-10-08

    Perinatal cerebral hypoxic-ischemic (HI) injury damages the architecture of neurovascular units (NVUs) and results in neurological disorders. Here, we differentiated adipose-derived stem cells (ASCs) toward the progenitor of endothelial progenitor cells (EPCs) and neural precursor cells (NPCs) via microenvironmental induction and investigated the protective effect by transplanting ASCs, EPCs, NPCs, or a combination of EPCs and NPCs (E+N) into neonatal HI injured rat pups. The E+N combination produced significant reduction in brain damage and cell apoptosis and the most comprehensive restoration in NVUs regarding neuron number, normal astrocytes, and vessel density. Improvements in cognitive and motor functions were also achieved in injured rats with E+N therapy. Synergistic interactions to facilitate transmigration under in vitro hypoxic microenvironment were discovered with involvement of the neuropilin-1 (NRP1) signal in EPCs and the C-X-C chemokine receptor 4 (CXCR4) and fibroblast growth factor receptor 1 (FGFR1) signals in NPCs. Therefore, ASCs exhibit great potential for cell sources in endothelial and neural lineages to prevent brain from HI damage.

  13. Fibroblast growth factor-2 induced by enriched environment enhances angiogenesis and motor function in chronic hypoxic-ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    Jung Hwa Seo

    Full Text Available This study aimed to investigate the effects of enriched environment (EE on promoting angiogenesis and neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI brain injury. HI brain damage was induced in seven day-old CD-1® mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min. At six weeks of age, the mice were randomly assigned to either EE or standard cages (SC for two months. Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. In order to identify angiogenic growth factors regulated by EE, an array-based multiplex ELISA assay was used to measure the expression in frontal cortex, striatum, and cerebellum. Among the growth factors, the expression of fibroblast growth factor-2 (FGF-2 was confirmed using western blotting. Platelet endothelial cell adhesion molecule-1 (PECAM-1 and α-smooth muscle actin (α-SMA were also evaluated using immunohistochemistry. As a result, mice exposed to EE showed significant improvements in rotarod and ladder walking performances compared to SC controls. The level of FGF-2 was significantly higher in the frontal cortex of EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the other hand, FGF-2 in the striatum significantly increased at 2 weeks after exposure to EE earlier than in the frontal cortex. Expression of activin A was similarly upregulated as FGF-2 expression pattern. Particularly, all animals treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on motor performance relative to mice not given anti-FGF-2. Immunohistochemistry showed that densities of α-SMA(+ and PECAM-1(+ cells in frontal cortex, striatum, and hippocampus were significantly increased following EE, suggesting the histological findings exhibit a similar pattern to the upregulation of FGF-2 in the brain. In conclusion, EE enhances endogenous angiogenesis and neurobehavioral functions

  14. Clinical Value of CT for Neonatal Hypoxic Ischemic Encephalopathy%CT对新生儿缺氧缺血性脑病的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    刘义康; 余红胜; 吉六舟

    2013-01-01

    Objective To study the clinical value of CT diagnosis and prognosis of hypoxic ischemic encephalopathy (HIE)in neonate.Methods Retrospective analysis of CT images of 40 cases diagnosed with HIE clinically or by CT was performed,and CT examinations were carried out before and after the systematic treatment.Results In the 40 cases,CT examination proved that there were 14 ones of mild brain injuries,17 ones of moderate injuries and 9 ones of severe injuries.The CT follow-up proved that for the patients with mild injuries,the low-density region shrinked or disappeared and SAH was absorbed,and that 15 patients with moderate injuries recovered,and that the remained 2 patients with moderated injuries and 9 ones with severe injuries progressed into encephalomalacia,brain atrophy,hydrocephalus,cerebral tissue calcification and etc.Conclusion CT examination can reflect the degree and dynamic changes of brain injuries of HIE,and thus can lay a foundation for clinical diagnosis as well as the evaluation of the curative effect and prognosis.%目的:研究CT对新生儿缺氧缺血性脑病(HIE)的诊断及预后表现,探讨CT对该病的临床应用价值.方法:回顾分析40例临床及CT诊断为HIE病例的CT影像资料,所有病例均经系统治疗前、后CT检查.结果:40例患儿治疗前CT初诊脑轻度损害14例、中度损害17例、重度损害9例;系统治疗后随访复查CT显示脑轻度损害病例脑实质低密度范围逐渐缩小或消失,SAH吸收,直至完全恢复正常.中度损害恢复正常15例,余下2例及9例重度损害演变为脑软化、脑萎缩、脑积水、脑组织钙化等.结论:CT检查能真实反映HIE脑组织损害程度及动态变化,可为临床诊断、疗效观察及预后评价提供影像学依据.

  15. Early clinical signs in neonates with hypoxic ischemic encephalopathy predict an abnormal amplitude-integrated electroencephalogram at age 6 hours

    OpenAIRE

    Horn, Alan R; Swingler, George H; Myer, Landon; Linley, Lucy L; Raban, Moegammad S; Joolay, Yaseen; Harrison, Michael C; Chandrasekaran, Manigandan; Rhoda, Natasha R; Robertson, Nicola J.

    2013-01-01

    Background An early clinical score predicting an abnormal amplitude-integrated electroencephalogram (aEEG) or moderate-severe hypoxic ischemic encephalopathy (HIE) may allow rapid triage of infants for therapeutic hypothermia. We aimed to determine if early clinical examination could predict either an abnormal aEEG at age 6 hours or moderate-severe HIE presenting within 72 hours of birth. Methods Sixty infants ≥ 36 weeks gestational age were prospectively enrolled following suspected intrapar...

  16. Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Sung-Rae Cho

    2016-09-01

    Full Text Available Transplantation of mesenchymal stem cells (MSCs has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min. At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS-control (CON, PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.

  17. Spatiotemporal Characteristics of Freezing of Gait in Patients After Hypoxic-Ischemic Brain Injury: A Pilot Study.

    Science.gov (United States)

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Yong Wook

    2016-05-01

    The objective of this study was to investigate spatiotemporal characteristics with gait variability in patients with freezing of gait (FOG) after hypoxic-ischemic brain injury (HIBI).Eleven patients showing FOG after HIBI and 15 normal controls were consecutively enrolled. We performed gait analysis using a computerized gait system (VICON MX-T10 Motion Analysis System) and compared spatiotemporal characteristics and gait variability in both groups. Additionally, we performed correlation analysis to identify the gait parameters associated with severity of freezing, which we measured based on unified Parkinson disease Rating Scale subscore.Spatiotemporal characteristic of FOG patients showed increased stance time and double support phase and decreased swing time, single support phase, stride length, step length, and gait velocity compared with normal controls (P step length asymmetry were significantly increased in HIBI patients with FOG (P step length, and gait velocity variability in HIBI patients with FOG compared with normal controls (P step length, and single support phase to be spatiotemporal parameters related to FOG severity (P < 0.05).Our findings suggest that bilateral gait coordination deterioration plays a considerable role for pathophysiology of FOG in HIBI patients. Additional studies with a larger number of subjects are needed to further investigate the neural mechanism of FOG after HIBI.

  18. Dysregulation of FMRP/mTOR Signaling Cascade in Hypoxic-Ischemic Injury of Premature Human Brain.

    Science.gov (United States)

    Lechpammer, Mirna; Wintermark, Pia; Merry, Katherine M; Jackson, Michele C; Jantzie, Lauren L; Jensen, Frances E

    2016-03-01

    In this study the authors investigated whether dysregulation of the fragile X mental retardation protein and mammalian target of rapamycin signaling cascade can have a role in the pathogenesis of encephalopathy of prematurity following perinatal hypoxia-ischemia. The authors examined the brain tissue of newborns with encephalopathy and compared it to age-matched controls with normal brain development and adults. In normal controls, the fragile X mental retardation protein expression in cortical gray matter spiked 4-fold during 36-39 gestational weeks compared to the adult, with a concomitant suppression of p70S6K and S6. In encephalopathy cases, the developmental spike of fragile X mental retardation protein was not observed, and fragile X mental retardation protein levels remained significantly lower than in normal controls. Importantly, this fragile X mental retardation protein downregulation was followed by a significant overexpression of p70S6K and S6. These novel findings thus suggest that premature hypoxic-ischemic brain injury can affect the fragile X mental retardation protein/mammalian target of rapamycin pathway, as otherwise observed in inherited syndromes of cognitive disability and autism spectrum disorders.

  19. Influence of inhibition of nitric oxide synthesis on cardiac function in the newborn lamb after hypoxic-ischemic injury

    NARCIS (Netherlands)

    Dorrepaal, C.A.; Bel, F. van; Steendijk, P.; Shadid, M.; Velde, E.T. van de; Baan, J.

    2000-01-01

    The aim of the present study was to investigate the effect of immediate post-hypoxic-ischemic (HI) inhibition of nitric oxide synthesis by N(ω)- nitro-L-arginine (NLA) on cardiac function and reactive oxygen species production. Fifteen newborn lambs were subjected to severe HI. Upon resuscitation 5

  20. UCH-L1 and GFAP Serum Levels in Neonates with Hypoxic-Ischemic Encephalopathy: A single center pilot study

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2014-12-01

    Full Text Available Objective - We examined two potential biomarkers of brain damage in HIE neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury. We hypothesized the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. Further, we hypothesized that serum samples of HIE neonates would have higher levels and would correlate with brain damage on MRI and later developmental outcomes.Study Design - Serum UCH - L1 and GFAP concentrations from HIE neonates(n = 16 were compared with controls(n = 11.Pearson correlation coefficients and a mixed model design examined the relationship between biomarker concentrations of HIE neonates and brain damage(MRI and developmental outcomes(Bayley - III.Result– Both biomarkers were detected in cord blood from control subjects.UCH - L1 concentrations were higher in HIE neonates(p < 0.001 and associated with cortical injury(p < 0.055 and later motor and cognitive developmental outcomes(p < 0.05.The temporal change in GFAP concentrations from birth to 96 hours of age predicted motor developmental outcomes(p < 0.05 and injury to the basal ganglia and white matter.Conclusion– UCH - L1 concentrations correlated with cortical injury and developmental delays and GFAP concentrations correlated with basal ganglia and white matter injury and motor delay in HIE affected patients.Researchers should continue to explore UCH - L1 and GFAP as promising serum biomarkers of brain damage and predictors of neurodevelopmental outcomes in neonates with HIE.

  1. CT Diagnosis of Neonatal Hypoxic-ischemic Encephalopathy%新生儿缺氧缺血性脑病的CT诊断

    Institute of Scientific and Technical Information of China (English)

    乔志刚

    2013-01-01

      目的:通过运用 CT 扫描判断新生儿缺氧缺血性脑病(HIE)的临床特征,探讨 CT 扫描对 HIE 的临床价值.方法:回顾性分析笔者所在医院2009-2011年3月收治的 HIE 患儿58例的 CT 表现、损伤程度及合并颅内出血的类型.结果:经 CT 诊断的58例 HIE 患儿中,轻度25例(43.10%),中度18例(31.03%),重度15例(25.87%);经随访复查,58例 HIE 患儿轻度 CT 阳性率12.00%;中度 CT 阳性率44.44%;重度 CT 阳性率53.33%.结论:CT 扫描能够准确判断 HIE 的临床特征,并为进一步确定此病的损伤范围、程度、分类以及合并症,并制定合理的诊疗方案提供科学依据,有较好的临床价值.%Objective:Through the use of CT scan to determine clinical features of neonatal hypoxic-ischemic encephalopathy(HIE),to explore the clinical value of the HIE.Methods:Retrospective analysis the CT feature,the degree of injury and the type of intracranial hemorrhage of 58 cases with HIE in our hospital from 2009 to March 2011.Results:The diagnosis by CT in 58 cases of HIE,mild 25 cases(43.10%) and 18 cases,moderate (31.03%),severe in 15 cases (25.87%),by the follow-up review,58 cases of mild HIE CT the positive rate of 12.00%;moderate CT-positive rate of 44.44%;severe CT-positive rate of 53.33%.Conclusion:CT scan can accurately determine the clinical features of HIE,and to further determine the damage range of the disease,the degree of classification,and complications,and to provide a scientific basis for rational treatment programs,it has better clinical value.

  2. Pontine axonal injury after brain trauma and nontraumatic hypoxic-ischemic brain damage.

    Science.gov (United States)

    Oehmichen, M; Meissner, C; Schmidt, V; Pedal, I; König, H G

    1999-01-01

    Experimental studies have shown that diffuse axonal injury is usually induced by positive or negative acceleration mechanisms. In order to determine the reliability of axonal injury (AI) as a marker of this type of traumatic insult, we compared cases of trauma-induced focal cortical hemorrhage without dural involvement (n = 67) with cases of trauma-induced subdural bleeding without cortical hemorrhage (n = 26). Both groups exhibited a wide range of post-traumatic survival times. The injuries in the first group were caused mainly by direct impact to the head, those in the second by acceleration/deceleration mechanisms. The investigations were based primarily on immunohistochemical demonstration of antibodies targeted to beta-amyloid precursor protein (beta-APP) in the pons as a marker of AI and the results were assessed semiquantitatively. No significant differences were found between the two groups. In both groups AI was detected in 80-100% of cases with survival times of more than 3 h and two thirds of all positive cases showed pronounced positivity. Additional comparison of cases of brain death due to mechanical trauma (n = 14) with cases of brain death due to non-mechanical trauma (n = 18) also disclosed no significant intergroup differences. Finally, investigations of the pons in cases of non-traumatic death due to cerebral hypoxia/ischemia (n = 51) demonstrated AI with the same frequency as in the other groups, although the expression tended to be less pronounced. Our results confirm that beta-APP expression in the pons is a reliable indicator of AI but does not discriminate between injuries caused by traumatic strain or shearing mechanisms and secondary damage due to cerebral hypoxia/ischemia or edema. In the large majority of cases with prolonged post-traumatic survival, it can therefore be assumed that AI in the pons is the consequence of primary and/or secondary events or a combination of both, as is common in non-missile head injury survived for more than

  3. Diffusion-weighted imaging in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients

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    Liu, A.Y.; Zimmerman, R.A.; Haselgrove, J.C.; Bilaniuk, L.T.; Hunter, J.V. [Hospital of the Univ. of Pennsylvania (HUP), Philadelphia (United States). Dept. of Radiology

    2001-11-01

    The purpose of our study was to determine the usefulness of echo-planar diffusion-weighted imaging (EPDI) in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients. Eighteen patients ranging in age from 3 weeks to 12 years were evaluated for evidence of ischemic/infarction changes on conventional MR and EPDI. Included in the study group were five patients with sickle cell disease, four with congenital heart disease, four with hypotensive episodes with various etiologies, three with sepsis, and two with encephalitis or meningitis. Patients were examined 2 h to 6 days after the initial insult, with follow-up studies in four patients at 1 to 62 days after the initial examination. After conventional MR imaging (T1, FSE T2, and FLAIR), diffusion-weighted MR imaging was performed using high-speed, single-shot EP techniques with TR 6000, TE 144, matrix 96 x 128, FOV 23.3 x 31 and five b values of 0, 160, 360, 640, and 1,000 s/mm{sup 2}. EPDI demonstrated abnormally increased signal in watershed ischemic/infarction zones in all initial cases. Apparent diffusion coefficients (ADC) were obtained in 59 lesions. When compared with radiographically normal (on EPDI) contralateral brain parenchyma, 45 demonstrated a relatively decreased ADC, while eight had normal ({+-} 10 %) and six had increased ADC. In four cases, signal abnormalities on EPDI were not seen or exceeded that seen with conventional MR imaging. In the remaining cases, signal abnormalities were obvious on EPDI and more subtle on conventional MR imaging. Follow-up studies demonstrated resolution of abnormal EPDI signal with persistent abnormalities on conventional imaging in some cases, while others revealed an increase in size or number of EPDI signal abnormalities, suggesting ongoing acute ischemic/infarctive changes. EPDI is a rapid, sensitive technique for detecting watershed ischemic/infarction changes in pediatric patients with hypoperfusion episodes, at times before such changes are

  4. Neuroprotective properties of Melissa officinalis after hypoxic-ischemic injury both in vitro and in vivo.

    Science.gov (United States)

    Bayat, Mohammad; Azami Tameh, Abolfazl; Hossein Ghahremani, Mohammad; Akbari, Mohammad; Mehr, Shahram Ejtemaei; Khanavi, Mahnaz; Hassanzadeh, Gholamreza

    2012-10-03

    Brain ischemia initiates several metabolic events leading to neuronal death. These events mediate large amount of damage that arises after some neurodegenerative disorders as well as transient brain ischemia. Melissa officinalis is considered as a helpful herbal plant in the prevention of various neurological diseases like Alzheimer that is related with oxidative stress. We examined the effect of Melissa officinalis on hypoxia induced neuronal death in a cortical neuronal culture system as in vitro model and transient hippocampal ischemia as in vivo model. Transient hippocampal ischemia was induced in male rats by tow vessel-occlusion for 20 min. After reperfusion, the histopathological changes and the levels inflammation, oxidative stress status, and caspase-3 activity in hippocampus were measured. Cytotoxicity assays showed a significant protection of a 10 μg/ml dose of Melissa against hypoxia in cultured neurons which was confirmed by a conventional staining (PMelissa treatment decrease caspase3 activity (PMelissa oil has also inhibited malon dialdehyde level and attenuated decrease of Antioxidant Capacity in the hippocampus. Pro-inflammatory cytokines TNF-α, IL-1β and HIF-1α mRNA levels were highly increased after ischemia and treatment with Melissa significantly suppressed HIF-1α gene expression (PMelissa officinalis could be considered as a protective agent in various neurological diseases associated with ischemic brain injury.

  5. Neuroprotective properties of Melissa officinalis after hypoxic-ischemic injury both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Bayat Mohammad

    2012-10-01

    Full Text Available Abstract Background Brain ischemia initiates several metabolic events leading to neuronal death. These events mediate large amount of damage that arises after some neurodegenerative disorders as well as transient brain ischemia. Melissa officinalis is considered as a helpful herbal plant in the prevention of various neurological diseases like Alzheimer that is related with oxidative stress. Methods We examined the effect of Melissa officinalis on hypoxia induced neuronal death in a cortical neuronal culture system as in vitro model and transient hippocampal ischemia as in vivo model. Transient hippocampal ischemia was induced in male rats by tow vessel-occlusion for 20 min. After reperfusion, the histopathological changes and the levels inflammation, oxidative stress status, and caspase-3 activity in hippocampus were measured. Results Cytotoxicity assays showed a significant protection of a 10 μg/ml dose of Melissa against hypoxia in cultured neurons which was confirmed by a conventional staining (P Discussion Results showed that Melissa officinalis could be considered as a protective agent in various neurological diseases associated with ischemic brain injury.

  6. Neuroprotective properties of Melissa officinalis after hypoxic-ischemic injury both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Mahnaz Khanavi

    2012-10-01

    Full Text Available Brain ischemia initiates several metabolic events leading to neuronal death. These events mediate large amount of damage that arises after some neurodegenerative disorders as well as transient brain ischemia. Melissa officinalis is considered as a helpful herbal plant in the prevention of various neurological diseases like Alzheimer that is related with oxidative stress.MethodsWe examined the effect of Melissa officinalis on hypoxia induced neuronal death in a cortical neuronal culture system as in vitro model and transient hippocampal ischemia as in vivo model. Transient hippocampal ischemia was induced in male rats by tow vessel-occlusion for 20 min. After reperfusion, the histopathological changes and the levels inflammation, oxidative stress status, and caspase-3 activity in hippocampus were measured.ResultsCytotoxicity assays showed a significant protection of a 10 mug/ml dose of Melissa against hypoxia in cultured neurons which was confirmed by a conventional staining (P<0.05. Melissa treatment decrease caspase3 activity (P<0.05 and TUNEL-positive cells significantly (P<0.01. Melissa oil has also inhibited malon dialdehyde level and attenuated decrease of Antioxidant Capacity in the hippocampus. Pro-inflammatory cytokines TNF-alpha, IL-1beta and HIF-1alpha mRNA levels were highly increased after ischemia and treatment with Melissa significantly suppressed HIF-1alpha gene expression (P<0.05.DiscussionResults showed that Melissa officinalis could be considered as a protective agent in various neurological diseases associated with ischemic brain injury.

  7. Mesenchymal Stem Cell Transplantation Attenuates Brain Injury After Neonatal Stroke

    NARCIS (Netherlands)

    van Velthoven, Cindy T. J.; Sheldon, R. Ann; Kavelaars, Annemieke; Derugin, Nikita; Vexler, Zinaida S.; Willemen, Hanneke L. D. M.; Maas, Mirjam; Heijnen, Cobi J.; Ferriero, Donna M.

    2013-01-01

    Background and Purpose-Brain injury caused by stroke is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. Mesenchymal stem cells (MSC) have been shown to improve outcome after neonatal hypoxic-ischemic brain injury mainly by secretion of growth factors stimulati

  8. Early prediction of the injuried regions in neonatal brain with hypoxic-ischemic encephalopathy by diffusion weighted imaging and measuring their apparent diffusion coefficient%弥散加权成像早期预测新生儿缺氧缺血性脑损伤区域及其表观弥散系数值改变

    Institute of Scientific and Technical Information of China (English)

    蔡清; 薛辛东; 富建华; 刘春丽; 轩哲; 张磊

    2011-01-01

    区域大部分为丘脑-中央沟周围皮层,仅少数为皮层及皮层下白质.中度HIE患儿的损伤区域较多样,依次为皮层及皮层下白质、脑室周围白质和丘脑-中央沟周围皮层.HIE患儿的DWI图像异常部位及未见异常部位的ADC值均有不同程度的下降.%Objective To elucidate that diffusion weighted imaging (DWI) can be used to predict the injured regions of neonatal brain with hypoxic-ischemic encephalopathy (HIE) in the early phase of injury, and to measure the apparent diffusion coefficient (ADC) values in the multiple regions of the brain.Method The participants in this study were twenty-six infants with HIE from neonatology ward hospitalized between July 2006 and July 2009.Nineteen patients had severe HIE, and seven had moderate HIE.DWI and conventional magnetic resonance imaging (MRI) were performed for each case within the first 72 hrs.The ADC values of eight regions of interest (ROIs) were measured in ten cases with severe HIE ( ADC values group). ROIs included posterior limb of internal capsule (PLIC), ventrolateral thalami, basal ganglia, perirolandic cortex, occipital cortex, centrum semiovale, brainstem, and frontal white matter.Twelve neonates were enrolled as the control subjects.Results During the first 72 hfs, the conventional MR1 of 26 patients showed subarachnoid hemorrhage in 5, subdural hemorrhage in 2, and mild high signal intensity in the cortex of only one patient.In the 19 cases with severe HIE, abnormal signal intensities were seen in ventrolateral thalami and perirolandie cortex of 17 patients ( 89% ), and the remaining 2 infants showed abnormal cortex and subcortical white matter.In 7 cases with moderate HIE, 4 had abnormal signal intensity in the cortex and subcortical white matter, 2 had abnormal periventricular white matter, and only one showed abnormal signal intensity in the ventrolateral thalami and perirolandic cortex.In the ADC values group, the average ADC values of posterior limb of

  9. Protective Effects of N-Acetyl-L-Cysteine in Human Oligodendrocyte Progenitor Cells and Restoration of Motor Function in Neonatal Rats with Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Dongsun Park

    2015-01-01

    Full Text Available Objective. Since oligodendrocyte progenitor cells (OPCs are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE, the present study was aimed at investigating the protective effects of N-acetyl-L-cysteine (NAC, a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats. Methods. In in vitro study, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. In in vivo study, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed. Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE. Conclusion. The results indicate that NAC exerts neuroprotective effects in vitro and in vivo by preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.

  10. Human Umbilical Cord Blood CD34-Positive Cells as Predictors of the Incidence and Short-Term Outcome of Neonatal Hypoxic-Ischemic Encephalopathy: A Pilot Study

    Science.gov (United States)

    Nasr Eldin, Mohamed Hassan; Amer, Hanaa A.; Abdelhamid, Adel E.; El Houssinie, Moustafa; Ibrahim, Abir

    2017-01-01

    Background and Purpose Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of neurological handicap in developing countries. Human umbilical cord blood (hUCB) CD34-positive (CD34+) stem cells exhibit the potential for neural repair. We tested the hypothesis that hUCB CD34+ stem cells and other cell types [leukocytes and nucleated red blood cells (NRBCs)] that are up-regulated during the acute stage of perinatal asphyxia (PA) could play a role in the early prediction of the occurrence, severity, and mortality of HIE. Methods This case-control pilot study investigated consecutive neonates exposed to PA. The hUCB CD34+ cell count in mononuclear layers was assayed using a flow cytometer. Twenty full-term neonates with PA and 25 healthy neonates were enrolled in the study. Results The absolute CD34+ cell count (p=0.02) and the relative CD34+ cell count (CD34+%) (p<0.001) in hUCB were higher in the HIE patients (n=20) than the healthy controls. The hUCB absolute CD34+ cell count (p=0.04), CD34+% (p<0.01), and Hobel risk scores (p=0.04) were higher in patients with moderate-to-severe HIE (n=9) than in those with mild HIE (n=11). The absolute CD34+ cell count was strongly correlated with CD34+% (p<0.001), Hobel risk score (p=0.04), total leukocyte count (TLC) (p<0.001), and NRBC count (p=0.01). CD34+% was correlated with TLC (p=0.02). Conclusions hUCB CD34+ cells can be used to predict the occurrence, severity, and mortality of neonatal HIE after PA. PMID:28079317

  11. Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates.

    Science.gov (United States)

    Lange, Sigrun; Rocha-Ferreira, Eridan; Thei, Laura; Mawjee, Priyanka; Bennett, Kate; Thompson, Paul R; Subramanian, Venkataraman; Nicholas, Anthony P; Peebles, Donald; Hristova, Mariya; Raivich, Gennadij

    2014-08-01

    Neonatal hypoxic ischaemic (HI) injury frequently causes neural impairment in surviving infants. Our knowledge of the underlying molecular mechanisms is still limited. Protein deimination is a post-translational modification caused by Ca(+2) -regulated peptidylarginine deiminases (PADs), a group of five isozymes that display tissue-specific expression and different preference for target proteins. Protein deimination results in altered protein conformation and function of target proteins, and is associated with neurodegenerative diseases, gene regulation and autoimmunity. In this study, we used the neonatal HI and HI/infection [lipopolysaccharide (LPS) stimulation] murine models to investigate changes in protein deimination. Brains showed increases in deiminated proteins, cell death, activated microglia and neuronal loss in affected brain areas at 48 h after hypoxic ischaemic insult. Upon treatment with the pan-PAD inhibitor Cl-amidine, a significant reduction was seen in microglial activation, cell death and infarct size compared with control saline or LPS-treated animals. Deimination of histone 3, a target protein of the PAD4 isozyme, was increased in hippocampus and cortex specifically upon LPS stimulation and markedly reduced following Cl-amidine treatment. Here, we demonstrate a novel role for PAD enzymes in neural impairment in neonatal HI Encephalopathy, highlighting their role as promising new candidates for drug-directed intervention in neurotrauma. Hypoxic Ischaemic Insult (HI) results in activation of peptidylarginine deiminases (PADs) because of calcium dysregulation. Target proteins undergo irreversible changes of protein bound arginine to citrulline, resulting in protein misfolding. Infection in synergy with HI causes up-regulation of TNFα, nuclear translocation of PAD4 and change in gene regulation as a result of histone deimination. Pharmacological PAD inhibition significantly reduced HI brain damage.

  12. Neonatal ischemic brain injury: what every radiologist needs to know

    Energy Technology Data Exchange (ETDEWEB)

    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E. [Seattle Children' s Hospital, University of Washington Medical Center, Department of Radiology, Seattle, WA (United States)

    2012-05-15

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  13. Molecular chaperones and hypoxic-ischemic encephalopathy

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    Cong Hua

    2017-01-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In

  14. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

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    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  15. Thompson评分在新生儿缺氧缺血性脑病中的应用%Application of Thompson score in neonatal hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    石芸; 李思秀

    2016-01-01

    Objective To explore the value of Thompson score in 5 hours after birth for hypoxic-ischemic encephalopathy (HIE) in early diagnosis, predicting severity and prognosis.Method Prospectively select neonates with birth asphyxia and abnormal nervous system performance in 5 hours after birth in the neonatal department of our hospital. Thompson score at age 3~5 hours and ambulatory electroencephalogram (AEEG) were recorded.Result 13 patients were dead, with Thompson score all≥ 21. As compared with Thompson score<7, the mothers whose babies with Thompson score≥7 had more pregnancy complications and/or abnormal events during baby birth; the Apgar scores at 1 and 5 minutes were lower; babies need more CPAP, ventilation and medication, more developed to medium-severe HIE , had abnormal AEEG and severely abnormal AEEG. The sensitivity of Thompson score in predicting severe HIE and in predicting the abnormal AEEG outcome are 96.9% and 94.8%; their specificity are 90.9% and 73.9% respectively.Conclusion Thompson score can be used as a method to rapid, economic predict severe HIE and abnormal AEEG. In our study, Thompson score may be more economic, accurately and convenient for clinician in HIE severity prediction than AEEG.%目的:探讨出生后早期行Thompson评分在诊断新生儿缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)的程度及预后判断中的价值。方法选择本院存在产时窒息史且出生5小时内出现异常神经系统表现的新生儿进行Thompson评分,并随访动态脑电图(ambulatory electroencephalogram,AEEG)变化。结果13例新生儿死亡,其Thompson评分均≥21分。相对于Thompson评分<7分组,Thompson评分≥7分组母亲更容易合并妊娠并发症和(或)产时特殊情况,新生儿1分钟、5分钟Apgar评分更低,更需要持续正压通气、机械通气和药物支持,发展成中重度HIE的比例更高,异常AEEG的比例更多,更易出

  16. 大麻素在围产期缺血缺氧性脑损伤的保护作用%Cannabinoid as a neuroprotective strategy in perinatal hypoxic-ischemic injury

    Institute of Scientific and Technical Information of China (English)

    Daniel Alonso-Alconada; Antonia Alvarez; Enrique Hilario

    2011-01-01

    Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn,leading to death or lifelong sequelae.Because of the fact that there is still no specific treatment for perinatal brain lesions due to the complexity of neonatal hypoxic-ischemic pathophysiology,the search of new neuroprotective therapies is of great interest.In this regard,therapeutic possibilities of the endocannabinoid system have grown lately.The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury,acting as a natural neuroprotectant.Concerning perinatal asphyxia,the neuroprotective role of this endogenous system is emerging these years.The present review mainly focused on the current knowledge of the cannabinoids as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.%围产期缺血缺氧一直是引起新生儿脑损伤的首要因素,往往导致死亡或终生后遗症.由于新生儿缺血缺氧性脑损伤的病理复杂性,目前还没有针对此病的特定疗法.因此,寻找新的神经保护性疗法正日益引起研究者的关注.在哺乳动物体内,大麻素系统能调节大范围的生理过程,而且在不同类型的急性脑损伤中也具有神经保护作用.近几年的研究表明,内源性大麻素系统在围产期窒息中也扮演着神经保护者的角色.本文主要就大麻素作为一种新的治疗策略在围产期缺血缺氧性脑损伤中的神经保护作用做一综述.

  17. Changes of plasma cardiotrophin-1 in neonates with hypoxic-ischemic encephalopathy and its correlation with myocardial injury%心肌营养素-1在新生儿缺氧缺血性脑病中的变化及与心肌损伤的相关性研究

    Institute of Scientific and Technical Information of China (English)

    刁玉巧; 江莲; 曲凡; 张会芬; 沈颖; 李力敏

    2015-01-01

    目的:探讨血浆心肌营养素‐1(CT‐1)在新生儿缺氧缺血性脑病(HIE)中的变化,并分析其与心肌损伤的相关性。方法该院儿科收治的足月H IE患儿45例(轻度15例、中度24例、重度6例),分为心肌损伤组19例和非心肌损伤组26例。20例健康新生儿作为健康对照组。使用双抗体夹心酶标免疫分析法检测血浆C T‐1水平。应用多普勒超声心动仪测定心输出量(CO )、左室射血分数(EF )、左室短轴缩短率(FS )。结果轻、中、重度HIE血浆 CT‐1水平较健康对照组均明显升高,差异有统计学意义(P<0.01),中、重度与轻度 HIE比较,CT‐1水平也明显升高,差异有统计学意义(P<0.01)。心肌损伤组血浆CT‐1水平较非心肌损伤组明显升高,差异有统计学意义(P<0.01)。心肌损伤组急性期血浆CT‐1水平明显高于恢复期,差异有统计学意义(P<0.01)。HIE患儿急性期CO、EF、FS明显降低,且CT‐1水平与CO、EF、FS均呈显著负相关。结论 HIE患儿急性期血浆CT‐1水平升高,且检测血浆CT‐1水平有助于早期诊断心肌损伤,判断病情,并能反映其心功能变化。%Objective The level of plasma cardiotrophin‐1(CT‐1)in neonates with hypoxic‐ischemic encepha‐lopathy(HIE)was observed to explore the correlation between its change and myocardial injury .Methods 45 neo‐nates with HIE (including 15 minor ,24 moderate and 6 severe) were divided into 2 groups :19 cases with myocardial injury ,26 cases without .20 healthy neonates were selected as the control group .The level of plasma CT‐1 was detec‐ted by double‐antibody sandwich enzyme immunoassay method .CO ,EF and FS were measured by Doppler echocar‐diography .Results Levels of plasma CT‐1 in neonates with minor、moderate and severe HIE were significantly in‐creased than those in normal neonates(P<0 .01) .Also CT‐1 levels of

  18. Prediction of Outcome in Neonates with Hypoxic-Ischemic Encephalopathy II: Role of Amplitude-Integrated Electroencephalography and Cerebral Oxygen Saturation Measured by Near-Infrared Spectroscopy.

    Science.gov (United States)

    Goeral, Katharina; Urlesberger, Berndt; Giordano, Vito; Kasprian, Gregor; Wagner, Michael; Schmidt, Lisa; Berger, Angelika; Klebermass-Schrehof, Katrin; Olischar, Monika

    2017-07-14

    Few data have been published on the combined use of amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS) for outcome prediction in neonates cooled for hypoxic-ischemic encephalopathy (HIE). Our aim was to evaluate the predictive values and the most powerful predictive combinations of single aEEG and NIRS parameters and the respective cut-off values with regard to short-term outcomes in HIE II. aEEG and NIRS were prospectively studied at the Medical University of Vienna in the first 102 h of life with regard to magnetic resonance imaging (MRI). Thirty-two neonates diagnosed with HIE II treated with hypothermia were investigated. The measurement period was divided into 6-h epochs. According to MRI, 2 outcome groups were defined and predictive values of aEEG parameters, regional cerebral oxygen saturation (rScO2), and the additional value of both methods combined were studied. Receiver operating curves (ROC) were obtained and area under the curve (AUC) values were calculated. ROC were then used to detect the optimal cut-off points, sensitivity, specificity, positive predictive values, and negative predictive values. At all time epochs, combined parameter scores were more predictive than single parameter scores. The highest AUC were observed between 18 and 60 h of cooling for the aEEG summation score (0.72-0.84) and for (background pattern + seizures) × rScO2 (0.79-0.85). At 42-60 h sensitivity was similar between those 2 scores (87.5-90.0%), but the addition of NIRS to aEEG led to an increase in specificity (from 52.4-59.1% to 72.7-90.5%). In HIE II, aEEG and NIRS are important predictors of short-term outcome. The combination of both methods improves prognostication. The highest predictive abilities were observed between 18 and 60 h of cooling. © 2017 S. Karger AG, Basel.

  19. [Neonatal hypoxic-ischemic nephropathy and urinary diagnostic indices: the utility of measuring tubular enzymes (NAG and AAP)].

    Science.gov (United States)

    Bertotti, A; De Marchi, S; Brovedani, P; Gaeta, G; Peratoner, L; Mangiarotti, M A

    1990-01-01

    Feto-neonatal hypoxia can cause a functional kidney impairment, which is often temporary and not clinically overt, but sometimes leading to acute renal failure. Hypoxic stress may result in a tubulo-interstitial damage, and kidney tubular enzymes determination has proved to be an easy, early, and non invasive method to define a tubular interstitial lesion. A major target of nephrotoxicity is the proximal tubular cell: alterations in brush-border membrane and cytoplasm result in increased turnover processes in the kidney cortex, following by a corresponding increased excretion of alanine-aminopeptidase (AAP) and N-acetyl-glucosaminidase (NAG) from the proximal tubular cells, long before glomerular or tubular functions are impaired. AAP and NAG excretion is directly correlated with the strength and the duration of toxic alteration of the proximal tubule. NAG and AAP have been already studied in the adults and the children; they have been chosen for this investigation with a double aim: 1) to define the amount of their urinary excretion in relation with gestational age at birth; 2) to evaluate if in the newborn, independently of the gestational age, their urinary concentration may be increased by ischaemic conditions caused by hypoxia. We studied 52 healthy newborns (7 preterm of 33-36 weeks and 45 full-term) and 16 newborns with feto-neonatal hypoxia (8 preterm of 26-36 weeks and full-term) at the forth day of life. Urinary NAG and AAP were assayed by colorimetric methods and the results expressed as mU/mg. creatininuria.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. 新生儿缺氧缺血性脑病MSCT与临床分度对比研究%Correlation Study on MSCT Manifestation of the Brain Damage and the Clinical Degrees in Neonatal Hypoxic-ischemic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    王业庆; 卓果然

    2012-01-01

    Objective:To investigate the multi-slice spiral CT (MSCT) manifestation in neonatal hypoxic-ischemic encephalopathy, and help improve awareness of the disease and clinical diagnosis. Methods:The brain MSCT was performed in 63 cases of clinically confirmed HIE .The MSCT manifestation and clinical data were retrospectively analysis. Results:Divide the cases by CT degrees, 33 cases are mild, accounting for 52%, 22 cases are moderate, accounting for 35% 8 cases are severe, accounting for 13%. The brain CT performance of 63 patients were related to newborn’s year, checking time and cure. Conclusion:MSCT scan can accurately diagnose the extent of HIE and its complications, MSCT scanning has important significance in finding of brain injury, evolution of prognosis and conduction of therapeutic schemes.%目的:探讨新生儿缺血缺氧性脑病MSCT表现,以提高对该病的认识及诊断水平。方法:对临床诊断为HIE患儿的脑部分别进行MSCT检查,并回顾性分析63例患儿的CT影像及临床资料。结果:CT分度,轻度33例,占52%;中度22例,占35%;重度8例,占13%。63例患儿脑部CT表现与年龄、治疗情况、检查时间相关。结论:MSCT能够准确诊断HIE的病变范围及其并发症,MSCT对判断脑损害、评估临床预后及制订治疗方案有重要价值。

  1. Clinical Application of Citicoline in the Treatment of Neonatal Hypoxic Ischemic Encephalopathy%胞磷胆碱治疗新生儿缺氧缺血性脑病的临床应用

    Institute of Scientific and Technical Information of China (English)

    邓纲

    2016-01-01

    Objective To analyze the clinical application value of the citicoline in the treatment of neonatal hypoxic ischemic encephalopathy .Method 24 cases of neonatal hypoxic ischemic encephalopathy were divided into study group and control group, 12 cases in each group.The control group uses the conventional symptomatic treatment.On the basis of the control group, study group was given citicoline treatment.The condition of the two groups were observed and compared.Result The total effective rate in the study group was signiifcantly higher than that in the control group,and the data were statistically signiifcant (P < 0.05). In the treatment effect of the patients with different condition of hypoxic ischemic encephalopathy, the total effective rate of the study group was also higher than that of the control group, and the data were statistically signiifcant (P < 0.05).The incidence rate of the study group was lower than that of the control group, and the data were statistically signiifcant (P< 0.05).Conclusion Patients of neonatal hypoxic ischemic encephalopathy with citicoline treatment on the basis of conventional symptomatic treatment achieve the effect which is better than patients of neonatal hypoxic ischemic encephalopathy with pure symptomatic treatment.%目的:对胞磷胆碱在新生儿缺氧缺血性脑病治疗中的临床应用价值进行分析。方法24例新生儿缺氧缺血性脑病患儿分为研究组和对照组,每组12例,对照组采用常规对症治疗,在对照组的基础上给予研究组胞磷胆碱治疗,对两组各项情况进行观察和对比。结果研究组获得的治疗总有效率明显高于对照组,对比数据具有统计学差异(P<0.05)。在不同病情缺氧缺血性脑病患儿获得的治疗效果上,研究组获得的治疗总有效率也均高于对照组,对比数据具有统计学差异(P<0.05)。研究组后遗症发生率低于对照组,对比数据具有统计学差异(P<0.05)

  2. Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

    Directory of Open Access Journals (Sweden)

    Fengbao Luo

    2016-08-01

    Full Text Available Tissue hypoxia/ischemia is a pathological feature of many human disorders including stroke, myocardial infarction, hypoxic/ischemic nephropathy, as well as cancer. In the kidney, the combination of limited oxygen supply to the tissues and high oxygen demand is considered the main reason for the susceptibility of the kidney to hypoxic/ischemic injury. In recent years, increasing evidence has indicated that a reduction in renal oxygen tension/blood supply plays an important role in acute kidney injury, chronic kidney disease, and renal tumorigenesis. However, the underlying signaling mechanisms, whereby hypoxia alters cellular behaviors, remain poorly understood. Mitogen-activated protein kinases (MAPKs are key signal-transducing enzymes activated by a wide range of extracellular stimuli, including hypoxia/ischemia. There are four major family members of MAPKs: the extracellular signal-regulated kinases-1 and -2 (ERK1/2, the c-Jun N-terminal kinases (JNK, p38 MAPKs, and extracellular signal-regulated kinase-5 (ERK5/BMK1. Recent studies, including ours, suggest that these MAPKs are differentially involved in renal responses to hypoxic/ischemic stress. This review will discuss their changes in hypoxic/ischemic pathophysiology with acute kidney injury, chronic kidney diseases and renal carcinoma.

  3. The neurobehavioral effect of Citicoline on hypoxic ischemic encephalopathy in neonatal%胞二磷胆碱对新生儿缺氧缺血性脑病神经行为的影响分析

    Institute of Scientific and Technical Information of China (English)

    王建国

    2011-01-01

    目的:探讨胞二磷胆碱对新生儿缺氧缺血性脑病神经行为的影响.方法:回顾性分析新生儿缺氧缺血性脑病患儿的临床治疗效果与神经行为影响结果,其中采用神经节苷脂治疗(对照组)32例,采用胞二磷胆碱治疗(治疗组)32例.结果:治疗组总有效率明显高于对照组,差异有统计学意义(X2=6.235 3,P<0.05).两组患儿在治疗前相关指标无差异.治疗后两组患儿在NABA评分、一般状态、原始反射之间的差异有统计学意义(t=7.852 1、6.235 3、6.3632,P<0.05),而主动肌张力、被动肌张力的差异无统计学意义(t=0.236 2、0.365 2,P>0.05).结论:临床在新生儿缺氧缺血性脑病综合治疗的基础上,尽早应用胞二磷胆碱治疗,会提高治疗有效率与改善预后,可推广应用.%Objective: To investigate the neurohehavioral effect of Citicoline on hypoxic ischemic encephalopathy in neonatal. Methods: To analyae neonatal hypoxic ischemic encephalopathy and the clinical treatment of the results of neurohehavioral effect, including treated by the Oganglioside (the control group) with 32 cases, and treated by the citicoline (the treatment group) with 32 cases. Resullts: The total effective rate of the treatment group was significantly higher than that of the control group (x2=6.235 3, P<0.05). The NABA valuse, capacity, performance status of the two groups had significantly difference (t=7.852 1. 6.235 3, 6.363 2, P<0.05). and active muscle tone, passive muscle tension of the two groups had not significantly different (t=0.236 2, 0.365 2, P>0.05). Conclusion: Citicoline on hypoxic ischemic encephalopathy in neonatal will improve efficiency and the prognosis, it can be generalized.

  4. Hypoxic-Ischemic Injury in the Developing Brain: The Role of Reactive Oxygen Species Originating in Mitochondria

    Directory of Open Access Journals (Sweden)

    Vadim S. Ten

    2012-01-01

    Full Text Available Mitochondrial dysfunction is the most fundamental mechanism of cell damage in cerebral hypoxia-ischemia and reperfusion. Mitochondrial respiratory chain (MRC is increasingly recognized as a source for reactive oxygen species (ROS in the postischemic tissue. Potentially, ROS originating in MRC can contribute to the reperfusion-driven oxidative stress, promoting mitochondrial membrane permeabilization. The loss of mitochondrial membranes integrity during reperfusion is considered as the major mechanism of secondary energy failure. This paper focuses on current data that support a pathogenic role of ROS originating from mitochondrial respiratory chain in the promotion of secondary energy failure and proposes potential therapeutic strategy against reperfusion-driven oxidative stress following hypoxia-ischemia-reperfusion injury of the developing brain.

  5. Hypoxic-ischemic injury in the developing brain: the role of reactive oxygen species originating in mitochondria.

    Science.gov (United States)

    Ten, Vadim S; Starkov, Anatoly

    2012-01-01

    Mitochondrial dysfunction is the most fundamental mechanism of cell damage in cerebral hypoxia-ischemia and reperfusion. Mitochondrial respiratory chain (MRC) is increasingly recognized as a source for reactive oxygen species (ROS) in the postischemic tissue. Potentially, ROS originating in MRC can contribute to the reperfusion-driven oxidative stress, promoting mitochondrial membrane permeabilization. The loss of mitochondrial membranes integrity during reperfusion is considered as the major mechanism of secondary energy failure. This paper focuses on current data that support a pathogenic role of ROS originating from mitochondrial respiratory chain in the promotion of secondary energy failure and proposes potential therapeutic strategy against reperfusion-driven oxidative stress following hypoxia-ischemia-reperfusion injury of the developing brain.

  6. Brain metabolism in patients with vegetative state after post-resuscitated hypoxic-ischemic brain injury: statistical parametric mapping analysis of F-18 fluorodeoxyglucose positron emission tomography

    Institute of Scientific and Technical Information of China (English)

    Yong Wook Kim; Hyoung Seop Kim; Young-Sil An

    2013-01-01

    Background Hypoxic-ischemic brain injury (HIBI) after cardiopulmonary resuscitation is one of the most devastating neurological conditions that causing the impaired consciousness.However,there were few studies investigated the changes of brain metabolism in patients with vegetative state (VS) after post-resuscitated HIBI.This study aimed to analyze the change of overall brain metabolism and elucidated the brain area correlated with the level of consciousness (LOC) in patients with VS after post-resuscitated HIBI.Methods We consecutively enrolled 17 patients with VS after HIBI,who experienced cardiopulmonary resuscitation.Overall brain metabolism was measured by F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) and we compared regional brain metabolic patterns from t7 patients with those from 15 normal controls using voxel-by-voxel based statistical parametric mapping analysis.Additionally,we correlated the LOC measured by the JFK-coma recovery scale-revised of each patient with brain metabolism by covariance analysis.Results Compared with normal controls,the patients with VS after post-resuscitated HIBI revealed significantly decreased brain metabolism in bilateral precuneus,bilateral posterior cingulate gyrus,bilateral middle frontal gyri,bilateral superior parietal gyri,bilateral middle occipital gyri,bilateral precentral gyri (PFEw correctecd <0.0001),and increased brain metabolism in bilateral insula,bilateral cerebella,and the brainstem (PFEw correctecd <0.0001).In covariance analysis,the LOC was significantly correlated with brain metabolism in bilateral fusiform and superior temporal gyri (P uncorrected <0.005).Conclusions Our study demonstrated that the precuneus,the posterior cingulate area and the frontoparietal cortex,which is a component of neural correlate for consciousness,may be relevant structure for impaired consciousness in patient with VS after post-resuscitated HIBI.In post-resuscitated HIBI,measurement of brain

  7. Neuroprotective and anti-inflammatory effects of the flavonoid-enriched fraction AF4 in a mouse model of hypoxic-ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    Paul G W Keddy

    Full Text Available We report here neuroprotective and anti-inflammatory effects of a flavonoid-enriched fraction isolated from the peel of Northern Spy apples (AF4 in a mouse of model of hypoxic-ischemic (HI brain damage. Oral administration of AF4 (50 mg/kg, once daily for 3 days prior to 50 min of HI completely prevented motor performance deficits assessed 14 days later that were associated with marked reductions in neuronal cell loss in the dorsal hippocampus and striatum. Pre-treatment with AF4 (5, 10, 25 or 50 mg/kg, p.o.; once daily for 3 days produced a dose-dependent reduction in HI-induced hippocampal and striatal neuron cell loss, with 25 mg/kg being the lowest dose that achieved maximal neuroprotection. Comparison of the effects of 1, 3 or 7 doses of AF4 (25 mg/kg; p.o. prior to HI revealed that at least 3 doses of AF4 were required before HI to reduce neuronal cell loss in both the dorsal hippocampus and striatum. Quantitative RT-PCR measurements revealed that the neuroprotective effects of AF4 (25 mg/kg; p.o.; once daily for 3 days in the dorsal hippocampus were associated with a suppression of HI-induced increases in the expression of IL-1β, TNF-α and IL-6. AF4 pre-treatment enhanced mRNA levels for pro-survival proteins such as X-linked inhibitor of apoptosis and erythropoietin following HI in the dorsal hippocampus and striatum, respectively. Primary cultures of mouse cortical neurons incubated with AF4 (1 µg/ml, but not the same concentrations of either quercetin or quercetin-3-O-glucose or its metabolites, were resistant to cell death induced by oxygen glucose deprivation. These findings suggest that the inhibition of HI-induced brain injury produced by AF4 likely involves a transcriptional mechanism resulting from the co-operative actions of various phenolics in this fraction which not only reduce the expression of pro-inflammatory mediators but also enhance pro-survival gene signalling.

  8. Regional Differences in Susceptibility to Hypoxic-Ischemic Injury in the Preterm Brain: Exploring the Spectrum from White Matter Loss to Selective Grey Matter Injury in a Rat Model

    Directory of Open Access Journals (Sweden)

    D. B. Selip

    2012-01-01

    Full Text Available Models of premature brain injury have largely focused on the white matter injury thought to underlie periventricular leukomalacia (PVL. However, with increased survival of very low birth weight infants, injury patterns involving grey matter are now recognized. We aimed to determine how grey matter lesions relate to hypoxic-ischemic- (HI mediated white matter injury by modifying our rat model of PVL. Following HI, microglial infiltration, astrocytosis, and neuronal and axonal degeneration increased in a region-specific manner dependent on the severity of myelin loss in pericallosal white matter. The spectrum of injury ranged from mild, where diffuse white matter abnormalities were dominant and were associated with mild axonal injury and local microglial activation, to severe HI injury characterized by focal MBP loss, widespread neuronal degeneration, axonal damage, and gliosis throughout the neocortex, caudate putamen, and thalamus. In sum, selective regional white matter loss occurs in the preterm rat concomitantly with a clinically relevant spectrum of grey matter injury. These data demonstrate an interspecies similarity of brain injury patterns and further substantiates the reliable use of this model for the study of preterm brain injury.

  9. Environmental enrichment promotes neural remodeling in newborn rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yankui Guo; Yalu Li; Zhenying Yang

    2011-01-01

    We evaluated the effect of hypoxic-ischemic brain damage and treatment with early environmental enrichment intervention on development of newborn rats, as evaluated by light and electron microscopy and morphometry. Early intervention with environmental enrichment intelligence training attenuated brain edema and neuronal injury, promoted neuronal repair, and increased neuronal plasticity in the frontal lobe cortex of the newborn rats with hypoxic-ischemic brain damage.

  10. 纳洛酮联合脑活素治疗新生儿HIE效果分析%Combination therapy with naloxone and cerebrolysin for hypoxic-ischemic encephalopathy in neonates

    Institute of Scientific and Technical Information of China (English)

    杜宝风; 王丽艳; 韩爱娜

    2011-01-01

    Objective To explore the efficacy of naloxone combined with cerebrolysin for hypoxic-ischemic encephalopathy in neonates. Methods 162 neonate patients were ramdonly assigned to receive oxygen inhalation, control of liquid intake, dehydration, anti-convulsion, energy mixture, citicoline,and naloxone (control group), or the former therapy plus cerebrolysin (study group, 81 neonates). The efficacy was assessed in the two goroups according to the clinical manifestations and incidence of sequelae. Results The efficacy was obviously greater in the study group than in the control group (96.3% vs. 88.9% for the effective rate, P<0.05) and the incidence of sequelae was lower. Conclusions Naloxone combined with cerebrolysin has a synergetic effect on the treatment of hypoxic-ischemic encephalopathy in neonates. It can improve blood perfusion into the ischemic areas of the brain, promote neural cellular metabolism, improve prognosis, and reduce nervous system sequelae.%目的 探讨纳洛酮联合脑活察治疗新生儿缺氧缺血性脑病的临床效果.方法 将我科缺氧缺血性脑病患儿随机分为治疗组和对照组各81例,对照组给予吸氧、限制液体入量、脱水、止痉及能量合剂、胞二磷胆碱、纳络酮,治疗组在此疗法基础上加用脑活素治疗.根据临床表现、后遗症发生情况等综合评价临床效果.结果 治疗组总有效率96.3%,对照组有效率88.9%.治疗组临床疗效明显高于对照组(P<0.05),后遗症的发生率低.结论 纳洛酮联合脑活素治疗新生儿缺氧缺血性脑病有协同作用,能改善脑缺血区血流灌注,促进神经细胞代谢,改善预后,减少神经系统后遗症.

  11. The effects of early exercises intervention for nervous movement functional recovery on neonate hypoxic ischemic encephalopathy%早期运动干预对新生儿缺氧缺血性脑病神经运动功能恢复的影响

    Institute of Scientific and Technical Information of China (English)

    肖绪武; 孙长凯; 刁敬军; 孙健梅

    2008-01-01

    Objective To investigate the assistant method for improving and promoting nervous movement functional recovery on neonate hypoxie ischemic encephalopathy. Methods Eighty-five patients with neonate hypoxic ischemic encephalopathy were divided into two groups: observed group (45 cases) and control group(40 cases). Observed group added early exercises intervention on basis of routine synthetic drug treatment, compared to control group which just purely synthetic drug treatment with neonatal behavior neurological assessment (NBNA), mental development index (MDI) and psychomotor development index (PDI). Results NBNA at 14 days [(38.84±1.56)scores] in observed group was significantly higher than that in control group [(36.12±2.23)scores]. PDI at 6, 12 months and MDI at 12 months in observed group were significantly higher than those in control group. Conclusion Early exercises intervention can promote nervous movement functional recovery on neonate hypoxic ischemic encephalopathy, prevent or lessen brain injury sequels, elevate life quality for patients with neonate hypoxic ischemic encephalopathy.%目的 探讨改善和促进新生儿缺氧缺血性脑病神经运动功能恢复的辅助疗法.方法 将85例新生儿缺氧缺血性脑病患儿随机分为两组:观察组(45例)和对照组(40例),观察组在常规综合药物治疗的基础上加用早期运动干预,对照组单纯常规综合药物治疗.比较两组新生儿行为神经评分(NBNA)、智力发育指数(MDI)和精神运动发育指数(PDI).结果 出生后7 d两组患儿NBNA比较差异无统计学意义,14 d观察组[(38.84±1.56)分]较对照组[(36.12±2.23)分]明显增高,两组比较差异有统计学意义.6个月两组MDI比较,差异无统计学意义,而PDI比较差异有统计学意义[(90.11±9.97)分和(86.35±11.26)分];12个月观察组MDI、PDI均较对照组明显增高,差异有统计学意义.结论 早期运动干预可促进新生儿缺氧缺血性脑病患儿神经运动功

  12. Application of the evidence-based nursing care to the neonates with hypoxic-ischemic encephalopathy%循证护理在缺氧缺血性脑病新生儿护理中的应用

    Institute of Scientific and Technical Information of China (English)

    石小娟; 袁瑞琴; 谢华蓉

    2011-01-01

    Objective: To evaluate the application effect of evidence - based nursing care in the neonatal care of hypoxic - ischemic encephalopathy. Methods: 74 neonates with hypoxic - ischemic encephalopathy were randomly divided into an observation group and a control group ( 37 neonates in each group ). The routine nursing care and evidence - based nursing care were respectively implemented in the control group and the observation group. The total effective rate of the treatment, incidence of complications , hospitalization days, satisfaction of the patient s families and the scores of MDI, PDI and Gesell scale respectively in 3,9,15 months before and after the implementation of nursing care were statistically processed and compared between the two groups. Results: The total effective rate of the treatment and satisfaction of the patients families were higher and the incidence of complications, hospitalization days were lower and shorter in the observation group than the control group ( P<0.05 ); the scoring of MDI, PDI and Gesell scale in 3 ,9,15 months after nursing care was superior in the observation group to the control group ( P <0. 05 ). Conclusion: The evidence - based nursing care has a good effect in the care of neonates with hypoxic - ischemic encephalopathy and can improve their quality of life and prognosis.%目的:探讨循证护理在缺氧缺血性脑病新生儿护理中的应用效果.方法:将74例缺氧缺血性脑病新生儿随机分为观察组和对照组各37例,对照组给予常规护理,观察组给予循证护理,将两组患者的治疗总有效率、并发症发生率、住院时间、家属满意率及护理前后3、9、15个月的MDI、PDI、Gesell量表评分进行统计及比较.结果:观察组治疗总有效率及家属满意度高于对照组、并发症发生率低于对照组、住院时间短于对照组(P<0.05),护理后3、9、15个月的MDI、PDI、Gesell量表评分均优于对照组(P<0.05).结论:循证护理在缺氧

  13. Effect of evidence-based nursing used in neonates with hypoxic ischemic encephalopathy in nursing experience%循证护理在缺氧缺血性脑病新生儿护理中的应用效果

    Institute of Scientific and Technical Information of China (English)

    刘颖

    2015-01-01

    Objective To explore the effect of evidence-based nursing used in neonates with hypoxic ischemic encephalopathy in nursing experience.Methods 75 cases obstetrics neonatal hypoxic ischemic encephalopathy in our hospital from 2012 January to 2013 October were collected and randomly divided into the observation group (38 cases) and control group(37 cases). Complications of clinical curative effect, two groups of children,hospitalization time and satisfaction of parents, at the time of admissionand after 1 years, the mental development index (MDI) and psychomotor development index (PDI) were all observed.ResultsThe total effective rate of observation group was 92.11%, It was significantly higher than the control group (81.08), the difference was significant (P0.05); After follow-up 1 years later, the observation group had 1 cases died(2.63%), the control group had 2 cases of death(5.41%), two mortality rate have no significant difference(P>0.05). After 1 years of treatment were observed in group MDI and PDI scores were significantly higher than those in the control group(P<0.05). Conclusion On neonatal hypoxic ischemic encephalopathy using evidence-basednursing in the method can effectively improve the quality of survival in children with obvious curative effect, long-term.%目的:探讨循证护理在缺氧缺血性脑病新生儿护理中的应用效果。方法选取2012年1月~2013年10月我院产科的缺氧缺血性脑病新生儿75例,随机分为观察组38例及对照组37例。对两组患儿临床疗效、并发症、住院时间及家长满意度,入院时及1年后智能发育指数(MDI)和运动发育指数(PDI)等进行观察。结果观察组的总有效率为92.11%,明显高于对照组的81.08%,两组比较差异有统计学意义(P<0.05)。观察组的并发症发生率低于对照组,两组比较差异有统计学意义(P<0.05)。住院时间短于对照组,家长满意度高于对照组,两组比较

  14. Ischemic injury suppresses hypoxia-induced electrographic seizures and the background EEG in a rat model of perinatal hypoxic-ischemic encephalopathy

    OpenAIRE

    2015-01-01

    The relationship among neonatal seizures, abnormalities of the electroencephalogram (EEG), brain injury, and long-term neurological outcome (e.g., epilepsy) remains controversial. The effects of hypoxia alone (Ha) and hypoxia-ischemia (HI) were studied in neonatal rats at postnatal day 7; both models generate EEG seizures during the 2-h hypoxia treatment, but only HI causes an infarct with severe neuronal degeneration. Single-channel, differential recordings of acute EEG seizures and backgrou...

  15. Ca²⁺/calmodulin-dependent protein kinase II contributes to hypoxic ischemic cell death in neonatal hippocampal slice cultures.

    Directory of Open Access Journals (Sweden)

    Qing Lu

    Full Text Available We have recently shown that p38MAP kinase (p38MAPK stimulates ROS generation via the activation of NADPH oxidase during neonatal hypoxia-ischemia (HI brain injury. However, how p38MAPK is activated during HI remains unresolved and was the focus of this study. Ca²⁺/calmodulin-dependent protein kinase II (CaMKII plays a key role in brain synapse development, neural transduction and synaptic plasticity. Here we show that CaMKII activity is stimulated in rat hippocampal slice culture exposed to oxygen glucose deprivation (OGD to mimic the condition of HI. Further, the elevation of CaMKII activity, correlated with enhanced p38MAPK activity, increased superoxide generation from NADPH oxidase as well as necrotic and apoptotic cell death. All of these events were prevented when CaMKII activity was inhibited with KN93. In a neonatal rat model of HI, KN93 also reduced brain injury. Our results suggest that CaMKII activation contributes to the oxidative stress associated with neural cell death after HI.

  16. Decreased levels of pNR1 S897 protein in the cortex of neonatal Sprague Dawley rats with hypoxic-ischemic or NMDA-induced brain damage

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    Hei, Ming-Yan; Tao, Hui-Kang; Tang, Qin; Yu, Bo; Zhao, Ling-Ling [Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan (China)

    2012-06-22

    Our objective was to investigate the protein level of phosphorylated N-methyl-D-aspartate (NMDA) receptor-1 at serine 897 (pNR1 S897) in both NMDA-induced brain damage and hypoxic-ischemic brain damage (HIBD), and to obtain further evidence that HIBD in the cortex is related to NMDA toxicity due to a change of the pNR1 S897 protein level. At postnatal day 7, male and female Sprague-Dawley rats (13.12 ± 0.34 g) were randomly divided into normal control, phosphate-buffered saline (PBS) cerebral microinjection, HIBD, and NMDA cerebral microinjection groups. Immunofluorescence and Western blot (N = 10 rats per group) were used to examine the protein level of pNR1 S897. Immunofluorescence showed that control and PBS groups exhibited significant neuronal cytoplasmic staining for pNR1 S897 in the cortex. Both HIBD and NMDA-induced brain damage markedly decreased pNR1 S897 staining in the ipsilateral cortex, but not in the contralateral cortex. Western blot analysis showed that at 2 and 24 h after HIBD, the protein level of pNR1 S897 was not affected in the contralateral cortex (P > 0.05), whereas it was reduced in the ipsilateral cortex (P < 0.05). At 2 h after NMDA injection, the protein level of pNR1 S897 in the contralateral cortex was also not affected (P > 0.05). The levels in the ipsilateral cortex were decreased, but the change was not significant (P > 0.05). The similar reduction in the protein level of pNR1 S897 following both HIBD and NMDA-induced brain damage suggests that HIBD is to some extent related to NMDA toxicity possibly through NR1 phosphorylation of serine 897.

  17. Decreased levels of pNR1 S897 protein in the cortex of neonatal Sprague Dawley rats with hypoxic-ischemic or NMDA-induced brain damage

    Directory of Open Access Journals (Sweden)

    Ming-Yan Hei

    2012-10-01

    Full Text Available Our objective was to investigate the protein level of phosphorylated N-methyl-D-aspartate (NMDA receptor-1 at serine 897 (pNR1 S897 in both NMDA-induced brain damage and hypoxic-ischemic brain damage (HIBD, and to obtain further evidence that HIBD in the cortex is related to NMDA toxicity due to a change of the pNR1 S897 protein level. At postnatal day 7, male and female Sprague Dawley rats (13.12 ± 0.34 g were randomly divided into normal control, phosphate-buffered saline (PBS cerebral microinjection, HIBD, and NMDA cerebral microinjection groups. Immunofluorescence and Western blot (N = 10 rats per group were used to examine the protein level of pNR1 S897. Immunofluorescence showed that control and PBS groups exhibited significant neuronal cytoplasmic staining for pNR1 S897 in the cortex. Both HIBD and NMDA-induced brain damage markedly decreased pNR1 S897 staining in the ipsilateral cortex, but not in the contralateral cortex. Western blot analysis showed that at 2 and 24 h after HIBD, the protein level of pNR1 S897 was not affected in the contralateral cortex (P > 0.05, whereas it was reduced in the ipsilateral cortex (P 0.05. The levels in the ipsilateral cortex were decreased, but the change was not significant (P > 0.05. The similar reduction in the protein level of pNR1 S897 following both HIBD and NMDA-induced brain damage suggests that HIBD is to some extent related to NMDA toxicity possibly through NR1 phosphorylation of serine 897.

  18. Changes of biological clock protein in neonatal rats with hypoxic-ischemic brain damage%缺氧缺血性脑损伤新生大鼠松果体钟基因表达的变化

    Institute of Scientific and Technical Information of China (English)

    李永富; 金美芳; 孙斌; 冯星

    2013-01-01

    Objective To study the effects of biological clock protein on circadian disorders in hypoxic-ischemic brain damage ( HIBD) by examining levels of CLOCK and BMAL1 proteins in the pineal gland of neonatal rats. Methods Seventy-two 7-day-old Sprague-Dawley (SD) rats were randomly divided into sham-operated and HIBD groups. HIBD model was prepared according to the modified Levine method. Western blot analysis was used to measure the levels of CLOCK and BMAL1 in the pineal gland at 0, 2, 12, 24, 36 and 48 hours after operation. Results Both CLOCK and BMAL levels in the pineal gland increased significantly 48 hours after HIBD compared with the sham-operated group ( P 0. 05 ) . Conclusions Levels of CLOCK and BMAL1 proteins in the pineal gland of rats increase significantly 48 hours after HIBD, suggesting that both CLOCK and BMAL1 may be involved the regulatory mechanism of circadian disorders in rats with HIBD.%目的 观察缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)新生大鼠松果体中CLOCK、BMAL1蛋白表达的变化,探讨钟基因表达异常在HIBD导致的昼夜节律紊乱中的作用.方法 72只7日龄新生Sprague-Dawley大鼠随机分为假手术组与HIBD模型组,每组36只.采用改良Levine法建立HIBD模型,用Western blot方法测定两组新生大鼠术后0、2、12、24、36、48 h松果体中CLOCK、BMAL1蛋白水平.结果 HIBD模型组松果体的CLOCK及BMAL1蛋白表达水平在HIBD后48 h高于假手术组(P<0.05),在0、2、12、24、36 h CLOCK及BMAL1蛋白表达水平与假手术组相比差异均无统计学意义(P>0.05).结论 HIBD新生大鼠松果体中CLOCK和BMAL1蛋白在损伤48 h后有显著升高,提示两者可能共同参与缺氧缺血时昼夜节律紊乱的发生.

  19. Effect of neonatal asphyxia on the impairment of the auditory pathway by recording auditory brainstem responses in newborn piglets: a new experimentation model to study the perinatal hypoxic-ischemic damage on the auditory system.

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    Francisco Jose Alvarez

    Full Text Available Hypoxia-ischemia (HI is a major perinatal problem that results in severe damage to the brain impairing the normal development of the auditory system. The purpose of the present study is to study the effect of perinatal asphyxia on the auditory pathway by recording auditory brain responses in a novel animal experimentation model in newborn piglets.Hypoxia-ischemia was induced to 1.3 day-old piglets by clamping 30 minutes both carotid arteries by vascular occluders and lowering the fraction of inspired oxygen. We compared the Auditory Brain Responses (ABRs of newborn piglets exposed to acute hypoxia/ischemia (n = 6 and a control group with no such exposure (n = 10. ABRs were recorded for both ears before the start of the experiment (baseline, after 30 minutes of HI injury, and every 30 minutes during 6 h after the HI injury.Auditory brain responses were altered during the hypoxic-ischemic insult but recovered 30-60 minutes later. Hypoxia/ischemia seemed to induce auditory functional damage by increasing I-V latencies and decreasing wave I, III and V amplitudes, although differences were not significant.The described experimental model of hypoxia-ischemia in newborn piglets may be useful for studying the effect of perinatal asphyxia on the impairment of the auditory pathway.

  20. Study on Therapeutic Effect of Tetramethylpyrazine on Hypoxic-Ischemic Encephalopathy of Newborn Infants

    Institute of Scientific and Technical Information of China (English)

    杨达胜; 王礼周; 李建国; 郭蕴琦

    2001-01-01

    @@The pathogenetic mechanism of neonatal hypoxic-ischemic encephalopathy (HIE) is complex and no specific effective therapeutic measure has been found so far. It's recently reported that the increase of intracellular calcium ion concentration resulting from the imequilibrium of intracellular and extracellular calcium ion, the opening of calcium channel and the influx of calcium ion is one of the important mechanisms of brain cell injury. Tetramethylpyrazine is one of the common medicine for treatment of cardiopathy, and encephalopathy, and has been verified to be a new-type antagonist of calcium channel(1). So, we chose neuron-specific enolase (NSE) and erythrocyte total calcium (EryCaT) as indexes to observe the curative effect of tetramethylpyrazine on HIE.

  1. Study on Therapeutic Effect of Tetramethylpyrazine on Hypoxic-Ischemic Encephalopathy of Newborn Infants

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The pathogenetic mechanism of neonatal hypoxic-ischemic encephalopathy (HIE) is complex and no specific effective therapeutic measure has been found so far. It's recently reported that the increase of intracellular calcium ion concentration resulting from the imequilibrium of intracellular and extracellular calcium ion, the opening of calcium channel and the influx of calcium ion is one of the important mechanisms of brain cell injury. Tetramethylpyrazine is one of the common medicine for treatment of cardiopathy, and encephalopathy, and has been verified to be a new-type antagonist of calcium channel(1). So, we chose neuron-specific enolase (NSE) and erythrocyte total calcium (EryCaT) as indexes to observe the curative effect of tetramethylpyrazine on HIE.……

  2. 新生儿缺氧缺血性脑病的CT临床价值及随访观察%The clinical diagnostic value of CT and follow-up study in neonatal hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    张秀芸; 丁娟; 宋丹

    2012-01-01

    目的 探讨新生儿缺氧缺血性脑病的CT诊断价值及其分度与预后的关系.方法 将109例(轻度61例、中度35例、重度组13例)有窒息缺氧病史,临床诊断为HIE的患儿行颅脑CT检查,初次CT扫描时间为生后5h~15天,并按影像分级标准分轻、中、重三度,其中有76例在生后1~6个月内进行了CT复查.结果 ①109例HIE患儿脑CT平扫均有不同程度的脑水肿征象,CT值在8~18HU之间.诊断为轻度HIE的66例;诊断为中度HIE的为31例,合并颅内出血9例;诊断为重度HIE的为12例,合并颅内出血7例.并将临床分度与CT分度资料经统计学处理进行比较分析,经统计学处理r =0.775,(P<0.01),认为CT分级与临床分级之间有密切的相关性;②随访复查:最后一次CT复查所见,正常45例,单纯脑沟加深13例,硬膜下积液7例,脑软化7例,脑积水3例,脑萎缩3例,死亡2例.结论 CT扫描检查是诊断HIE的主要手段,能够准确的显示病变和范围,确定是否合并颅内出血及出血类型,对HIE脑损伤程度及预后的有较好的评估价值.%Objective To explore the diagnostic value of CT in neonates with hypoxic-ischemic encephalopathy C HIE), and the relationship between indexing and the prognosis. Methods The CT examinations were performed in 109 cases (mild group: 61 cases, moderate group: 35 cases, and severe group:13 cases) of neonates with apneic hypoxia history which were diagnosed by clinic. The initial CT scanning was performed at 5 hours to 15 days after birth. And the CT image grading standards were divided into mild, moderate and severe degree. 76 cases were performed CT re-examination within 1 ~ 6 month after birth. Results ① 109 HIE neonates showed different degrees of crebral edema symptoms through CT plain film scanning, CT values were between 8-18 HU. 66 cases were diagnosed as mild HIE. 31 cases were diagnosed as moderate HIE with 9 cases of in-tracranial hemorrhage (ICH). 12 cases were diagnosed

  3. Analysis on early treatment and prognosis of neonatal hypoxic - ischemic encephalopathy%新生儿缺氧缺血性脑病早期治疗及预后分析

    Institute of Scientific and Technical Information of China (English)

    刘艳龙

    2012-01-01

    Objective; To explore the clinical efficacy of early treatment of neonatal hypoxic - ischemic encephalopathy (HIE) . Methods; A total of 50 neonates with HIE who were treated in pediatric department of the hospital were collected as observation group, and 20 neonates with HIE who were treated with routine treatment were selected as control group, the neonates in observation group were treated with cerebrolysin combined with compound salvia miltiorrhiza injection based on control group, the clinical efficacies in the two groups were analyzed and compared. Results: The obvious effective rate and total effective rate in observation group were 36.0% and 98. 0% , respectively , which were significantly higher than those in control group ( P < 0.05 ) . NBNA scores after one course of treatment and at four weeks after birth in observation group were significantly higher than those in control group (P < 0.05 ) , the incidences of adverse reactions in the two groups were low. Conclusion: Cerebrolysin combined with compound salvia miltiorrhiza injection is effective in treatment of neonatal HIE, and the safety is good.%目的:探讨新生儿缺氧缺血性脑病早期治疗的临床效果.方法:收集近期北京市房山区妇幼保健院儿科收治的50例新生儿缺氧缺血性脑病患儿作为观察组,并将之前采用常规治疗的20例患儿作为对照组,观察组在对照组的基础上联合脑活素及复方丹参注射液,分析比较两组临床疗效.结果:观察组显效率、总有效率分别为56.0%、98.0%,均显著优于常规治疗的对照组(P<0.05),观察组治疗1个疗程后与出生后4周NBNA评分均明显优于对照组(P<0.05),两组不良反应率均较低.结论:脑活素及复方丹参注射液联合治疗新生儿缺氧缺血性脑病的临床疗效确切,且安全性良好.

  4. 新生儿缺血缺氧性脑病的早期护理干预体会%Neonatal Hypoxic-ischemic Encephalopathy Early Nursing Intervention Experience

    Institute of Scientific and Technical Information of China (English)

    程转运

    2012-01-01

      目的探讨早期护理干预对新生儿缺血缺氧性脑病(HIE)患儿智力发育及运动发育的影响.方法选择医院2005年7月至2009年10月收治的20例 HIE 患儿设为对照组,采用常规护理方法,另选择2009年2月至2012年6月收治的21例 HIE 患儿,设为观察组,在常规护理的基础上结合有针对性的护理方法,对比两组 HIE 患儿智力发育指数(MDI)和运动发育指数(PDI)的变化情况.结果两组患儿经护理后观察组 NBNA 评分、MDI 和 PDI 值显著高于对照组,差异有显著性意义(P <0.05).结论在对新生儿缺氧缺血性脑病患儿治疗的基础上,结合早期有针对性的护理干预措施能提高患儿的 NBNA 评分、智力发育指数和运动发育指数,减少脑瘫、智障和癫痫等后遗症的发生.%  Objective To investigate the early nursing intervention on mental development and motor development of children with neonatal hypoxic-ischemic encephalopathy (HIE). Methods select hospitals from July 2005 to October 2009, 20 patients were treated with HIE is set to the control group, using conventional methods of care, the other to select from February 2009 to June 2012, 21 patients admitted with HIE, set for the observation group, on the basis of the usual care combined with targeted care, comparing the two groups with HIE mental development index (MDI) and psychomotor development index (PDI) changes. Results The two groups of children after care after the observation group the NBNA score, MDI and PDI values significantly higher than that of the control group, the difference was statistically significant (P <0.05). Conclusion In the treatment of neonatal hypoxic-ischemic encephalopathy based on combined early targeted nursing interventions the NBNA score can improve children's mental development index and psychomotor development index, to reduce cerebral palsy, mental retardation and epilepsy and other sequelae.

  5. 低场MRI和多层螺旋CT对新生儿缺氧缺血性脑病的诊断价值%Value of Low-Field MRI and MSCT in Diagnosing Neonatal Hypoxic Ischemic Encephalopatly

    Institute of Scientific and Technical Information of China (English)

    梁秀梅

    2012-01-01

    Objective To analyze CT and MRI signs of neonatal hypoxic ischemic encephalopatly (HIE) and probe into the value of low - field MRI and multislice spiral CT( MSCT) in early diagnosis of HIE. Methods The CT and MRI traits of 26 patients, including 10 prematures and 16 term infants with HIE, were analyzed retrospectively. Results Edema of white matter, watershed region cerebral infarction and cerebral hemorrhage and/or intraventricular hemorrhage were found in 10 prematures. Subcortical edema, watershed region cerebral infarction and intractanial hemorrhage were found in 16 term infants. Out of the 17 CT cases, 14 cases featured the diagnosis results consistent with their clinical diagnosis, indicating a coincidence rate of 82. 35%. For the 13 MRI cases, 11 cases had the diagnosis results identical to their clinical diagnosis, showing a coincidence rate of 92. 31%.Conclusions Both MSCT and MRI are sensitive to cerebral edema, infarction and hemorrhage, and CT and MRI should be selected in terms of pathogenetic condition and course of disease to achieve early diagnosis.%目的 分析新生儿缺氧缺血性脑病(neonatal hypoxic-ischemic encephalopathy,HIE)的CT、MRI征象,探讨低场MRI和多层螺旋CT对HIE的早期诊断价值.方法 收集2009年12月至2011年8月,临床证实并行颅脑CT或/和MRI检查为HIE的患者26例,男性20例,女性6例;年龄30 min至17d,平均3.12d(≤1d者3例、1~5 d者21例),回顾性分析CT检查17例和MRI检查13例(4例患儿同时进行了CT、MRI检查)资料.结果 10例早产儿的脑部损伤以脑室旁白质水肿、分水岭性脑梗死、脑实质或/和脑室内出血为主,16例足月儿脑部损伤以大脑皮层下旁矢状区白质水肿、分水岭区脑梗死、颅内脑外出血为主;17例CT诊断有14例与临床诊断相符合,符合率82.35%,13例MRI诊断有12例与临床诊断相符合,符合率92.31%.结论 多层螺旋CT及低场MRI检查对HIE致脑部损伤包括脑水肿、脑梗死

  6. Clinical and Diagnostic Value of CT in Neonates with Hypoxic Ischemic Encephalopathy%新生儿缺氧缺血性脑病的临床与CT诊断价值

    Institute of Scientific and Technical Information of China (English)

    张宗权; 刘文军; 刘克平; 冯黎明

    2016-01-01

    Objective To observe the change of neonatal hypoxic ischemic encephalopathy (HIE) of CT and diagnostic value. Methods The clinical and MSCT imaging data of 45 cases with HIE were retrospectively analyzed. Results CT could clearly show the brain parenchymal changes caused by brain ischemia and hypoxia, range and degree of involvement, and intracranial hemorrhage, deformity. Conclusion The use of CT technology, could signiifcantly improve the clinical accuracy of HIE diagnosis, and would have important diagnostic values on cerebral edema, infarction, intracranial hemorrhage and parts of the scope and type, and clinical signiifcance on the prognosis of HIE.%目的:探讨新生儿缺氧缺血性脑病的CT改变及诊断价值。方法对45例缺氧缺血性脑病(HIE)的临床及CT影像资料进行回顾分析。结果 CT能够清楚显示颅脑缺氧缺血后引起的脑实质改变,病变累及范围及程度,以及颅内出血、畸形等。结论运用CT检查技术,能够明显提高临床对HIE诊断的准确率,并对脑水肿、梗死及颅内出血的部位、范围及类型都具有明确的诊断价值,对HIE预后有着十分重要的临床意义。

  7. A clinical and cranial CT analysis of neonatal hypoxic-ischemic encephalopathy%新生儿缺氧缺血性脑病临床表现和头颅CT对比分析

    Institute of Scientific and Technical Information of China (English)

    陶松雪; 潘家华

    2011-01-01

    目的 探讨新生儿缺氧缺血性脑病(HIE)临床与CT之间的关系.方法 将HIE的临床表现与CT表现进行对比分析,统计学方法为Kappa检验,秩和检验.结果 新生儿HIE的临床分度与CT分度存在一致性,早产儿与足月儿HIE分度比较差异无统计学意义,低出生体重儿与正常体重儿HIE的CT分度比较差异有统计学意义.HIE程度越重,脑出血的发生率越高.结论 HIE临床分度和CT分度具有一定的一致性,低出生体重儿与正常体重儿比较通常病情较重,临床分度重者更易并发颅内出血.%Aim To explore the relationship between clinical symptom and CT display of neonatal hypoxic-ischemic encephalopathy.Methods CT and clinical classifications of HIE were contrasted by kappa test and rank sum test. Results CT degrees were very similar to clinical degrees. There was no obvious difference between premature infant category and that of mature infant. There was an obvious difference of HIE CT categories between low-birth-weight infants and normal-weight infants. Incidence of intracranial hemorrhage was higher in serious cases of HIE. Conclusion CT degrees of HIE were very similar to clinical degrees. Clinical degrees of low-birth-weight infants were more serious than that of normal-weight infants. Intracranial hemorrhage was more likely to happen in serious cases.

  8. 足月新生儿缺氧缺血性脑病的脑部磁共振成像随访及预后评估%MRI evaluation of prognosis for hypoxic ischemic encephalopathy in term neonates

    Institute of Scientific and Technical Information of China (English)

    吴君; 徐睿霞; 尹桂秀

    2013-01-01

    Objectives To explore the characteristics and value of magnetic resonance imaging (MRI) in predicting prognosis of hypoxic ischemic encephalopathy (HIE) in neonatal period, at 4 months and 4 years old. Methods Twenty-four patients with HIE were examined by MRI. Their MRI results in the neonatal period, at month 4 and year 4 and neurological functions at year 4 were compared. Results Periventricular signal alterations and deep gray matter involvement were common in HIE neonates. The neonates with deep gray matter involvement usually had neurological malfunction and poor prognosis. The patients with encephalomalacia and periventricular leukomalacia at 4 months and 4 years old also had poor prognosis. The abnormal MRI ifndings in HIE children at 4 month and 4 year old predicted the occurrence of neurological malfunction. Con-clusions The MRI of infant at 4 months old is important in prediction of neurological malfunction and provides guidance of clinical intervention for children with HIE.%目的:探讨足月新生儿缺氧缺血性脑病(HIE)患儿在新生儿期、出生后4个月和4岁时的脑部磁共振成像(MRI)表现及其与预后的关系。方法对24例HIE患儿进行定期MRI检查;分析和比较新生儿期、出生后4个月和4年的MRI检查结果,及患儿4岁时的神经功能。结果 HIE患儿新生儿期MRI常表现为脑室周围白质信号改变和深部灰质受累。新生儿期深部灰质受累患儿,常表现为神经功能不良,预后较差;复查MRI表现为脑软化和脑室周围白质软化患儿的预后也较差。出生后4个月和4年时的MRI检查预测HIE患儿神经功能的阳性预测值高。结论 HIE患儿出生4个月行MRI检查较为重要,可预测患儿今后神经功能结果,指导临床干预。

  9. Analysis of CT Diagnostic Features and Clinical Manifestations of Neonatal Hypoxic Ischemic Encephalopathy%新生儿缺氧缺血性脑病CT诊断特点与临床表现分析

    Institute of Scientific and Technical Information of China (English)

    胡龙非; 陈光真; 姜燕; 武宝华

    2016-01-01

    Objective To explore the CT diagnostic features and clinical manifestations of neonatal hypoxic ischemic encephalopathy.Methods 37 cases of newborns with hypoxic ischemic encephalopathy who were born in the obstetrical department of our hospital during January 2014 to July 2015 were taken as the research objects. All the newborns received CT examination in postnatal 2 weeks. The results of clinical graduation were compared with the results of CT graduation and the CT imaging features of HIE were summarized.Results Among the 37 cases, the results of clinical graduation were mild in 11 cases, moderate in 21 cases and severe in 5 cases. The results of CT graduation were normal in 2 cases, mild in 9 cases, moderate in 20 cases and severe in 7 cases. The diagnostic accuracy of mild, moderate and severe were 77.8% (7/9), 80.0% (16/20) and 71.4% (5/7), respectively. CT manifested as diffused distribution of low density lesions in cerebral hemisphere white matter. CT value was between 16 - 20Hu and the boundaries were blurred.Conclusion The clinical manifestations of HIE are hyperexcitability, active primitive reflex, changes of muscular tension, drowsiness, loss of normal wake-sleep cycle and miosis, et al. CT examination can clearly identify the location and extent of HIE lesions and the condition of intracranial hemorrhage. It can grasp the severity of the disease to evaluate the pathogenetic condition. Through follow-up, the prognosis and outcome are evaluated, which plays an important role in clinical diagnosis and treatment.%目的:探析新生儿缺氧缺血性脑病的CT诊断特点及临床表现。方法以我院产科2014年1月-2015年7月出生37例缺氧缺血性脑病新生儿进行研究,均于患儿出生2周内行CT检查。将临床分度结果与CT分度结果进行比较,总结HIE的CT征象特点。结果37例患儿中,临床分度结果为11例轻度、21例中度、5例重度,CT分度结果为2例正常、9例轻度、20例中度、7例

  10. Monitoring of neurological parameters in newborns with hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Đinđić Jasmina

    2006-01-01

    Full Text Available Asphyxia i a condition caused by lack of oxygen in tissues and organs. The basic pathogenic mechanisms of asphyxia are: 1hypoxemia, 2 ischemia. The effects of perinatal asphyxia on the brain of a neonatal baby are critical in development of hypoxic-ischemic encephalopathy. The diagnosis of hypoxic-ischemic encephalopathy is based on clinical data including course of pregnancy and delivery (Apgar score and especially on the neurological status of the newborn (consciousness, tonus, convulsions, reflexes, vegetative functions, etc. and it can be confirmed by biochemical analysis and neurological examinations. The aim of this paper is to determine the importance of prenatal and perinatal risk factors for hypoxic-ischemic encephalopathy, as well as their effects on the development of neurological complications and further neurological problems. The research included 148 newborn infants born in the period from January 1, 1996 to January 1, 1999, with gestational age of 27 to 42 weeks, with hypoxic ischemic lesions of the central nervosus system. The control group included 58 children of the same age and the same gestation, with generalized hypotonia ("floppy infant" but without any signs of hypoxic ischemic lesions of the central nervous system. In the group of examined newborn infants with hypoxic ischemic lesions, from 149 children 1 (0.67% died, 87 (53.89% had normal findings, whereas the handicap was established in 61 (40.94%. Perinatal asphyxia affects the fetus and newborn infants not by individual factors, but with at least three or four associated factors. The disorders caused by asphyxia are in inverse proportion to the duration and intensity of hypoxic insults and the gestational age of the newborn. .

  11. Early Predictors of Neurodevelopmental Adverse Outcome in Term Infants with Postasphyxial Hypoxic Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Khaled Abdulqawi

    2011-11-01

    Full Text Available Background: Neonatal brain injury due to intrapartum asphyxia is an important cause of cerebral palsy, mental retardation, and epilepsy. In developing countries, the incidence of post asphyxial neurological damage is particularly high. Despite advances in perinatal care over the past three decades, the incidence of cerebral palsy attributed to birth asphyxia has not changed.Objectives: To predict the outcome of postasphyxial hypoxic ischemic encephalopathy early in the neonatal period, for proper counseling of the parents, to get benefit in clinical practice and to select patients who will benefit from recent management strategies.Study Design: This study was conducted on 63 asphyxiated full term newborn infants who developed Hypoxic-Ischemic Encephalopathy (HIE admitted at Neonatal Intensive Care Unit of Al-Jedaany Hospital, Jeddah, Kingdom Saudi Arabia in the period from May 2006 to January 2008. They were classified according to Sarnat and Sarrnat staging of HIE into the following: 16 with stage I, HIE (Group I, 19 with stage II, HIE (Group II and 20 with stage III, HIE (Group III. Twenty full term healthy newborn infants, age and weight-matched, were served as a control. All infants were subjected to the following tests: cord blood gases at birth, and Urine sample for testing urinary lactate / creatinine ratio. Also a real-time cranial ultrasonography was done for infants who had HIE. Follow up of the cases was done by the followings: A neurodevelopmental clinical evaluation every three months till the age of one year of life was done for the cases and control infants. An Electroencephalogram (EEG and auditory brainstem evoked response (ABR were done at the age of three months and a second ABR at the age of six months for cases with abnormal previous ABR. Results: Group III (stage III, HIE has significantly increased initial, maximum and day 7 HIE scores (16.4 ± 3.1, 18.15 ± 2.79 and 13 ± 5.79 respectively compared with group I&II. Also

  12. Investigation of the effect and mechanism of hyperbaric oxygenation therapy on neonatal hypoxic-ischemic encepha-lopathy with SPECT%新生儿缺氧缺血脑病高压氧治疗SPECT研究

    Institute of Scientific and Technical Information of China (English)

    贾少微; 易治; 廖建湘

    2001-01-01

    目的应用SPECT评价新生儿缺氧缺血脑病HBO的疗效,探讨治疗机理.方法研究对象34例新生儿,正常新生儿组3例,HBO组HIE患儿20例,对照组HIE患儿11例.2组HIE患儿在治疗前和治疗后各接受一次SPECT检查.结果治疗前SPECT示31例HIE患儿有46个大小不同的局灶性血流灌注和功能缺损或低下区.HBO组HIE患儿经1~2个疗程的HBO治疗后,脑内原有局灶性血流灌注和功能缺损或低下区缩小或消失.对照组的HIE患儿虽也有一定好转,但恢复程度不及HBO组,2组之间的疗效差异显著(P<0.01).结论 HBO治疗HIE患儿疗效显著,主要是通过增加脑组织增加局部脑血流灌注和含氧量,来改善脑细胞的缺氧状态,激发脑细胞的活性,促进损伤脑细胞的修复.%Objective To evaluate the effect of HBO on neonatal hypoxic-ischemic encephalopathy with SPECT, and to explore the mechanisms.Methods The research subjects were totally 34 newborn babies, including 3 normal neonates. The group treated with HBO included 20 babies with HIE, and the control group contained 11 HIE babies. All babies in both groups received SPECT exams before and after the treatments. Results SPECT before treatment showed 46 foci of low perfusion and functional defect or insufficiencies in 31 HIE babies. SPECT after 1-2 period of treatments of HBO therapy in HIE babies showed disappeared or reduced low perfusion and functional defect or insufficiency in the brains. The HIE babies in the control group showed improvement with less degree than HBO treated babies. There were significant differences (P<0.01) between two groups. Conclusion The effect of HBO on HIE babies were prominent. The treatment can improve the hypoxic status of brain cell through increase the regional cerebral blood flow perfusion and oxygen content of the brain tissue, then provoked the brain cells activities, and at last, enhance the repair of the injured brain cells.

  13. 脑活素治疗新生儿缺氧缺血性脑病100例临床观察治疗与护理%100 Cases of Clinical Treatment and Nursing of Cerebrolysin in Treatment of Hypoxic-ischemic Encephalopathy in Neonate

    Institute of Scientific and Technical Information of China (English)

    孟宪英

    2013-01-01

    Objective:To observe the efficacy and explore nursing intervention of cerebrolysin in treatment of hypoxic-ischemic encephalopathy in neonate. Methods:100 neonates were treated by cerebrolysin, and cooperated with general nursing, intensive care, maintain heat and control liquid, etc. Results:79 cases were marked effect, 20 cases were improved, and 1 case was invalid. The total effective rate was 99%. Conclusion:Cerebrolysin in treatment of hypoxic-ischemic encephalopathy in neonate has exact efficacy, and it has obvious toxic and side effect. It is worthy of popularization.%  目的:观察脑活素治疗新生儿缺氧缺血性脑病的疗效及探讨其护理措施。方法:100例患儿均应用脑活素进行治疗,并配合一般护理、重症监护、维持热量和控制液量等护理措施。结果:显效79例,好转20例,无效1例,总有效率99%。结论:脑活素治疗新生儿缺氧缺血性脑病疗效确切,无明显毒副作用,值得临床推广。

  14. Meta-analysis of clinical efficacy and safety of hypothermia for neonates with hypoxic ischemic encephalopathy%亚低温治疗新生儿缺氧缺血性脑病临床效果的Meta分析

    Institute of Scientific and Technical Information of China (English)

    孙金峤; 陈燕琳; 周文浩

    2009-01-01

    encephalopathy (HIE) newborns who were treated with mild hypothermia using meta-analysis method. Methods The standard search strategy of the Neonatal Review Group as outlined in the Cochrane Library ( Issue 2, 2007) was used. RCTs evaluating therapeutic hypothermia in newborns with hypoxic ischemic eneephalopathy were identified by searching the PubMed, EMBASE, Ovid, Springer and CNKI database with the terms "Infant or neonate and asphyxia or hypoxie-ischemic encephalopathy and hypothermia". No language restrictions were applied. RCTs comparing the usage of therapeutic hypothermia with standard care in eneephalopathic newborn infants with evidence of peripartum asphyxia and without recognizable major congenital anomalie s wereincluded. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and other indicators of neurodevelopmental outcome. Two review authors independently selected, assessed the quality of the included studies and extracted data. Authors were contacted for further information. Meta-analysis was performed using relative risk and risk difference for dichotomous data with 95% confidence intervals. Results Nine trials involving 785 neonates were included in the analysis. Cooling techniques and the definition and severity of neuredevelopmental disability differed among studies. Overall, there was evidence of a significant effect of therapeutic hypothermia on the outcomes of mortality ( RR = 0.73, 95% CI: 0. 58 - 0.91 ) and neuredevelopmental disability at 18 to 22 months ( RR = 0. 70,95% CI : 0. 53 - 0. 92). Moreover, hypothermia significantly decreased the incidence of disabling cerebral palsy (RR =0. 72, 95% CI: 0. 53 -0.98).However, hypothermia had no effect on developmental delay ( BR = O. 73, 95% CI : 0.53 - 0.99), blindness ( RR = 0.57, 95% CI: 0.30 - 1.08) and hearing loss ( RR = 1.52, 95% CI: 0.71 - 3.25 ) in newborns with HIE. Adverse effects included benign sinus bradycardia

  15. Application of spiral CT examination in neonatal hypoxic-ischemic encephalopathy%螺旋CT检查在新生儿缺血缺氧性脑病中的应用

    Institute of Scientific and Technical Information of China (English)

    刘学荣; 贺杰

    2013-01-01

    目的探讨新生儿缺血缺氧性脑病(hypoxie-ischemic enceph-alopathy,HIE)的螺旋CT表现特点及其应用价值。方法回顾性分析60例HIE的CT表现,依据病灶范围观察轻度至重度HIE的CT表现特征。结果60例临床诊断为HIE的患者中54例有异常CT表现,6例未见异常。51例病变CT值在10~18HU之间,3例病变CT值在18~21HU之间。脑实质出血1例,蛛网膜下腔出血者4例。复查外部性脑积水4例,脑软化5例、脑萎缩1例。结论螺旋CT检查对HIE的诊断具有较高的准确性,可对临床的治疗及预后提供真实而客观的依据%Objective To investigate the spiral CT performance features of neonatal hypoxic-ischemic encephalopathy (HIE) and its application value. Methods The CT performance of 60 patients with HIE was analyzed retrospectively and the CT performance features of mild to severe HIE were observed according to the lesion range. Results Of the 60 patients clinically diagnosed with HIE, 54 patients had abnormal CT performance and 6 patients did not. Fifty-one patients had a CT value ranging from 18-21HU. Brain parenchyma bleeding was found in 1 patient and subarachnoid hemorrhage was found in 4 patients. Reexamination found external hydrocephalus in 4 patients, encephalomalacia in 5 patients and cerebral atrophy in 1 patient. Conclusion Spiral CT examination is accurate in the diagnosis of HIE and can provide true and objective basis for clinical treatment and prognosis.

  16. 缺氧缺血性脑病新生儿食欲素、瘦素水平及意义%Serum levels of oexin and leptin and their significance in neonates with hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    刘桂玲; 赵丽娜; 任常军; 王娜

    2012-01-01

    目的 探讨缺氧缺血性脑病(HIE)对新生儿血清食欲素水平的影响,及食欲素与瘦索之间的相关性.方法HIE新生儿61例,轻度HIE 30例、中度HIE 20例、重度HIE 11例,正常对照新生儿31例,采用放射免疫分析法(RIA)测定新生儿生后24、72 h的血清食欲素、瘦素水平,并分析食欲素与瘦素之间的相关性.结果轻、中、重度HIE新生儿以及正常对照新生儿,生后24、72 h的血清食欲素水平差异有统计学意义(F=3.746、3.262,P均<0.05),轻、中、重度HIE新生儿生后24、72 h的食欲素水平均高于正常对照组,且随HIE程度加重逐渐升高.轻、中、重度HIE新生儿以及正常对照新生儿,生后24,72 h的血清瘦索水平的差异均有统计学意义(F=3.534,2.821,P均<0.05),轻、中、重度HIE新生儿生后24、72 h的瘦素水平均低于正常对照组,且随HIE程度加重逐渐性降低.HIE新生儿的血清食欲素水平与瘦素水平于24、72 h均呈负相关(r=-0.293、-0.301,P均<0.05).结论HIE新生儿食欲素、瘦素水平与HIE的临床进展相关.%Objective To investigate the effect of hypoxic-ischemic encephalopathy (HIE) on orexin level, and the correlation between serum orexin level and leptin level. Methods A total of 61 neonates with HIE were divided into three groups, mild HIE group (n=3Q), moderate HIE group (n=20), serious HIE group (n=11) and 31 healthy neonates were assigned in control group. The serum concentrations of orexin and leptin were measured by radioimnmnoassay (RIA), and the relationship between the orexin and leptin levels was analyzed. Results Orexin concentrations at 24 hours and 72 hours after birth in neonates with HIE were higher compared with normal control group, and the orexin level increased gradually with the grades of HIE. The difference was statistically significant among groups (F=3.746, 3.262, P<0.05). Leptin concentrations at 24 hours and 72 hours a tier birth in neonates with HIE were lower compared

  17. Short-time effect of selective head cooling on neonatal hypoxic-ischemic encephalopathy%亚低温治疗新生儿缺氧缺血性脑损伤的近期疗效分析

    Institute of Scientific and Technical Information of China (English)

    易彬; 刘东海

    2010-01-01

    Objective To assess short-time effect of selective head cooling on neonatal hypoxic-ischemic encephalopathy induced by perinatal asphyxia. Methods Twenty-three infants of moderate/severe hypoxic ischemic encephalopathy (HIE) were divided into treatment group ( 14 cases) and control group (9 cases). The head hypothermia in the treatment group [rectal temperature ( 34. 0 ~ 35.0) ℃, nasopharyngeal temperature (34. 0 ± 0. 5 ) ℃]was induced by circulating water cooling cap for up to 72 h. Control group were treated routinely. All newborns were monitored and analyzed for blood pressure, heart rate, neurological function. Neonatal behavioral neurological assessment (NBNA) was conducted for assessment of neurobehavioral development on day 28 after birth. Results Treatment group showed slower hear rate as nasopharyngeal temperature decreased and there was significant difference as compared with the control group ( P < 0.05 ). Apnea and arrhythmia were not found in either group. As compared with the control group, treatment group showed better results in seizure incidence, recovery of neonatal reflex( embracing reflection, sucking reflex and grasp reflex), and improvement of limb muscle tension. The NBNA score on day 28 was much higher in hypothermia group(35.00 ± 1.41 ) than that of control group(30. 67 ± 1.58) and there was significant difference (P < 0.05). Conclusion Selective head cooling is safe for newborns with moderate/severe HIE if the nasopharyngeal temperature maintains at (34 :± 0. 5 ) ℃, rectal temperature at 34 ~ 35 ℃. Selective head cooling can effectively improve the short-term nervous symptoms and the neurobehavioral score,but the long-term efficacy remains to be further studied.%目的 评价亚低温治疗对于围产期窒息后新生儿缺氧缺血性脑损伤的短期疗效.方法 将23例中重度缺氧缺血性脑病(HIE)新生儿分为治疗组(14例)和对照组(9例).治疗组采用选择性头部降温方法,使新生儿直

  18. Expression of Clock genes in the pineal glands of newborn rats with hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Bin Sun; Xing Feng; Xin Ding; Li Bao; Yongfu Li; Jun He; Meifang Jin

    2012-01-01

    Clock genes are involved in circadian rhythm regulation,and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal.This study aimed to determine the expression of the clock genes Clock and Bmall,in the pineal gland of rats with hypoxic-ischemic brain damage.Results showed that levels of Clock mRNA were not significantly changed within 48 hours after cerebral hypoxia and ischemia.Expression levels of CLOCK and BMAL1 protein were significantly higher after 48 hours.The levels of Bmall mRNA reached a peak at 36 hours,but were significantly reduced at 48 hours.Experimental findings indicate that Clock and Bmall genes were indeed expressed in the pineal glands of neonatal rats.At the initial stage (within 36 hours) of hypoxic-ischemic brain damage,only slight changes in the expression levels of these two genes were detected,followed by significant changes at 36 48 hours.These changes may be associated with circadian rhythm disorder induced by hypoxic-ischemic brain damage.

  19. 缺氧缺血性脑病新生儿纳洛酮治疗前后血浆β-内啡肽的改变%Alteration of serum beta-endorphin before and after the treatment of naloxone in neonates with hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    唐兰芬; 陈铭珍; 孟琼; 苏赞彩; 揭育丽

    2004-01-01

    BACKGROUND:Cerebral hypoxic ischemia could activate serials of biologic reactions and induce the changes in the expressions of multiple substances in neurons,which thereby further mediates injuries in brain tissues. There are few researches at present regarding to whether β-endorphin participates in the therapeutic process of naloxone in the treatment of neonatal hypoxic-ischemic encephalopathy(HIE). OBJECTIVE:To observe the alteration of serum beta-endorphin(β-endorphin) before and after the treatment of naloxone for the discussion of the protective effects of naloxone in neonatal HIE. DESIGN:A non-randomised controlled trial based on diagnosis. SETTING and PARTICIPANTS:A total of 38 mature infants with HIE were selected into HIE group from the department of neonate of Guangdong Medical University Affiliated Hospital during October 1996 to October 1997 including 26 male and 12 female cases.25 normal mature neonates were selected into normal group from the Infant Room of Obstetrical Department, Affiliated Hospital of Guangdong Medical College,including 15 male and 10 male subjects. INTERVENTIONS:Serum β-endorphin was detected within 72 hours after born(acute stage,before therapy) and at 7 to 10 days(recovery period) respectively in 38 HIE neonates, and within 72 hours after born in 25 normal neonates as well.38 HIE neonates were randomly allocated into naloxone group and non-naloxone group for the observation of the clinical therapeutic effectiveness and the alteration of serum β-endorphin before and after therapy.Main outcome measures: serum content of β-endorphin in neonates of each group. RESULTS:Serum β-endorphin significantly elevated at acute stage in 38 HIE neonates compared with that of 25 normal neonates[(620.35± 140.92) ng/L,(373.70± 146.69) ng/L,t=6.16,P0.05].There was no significance in the comparison of differences of serum β-endorphin before and after therapy between naloxone group and non-naloxone group; however,naloxone could reduce the

  20. Effect comparison of citicoline combined with ganglioside in the treatment of neurobehavior in neonatal hypoxic ischemic encephalopathy%胞二磷胆碱联合神经节苷脂治疗新生儿缺氧缺血性脑病神经行为的效果对比

    Institute of Scientific and Technical Information of China (English)

    岑惠玲; 赖春华

    2015-01-01

    Objective To investigate the effect of citicoline combined with ganglioside in the treatment of neurobehavior in neonatal hypoxic ischemic encephalopathy. Methods A total of 40 children with neonatal hypoxic ischemic encephalopathy as study subjects were randomly divided into experimental group and control group, with 20 cases in each group. The control group received ganglioside for treatment, and the experimental group received additional citicoline. Comparisons were made on primitive reflex, general state, improvement in neonatal behavioral neurological assessment (NBNA), and clinical effect of the two groups. Results The control group had much lower total effective rate than the experimental group, and the difference had statistical significance (P<0.05). After treatment, the experimental group had better primitive reflex, general state, and NBNA score than the control group, and the difference had statistical significance (P<0.05). Conclusion Comparing with single ganglioside treatment, combination of citicoline and ganglioside in treating neonatal hypoxic ischemic encephalopathy has better effect and more obvious improvement in neurobehavior.%目的:探讨胞二磷胆碱联合神经节苷脂治疗新生儿缺氧缺血性脑病神经行为的效果。方法40例新生儿缺氧缺血性脑病患儿作为研究对象,随机分为实验组和对照组,每组20例。对照组采用神经节苷脂治疗,实验组在对照组基础上加用胞二磷胆碱治疗,比较两组患儿原始反射、一般状态、新生儿神经行为评分(NBNA)改善情况和临床治疗效果。结果对照组总有效率显著低于实验组,差异有统计学意义(P<0.05)。经过治疗后实验组患儿原始反射、一般状态和NBNA评分均高于对照组,差异有统计学意义(P<0.05)。结论新生儿缺氧缺血性脑病的治疗中,与单用神经节苷脂相比,加用胞二磷胆碱后的治疗效果更佳,对神经行为的改善作用更为显著。

  1. The correlation between prenatal fever and neonatal hypoxic-ischemic Encephalopathy%产前发热与新生儿缺氧缺血性脑病的关系

    Institute of Scientific and Technical Information of China (English)

    卢钺成

    2012-01-01

    Objective To investigate the correlation between prenatal fever and neonatal hypoxic - ischemic en-cephalopathy ( HIE ). Methods Maternal fever and other data during pregnancy were recorded from 12 845 pregnant females. Retrospective cohort study was performed, while 897 cases with maternal fever over 38. 5℃ and 571 cases with maternal fever lower than 38. 5℃ were assigned into high fever group and low fever group, respectively. Meanwhile, 816 cases with maternal fever lasting less than 24 h and 652 cases with maternal fever lasting longer than 24 h were assigned into short time group and long time group, respectively. Furthermore, 900 matched cases without maternal fever were selected as control group. Logistic regression model was adopted in the analysis. Results The incidence of maternal fever during pregnancies was 11. 4%. The incidences of HIE in high fever group, low fever group, and long time group, were significantly higher than that in control group, so were in logistic regression model adjusted with confounders. Conclusion Prenatal fever during pregnancy is a human teratogen. We should actively prevent prenatal fever, and select scientific and rational treatment for the fever as soon as possible to reduce the risk of HIE.%目的 探讨产前发热对新生儿缺氧缺血性脑病(HIE)发生的影响.方法 分析12 845例在妇产科分娩的产妇的孕期发热和一般情况资料,据产前1周体温38.5℃和持续时间24 h为界,将1 468例产前1周内有发热史的产妇分为高热组和低热组、短时间组和长时间组,并从同期孕期无发热史的产妇中抽取900例作为对照组.采用logistic回归分析,分析产前发热与新生儿HIE之间的相关性.结果 产前1周有发热史的产妇占产妇总数的11.4%;与对照组相比,低热组、高热组和长时间组的新生儿HIE的发生率均显著升高,即使在控制了潜在混杂因素之后差异仍有统计学意义;但未发现该病的发生与持

  2. 早期综合干预防治新生儿缺氧缺血性脑病后遗症的临床效果分析%Effect of early intervention in prevention and treatment of neonatal hypoxic-ischemic encephalopathy sequelae

    Institute of Scientific and Technical Information of China (English)

    罗佩施

    2012-01-01

    Objective To investigate the effect of early intervention on neonatal hypoxic-ischemic encephalopathy sequelae.Methods 42 children with neonatal hypoxic-ischemic encephalopathy who had been hospitalized during the period of July 2008 to September 2011 were randomly divided into two groups.The control group received conventional therapy,while the study group received early intervention in addition to conventional treatment.Mental development indexes and psychomotor development indexes were observed and then compared between the two groups three and six months after intervention.Results The general information did not differed significantly between the two groups ( P> 0.05 ).Mental development indexes and psychomotor development indexes were better in the study group than in the control group ( P<0.05 ).Conclusions Early comprehensive intervention for neonatal hypoxic-ischemic encephalopathy is beneficial in reducing sequelae and improving intellectual,mental and motor development in children.%目的 探讨早期综合干预对新生儿缺氧缺血性脑病后遗症的效果.方法 将2008年7月至2011年9月收治的新生儿缺氧缺血性脑病患儿42例随机分为两组,对照组给予常规治疗,实验组给予早期综合干预联合常规治疗,观察对比两组患儿干预3个月、6个月的智力发育指数和心理运动发育指数.结果 两组患儿的一般资料比较差异无显著性,P>0.05;实验组3个月、6个月的智力发育指数和心理运动发育指数高于对照组患者,P< 0.05.结论 对新生儿缺氧缺血性脑病患儿给予早期综合干预有助于减少其后遗症,提高患儿智力、心理和运动发育.

  3. Neural stem cells may be uniquely suited for combined gene therapy and cell replacement: Evidence from engraftment of Neurotrophin-3-expressing stem cells in hypoxic-ischemic brain injury.

    Science.gov (United States)

    Park, Kook In; Himes, B Timothy; Stieg, Philip E; Tessler, Alan; Fischer, Itzhak; Snyder, Evan Y

    2006-05-01

    Previously, we reported that, when clonal neural stem cells (NSCs) were transplanted into brains of postnatal mice subjected to unilateral hypoxic-ischemic (HI) injury (optimally 3-7 days following infarction), donor-derived cells homed preferentially (from even distant locations) to and integrated extensively within the large ischemic areas that spanned the hemisphere. A subpopulation of NSCs and host cells, particularly in the penumbra, "shifted" their differentiation towards neurons and oligodendrocytes, the cell types typically damaged following asphyxia and least likely to regenerate spontaneously and in sufficient quantity in the "post-developmental" CNS. That no neurons and few oligodendrocytes were generated from the NSCs in intact postnatal cortex suggested that novel signals are transiently elaborated following HI to which NSCs might respond. The proportion of "replacement" neurons was approximately 5%. Neurotrophin-3 (NT-3) is known to play a role in inducing neuronal differentiation during development and perhaps following injury. We demonstrated that NSCs express functional TrkC receptors. Furthermore, the donor cells continued to express a foreign reporter transgene robustly within the damaged brain. Therefore, it appeared feasible that neuronal differentiation of exogenous NSCs (as well as endogenous progenitors) might be enhanced if donor NSCs were engineered prior to transplantation to (over)express a bioactive gene such as NT-3. A subclone of NSCs transduced with a retrovirus encoding NT-3 (yielding >90% neurons in vitro) was implanted into unilaterally asphyxiated postnatal day 7 mouse brain (emulating one of the common causes of cerebral palsy). The subclone expressed NT-3 efficiently in vivo. The proportion of NSC-derived neurons increased to approximately 20% in the infarction cavity and >80% in the penumbra. The neurons variously differentiated further into cholinergic, GABAergic, or glutamatergic subtypes, appropriate to the cortex. Donor

  4. The observation of hypoxic-ischemic encephalopathy in the neonates with color Doppler energy image%彩色多普勒能量图对新生儿缺氧缺血性脑病的观察

    Institute of Scientific and Technical Information of China (English)

    周德江; 张灌生; 童良辉; 赵芬

    2000-01-01

    目的 探讨新生儿缺氧缺血性脑病(HIE)脑血流的变化规律.方法 应用彩色多普勒能量图(a)E)对34例HIE患儿及25例正常新生儿的大脑内侧面上部边缘血管网及脑动脉血流参数进行了对照观察.结果 在生后24 h内,HIE患儿脑血流灌注减少,大脑内侧面上部边缘小动脉血流直径缩小,网络稀疏,甚至难以显示;脑动脉流速较正常显著下降,阻力指数显著增高(P<0.01).之后,除了2例重度患儿持续"少灌注"状态而死亡外,其余患儿脑血流灌注开始增加,大脑内侧面上部边缘小动脉血流直径扩大,血管网络逐渐恢复,脑动脉流速增加,阻力指数下降.从24~96 h,中重度患儿中有9例呈现"多灌注"损伤表现,患儿病情及脑水肿声像图征象均加重,边缘小动脉血流直径及各流速参数亦大于正常(P<0.05).其余患JL~tl未观察到"多灌注"损伤表现.结论 用CDE监测HIE患儿大脑内侧面上部边缘血管网及脑动脉血流参数,对判断"少灌注"损伤有重要价值.对是否存在"多灌注"损伤,尚需结合临床表现及脑声像图综合判断,才能得出正确结论.%Objective To study the cerebral blood flow changes of neonates with hypoxic-ischemic encephalopathy(HIE).Methods The arteriosum fete of upper border of medial surface of the cerebral hemisphere(ARUMS)and the blood flow parameters of cerebral arteries(CA)in 34 neonates with HIE and 25 health neonates were observed and compared by color Doppler energy image(CDE).Results The cerebral perfusion of neonates with HIE were decreased within 24 h after birth.the blood flow diameters of arteriolae of ARUMS were redUCed,and the ARUMS were few and scattered,even it were hardly showed;The velocity of CA wasdecreased and resistance index(RI)WaS significantly rised compared with health neonates(P<0.01). Afterwards,except for 2 severe cases,who were in continuous hypoperfusion and died,in the others,the cerebral perfusion started to be increased

  5. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment.

    Science.gov (United States)

    Li, Xianchao; Hou, Wensheng; Wu, Xiaoying; Jiang, Wei; Chen, Haiyan; Xiao, Nong; Zhou, Ping

    2014-02-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600-1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2), an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 10(6) bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2) for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage.

  6. 全身亚低温治疗新生儿缺氧缺血性脑病的临床观察%Clinical Observation of Systemic Hypothermia in Neonates with Hypoxic-ischemic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    王月玲

    2014-01-01

    Objective To investigate the clinical efficacy of mild hypothermia therapy for neonatal hypoxic ischemic encephalopathy in full-term neonates with severe HIE. Methods 37cases were randomly divided into two groups, the mild hypothermia group 19 cases, control group 18 cases. Two groups of children with birth weight, gestational age, there was no significant difference in clinical index. Treatment group was treated with mild hypothermia during 6 h after birth, maintain the nasopharyngeal temperature at 33-34 ℃, rectal temperature maintained at 33-34 ℃, persistent 72 h after rewarming, other therapies of the two groups were the same. The two groups underwent ECG, blood pressure, transcutaneous oxygen saturation, nasopharyngeal temperature, rectal temperature continuous monitoring. Detection of blood electrolytes, blood glucose, liver and kidney function, blood gas analysis, platelet, and the neonatal behavioral neurological assessment (NBNA)to evaluate the development of nerve behavior. Results No bleeding, severe infection and death in both two groups. Mild hypothermia therapy during the heart rate decreased by an average of 30 times/min, blood pressure and respiration did not change significantly, without arrhythmia and pulmonary hypertension associated with hypothermia found. The blood sodium, potassium, calcium in low temperature before and after treatment, and the control group showed no significant difference. Treatment of HIE children had metabolic acidosis, some children with acute renal dysfunction, are corrected gradually after treatment. Two groups of children born after 28 days of NBNA score, treatment group was obviously higher than that of the control group, P<0.01. Conclusion No serious adverse reaction of systemic hypothermia on neonatal HIE, to prevent and reduce the sequelae of nervous system, have a good clinical effect and improve the quality of life.%目的:探讨全身亚低温治疗新生儿缺血缺氧性脑病的临床疗效。方

  7. Hypoxic-ischemic changes in SIDS brains as demonstrated by a reduction in MAP2-reactive neurons.

    Science.gov (United States)

    Oehmichen, Manfred; Woetzel, Fabian; Meissner, Christoph

    2009-03-01

    Sudden infant death syndrome (SIDS) is characterized by a lack of any known morphological or functional organ changes that could explain the lethal process. In the present study we investigated the hypothesis of an association between hypoxic/ischemic injury and SIDS deaths. In a previous study, we could demonstrate by quantitative immunohistochemistry a distinct drop in microtubule-associated protein (MAP2) reactivity in neurons of adult, human brains secondary to acute hypoxic-ischemic injuries. Here we applied the same method on sections of the frontal cortex and hippocampus of 41 brains of infants younger than 1 year of age. For each brain area 100 selected neurons were evaluated for their MAP2 reactivity in the different layers of the frontal cortex and in the different segments of the hippocampus. Three groups were compared: (1) SIDS victims (n = 17), (2) infants with hypoxia/ischemia (control group one; n = 14), (3) infants without hypoxic/ischemic injury (control group two; n = 10). The SIDS group and hypoxic/ischemic group exhibited a general reduction in the number of MAP2 reactive neurons in comparison with the non-hypoxic/ischemic injury group. The SIDS group also had a significantly lower (P < 0.05) number of reactive neurons in the CA2 and CA3 areas of the hippocampus than did control group two. No difference was detected between the SIDS group and control group one. The SIDS brains were thus found to display hypoxic/ischemic features without however providing evidence as to the cause of the oxygen reduction.

  8. Clinic-like animal model for causal-pathogenetical investigations of hypoxic-ischemic brain injuries. Combined application of the radioactive labelled microsphere method and Positron Emission Tomography. Kliniknahes Tiermodell fuer kausal-pathogenetische Untersuchungen hypoxisch-ischaemischer Hirnschaedigung. Kombinierter Einsatz von Mikrosphaeren-Methode und Positronen-Emissions-Tomographie

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, R.; Zwiener, U.; Bergmann, R. (Univ. Jena, Inst. fuer Pathologische Physiologie (Germany)); Manfrass, P.; Enghardt, W.; Fromm, W.D. (Zentralinstitut fuer Kernforschung, Bereich Festkoeper- und Kernphysik, Rossendorf (Germany)); Hoyer, D.; Guenther, K. (Leipzig Univ., Radiologische Klinik (Germany)); Schubert, H. (Univ. Jena, Tierexperimentelles Zentrum (Germany)); Beyer, R.; Beyer, G.J.; Steinbach, J.; Kretzschmer, M. (Zentralinstitut fuer Kernforschung, Bereich Radioaktive Isotope, Rossendorf (Germany))

    1990-01-01

    The complex nature of the pathogenesis in hypoxic-ischemic brain injuries equires the combined determination of the dynamics of main factors in these disturbing processes. The application of suitable methods for registration of such pathogenetic processes is shown in an adequate animal model for simulating the early hypoxic-ischemic brain injuries. That the radioactive labelled microsphere technique is suitable to comprehend quantitively the dynamics of the intracerebral redistribution of the circulating blood due to hypoxia/hypercapnia by simultaneous-multiple measuring of the regional cerebral blood flow. Therefore, at the first time an inadequate hypoxic-induced blood flow increase was shown in large parts of the forebrain in intrauterine growth retarded newborn piglets. For estimation of the regional cerebral glucose utilization in newborn piglets, the {sup 18}F-FDG Positron Emission Tomography is introduced. The measurements were carried out on a stationary high-density avalanche chamber (HIDAC) camera and yielded the fundamental application of this camera model for PET investigations also in the newborn brain due to the very good spatial resolution. (orig.).

  9. Recent Information on the Pathogenesis and Treatment of Hypoxic-Ischemic Brain Lesions in Newborns

    Directory of Open Access Journals (Sweden)

    G. A. Karkashadze

    2016-01-01

    Full Text Available Hypoxic-ischemic brain lesions in children are the main environmental (non-genetic factor in forming severe neurological pathology with subsequent disability. Scientists see the improvement of therapeutic approaches in acute phase of the disease as a main way to reduce the severity of neurologic complications. Due to the achievements in neuroscience in the field of perinatal hypoxicischemic injury mechanisms, three energy phases of pathologic events deployment were identified: primary (up to 6 hours from the lesion, secondary (6 to 24–48 h after the lesion and distal tertiary (during few weeks, months. At the same time, necrosis, apoptosis, glutamate excitotoxicity, oxidative stress, inflammation, angiogenesis and neurogenesis make up separate links of destruction process. On the basis of new data on the pathogenesis of the disease, scientists from different countries have already offered modern treatment methods for perinatal hypoxic-ischemic injury with erythropoietin, allopurinol, melatonin, N-acetylcysteine, magnesium sulphate, albumin, -interferon, as well as with the help of controlled hypothermia, xenon, the use of stem cells, etc. This article presents a review of new data on pathogenesis and promising treatment methods for perinatal hypoxic-ischemic injuries.

  10. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Ying-bo Li

    2015-01-01

    Full Text Available Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 µM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent experiments. Whole-cell patch clamp showed that neural stem cells induced by 20 µM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypoxic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

  11. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Distefano, Giuseppe; Praticò, Andrea D

    2010-09-16

    Hypoxic-ischemic encephalopathy (HIE) is the most important cause of cerebral damage and long-term neurological sequelae in the perinatal period both in term and preterm infant. Hypoxic-ischemic (H-I) injuries develop in two phases: the ischemic phase, dominated by necrotic processes, and the reperfusion phase, dominated by apoptotic processes extending beyond ischemic areas. Due to selective ischemic vulnerability, cerebral damage affects gray matter in term newborns and white matter in preterm newborns with the typical neuropathological aspects of laminar cortical necrosis in the former and periventricular leukomalacia in the latter. This article summarises the principal physiopathological and biochemical processes leading to necrosis and/or apoptosis of neuronal and glial cells and reports recent insights into some endogenous and exogenous cellular and molecular mechanisms aimed at repairing H-I cerebral damage.

  12. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Praticò Andrea D

    2010-09-01

    Full Text Available Abstract Hypoxic-ischemic encephalopathy (HIE is the most important cause of cerebral damage and long-term neurological sequelae in the perinatal period both in term and preterm infant. Hypoxic-ischemic (H-I injuries develop in two phases: the ischemic phase, dominated by necrotic processes, and the reperfusion phase, dominated by apoptotic processes extending beyond ischemic areas. Due to selective ischemic vulnerability, cerebral damage affects gray matter in term newborns and white matter in preterm newborns with the typical neuropathological aspects of laminar cortical necrosis in the former and periventricular leukomalacia in the latter. This article summarises the principal physiopathological and biochemical processes leading to necrosis and/or apoptosis of neuronal and glial cells and reports recent insights into some endogenous and exogenous cellular and molecular mechanisms aimed at repairing H-I cerebral damage.

  13. Influence of nursing intervention on the prognosis of neonatal hypoxic ischemic encephalopathy%护理干预对新生儿缺氧缺血性脑病预后的影响

    Institute of Scientific and Technical Information of China (English)

    欧阳晓红; 丘惠娴; 陈秀琼

    2014-01-01

    目的:探讨护理干预对新生儿缺氧缺血性脑病预后的影响。方法选取2011年3月-2013年3月我院儿科进行治疗的患儿60例,随机分为对照组与干预组各30例。对照组进行常规护理,干预组在此基础上进行护理干预。对两组患儿的临床疗效及3,6,9,12个月的运动发育指数(PDI)及平均智能发育指数(MDI)进行及预后情况进行比较。结果干预组总有效率为93.33%,明显高于对照组的76.67%,两组比较,差异显著(P<0.05)。两组患儿的3个月的运动发育指数比较,差异不显著;干预组患儿的6,9,12个月的运动发育指数显著高于对照组,两组比较,差异显著(P<0.05)。干预组患儿的平均智能发育指数在3,6,9,12个月时比较,显著高于对照组,差异显著(P<0.05)。干预组的并发症发生率(20.00%)明显低于对照组的发生率(43.33%),两组比较差异显著(P<0.05)。结论对HIE 患儿进行护理干预,可以改善预后,促进智力发育,降低后遗症的发生率。%ObjectiveTo explore the influence of nursing intervention on the prognosis of neonatal hypoxic ischemic encephalopathy.Methods60 cases of Pediatrics were collected from 2011 March -2013 year in March in the hospital, and were randomly divided into control group and intervention group with 30 patients in each group. The control group was given routine nursing,the intervention group on the basis ofnursing intervention.Clinical efficacy of the two groups of children withand 3,6,9,12 months of psychomotor development index (PDI) and average intelligence development index (MDI) and prognosis were compared.ResultsThe intervention group the total effective rate was 93.33%, significantly higher than that in control group 76.67%,two groups,significant difference(P<0.05).Development of 3 months of two groups of children with index,the difference was not significant; the intervention

  14. Relationship between electroencephalography and magnetic resonance imaging findings after hypoxic-ischemic encephalopathy at term.

    Science.gov (United States)

    El-Ayouty, Mostafa; Abdel-Hady, Hesham; El-Mogy, Sabry; Zaghlol, Hamed; El-Beltagy, Mohamed; Aly, Hany

    2007-09-01

    Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Electroencephalography (EEG) and brain magnetic resonance imaging (MRI) are frequently performed in these infants, but the prognostic value of the combined use of EEG and MRI needs additional exploration. The purpose of this study was to investigate, in neonates with HIE, the role of early EEG and conventional MRI in the prediction of infants at risk for persistent encephalopathy at 18 months of age. Thirty-four term infants with HIE were enrolled in this prospective study. EEG was recorded within the first 72 hours after birth and a brain MRI scan was done between 1 and 4 weeks of age. Denver Developmental Screening Test II was performed at 6, 12, and 18 months of age. Three infants (9%) had mild HIE, 21 infants (62%) had moderate HIE, and 10 infants (29%) had severe HIE. The EEG background was normal, moderately, severely, and extremely discontinuous in eight (24%), three (9%), sixteen (47%), and seven (20%) neonates, respectively. EEG background activities correlated significantly with HIE severity (p = 0.0001). MRI findings significantly correlated with EEG background (p = 0.001). Normal MRI scans and minimal basal ganglia lesions were always associated with normal EEG background. Patients with severe basal ganglia and thalamic lesions in MRI (n = 2) had extreme discontinuous EEG background. For the prediction of poor outcomes, abnormal EEG background activity had a sensitivity (Sn) = 100%, a specificity (Sp) = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 100%, whereas values of abnormal MRI scans were Sn of 100%, Sp = 43%, PPV = 82%, and NPV=100%. EEG background activity is the best element to predict abnormal outcomes. Severe basal ganglia and thalamic injuries on MRI scans are associated with poor outcomes. Otherwise, MRI does not contribute to the prediction of outcomes at 18 months of age.

  15. Erythropoietin levels in serum and cerebrospinal fluid of neonates with hypoxic-ischemic encephalopathy%新生儿缺氧缺血性脑病血清及脑脊液中促红细胞生成素的变化

    Institute of Scientific and Technical Information of China (English)

    陈宁; 毛健; 杜悦

    2005-01-01

    Objective To observe the changes of erythropoietinerythrogenin (Epo) in serum and cerebrospinal fluid (CSF) in neonates with hypoxic-ischemic encephalopathy (HIE), and to study the relationship between Epo levels and brain injury. Methods Serum Epo levels were measured by radioimmunoassay in 26 neonates with HIE (HIE group, 8 mild, 10 moderate and 8 severe ) and 8 normal neonates ( Control group) at 0-24 hrs, 48-72 hrs and 7-10 days of their lives. CSF Epo levels were measured at 48-72 hrs of their lives and brain MRI scans were taken 7-10 days after birth in the HIE group. Results In the Control group, serum Epo levels decreased significantly within days after birth ( P < 0.05 );However, in the HIE group serum Epo levels increased during 1-3 days then decreased thereafter; Significantly decreased levels were observed only in mild HIE neonates ( P < 0.05). In every time period, the serum Epo concentration in severe HIE neonates was significantly higher than in mild and moderate HIE neonates. It was also observed that CSF Epo levels in severe HIE neonates were significantly higher than those of mild and moderate HIE neonates ( P < 0.01 ). There was a significant linear and positive correlation between serum and CSF Epo levels at 48-72 hrs in severe HIE neonates ( r =0. 76, P < 0.05 ), but not in mild and moderate HIE neonates. CSF Epo levels in neonates with severe cranial MRI abnormalities were significantly higher than those of neonates with mild and moderate cranial MRI abnormalities ( P <0.01 ). Conclusions The maintained and increased serum Epo levels may be a marker of severe hypoxic-ischemia in neonates with HIE. CSF Epo levels can reflect the severity of cerebral hypoxia-ischemia; Impaired blood-brain barrier might account for the increased CSF Epo levels.%目的探讨缺氧缺血性脑病(HIE)患儿血清和脑脊液(CSF)中促红细胞生成素(Epo)的变化,观察Epo与脑损伤的关系.方法对26例HIE患儿(轻度8例,中度10例,重度8例)和8例

  16. The Predictive Value of Combining Umbilical Arterial and Radial Arterial pH for Neonatal Hypoxic Ischemic Encephalopathy%脐带血联合动脉血pH值对新生儿缺血缺氧性脑病的预测价值

    Institute of Scientific and Technical Information of China (English)

    郭晓辉; 李华英; 夏俊霞; 沙文琼; 陈淑芳

    2011-01-01

    目的 探讨脐带血联合动脉血pH值对新生儿缺血缺氧性脑病(HIE)的预测价值.方法 选取2009年4月至2011年1月在深圳市人民医院分娩的无严重畸形的7 456例活产婴儿作为研究对象,对其脐动脉血pH值与新生儿缺血缺氧性脑病的相关性进行分析,并随机选择481例新生儿于出生后1h行桡动脉血气分析.结果 7 456例脐动脉血pH为7.10~7.42.以脐带血pH<7.10为指标预测新生儿HIE的阳性预测值为35.57%,敏感性42.06%.脐带血联合出生后1h动脉血pH值预测HIE的敏感性为60.00%,阳性预测值71.79%.联合检测与单项检测临床符合率比较,差异有统计学意义(P<0.01).结论 脐带血pH<7.10且出生1h动脉血pH<7.3对新生儿缺血缺氧性脑病有预测意义.脐动脉血pH<7.10的新生儿应常规于出生后复查桡动脉血pH值.%Objective To study the predictive value of combining radial arterial blood and umbilical arterial blood gas analysis for hypoxic ischemic encephalopathy (HIE). Methods 7 456 neonates without severe deformity,bom in Shenzhen People's Hospital from April 2009 to January 2011, were recruited into our research. The correlation between umbilical arterial blood gas analysis and neonatal hypoxic ischemic encephalopathy were analyzed. 481 cases were randomly selected for radial arterial blood gas analysis an hour after birth. Results The pH values of umbilical arterial blood ranged from 7.10 to 7.42. There was a significant correlation between HIE and the pH value of umbilical arterial blood (P < 0.05). Taken pH<7.10 as an indicator to assess neonatal HIE,the positive predictive value and sensitivity were 35.5% and 42.06%, respectively. The positive predictive value and sensitivity of combining radial arterial with umbilical arterial blood gas analysis were 71.79% and 60.00%, respectively. The difference in clinical coincidence rates between combined test and single test was statistically significant (P < 0

  17. Short-term effect of erythropoietin on brain lesions and aquaporin-4 expression in a hypoxic-ischemic neonatal rat model assessed by magnetic resonance diffusion weighted imaging and immunohistochemistry.

    Science.gov (United States)

    Brissaud, Olivier; Villega, Frédéric; Pieter Konsman, Jan; Sanchez, Stéphane; Raffard, Gérard; Franconi, Jean-Michel; Chateil, Jean-François; Bouzier-Sore, Anne-Karine

    2010-08-01

    Erythropoietin (Epo) is an endogenous cytokine that regulates hematopoiesis and is widely used to treat anemia. In addition, it has recently increased interest in the neurosciences since the new concept of Epo as a neuroprotective agent has emerged. The potential protective effect of human recombinant Epo (r-hu-Epo) on a hypoxic-ischemic (HI) pup rat model was studied. Cerebral HI was obtained by permanent left carotid artery ligature of pups followed by a 2-h hypoxia. Three hours after carotid occlusion, brain lesions were assessed by magnetic resonance diffusion weighted imaging. Intraperitoneal administration of r-hu-Epo (30,000 U/kg dose) limited both the HI-induced brain lesion area and the decrease in apparent diffusion coefficient (ADC) in the lesion. To identify potential mechanisms underlying the effects of Epo, immunohistochemical detection of caspase-3 and water channel protein aquaporin-4 (AQP4) were performed. No early apoptosis was detected, but up-regulation of AQP4 expression was observed in HI pups that received r-hu-Epo compared with HI animals without treatment. This study demonstrates an early neuroprotective effect of Epo with regard to brain lesion area and ADC values. One possible mechanism of Epo for decreasing brain edema and cellular swelling could be a better clearance of water excess in brain tissue, a process possibly mediated by AQP4.

  18. 神经系统特异性蛋白质在新生儿缺氧缺血性脑病中的诊断价值%Value of specific proteins of the nervous system in the diagnosis of neonatal hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    林书英; 樊绍曾; 曾纪骅

    2001-01-01

    Objective To determine some specific proteins of the nervous system such as the neuron-specific enolase (NSE), S-100 protein (S-100), myelin basic protein (MBP) and creatine kinase isoenzyme BB (CK-BB) in cerebrospinal fluid (CSF) and plasma of asphyxiated newborns during early stage of hypoxic-ischemic encephalopathy (HIE), and its correlation with the severity of the disease and long-term outcome. Methods 71 full-term and near full-term neonates were enrolled in the study. 16 babies without neurological disease were assigned to the control group. Another 55 babies were in the HIE group. Among them, there were 20 with mild HIE, 28 with moderate,and 7 with severe HIE. CSF and plasma specimens were obtained at 9-92 hours (mean: 33.5 hours) postnatal in the HIE group. NSE/S 100/MBP were measured by immunoradiometric assay, CK-BB by agarose electrophoresis. Babies with HIE were followed-up after discharged from the hospital. Neurological outcome was assessed by physical examination and Gesell developmental diagnosis. Results 80% (41/51) of the infants survived at the time of discharge were followed-up for 3~13 months (mean:6.5 months). 25 infants were normal, 9 slightly abnormal, and 7 seriously abnormal. Although the plasma levels of NSE, and CK-BB correlated with the degree of HIE, they could not predict accurately the long-term outcome. NSE, S-100, MBP and CK-BB in CSF were correlated not only to the severity of the disease, but also to the long-term outcome. Among the four markers, NSE and S-100 were the most sensitive and specific in the prediction of the degree of brain injury. Conclusion NSE and S-100 in CSF are the most reliable markers for early estimation of the degree of HIE in neonates. (Shanghai Med J, 2001,24:233-235)%目的评价缺氧缺血性脑病(HIE)新生儿脑脊液(CSF)和血浆中神经元特异性稀醇化酶(NSE)、S-100蛋白(S-100 protein,S-100)、髓鞘碱性蛋白(MBP)、肌酸磷酸激酶脑型同工酶(CK-BB)等神经系统特异

  19. Experimental models of perinatal hypoxic-ischemic brain damage.

    Science.gov (United States)

    Vannucci, R C

    1993-01-01

    Animal research has provided important information on the pathogenesis of and neuropathologic responses to perinatal cerebral hypoxia-ischemia. In experimental animals, structural brain damage from hypoxia-ischemia has been produced in immature rats, rabbits, guinea pigs, sheep and monkeys (18, 20, 24, 25, 38). Of the several available animal models, the fetal and newborn rhesus monkey and immature rat have been studied most extensively because of their similarities to humans in respect to the physiology of reproduction and their neuroanatomy at or shortly following birth. Given the frequency of occurrence of human perinatal hypoxic-ischemic brain damage and the multiple, often severe neurologic handicaps which ensue in infants and children, it is not surprising that the above described animal models have been developed. These models have provided the basis for investigations to clarify not only physiologic and biochemical mechanisms of tissue injury but also the efficacy of specific management strategies. Hopefully, such animal research will continue to provide important information regarding how best to prevent or minimize the devastating consequences of perinatal cerebral hypoxia-ischemia.

  20. Role of gap junction and connexin-43 in hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Jieying Lin; Niyang Lin

    2006-01-01

    OBJECTEVE:Gap junctin (GJ)is the structural basis for direct intercellular communication of nerve cells . Connexin(Cx) is the protein subunit for constructling GJ channel. Among them, Cx43is closely related with nervous system. Both Cx43 and nervous system play an important role in the pathophysiological development of hypoxic-ischemic injury. We are in attempt to investigate GJ,Cx43 and their correlations with hypoxic-ischemic brain damage by research.DATA SOURCES:Using the terms "brain gap junction"in English and "gap junction"in Chinese, we searched the Medline database and Chinese BioMedical Literature Database as well as China Hospital Knowledge Database to identify the articles published from 1996 to 2006 about GJ and brain hypoxic-ischemic injury.STUDY SELECTION:The articles were selected firstly and abstracts of 250 articles were read thuugh.Articles in which the experimental design met randomized controlled principle were included,and study articles and case reports with repetitve contents were excluded.DATA EXTRACTION:Among 53 included correlative articles, 23 were excluded for repetitive contents and the other 30 were analyzed.DATA SYNTHESIS:GJ,widely esistling in nervous system,plays a key role in maintainling normal differentiation and development as well as physiological function brain tissue.GJ channel is a hydrophilic,low-selectivity and lowohmic channel, which can provide direct channel for intercellular substance transmission and information communication. It plays an important role in the differentiation and development of nerve cells and regulation of physiological function,The funtions of GJ channel are regulated by many factors,which invilved intracellular Ph value, Ca2+concentration, ATP concentration, phosphorylation of Cx, transchannel pressure,some neurohormonal factors,regulatory factors of protein and so on. Cx43 is the main component of GJ channel in the brain tissues. Its expression in the brain tissue of mammal is the strongest

  1. Effects of early application of naloxone combined with dopamine on moderate and severe neonatal neurobehavioral development of hypoxic ischemic encephalopathy%早期应用纳洛酮联合多巴胺对中重度缺氧缺血性脑病新生儿神经行为发育的影响

    Institute of Scientific and Technical Information of China (English)

    郭鹏

    2015-01-01

    目的 探讨早期应用纳洛酮联合多巴胺对中重度缺氧缺血性脑病新生儿神经行为发育的影响.方法 选取117例中重度缺氧缺血性脑病新生儿为研究对象,采用简单抽样法分成联合用药组(A组,n=60)和常规治疗组(B组,n =57)两组.B组予以早期常规治疗,A组在上述基础上采用纳洛酮联合多巴胺方案.进行为期1年随访,使用Gesell量表行发育商数评估,对比两组患儿治疗前后DQ值变化情况,记录其适应行为、语言行为、个人社会行为及运动行为等四项行为领域评估均值.结果 治疗后,两组DQ值均较治疗前明显提升,其中A组治疗后第12个月达到(103.3±1.1)分,明显高于B组[(97.7±1.2)分],差异有统计学意义(P<0.05).随访期内,A组Gesell量表各行为领域评估均值均明显高于B组,差异有统计学意义(P<0.05).结论 对中重度缺氧缺血性脑病新生儿临床治疗早期予以纳洛酮联合多巴胺方案,疗效确切,值得临床推广.%Objective To investigate the effects of early application of naloxone combined with dopamine on moderate and severe neonatal neurobehavioral development of hypoxic ischemic encephalopathy.Methods A total of 117 cases of moderate and severe neonatal hypoxic-ischemic encephalopathy were selected as the research objects,and were divided into combined treatment group (group A,n =60) and routine treatment group (group B,n =57) using simple sampling method.The patients in group B were given early conventional treatment,and the patients in group A were given naloxone combined with dopamine on the basis of above scheme.One year follow-up of behavior stage was made,using the Gesell scale for developmental quotient evaluation,compared change DQ value before and after treatment in two groups,recording adaptive behavior,language behavior,personal social behavior and exercise behavior,assessment mean value in the field.Results After treatment,DQ values were significantly higher than

  2. 选择性头部亚低温治疗出生6~12 h新生儿缺氧缺血性脑病的临床效果%Clinical efficacy study of selective head hypothermia in the treatment of born 6-12 h neonatal hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    陈少波; 杨春晖; 彭嘉恒; 赖春华; 莫兆冬; 王维琼; 杨冰岩

    2015-01-01

    Objective To study the clinical efficacy of selective head hypothermia in the treatment of born 6-12 h neonatal hypoxic-ischemic encephalopathy. Methods 80 cases of birth 6-12 h occurred neonatal hypoxic-ischemic encephalopathy who were treated in Boai Hospital of Zhongshan City from January 2013 to September 2014 were se-lected, these children were divided into study group and control group by random sampling method, 40 cases in each group. Children of the control group were given conventional treatment, while children of the study group were given selective head hypothermia treatment on the basis of conventional therapy, then the NSE concentration, neurodevelop-mental scores big sports DQ value, the occurrence of serious adverse outcomes of children in the two groups were ana-lyzed. Results The 1, 2, 3 d NSE concentrations of children in the study group were significantly lower (P<0.05), the neurodevelopmental scores big sports DQ value was significantly higher (P<0.05), the rate of serious adverse outcomes (27.5%) was significantly lower than the control group (52.5%) (P<0.05). Conclusion The clinical application efficacy of selective head hypothermia is significant in the treatment of born 6-12 h neonatal hypoxic-ischemic encephalopathy.%目的:研究应用选择性头部亚低温治疗出生6~12 h新生儿缺氧缺血性脑病临床疗效。方法运用随机抽样的方法选取2013年1月~2014年9月中山市博爱医院新生儿科收治的出生6~12 h发生缺氧缺血性脑病的新生儿80例,依据随机数字表法将其分为研究组和对照组,每组各40例。对照组患儿给予常规治疗,研究组患儿在常规治疗基础上加选择性头部亚低温治疗。统计分析两组患儿的NSE浓度、神经发育评分大运动DQ值、CR发生情况。结果研究组患儿1、2、3 d的NSE浓度均显著低于对照组(P<0.05),神经发育评分大运动DQ值显著高于对照组(P<0.05),脑瘫率(27.5%)显著低于对照组(52

  3. Immunohistochemical investigation of hypoxic/ischemic brain damage in forensic autopsy cases.

    Science.gov (United States)

    Kitamura, O

    1994-01-01

    A neuropathological study of 41 forensic autopsy cases of hypoxic/ischemic brain damage has been undertaken, using immunohistochemical staining to detect the 70-kDa heat shock protein (hsp70) and the status of the glial cells. In cases surviving 2-5 h after hypoxic/ischemic injury, ischemic cell changes were seen whereas glial reactions were not apparent. In cases of longer survival, neuronal necrosis and a loss of neurons were seen, and these changes were accompanied by proliferation of glial fibrillary acidic protein (GFAP), vimentin-positive astrocytes and microglia which transformed into rod cells or lipid-laden macrophages. In cases with a history of hypoxic attacks, GFAP-positive and vimentin-negative astrocytes had proliferated in the CA3 and CA4 regions of hippocampus. The cases of severe hypoxic injury, such as an asthmatic attack and choking, showed no ischemic changes in the hippocampal neurons. On the other hand, the CA1 pyramidal cells showed neuronal necrosis in a patient suffering from tetralogy of Fallot (TOF), who survived for 2 h after a traffic accident. Therefore, it is suggested that even moderate hypoxic injury induces astrocytosis in the CA3 and CA4 regions and may affect the neuronal proteins and the metabolism, and that in cases with a history of hypoxic attacks neuronal damage may be severe even several hours after ischemic injury. The protein hsp70 expression was found in the CA2, CA3 and CA4 regions in cases of long-term survival after severe hypoxic/ischemic injury and in cases of alcoholic intake or toluene abuse just before acute death.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. CT值联合Apgar评分与新生儿缺氧缺血性脑病严重程度相关性研究%Correlation Study of CT Value Joint Apgar Score and Severity of Neonatal Hypoxic Ischemic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    黄宏亮

    2015-01-01

    目的:研究CT值联合Apgar评分与新生儿缺氧缺血性脑病(HIE)严重程度的相关性.方法:选取2014年1月-2015年4月本院收治的HIE患儿200例,临床分度轻度组108例,中度组65例,重度组27例,测定各组CT值与Apgar评分.结果:三组患者的CT值与Apgar评分比较差异具有统计学意义(P<0.05).结论:CT值、Apgar评分与HIE临床分度关系密切,两者联用可较准确判定HIE的严重程度.%Objective:To study the correlation between CT score and Apgar score and the severity of neonatal hypoxic ischemic encephalopathy (HIE).Method:From January 2014 to April 2015,200 patients with HIE were selected, 108 cases of clinical index mild group,65 cases of moderate group,27 cases of severe group,and the CT score and Apgar score were determined.Result:The difference of CT score and Apgar score between the three groups was statistically significant (P<0.05).Conclusion:CT score and Apgar score are closely related with clinical classification of HIE, and the severity of HIE is more accurate than that of the two.

  5. Effects of pre- and postnatal protein malnutrition in hypoxic-ischemic rats.

    Science.gov (United States)

    Sanches, Eduardo Farias; Arteni, Nice Sarmento; Spindler, Christiano; Moysés, Felipe; Siqueira, Ionara Rodrigues; Perry, Marcos Luis; Netto, Carlos Alexandre

    2012-02-15

    Neonatal hypoxic-ischemic encephalopathy (HI) is a major cause of nervous system damage and neurological morbidity. Perinatal malnutrition affects morphological, biochemical and behavioral aspects of neural development, including pathophysiological cascades of cell death triggered by ischemic events, so modifying resulting brain damage. Female Wistar rats were subjected to protein restriction during pregnancy and lactation (control group: 25% soybean protein; malnourished group: 7%). Seven days after delivery (PND7), their offspring were submitted to unilateral cerebral HI; rats were then tested for sensorimotor (PND7 and PND60) and memory (PND60) functions. Offspring of malnourished mothers showed marked reduction in body weight starting in lactation and persisting during the entire period of observation. There was a greater sensorimotor deficit after HI in malnourished (M) animals, in righting reflex and in home bedding task, indicating an interaction between diet and hypoxia-ischemia. At PND60, HI rats showed impaired performance when compared to controls in training and test sessions of rota-rod task, however there was no effect of malnutrition per se. In the open field, nourished HI (HI-N) presented an increase in crossings number; this effect was not present in HI-M group. Surprisingly, HI-M rats presented a better performance in inhibitory avoidance task and a smaller hemispheric brain damage as compared to HI-N animals. Our data points to a possible metabolic adaptation in hypoxic-ischemic animals receiving protein malnutrition during pregnancy and lactation; apparently we observed a neuroprotective effect of diet, possibly decreasing the brain energy demand, under a hypoxic-ischemic situation. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Observation on the curative effect of phenobarbitone combined with naloxone in treatment of neonatal hypoxic-ischemic encephalopathy%苯巴比妥和纳洛酮联合治疗新生儿缺氧缺血性脑病疗效观察

    Institute of Scientific and Technical Information of China (English)

    刘江海

    2012-01-01

    目的:观察苯巴比妥联合纳洛酮治疗新生儿缺氧缺血性脑病(hypoxic ischemic encephalopathy,HIE)的临床疗效.方法:将68例缺氧缺血性脑病患儿随机分为两组,对照组给予吸氧、控制惊厥、减轻脑水肿、维持电解质平衡等常规治疗,治疗组在常规治疗的基础上给予苯巴比妥4.5μg/(kg·min),同时加用盐酸纳洛酮0.1 mg/(kg·d),输液泵维持24h持续经脉滴注,连用7天.观察两组患儿的临床疗效、意识恢复时间、反射恢复时间、肌肉张力的恢复时间以及不良反应.结果:治疗组与对照组的总有效率分别为88.24% (30/34)、76.47% (26/34),两组比较P<0.05;治疗后的意识恢复时间、反射恢复时间、肌肉张力的恢复时间治疗组均较对照组明显缩短(P<0.01).结论:苯巴比妥可以降低HIE的发生率,与纳洛酮联用对预防HIE发生颅内出血及降低惊厥具有较好疗效,且安全性较高.%Objective: To observe the clinical efficacy of phenobarbitone combined with naloxone in treatment of neonatal hypoxic - ischemic encephalopathy ( HIE) . Methods; Sixty - eight neonates with HIE were divided into two groups randomly, the neonates in control group were treated with routine therapies, including oxygen inhalation, controlling convulsions, relieving cerebral edema, and maintaining electrolyte balance; while the neonates in treatment group were treated with phenobarbitone (4.5 (μg· kg-1 o min-1) and naloxone hydrochloride (0. lmg·kg-1·d-1) based on the therapies used in control group, continuous intravenous drip for seven days. The clinical efficacies, the recovery times of consciousness, the recovery times of muscular tension, and adverse reactions in the two groups were observed. Results; The total effective rates in treatment group and control group were 88. 24% (30/34) and 76.47% (26/34), respectively , there was significant difference between the two groups (P < 0.05); the recovery times of consciousness

  7. Perinatal hypoxic-ischemic encephalopathy: severity determinants and outcomes

    Directory of Open Access Journals (Sweden)

    Liliana Teixeira

    2014-06-01

    Full Text Available Perinatal hypoxic-ischemic encephalopathy (HIE after perinatal asphyxia is one of the most critical pathologic conditions in neonatal medicine due to the potential for neurological sequelae in later life. The aim of our study is to identify the factors that are associated with a higher degree of severity in HIE and evaluate the outcomes. We performed a retrospective study of all newborns with HIE treated at our neonatal intensive care unit (NICU from January 2010 to December 2013. Data collected include information about prenatal period, peripartum period, demographic characteristics, admission and evolution during NICU stay and outcomes (assessed in three different times: at discharge, at 6-9 months and 18 months. Forty seven newborns were enrolled in our study, 11 (23.4% with mild HIE, 21 (44.7% with moderate HIE and 15 (31.9% with severe HIE. Prenatal, perinatal and demographic data showed no statistically significant differences between groups. Statistically significant differences were found in values of Thompson score (p < 0.0001, abnormal aEEG/EEG at admission (p = 0.025 and at 48 hours (p = 0.018, need of mechanical ventilation (p = 0.004, acute renal failure (p = 0.002 and length of stay (p = 0.038 with high rates in the moderate and severe HIE groups. Regarding the outcomes, statistically significant differences were found in the prevalence of death (p = 0.010; need of antiepileptic drugs at discharge (p = 0.001; motor deficits requiring physiotherapy (p = 0.046, abnormal deep tendon reflex (p = 0.006 and need of antiepileptic drugs (p = 0.001 at 6-9 months follow-up; and cerebral palsy with cognitive impairment at 18 months (p = 0.041 with high rates in the severe HIE group. These results suggest that Thompson score, abnormal aEEG/EEG at admission and at 48 hours, mechanical ventilation, acute renal failure and length of stay are associated with more severe HIE. We also concluded that more severe HIE reflects worse outcomes whereas

  8. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

    Institute of Scientific and Technical Information of China (English)

    Xianchao Li; Wensheng Hou; Xiaoying Wu; Wei Jiang; Haiyan Chen; Nong Xiao; Ping Zhou

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hy-poxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efifciencies are relatively low. Red or near-infrared light from 600-1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migra-tion and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2, an increasing number of green lfuorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 106 bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2 for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental ifndings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypox-ic-ischemic brain damage.

  9. Expression of Caspase-12 in neonatal rats with hypoxic-ischemic brain damage and the effect of Shenfu injection%缺氧缺血性脑损伤新生大鼠Caspase-12的表达及参附注射液对其的影响

    Institute of Scientific and Technical Information of China (English)

    吴宏伟; 王军; 王伟; 高继生; 杨秋丽

    2012-01-01

    Objective: To research the expression of Caspase - 12 in hippocampal neuronal cells of neonatal rats with hypoxic - ischemic brain damage ( HIBD) and the effect of Shenfu injection, and explore the probable mechanism of apoptosis after HIBD and the neuro-protective mechanism of Shenfu injection. Methods; The neonatal seven - day - old SD rats were randomly divided into sham operation group (S group) , normal saline control group (C group) , Shenfu treatment group (SF group) , then the rats in each group was divided into 3 -hour subgroup, 6 - hour subgroup, 12 - hour subgroup, 24 - hour subgroup, 3 - day subgroup, and 7 - day subgroup, 8 rats in each subgroup , Rice method was used to establish HIBD models of neonatal rats, the brain tissue samples of right hippocampus were obtained for homogenate, reverse transcription - polymerase chain reaction ( RTPCR) was used to detect the expression of Caspase - 12 mRNA,Western blot was used to detect the expression of Caspase - 12 pro-tein, and TUNEL method was used to detect the change of apoptotic morphology. Results: The expression level of Caspase - 12 mRNA in S group was the lowest, the expression levels of Caspase - 12 mRNA in C group and SF group peaked at 12 hours, and the expression levels of Caspase - 12 mRNA in SF group at 6 hours, 12 hours, 24 hours, and 3 days were statistically significantly lower than those in C group (P <0. 01) ; the expression level of Caspase - 12 protein in S group was the lowest, the expression levels of Caspase - 12 protein at 3 hours after hypoxia and ischemia in C group and SF group were statistically significantly higher than that in S group (P <0. 01) , which peaked at 24 hours, and on the seventh day, the expression levels of Caspase - 12 protein in C group and SF group were still statistically significantly higher than that in S group (P <0. 01) , the expression levels of Caspase - 12 protein at 12 hours, 24 hours, and 3 days in SF group were statistically significantly lower than

  10. Progesterone treatment before experimental hypoxia-ischemia enhances the expression of glucose transporter proteins GLUT1 and GLUT3 in neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Xinjuan Li; Hua Han; Ruanling Hou; Linyu Wei; Guohong Wang; Chaokun Li; Dongliang Li

    2013-01-01

    Progesterone is an efficient candidate for treating stroke and traumatic brain damage.The current study was designed to investigate the effects of progesterone on glucose transporter proteins (GLUT1 and GLUT3) during hypoxic-ischemic injury in a neonatal rat model.We demonstrated strong staining for GLUT1 in the walls of blood vessels and GLUT3 immunoreactivity in hippocampal neurons after hypoxiaischemia.Hypoxia-ischemia elevated GLUT1 and GLUT3 at both the mRNA and protein levels in the hippocampus,and pre-treatment with progesterone (8 mg/kg) further enhanced their accumulation until 24 h after hypoxic-ischemic injury.These results showed that progesterone treatment induced the accumulation of both GLUT1 and GLUT3 transporters,and an energy-compensation mechanism may be involved in the neuroprotective effect of progesterone during hypoxic-ischemic injury after cerebral ischemic attacks.

  11. 高压氧结合脑活素治疗新生儿缺氧缺血性脑病148例疗效分析%Hyperbaric Oxygen Combined with Cerebrolysin in Treatment of 148 Cases of Neonatal Hypoxic- Ischemic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    李虎; 万俊; 凌厉; 刘桂华; 刘静

    2011-01-01

    The effect of hyperbaric oxygen for the treatment of neonatal hypoxic-ischemic encephalopathy was abserved. 296 cases of children with neonatal hypoxic-ischemic encephalopathy diagnosis and sub-standard in light, medium and severe were chosen for the study in our hospital neonatal wards from October 1999 to October 2006. They were divided into two groups randomly: control group (148 cases for the cerebrolysin group) and observation group (148 cases for the hyperbaric oxygen and cerebrolysin group). The YLCO. 5 - 1 infant hyperbaric oxygen chamber was setected, with the entire cabin of oxygen, and pressure 0. 05~0. 06 Mpa. Boost and buck 0. 5 hour, and the regulator one hour, during which a regulator in the 20 minute ventilation, one time per day, 7 times for a course of treatment. The earliest of the observation group getting-into the cabin for the first time was 25 hours after birth, while the average time for the first time getting-into the cabin was 60. 8 hours after birth. The effect of the observation group was better. According to the statistical analysis (x2 = 3. 95, P < 0. 05) , significant difference was showed, and the follow-up screening DDST NBNAp score and the observation group were significantly better than the control group. Early application of hyperbaric oxygen in the treatment of neonatal hypoxicischemic encephalopathy is effective, safe and reliable.%探讨高压氧治疗新生儿缺氧缺血性脑病的疗效.选择1999年10月至2006年10月我院新生儿病房中符合新生儿缺氧缺血性脑病诊断及分度标准的轻、中、重度患儿296例为研究对象.随机分成两组,对照组148例为脑活素治疗组,观察组148例为高压氧加脑活素治疗组,选用YLC0.5-1型婴儿高压氧舱,全舱给氧,压力0.05~0.06 Mpa.升压及降压各0.5 h,稳压1 h,其间稳压换气1次20 min,每天1次,7次为1疗程.本组首次入舱时间最早为生后25 h,平均首次人舱时间为60.8 h.观察组疗效明显高于

  12. 单唾液酸四已糖神经节苷酯联合胞二磷胆碱治疗中、重度新生儿缺氧缺血性脑病的疗效分析%Effects of Monosialotetrahexosylganglioside Combined with Citicoline in Treatment of Maderate and Severe Neonatal Hypoxic-Ischemic Emcephalopathy

    Institute of Scientific and Technical Information of China (English)

    管玉成; 曹甦

    2014-01-01

    Objective:To investigate the clinical effieacy of the Monosialotetrahexosylganglioside(GM-1) combined with citicoline in the treatment of severe neonatal hypoxic-ischemic encephalopathy(HIE). Method:From January 2010 to January 2010 ,the data of 98 children with severe HIE were retrospectively analyzed in department of pediatric in our hospital. All the cases were treated by three in the support and the basis of the three symptomatic .The control group(n=49) was treated with citicoline(CDPC)together with conventional trerapy for HIE. The treatment group(n=49)was treated with GM-1 on the basis of the control group. The symptoms and signs of the two groups were observed.Brain CT and the neonatal behavioral neurological assessment(NBNA)scores of the two groups were evaluated. Result:The total effective rate in the observation group was 93.86%,significantly higher than that in the control group. Brain CT changes in treatment group was better than that in the control group.The NBNA scores(2 d)in the treatment group was no significant difference,the NBNA scores(7,14,28 d)were significantly higher than those in the control group(P0.05),生后7、14、28 d评分治疗组明显高于对照组,差异均具有统计学意义(P<0.05)。结论:GM-1与CDPC合用可发挥协同作用,促进受损神经细胞功能修复,逆转脑缺氧缺血后神经功能障碍,显著提高脑机能,可明显改善中重度HIE的临床症状,适于临床推广。

  13. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Ying-bo Li; Yan Wang; Ji-ping Tang; Di Chen; Sha-li Wang

    2015-01-01

    Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10–80 μM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent exper-iments. Whole-cell patch clamp showed that neural stem cells induced by 20 μM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypox-ic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplantedvia intracerebroventricular injection. These tests conifrmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a signiifcantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-speciifc enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

  14. 电针结合穴位注射治疗新生儿缺血缺氧性脑病的初步临床研究%Clinical Study of Neonatal Hypoxic Ischemic Encephalopathy Treated by Electro Acupuncture Combined with Acupoint Injection

    Institute of Scientific and Technical Information of China (English)

    郑雪松; 汪蓉; 吴胜英

    2015-01-01

    目的:研究电针联合穴位注射单唾液酸四己糖神经节苷脂钠治疗新生儿缺血缺氧性脑病的临床疗效及机制,为此类疾病提供新的综合治疗方案.方法:选取2014 年3月~2015 年3 月本院收治的166例缺血缺氧性脑病新生患儿,按出生先后顺序随机分治疗组、观察组,治疗组每日吸氧及静脉滴注胞二磷胆碱、能量等对症治疗,观察组在此治疗基础上头针及体针电针刺激20 min,并取"四神通、百会、足三里"穴位注射单唾液酸四己糖神经节苷脂钠.动态观察治疗前、7天、14天、21天脑电图( EEG )病理性棘波振幅、局部脑血流量( rCBF );测定血浆( CK-BB );采用新生儿20 项神经行为评分办法( NBNA)评分并统计总有效率.结果:观察组于第7天、14天、21天 CK-BB及EEG明显降低、NBNA及rCBF显著提高(F=33.579,P<0.05),总有效率达97.59%,与治疗组比较P<0.05,差异均有统计学意义.结论:通过对缺血缺氧性脑病新生儿头针、体针电针刺激可疏通经络、激发患儿经气,松弛新生儿局部脑缺血区血管平滑肌以改善脑缺血区微循环而达到增加脑血流量的目的,穴位注射单唾液酸四己糖神经节苷脂钠可营养脑组织及修复受损神经纤维而促进脑功能的恢复.%Objective:To study the effect of electroacupuncture combined with acupoint injection single sialic acid four hexose ganglioside sodium in the treatment of neonatal hypoxic ischemic encephalopathy,and to pro-vide a new scheme of comprehensive treatment.Methods:From March 2014 to March 2015 in our hospital 166 cases of neonatal hypoxic ischemic encephalopathy in children by birth order were randomly divided into a treat -ment group and an observation group.The treatment group was given oxygen inhalation and intravenous infusion of cytoplasmic two choline,energy and other symptomatic treatment,and the treatment group was given the treat-ment on the basis of scalp acupuncture and body

  15. Mild hypothermia combined with neural stem cell transplantation for hypoxic-ischemic encephalopathy:neuroprotective effects of combined therapy

    Institute of Scientific and Technical Information of China (English)

    Lin Wang; Feng Jiang; Qifeng Li; Xiaoguang He; Jie Ma

    2014-01-01

    Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia (27-28°C) can increase the survival rate of neural stem cells (1.0 × 105 /μL) transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hy-pothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our ifndings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inlfammatory and an-ti-apoptotic mechanisms.

  16. Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Raul Chavez-Valdez

    2012-01-01

    Full Text Available Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis “continuum” in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3 leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI.

  17. Effect observation of nerve growth factor combined with cerebrolysin applied in neonatal hypoxic ischemic encephalopathy%神经生长因子联合脑活素应用于新生儿缺氧缺血性脑病中的效果观察

    Institute of Scientific and Technical Information of China (English)

    韩传映

    2015-01-01

    目的:探究神经生长因子联合脑活素应用于新生儿缺氧缺血性脑病(HIE)的临床效果。方法:收治HIE患者80例,分两组。脑活素组给予脑活素治疗,联合组给予神经生长因子联合脑活素治疗,观察两组患者的临床效果。结果:联合组总有效率高于脑活素组(P<0.05);治疗1周后,联合组NBNA评分优于脑活素组(P<0.05)。结论:神经生长因子联合脑活素治疗的效果明显优于单纯脑活素治疗。%Objective:To explore the clinical effect of nerve growth factor combined with cerebrolysin applied in neonatal hypoxic ischemic encephalopathy.Methods:80 HIE patients were selected and divided into two groups.The cerebrolysin group were given cerebrolysin treatment.The combination group were given nerve growth factor combined with cerebrolysin treatment.The clinical effects of patients in two groups were observed.Results:The total effective rate of the combination group was higher than that of the cerebrolysin group(P<0.05).After 1 week of treatment,the NBNA score of the combination group was better than that of the cerebrolysin group(P<0.05).Conclusion:The effect of nerve growth factor combined with cerebrolysin is significantly better than that of simple cerebrolysin treatment.

  18. 亚低温联合高压氧治疗新生儿缺血缺氧性脑病的临床研究%Clinical research of mild hypothermia combined with hyperbaric oxygen in the treatment of neonatal hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    王长芹

    2010-01-01

    目的 探讨亚低温联合高压氧治疗新生儿缺血缺氧性脑病(HIE)的临床效果.方法 将75例新生儿HIE患者随机分为高压氧联合亚低温治疗组(治疗组)40例和对照组35 例;对照组接受常规综合治疗,治疗组在此基础上行早期高压氧联合亚低温治疗.两组患儿在生后4、14 d进行新生儿神经行为测定,3、6、12个月进行婴幼儿智能运动发育检查测定.结果 两组患儿出生后4 d测定值比较差异无统计学意义(t=0126,P>0.05),生后14 d测定值高压氧组与对照组比较差异有统计学意义(t=2.48,P0.05).The NBNA score when the newborns were 14 days had obvious difference between the two groups(t=2.48,P<0.05).The index of mental and psychomotor development when the newborns were 3 months,6months and 12 months in mild hypothermia complicated with heperbaric oxygen therapy group was obviously higher than that in control group.There were obvious difference between the two groups(P<0.05).Conclusions Mild hypothermia complicated with heperbaric oxygen therapy have obvious near ang long neurological protective action on neonatal hypoxic-ischemic encephalopathy and can improve the living quality.The treatment effect is positive.

  19. Efficacy of early intelligence intervention combined with monosialotetrahexosylganglioside sodium treatment on rehabilitation outcome of neonatal hypoxic-ischemic encephalopathy%早期智力干预联合神经节苷脂钠在新生儿缺氧缺血性脑病康复治疗中的作用

    Institute of Scientific and Technical Information of China (English)

    马晓燕; 韦红; 耿松乔; 陆国云

    2015-01-01

    目的::探讨早期智力干预联合神经节苷脂钠对新生儿缺氧缺血性脑病( HIE)的康复疗效。方法:选择新生儿HIE78例,分为治疗组(神经节苷脂钠+早期智力干预)41例,对照组(单用神经节苷脂钠)37例。于患儿6个月龄时应用Gesell量表评价2组患儿发育商,并进行对比分析。结果:治疗组的大动作能、精细动作能、应物能、言语能、应人能5个能区的发育商评分均高于对照组(P<0.05~P<0.01)。结论:早期智力干预对改善HIE患儿的神经系统发育具有积极作用,能改善脑损伤患儿的感知认知水平。%Objective:To investigate efficacy of combination of early intelligence intervention with monosialotetrahexosylganglioside (GM1) sodium treatment on rehabilitation outcome of neonatal hypoxic-ischemic encephalopathy(HIE). Methods:Seventy-four cases of neonatal HIE were enrolled and randomly assigned into two groups:the treatment group who received both GM1 sodium and early intelligence intervention(41 cases);control group who received GM1 sodium alone(37 cases). The neonates were assessed by the Gesell Development Scale at age of 6 months. Results:The average scores in the treatment group for functions of gross motor, fine motor,language,and social reactions were all higher than that of the control group(P <0. 05 to P <0. 01). Conclusions:Early intelligence intervention led to better neurodevelopmental outcome in neonatal HIE by improving cognitive development and perceptual skills.

  20. Neuroprotective role of ibuprofen in hypoxic-ischemic brain damage in neonatal rats%布洛芬对新生大鼠缺氧缺血后脑损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    乔丽丽; 沈伟勤

    2013-01-01

    Objective To investigate neuroprotective effect of ibuprofen on neonatal rats brain damage after hypoxia-ischemia (HI). Methods Fourty 7-day-old mice were divided to normal saline (NS) group, ibuprofen group, HI+NS group, and Hl+ibuprofen group. The HI+NS group and Hl+ibuprofen group subjected to unilateral ligation of the left common carotid artery (ischemia) and 50 min of hypoxia for set up HI model. An initial dose of ibuprofen lOOmg/kg was administered 2 hours after HI followed by a maintenance dose 50mg/kg every 24 hours for 6 days in Hl+ibuprofen group and ibupreofen group. The mice were sacrificed 7 days after HI. The grey matter, microtubule-associated protein-2 (MAP-2) and white matter, myeline basic protein (MBP) and neurofilameng (NF) injury were detected by immunohistochemical staining. The number of galectin-3 positive cells were counted in Cortex, DG, CA area. Results In NS group and ibuprofen group, the grey matter was normal and does not appear infarct. In Hl+ibuprofen group, the infarct area was (33.18+4.57) mm and the infarct volume was (39.18+4.29) mm3. In HI+NS group, the infarct area was (35.23+4.15) mm2 and the infarct volume was (40.23+4.65) mm3. There was no difference between two groups (t=34.54, 42.38, P>0.05). In Hl+ibuprofen group, the loss of MBP was (42.32+7.56)% and the loss of neurofilament (NF) was (40.34+6.83)%. In HI+NS group, the loss of MBP was (31.34+5.67)% and the loss of NF was (30.82+5.24)%. There were significant differences between two groups (t=13.51, 11.56, P0.05).HI+生理盐水组脑白质MBP损失为(42.32±7.56)%,NF为(40.34±6.83)%;HI+布洛芬组分别为(31.34±5.67)%、(30.82±5.24)%,两组差异有统计学意义(t=13.51、11.56,P均<0.05).HI+布洛芬组Cortex区的galectin-3细胞较HI+生理盐水组明显下降,差异有统计学意义(U=11.52,P<0.05).结论 布洛芬对HI后大脑的白质有明显保护作用,可能与降低小胶质细胞活性有关;但对大脑灰质无明显保护作用.

  1. Development of cerebral gray and white matter injury and cerebral inflammation over time after inflammatory perinatal asphyxia

    NARCIS (Netherlands)

    Bonestroo, Hilde J C; Heijnen, Cobi J.; Groenendaal, Floris; Van Bel, Frank; Nijboer, Cora H.

    2015-01-01

    Antenatal inflammation is associated with increased severity of hypoxic-ischemic (HI) encephalopathy and adverse outcome in human neonates and experimental rodents. We investigated the effect of lipopolysaccharide (LPS) on the timing of HI-induced cerebral tissue loss and gray matter injury, white m

  2. Observation on the curative effect of monosialotetrahexosylganglioside sodium salt injection for treatment of neonates with moderate and severe hypoxic-ischemic encephalopathy%单唾液酸四己糖神经节苷脂钠注射液治疗中、重度新生儿缺氧缺血性脑病疗效观察

    Institute of Scientific and Technical Information of China (English)

    赵玉萍; 彭晓康

    2012-01-01

    目的:探讨应用单唾液酸四己糖神经节苷脂钠治疗中、重度新生儿缺氧缺血性脑病(HIE)的疗效及对预后的影响,为临床治疗提供参考依据.方法:将92例中、重度HIE患儿随机分为对照组和治疗组,两组均予支持疗法和对症处理,对照组应用胞二磷胆碱,而治疗组应用单唾液酸四己糖神经节苷脂钠,两组方法及疗程相同,最后比较两组NBNA评分.所有病例均于出生后3、6、9、12个月时测定发育商(DQ),对两组临床疗效及预后进行比较.结果:治疗组呼吸改善时间、惊厥消失时间、症状及体征全部消失时间少于对照组;治疗组后遗症发生率低于对照组,治疗组NBNA评分及DQ高于对照组,差异均具有统计学意义(P<0.01).结论:与胞二磷胆碱相比,单唾液酸四己糖神经节苷脂钠治疗中、重度HIE的总有效率有所提高,患儿惊厥易于控制,意识障碍及肌张力等神经症状及体征恢复快,且在改善HIE的预后方面效果显著,可降低后遗症发生率及新生儿死亡率,无任何不良反应,适于临床推广使用.%Objective; To explore the curative effect of monosialotetrahexosylganglioside sodium salt injection for treatment of neonates with moderate and severe hypoxic - ischemic encephalopathy ( HIE) and its impact on prognosis, provide reference for clinical treatment. Methods; A total of 92 neonates with HIE were randomly divided into control group and treatment group, the neonates in the two groups received supporting treatment and symptomatic treatment, then the neonates in control group were treated with cytidine diphosphate choline, the neonates in treatment group were treated with monosialotetrahexosylganglioside sodium salt injection, the methods and courses of treatment in the two groups were the same, NBNA scores in the two groups were compared- Development quotients ( DQs) were measured in all the neonates at 3 , 6, 9, and 12 months after birth; clinical curative

  3. 高压氧舱治疗新生儿缺血缺氧性脑病的临床护理%Nursing Experience of Hyperbaric Oxygen in the Treatment of Neonatal Hypoxic Ischemic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    王献梅; 林杨; 张秋迟

    2015-01-01

    目的总结高压氧舱治疗新生儿缺血缺氧性脑病( HIE)的护理措施。方法选取69例新生儿缺血缺氧性脑病患儿作为研究对象,总结高压氧治疗期间的护理措施。结果通过积极治疗和精心护理,患儿脑水肿及高颅压症状明显改善。结论高压氧治疗新生儿缺血缺氧性脑病必须严格遵守和高度重视高压氧治疗的护理技术管理,以减轻患儿痛苦,缩短病程,改善预后,提高生存质量。%Objective Conclusion hyperbaric treatment of neonatal hypoxic ischemia encephalopathy (HIE) nursing measures.Methods Select 69 cases of neonatal hypoxic ischemia encephalopathy children as the research object,summarizes the nursing measures during the hyperbaric oxygen therapy.Results Through active treatment and careful nursing,cerebral edema and high cranial pressure symptoms improved significantly.Conclusion Hyperbaric oxygen treatment of neonatal hypoxic ischemia encephalopathy must strictly abide by and at aches great importance to the hyperbaric oxygen treatment of nursing management technology,to al eviate the children with pain,shorten the course of the disease and improve prognosis,improve the quality of survival.

  4. Meta-Analysis of Adjuvant Therapy of Cattle Encephalon Glycoside and Ignotin in Treatment of Neonatal Hypoxic-Ischemic Encephalopathy%脑苷肌肽佐治新生儿缺氧缺血性脑病的Meta分析

    Institute of Scientific and Technical Information of China (English)

    赵润; 贵仁伍; 任静

    2013-01-01

    Objective To evaluate the clinical effect and safety of the basic treatment plus the adjuvant therapy of cattle encephalon glycoside and ignotin in treating neonatal hypoxie-ischemic encephalopathy (HIE).Methods MEDLINE,EMBase,Cochrane Library,CBM,CNKI,VIP and Wanfang database were systematically retrieved for collecting the randomized controlled trials (RCT) of the basic treatment plus the adjuvant therapy of encephalon glycoside and ignotin and simple basic treatment in treating neonatal HIE.The included studies were performed the quality evaluation and the meta-analysis on the homogeneity studies.Results A total of 11 RCTs were included,scoring 3 by the Jadad scoring method.The meta-analysis results indicated that the significantly effective rates had statistical difference between the two groups[RR=1.81,95% CI(1.53,2.14)];the neonatal behavioral neurological assessment (NBNA) scores had statistical difference between the two groups [MD=4.30,95% Cl(2.24,6.35)];the differences in the the recovery time of the consciousness disturbance,seizures stop,anterior fontanel tension,primitivie reflex and muscular tension between the study group and the control group had statistical significance,[MD(95% CI) was-1.6(-2.15,-1.07),-1.21 (-1.84,-0.59),-1.53 (-2.07,-0.99),-2.27 (-3.10,-1.43) and-1.66 (-2.42,-0.90) respectively].Conclusion Based on the present clinical studies,adding cattle encephalon glycoside and ignotin on the basic treatment for treating neonatal HIE can increase the effect with good safety.%目的 评价基础治疗加用脑苷肌肽佐治新生儿缺氧缺血性脑病(HIE)的临床疗效和安全性.方法 系统检索MEDLINE,EMBase,Cochrane Library,CBM,CNKI,VIP及万方数据库,纳入HIE患儿基础治疗加用脑苷肌肽对比单纯基础治疗的随机对照试验(RCT),对纳入研究进行质量评价,并对同质性研究进行Meta分析.结果 共纳入11个RCT,Jadad评分均为3分.Meta分析显示,两组显效率差异有统计学意义[RR=1

  5. The Value of CT to Evaluate the Diagnosis and Prognosis of Neonatal Hypoxic Ischemic Encephalopathy%CT对新生儿缺血缺氧性脑病的诊断及预后评估的价值

    Institute of Scientific and Technical Information of China (English)

    高岩

    2015-01-01

    Objective To study the diagnosis value of CT for newborn hypoxia anoxic encephalopathy. Methods To choose our hospital neonatal hypoxic ischemia encephalopathy and 50 cases of children with typical symptoms, to patients with CT diagnosis and fol ow-up after treatment. Results 17 cases of mild in newborns, 26 cases of moderate, 6 cases of severe patients, there are 1 case combined cerebral hemorrhage in children with severe disease, 1 case with death. Conclusion CT diagnosis of neonatal hypoxic ischemia encephalopathy have high diagnostic value, can clear the change of the cases, for the diagnosis and prevention of early disease has a positive clinical significance.%目的:研究CT对新生儿缺血缺氧性脑病的诊断价值和预后评估。方法选取我院新生儿缺血缺氧性脑病50例患儿进行研究,对患者进行CT诊断且治疗后进行随访。结果轻度患儿17例,中度26例,重度6例,重度患儿中有1例合并脑出血,1例患儿死亡。结论 CT诊断对新生儿缺血缺氧性脑病有较高的诊断价值,可明确患儿的病情变化,对疾病的早期诊断和预防有积极的临床意义。

  6. [Application of pulse-coupled neural network combined with genetic algorithm on MR images of hypoxic-ischemic encephalopathy].

    Science.gov (United States)

    Liu, Li; Shi, Haiying; Huo, Liqin; Zhang, Feng; Zheng, Chongxun; You, Jia; He, Xining; Zhang, Jie

    2011-10-01

    This paper is to provide a basis for the establishment of an early diagnostic system for hypoxic-ischemic encephalopathy (HIE) by performing segmentation and feature extraction of lesions on the MR images of neonatal babies with HIE. The segmentation on MR images of HIE based on the genetic algorithm (GA) combined with a pulse-coupled neural network (PCNN) were carried out. There were better segmentation results by using PCNN segmentation based on GA than PCNN segmentation with fixed parameters. The data suggested that a PCNN based on GA could provide effective assistance for diagnosis and research.

  7. THE FETAL PROGNOSIS INFLUENCE OF EARLY NURSING INTERVENTION ON NEONATAL PATIENT WITH HYPOXIC ISCHEMIC ENCEPHALOPATHY%早期护理干预对新生儿缺氧缺血性脑病患儿预后的影响

    Institute of Scientific and Technical Information of China (English)

    张景英

    2014-01-01

    Objective To investigate how the early nursing intervention in neonatal patient with hypoxic is-chemic encephalopathy (HIE) affects the fetal progno-sis .Methods Divided 100 cases of children with HIE in our hospital from 2010 January to 2012 June ran-domly into the control group and the experimental group ,50 cases in each group .The control group re-ceived conventional therapy and nursing care ,w hile the experimental group ,besides routine treatment and nursing ,were given the early nursing intervention by professional nurses .Then ,the prognosis of two groups was evaluated .Results In the experimental group ,both the mental development index (MDI) and psychomotor development index (PDI) were higher than those of the control group ( P<0 .005) .Conclu-sion Early nursing intervention can promote the mental and physical development of children with HIE and therefore ,improve the living quality of children .%目的:探讨早期护理干预对新生儿缺氧缺血性脑病(H IE )患儿预后的影响。方法兰陵县人民医院2009年12月至2012年6月收治100例HIE患儿,随机分组。对照组50例只进行常规治疗和护理,实验组50例在常规治疗护理外给予早期护理干预,分析两组患儿预后。结果实验组智能发育指数(MDI)、运动发育指数(PDI)均高于对照组( P <0.05)。结论早期护理干预可促进HIE患儿智力及运动发育,提高患儿的生存质量。

  8. Enhanced neurogenesis in neonatal rats after hypoxic-ischemic brain damage%新生鼠脑缺氧缺血损伤后神经细胞再生增加

    Institute of Scientific and Technical Information of China (English)

    孟淑珍; 韩晓华; 韩玉昆

    2005-01-01

    目的许多研究已证实成年鼠脑缺血后神经细胞再生增加,但新生鼠脑缺氧缺血后神经细胞再生如何尚不太清楚.本文旨在调查新生鼠脑缺氧缺血后神经再生情况.方法24只7日龄新生鼠分为对照组(n=8)和缺氧缺血组(n=16),缺氧缺血组于缺氧后24 h行MR扫描以证实脑梗塞灶产生.术后或缺氧后第2~6天每日腹腔注射1次BrdU标记新生的细胞,应用免疫荧光法检查缺血缺氧后1周和4周时神经再生情况.结果缺氧缺血后1周或4周时缺血侧脑室管膜下区(SVZ)明显增宽.缺血侧SVZ的BrdU阳性细胞数在缺氧缺血后1周时显著高于对照组和非缺血侧(P<0.05),缺氧缺血后4周时较1周时下降,但仍显著高于对照组(P<0.05).缺血侧海马齿状回颗粒细胞层下区(SGZ)的BrdU阳性细胞数在缺氧缺血后1周增高,明显高于对照组(P<0.05),缺氧缺血后4周时较1周时减少,但仍显著高于对照组(P<0.05).缺氧缺血后1周或4周时在皮质和纹状体梗塞坏死灶周围可见散在分布的BrdU阳性细胞.结论新生鼠与成鼠类似,脑缺氧缺血后神经再生增强,提示不成熟脑具有一定自身修复能力.%Objective Many studies have demonstrated that neurogenesis is enhanced after cerebral ischemia in the adult rats. However, little is known about neurogenesis in the brain of neonatal rats after hypoxia-ischemia (HI). This study investigated neurogenesis in neonatal rats 1 and 4 weeks after HI. Methods Twenty-four seven-day-old Wistar rats were randomly assigned into Control group (n = 8) and Experimental group (n = 16). HI was induced by ligating the right common carotid artery combined with hypoxia exposure (8% oxygen in nitrogen) in the Experimental group. In the Control group, the right common carotid artery was isolated but not ligated and there was no exposure to hypoxia. MR imaging was performed 24 hrs after HI to confirm the formation of infarct. Bromodeoxyuridine (BrdU) was

  9. 全身亚低温治疗中、重度新生儿缺氧缺血性脑病的效果及安全性%Efficacy and safety of systemic mild hypothermia treatment for moderate or severe neonatal hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    吴联强; 王瑞泉; 张伟峰; 陈冬梅

    2015-01-01

    Objective To explore the efficacy and safety of systemic mild hypothermia in management of neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE).Methods A retrospective case-control study was conducted on 75 neonates with moderate or severe HIE,who were admitted to the Neonatal Intensive Care Unit of Teaching Hospital of Fujian Medical University (Quanzhou Children's Hospital) from January 1,2011 to May 31,2015.The 75 neonates were divided into two groups,the conventional treatment group (33 cases,control group) and the mild hypothermia treatment group (42 cases,hypothermia group).Sequential management protocol for all subjects was followed,including amplitude-integrated electroencephalogram (aEEG) before treatment,aEEG and brain MRI at one week after birth,neonatal behavioral neurological assessment (NBNA) on the 14th day after birth,and determination of mental and psychomotor development index with Bayley Scales of Infant and Toddler Developmental at 18 months old.Adverse reactions,serious disability cases and deaths during the study were also recorded.Two sample-t test and Chi-square test were as statistical methods.Results There were six death cases in the control group,but on one died in the hypothermia group.In the survivals,The maximum voltage and minimum voltage in the hypothermia group were higher at 7-day old than that before treatment [maximum voltage:(31.3 ±2.4) vs (18.1± 2.2) μ V;minimum voltage:(13.5±2.1) vs (6.1 ±1.5) μ V,t=8.591 and 5.314,both P < 0.05],and also higher than that of control group [(25.2±3.1) and (9.3±3.1) μV,respectively,both P ≤ 0.05].Compared with the control group,there were more babies with normal head MRI [43%(18/42) vs 18%(6/33),x2=4.814,P ≤ 0.05] in the hypothermia group at 7-day old and less cases of severe disability [21%(9/42) vs 45%(15/33),x2=4.902,P ≤ 0.05] and deaths [0%(0/42) vs 18%(6/33),x2=6.098,P ≤ 0.05].Higher NBNA score at 14 day and Bayley developmental index at 18

  10. Clinical observation of cytidine disodium triphosphate combined with mouse nerve growth factor in treatment of neonatal hypoxic ischemic encephalopathy%三磷酸胞苷二钠联合鼠神经生长因子治疗新生儿缺氧缺血性脑病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    丁玉红; 闫俊梅; 闫静

    2015-01-01

    .05). ConclusionCytidine disodium triphosphate combined with mouse nerve growth factor has good clinical curative effect in treatment of neonatal hypoxic ischemic encephalopathy, and can improve neural function and life quality, which has certain clinical application value.

  11. Function and mechanism of cytokines in cerebral hemodynamic regulation in neonatal hypoxic-ischemic encephalopathy%缺氧缺血性脑病患儿脑血流动力学调节中免疫细胞因子的作用及其机制

    Institute of Scientific and Technical Information of China (English)

    刘敬; 古梅; 黄醒华; 李坚; 翟桂荣; 王琪

    2004-01-01

    BACKGROUND: Whether the cerebral hemodynamic regulation by immune cell factors can be carried out through adjusting vascular active factors such as endothelin-1(ET-1),calcitonin gene-related peptide(cGRP),and C-type natriuretic peptide(CNP). OBJECTIVE: To explore the function and mechanism of cytokines in cerebral hemodynamic regulation in neonates with hypoxic-ischemic encephalopathy(HIE). DESING: Non-randomized controlled trial. RESULTS: In HIE group plasma level of TNF α was increased and IL-6 and IL-8 level was decreased,which correlated with disturbed cerebral hemodynamics and changes in ET-1,CGRP,and CNP levels.To be specific,resistance index(RI) was negatively correlated with IL-6 level(r=- 0.61, P< 0.01),and positively correlated with IL-8 and TNF α (r=0.80, 0.72,P< 0.01).IL-6 had negative correlation with ET-1( r=- 0.54, P< 0.01), and positive correlation with CNP and cGRP(r=0.49, 0.52, P< 0.01).By contrast,IL-8 and TNF α were positively correlated with ET-1(r=0.61, 0.72, P< 0.01) and negatively correlated with CNP and CGRP(r=- 0.51,- 0.63, P< 0.01). CONCLUSION: Plasma levels of IL-6,IL-8 and TNF α following HIE in neonates may regulate cerebral hemodynamics by adjusting the changes of ET-1,CGRP and CNP, thus participating in pathophysiologic mechanism of HIE.%背景:细胞因子对脑血流动力学的调节作用是否通过调节血浆内皮素- 1( endothelin-1,ET-1)、降钙素基因相关肽( calcitonin gene-related peptide,cGRP)、 C型利钠肽( C-type natriuretic peptide,CNP)等血管活性因子的变化而实现的.目的:探讨细胞因子对缺氧缺血性脑病 (hypoxic-ischemic encephalopathy,HIE)患儿脑血流动力学的调节作用及其机制.设计:非随机对照实验研究.地点、材料和干预:研究对象为 1999- 05/2001- 06来源于首都医科大学附属北京妇产医院,用放射免疫法检测 40例 HIE患儿与 40例正常新生儿生后 1, 3,和 7 d外周血白细胞介素- 6( interleukin-6, IL-6) ,

  12. [Multicenter program for the integrated care of newborns with perinatal hypoxic-ischemic insult (ARAHIP)].

    Science.gov (United States)

    Arnáez, J; Vega, C; García-Alix, A; Gutiérrez, E P; Caserío, S; Jiménez, M P; Castañón, L; Esteban, I; Hortelano, M; Hernández, N; Serrano, M; Prada, T; Diego, P; Barbadillo, F

    2015-03-01

    Newborns with perinatal indicators of a potential hypoxic-ischemic event require an integrated care in order to control the aggravating factors of brain damage, and the early identification of candidates for hypothermia treatment. The application of a prospective, populational program that organizes and systematizes medical care during the first 6 hours of life to all newborns over 35 weeks gestational age born with indicators of a perinatal hypoxic-ischemic insult. The program includes 12 hospitals (91,217 m(2)); two level i centers, five level ii centers, and five level iii hospitals. The program establishes four protocols: a) detection of the newborn with a potential hypoxic-ischemic insult, b) surveillance of the neurological repercussions and other organ involvement, c) control and treatment of complications, d) procedures and monitoring during transport. From June 2011 to June 2013, 213 of 32325 newborns above 35 weeks gestational age met the criteria of a potential hypoxic-ischemic insult (7.4/1000), with 92% of them being cared for following the program specifications. Moderate-severe hypoxic-ischemic encephalopathy was diagnosed in 33 cases (1/1,000), and 31 out of the 33 received treatment with hypothermia (94%). The program for the Integrated Care of Newborns with Perinatal Hypoxic-Ischemic Insult has led to providing a comprehensive care to the newborns with a suspected perinatal hypoxic-ischemic insult. Aggravators of brain damage have been controlled, and cases of moderate-severe hypoxic-ischemic encephalopathy have been detected, allowing the start of hypothermia treatment within the first six hours of life. Populational programs are fundamental to reducing the mortality and morbidity of hypoxic-ischemic encephalopathy. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  13. The effect of early nursing intervention on mental, motor function and prognosis of neonates with hypoxic ischemic encephalopathy%早期护理干预对新生儿缺氧缺血性脑病患儿智力和运动功能及预后的影响

    Institute of Scientific and Technical Information of China (English)

    李莉

    2015-01-01

    Objective To study the effect of early nursing intervention on mental,motor function and prognosis neonatal hypoxic ischemic encephalopathy.Methods A total of 96 new-borns with hypoxia ischemic encephalopathy were randomly divided into observation group (n =48)and control group (n =48)according to the digital method.Control group given conventional nursing,the observation group was given early nursing intervention on the basis of the control group,mental development index and motor development level were compared of two groups,two groups of children with developmental quotient level were followed up for 6 months,nursing job satisfaction,and the prognosis of two groups were compared.Results There was no significant difference in mental development index and motor development index before intervention in the two groups(P >0.05).After intervention for 1 month and 6 months,mental development index and motor development index in observation group were significantly higher than the control group,the differences were statistically significant (P <0.05).Each index levels of development quotient af-ter followed up for 6 months in observation group were significantly higher than that in the control group,differences were statistically significant (P <0.05).Nursing satisfaction rate in the obser-vation group was significantly higher than that of control group,the difference was statistically sig-nificant (P <0.05).Well-prognosis ratio of patients in the observation group was significantly higher than that of control group,the difference was statistically significant (P <0.05).Conclu-sion Early nursing intervention in children with hypoxic ischemic encephalopathy can improve its mental and motor functions,and promote positive outcomes.%目的:研究早期护理干预对新生儿缺氧缺血性脑病患儿智力和运动功能及预后的影响。方法选择接受缺氧缺血性脑病治疗的新生儿96例为研究对象,随机分成观察组及对照组各48

  14. 促红细胞生成素对缺氧缺血性脑损伤新生大鼠水通道蛋白4表达的影响%Effect of Erythropoietin on Expression of Aquaporin 4 in Neonatal Rats with Hypoxic-Ischemic Brain Damage

    Institute of Scientific and Technical Information of China (English)

    邵长荣; 姜红

    2012-01-01

    -rin 4 (AQP - 4) in brain tissue of neonatal rats with hypoxic - ischemic brain damage ( HIBD). Methods One hundred seven - day - old Sprague - Dawley(SD) rats were randomly divided into sham - operated group, control group, EPO low - dose group, EPO medium - dose group, EPO high - dose group( each group had 20 cases). The right carotid artery of rats in sham - operated group were only isolated, without ischemia,hypoxia and medication,while the other 4 groups were made by shearing right arteria carotis communis and breathing 80 mL · L-1 oxygen and 920 mL · L-1 nitrogen for 2 h. Then EPO low - dose group,EPO medium - dose group,EPO high - dose group received an intra-peritoneal injection of EPO with dose of 1 000 IU · kg-1,2 500 11) · kg-1, and 5 000 IU · kg -1 respectively in 0 hour,1 day,3 days,5 days. The other 2 groups received equivalent saline at the same time. Ten rats in each group were randomly executed on the 3rd and 7th day after the hypoxic - ischemic operation( n = 10). The AQP -4 expression in neonatal rats brain was examined by using immunohistochemical technique and image quantitative analysis respectively on the 3rd,7th day after the operation. Results 1. The number of AQP -4 positive cells in control group[(42.60±4.82) cells] was significantly higher than that in other groups on the 3rd day[ (26.60 ±4.67) cells,(36.60 ±3.97) cells, (20.80 ±7.90) cells, (23.00 ±9.60) cells, P, 0.05). 2. The number of AQP -4 positive cells in control group[(46. 20 ±5. 07) cells] was higher than that in sham - operated group,EPO medium - dose group and EPO high —dose group on the 7th day[ (16. 80 ±4.65) cells, (33.20 ±4.38) cells, (25-60 ±7.63) cells,P. <0.05]. The number of AQP-4 positive cells in EPO high -dose group was less than that in EPO medium -dose group,and that in EPO medium-dose group was less than that in EPO low -dose group,too(Pa <0.05). By HE staining, the damage of brain tissue in the hippocampal region in EPO low - dose group, EPO medium

  15. Doppler Ultrasound Detection of Neonatal Hypoxic Ischemic Encephalopathy Correlation with Gestational Hypertension Disease%多普勒超声检测新生儿缺氧缺血性脑病与妊娠期高血压疾病的相关性

    Institute of Scientific and Technical Information of China (English)

    周洁丽; 陈茀; 路竑璋

    2014-01-01

    新生儿缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)是围生期窒息引起新生儿脑损伤,多普勒超声对该病早期诊断及动态观察具一定价值.妊娠期高血压疾病(hypertensive disorders complicating pregnancy,HDCP)孕妇产出新生儿不良结局的概率明显增高,本文综合文献,现综述如下.

  16. Sequential treatment of neonatal hypoxic ischemic encephalopathy with a modified oxygen mask in an air-pressurized chamber%高压氧联合常规药物序贯治疗新生儿缺氧缺血性脑病的临床研究

    Institute of Scientific and Technical Information of China (English)

    卢晓欣; 房卫红; 彭慧平; 汤永建; 林茂英; 王承峰

    2008-01-01

    Objective To observe the efficacy, benefits and shortcomings of pressurized air therapy for neo- natal hypoxic ischemic encephalopathy (HIE). Methods One hundred and nine neonates with HIE were treated with hyperbaric oxygen (HBO) with a continuing oxygen supplement from an improved oxygen mask plus a 2.5-1itre breathing sacculus proprius in a large air-pressurized oxygen chamber. Among them there were 70 cases treated with 3-6 courses of HBO + drug therapy, 39 cases treated with a single session of HBO + drug therapy, and 32 treated with drug therapy alone. Motor development was assessed using the Chinese infantile intelligence development test scale at the ages of 3, 6 and 12 months. Results The sequential HBO + drug group achieved significantly better average motor development than the single session group or the drug only group. There was mo significant difference between the single treatment group and the drug only group. The proportion of abnormal CT results 12 months after treatment was significantly higher in the drug only group than in the sequential HBO + drug group. Conclusion Sequential HBO + drugs therapy with the improved oxygen mask is preferable to a single session of HBO + drug treatment or drug therapy alone.%目的 探讨在空气加压氧舱中新生儿缺氧缺血性脑病的治疗方法及其疗效.方法 将缺血缺氧性脑病患儿142例分为高压氧+药物多疗程序贯治疗组(序贯治疗组,n=70)、高压氧+药物单疗程治疗组(单疗程组,n=39)和单纯药物治疗组(药物治疗组,n=33).3组患儿均采用常规药物治疗,而序贯治疗组和单疗程组在常规药物治疗的基础上另在大型空气加压舱中,采用改良封闭式吸氧头罩+2.5 L呼吸球囊连续供氧方式进行高压氧治疗,序贯治疗组连续治疗3个疗程,单疗程组仅治疗1个疗程.3组患儿均于3,6和12月龄时行智能和运动发育评估,另于12月龄时行头颅CT复查.结果 智能发育评分序贯治疗组显著

  17. Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Kim, John J; Buchbinder, Nathan; Ammanuel, Simon; Kim, Robert; Moore, Erika; O'Donnell, Neil; Lee, Jennifer K; Kulikowicz, Ewa; Acharya, Soumyadipta; Allen, Robert H; Lee, Ryan W; Johnston, Michael V

    2013-01-01

    Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE). Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%-50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors. Using a piglet model, we confirmed that our device fits the specific parameters of therapeutic hypothermia, lowering the body temperature to 33.5°C with a 1°C margin of error. After the therapeutic hypothermia treatment, warming is regulated by adjusting the amount of water added and the location of baby inside the device. Our invention uniquely limits the amount of electricity required to power and operate the device compared with current expensive and high-tech devices available in the United States. Our device costs a maximum of 40 dollars and is simple enough to be used in neonatal intensive care units in developing countries.

  18. Brain diffusivity in infants with hypoxic-ischemic encephalopathy following whole body hypothermia: preliminary results.

    Science.gov (United States)

    Artzi, Moran; Sira, Liat Ben; Bassan, Haim; Gross-Tsur, Varda; Berger, Irit; Marom, Ronella; Leitner, Yael; Bental, Yoram; Shiff, Yakov; Geva, Ronny; Weinstein, Maya; Bashat, Dafna Ben

    2011-10-01

    Hypoxic-ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic-ischemic encephalopathy: cooled; (2) three infants with hypoxic-ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic-ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment.

  19. Efficacy of passive hypothermia and adverse events during transport of asphyxiated newborns according to the severity of hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Carreras, Nuria; Alsina, Miguel; Alarcon, Ana; Arca-Díaz, Gemma; Agut, Thais; García-Alix, Alfredo

    2017-08-18

    To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4±1.4°C and mean transfer time was 3.3±2.0h. Mean age at arrival was 5.6±2.5h. Temperature at arrival was between 33 and 35°C in 41 (61%) infants, between 35°C and 36.5°C in 15 (22%) and transport is greater in newborns with severe hypoxic-ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  20. 促红细胞生成素对新生鼠缺氧缺血性脑损伤后5-溴-2-脱氧尿嘧啶核苷表达的影响%Effects of erythropoietin on the expression of 5 -bromo -2 -deoxyuridine in subgranular zone of neonatal rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    段淼; 曹云涛

    2015-01-01

    目的:探讨促红细胞生成素( EPO)对新生鼠缺氧缺血性脑损伤( HIBD)后海马颗粒下带(SGZ)5-溴-2-脱氧尿嘧啶(BrdU)表达的影响。方法选择7日龄新生Wistar大鼠制备新生鼠HIBD动物模型,按照体重将新生鼠随机分为假手术组、HIBD模型组、EPO实验组( EPO 5 U・ g-1・ d-1×14 d)。在术后第14天、第21天、第28天,动态检测海马SGZ区BrdU阳性细胞数。结果海马SGZ区BrdU阳性细胞表达:3组新生大鼠在术后第14至28天,BrdU阳性细胞数随着新生鼠日龄增加而明显减少( P<0.01);在术后第14天、第21天、第28天,3组新生大鼠的海马SGZ区BrdU阳性细胞数以EPO实验组最多,其次为HIBD模型组,假手术组最少。在术后第21天,假手术组、HIBD模型组、EPO实验组的海马SGZ区BrdU阳性细胞数分别为8.08±1.62,25.71±4.18,32.21±8.63。在术后第14天、第21天,3组间两两比较差异有统计学意义( P<0.01);术后第28天,实验组与模型组比较差异有统计学意义( P<0.05)。结论新生鼠HIBD早期给予EPO干预治疗对新生鼠缺氧缺血性脑损伤可能有神经保护作用。%Objective To investigate the effect of erythropoietin( EPO) on the expression of 5-bromo-2-deoxyuridine( BrdU) in subgranular zone ( SGZ ) of neonatal rats with hypoxic -ischemic brain damage ( HIBD).Methods Animal HIBD model of seven-day-old newborn Wistar rat was made, and then the model rats were randomly divided into two groups: the model group of HIBD and the EPO trial group ( EPO 5 U・ g-1・ d-1 for 14 d).The expressions of BrdU in dentate gy-rus were examined with immunohistochemical staining and image quanti-tative analysis in fourteen days, twenty -first days and twenty -eight days after the operation.Results The expression of BrdU in SGZ: The number of BrdU -positive cell in SGZ of hippocampal region was gra-dually decreasing accompany

  1. Long-Term Neuropathological Changes Associated with Cerebral Palsy in a Nonhuman Primate Model of Hypoxic-Ischemic Encephalopathy.

    Science.gov (United States)

    McAdams, Ryan M; Fleiss, Bobbi; Traudt, Christopher; Schwendimann, Leslie; Snyder, Jessica M; Haynes, Robin L; Natarajan, Niranjana; Gressens, Pierre; Juul, Sandra E

    2017-01-01

    Cerebral palsy (CP) is the most common motor disability in childhood, with a worldwide prevalence of 1.5-4/1,000 live births. Hypoxic-ischemic encephalopathy (HIE) contributes to the burden of CP, but the long-term neuropathological findings of this association remain limited. Thirty-four term Macaca nemestrina macaques were included in this long-term neuropathological study: 9 control animals delivered by cesarean section and 25 animals with perinatal asphyxia delivered by cesarean section after 15-18 min of umbilical cord occlusion (UCO). UCO animals were randomized to saline (n = 11), therapeutic hypothermia (TH; n = 6), or TH + erythropoietin (Epo; n = 8). Epo was given on days 1, 2, 3, and 7. Animals had serial developmental assessments and underwent magnetic resonance imaging with diffusion tensor imaging at 9 months of age followed by necropsy. Histology and immunohistochemical (IHC) staining of brain and brainstem sections were performed. All UCO animals demonstrated and met the standard diagnostic criteria for human neonates with moderate-to-severe HIE. Four animals developed moderate-to-severe CP (3 UCO and 1 UCO + TH), 9 had mild CP (2 UCO, 3 UCO + TH, 3 UCO + TH + Epo, and 1 control), and 2 UCO animals died. None of the animals treated with TH + Epo died, had moderate-to-severe CP, or demonstrated signs of long-term neuropathological toxicity. Compared to animals grouped together as having no CP (no-CP; controls and mild CP only), animals with CP (moderate and severe) demonstrated decreased fractional anisotropy of multiple white-matter tracts including the corpus callosum and internal capsule, when using Tract-Based Spatial Statistics (TBSS). Animals with CP had decreased staining for cortical neurons and increased brainstem glial scarring compared to animals without CP. The cerebellar cell density of the internal granular layer and white matter was decreased in CP animals compared to that in control animals without CP. In this nonhuman primate HIE

  2. Systematic Review and Meta-Analysis of Therapeutic Hypothermia in Animal Models of Spinal Cord Injury

    OpenAIRE

    Batchelor, Peter E; Peta Skeers; Ana Antonic; Taryn E Wills; David W Howells; Macleod, Malcolm R; Sena, Emily S.

    2013-01-01

    Background Therapeutic hypothermia is a clinically useful neuroprotective therapy for cardiac arrest and neonatal hypoxic ischemic encephalopathy and may potentially be useful for the treatment of other neurological conditions including traumatic spinal cord injury (SCI). The pre-clinical studies evaluating the effectiveness of hypothermia in acute SCI broadly utilise either systemic hypothermia or cooling regional to the site of injury. The literature has not been uniformly positive with con...

  3. 枸橼酸咖啡因对新生大鼠缺氧缺血性脑损伤后髓鞘碱性蛋白的影响%Effects of caffeine citrate on myelin basic protein in neonatal rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    徐发林; 程慧清; 王彩红; 张彦华; 郭佳佳

    2015-01-01

    目的:研究枸橼酸咖啡因对新生大鼠缺氧缺血性脑损伤(HIBD)后脑白质髓鞘碱性蛋白(MBP)表达的影响及其相关机制。方法将48只7日龄Sprague-Dawley新生大鼠随机分为假手术组、HIBD组和枸橼酸咖啡因干预组,每组16只。左侧颈总动脉结扎并缺氧(80 mL/L氧气和920 mL/L氮气)2 h制作HIBD模型;假手术组仅分离左侧颈总动脉,不行结扎及缺氧处理;干预组在缺氧缺血前、缺氧缺血后0、24、48、72 h给予枸橼酸咖啡因(20 mg/kg)腹腔注射,HIBD组分别在同一时间点以等量生理盐水行替代腹腔注射。各组大鼠于12日龄处死,采用免疫组织化学法检测左侧脑皮层下白质MBP的表达;实时荧光定量逆转录聚合酶链式反应技术(Real-time PCR)检测各组大鼠左侧脑组织腺苷A1受体(A1R)和A2a受体(A2aR)mRNA的含量。结果 HIBD组左侧脑皮质下白质MBP表达较假手术组明显减少(P<0.05),干预组较HIBD组MBP表达增多,但仍低于假手术组(P<0.05);HIBD组A1R mRNA较假手术组显著上调(P<0.05),干预组A1R mRNA较HIBD组显著下降(P<0.05)。结论枸橼酸咖啡因能减轻缺氧缺血后新生大鼠脑白质损伤,这种保护作用可能与下调腺苷A1R表达有关。%Objective To study the effects of caffeine citrate on myelin basic protein (MBP) expression in the cerebral white matter of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the related mechanism. Methods Forty-eight seven-day-old Sprague-Dawley neonatal rats were randomly assigned to 3 groups:sham operation (n=16), HIBD (n=16) and HIBD+caffeine citrate (n=16). The rats in the HIBD and HIBD+caffeine citrate groups were subjected to left common carotid artery ligation, and then were exposed to 80 mL/L oxygen and 920 mL/L nitrogen for 2 hours to induce HIBD. The rats in the sham operation group were only subjected to a sham operation, without the left common

  4. Doxycycline treatment in a neonatal rat model of hypoxia-ischemia reduces cerebral tissue and white matter injury: a longitudinal magnetic resonance imaging study.

    Science.gov (United States)

    Widerøe, Marius; Havnes, Marianne B; Morken, Tora Sund; Skranes, Jon; Goa, Pål-Erik; Brubakk, Ann-Mari

    2012-07-01

    Doxycycline may potentially be a neuroprotective treatment for neonatal hypoxic-ischemic brain injury through its anti-inflammatory effects. The aim of this study was to examine any long-term neuroprotection by doxycycline treatment on cerebral gray and white matter. Hypoxic-ischemic brain injury was induced in 7-day-old rats. Pups were treated with either doxycycline (HI+doxy) or saline (HI+vehicle) by intraperitoneal injection at 1 h after hypoxia-ischemia (HI). At 6 h after HI, MnCl(2) was injected intraperitoneally for later manganese-enhanced magnetic resonance imaging (MRI). MRI was performed with diffusion-weighted imaging on day 1 and T(1) -weighted imaging and diffusion tensor imaging at 7, 21 and 42 days after HI. Animals were killed after MRI on day 42 and histological examinations of the brains were performed. There was a tendency towards lower lesion volumes on diffusion maps among HI+doxy than HI+vehicle rats at 1 day after HI. Volumetric MRI showed increasing differences between groups with time after HI, with less cyst formation and less cerebral tissue loss among HI+doxy than HI+vehicle pups. HI+doxy pups had less manganese enhancement on day 7 after HI, indicating reduced inflammation. HI+doxy pups had higher fractional anisotropy on diffusion tensor imaging in major white matter tracts in the injured hemisphere than HI+vehicle pups, indicating less injury to white matter and better myelination. Histological examinations supported the MRI results. Lesion size on early MRI was highly correlated with final injury measures. In conclusion, a single dose of doxycycline reduced long-term cerebral tissue loss and white matter injury after neonatal HI, with an increasing effect of treatment with time after injury. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  5. Curative effect analysis of mild hypothermia in treatment of neonatal hypoxic-ischemic encephalopathy and follow-up study of 36 children aged 18 months%亚低温治疗新生儿缺氧缺血性脑病36例疗效分析及18月龄随访调查

    Institute of Scientific and Technical Information of China (English)

    蔡成; 龚小慧; 裘刚; 魏东; 胡勇; 颜崇兵; 孙婧婧

    2014-01-01

    目的 探讨亚低温(MH)治疗中重度新生儿缺氧缺血性脑病(HIE)的疗效及安全性,并随访出院后18月龄患儿神经运动发育情况.方法 选取2007年1月至2013年12月在新生儿重症监护病房(NICU)住院治疗的中重度HIE患儿61例,依据上海市儿童医院NICU购买MH治疗仪前后分为常规治疗组(25例)和MH治疗组(36例),分别在治疗前、治疗72 h描记振幅整合脑电图(aEEG),记录出生28 d新生儿20项行为神经测定评分(NBNA),采用标准化的贝利(Bayley)婴儿发育量表对出院后18月龄患儿进行神经行为发育评价,同时观察MH治疗的不良反应、严重伤残例数及死亡例数.结果 MH治疗组治疗前aEEG与常规治疗组比较差异无统计学意义[最高电压:(22.4±3.1) μV比(18.6±±2.5) μV,最低电压:(8.2±2.6)μV比(6.5±1.9)μV,t=1.264、0.852,P均>0.05];但治疗72 h描记aEEG比较差异有统计学意义[最高电压:(24.1±3.2)μV比(30.6±2.8) μV,最低电压:(9.7±3.4)μV比(13.3±2.2) μV,t=6.376、4.257,P均<0.05],MH治疗组严重伤残例数[24.0%(6/25例)比5.6%(2/36例)x22=4.405,P<0.05]及死亡例数[16.0%(4/25例)比0(0/36例),x2 =6.164,P<0.05]明显下降,出生28 d NBNA[(35.9±±2.1)比(39.1±1.6),t=3.361,P<0.05]、随访18月龄标准化的Bayley婴儿发育量表进行神经行为发育评价差异有统计学意义[神经发育指数(MDI):(85.2±10.7)比(96.5±13.1),t=7.839,P<0.05].MH治疗过程中极少数发生呼吸暂停、凝血功能异常及心律失常等不良反应.结论 MH治疗中重度HIE安全有效,可显著降低中重度HIE患儿病死率,改善0~18月龄婴幼儿神经系统发育障碍,明显提高婴幼儿Bayley发育量表神经行为发育评分.%Objective To explore the efficacy and safety of mild hypothermia (MH) in treating the infants with moderate-to-severe neonatal hypoxic-ischemic encephalopathy(HIE),and to make a follow-up of the nerve motor development of the infants at 18 months old

  6. Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Allen RH

    2013-01-01

    Full Text Available John J Kim,1,2 Nathan Buchbinder,1,† Simon Ammanuel,1,4,5,† Robert Kim,1,† Erika Moore,1 Neil O'Donnell,1 Jennifer K Lee,3 Ewa Kulikowicz,3 Soumyadipta Acharya,1 Robert H Allen,1,9 Ryan W Lee,6,7 Michael V Johnston4–81Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, 2The James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins University School of Medicine, 3Department of Anesthesia and Critical Care Medicine, Johns Hopkins University, 4Kennedy Krieger Institute, 5Hugo W Moser Research Institute, 6Department of Neurology, 7Department of Pediatrics, 8Department of Physical Medicine and Rehabilitation Johns Hopkins University School of Medicine, Baltimore, MD; 9Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA†These authors contributed equally to this workAbstract: Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE. Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%–50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors

  7. Influence on learning and memory in neonatal rats with hypoxic-ischemic encephalopathy by transplantation of human mesenchymal stem cells%人骨髓间充质干细胞移植对缺氧缺血性脑病新生大鼠学习记忆功能的影响

    Institute of Scientific and Technical Information of China (English)

    赖文玉; 刘畅; 吴燕云; 麦友刚; 苏浩彬; 黄文革; 欧阳颖; 张红珊; 李文益

    2008-01-01

    Objective To evaluate the transplantation of human mesenchymal stem cells (hMSCs) into cerebral ventricle of neonatal rats with hypoxic-ischemic encephalopathy (HIE) ,to investigate the survival and migration of hMSCs,and the long-term effects of hMSCs on scores of learning and memory in rats. Method hMSCs were purified by culture-expanded in vitro and then labeled with the fluorescent tracker CM-DiI. Postnatal 7-day newborn rats were randomly divided into three groups:sham operation (n=10),HIE (n=10),and HIE-hMSCs (n=20).HIE-hMSCs rat model was established as follows: 72 h after hypoxic-ischemia,5 μl hMSCs(1×106 ceus/μl)were injected into the left cerebral ventricle of rats by using stereotactic instrument. All the animals were tested for the spatial learning and memory ability in the Morris water maze at week 6. The rats were decapitated and their brain tissues were sectioned to identify the transplanted cells under fluorescent microscope and to examine survival neurons in hippocampal CA1 zone by HE staining. Results hMSCs survived in rat brain for exceeding 5 weeks. Two weeks after transplantation,the marked hMSCs gave out red lights spreading along the two sides of needle canal. Five weeks after transplantation,the distribution of cells near the canal was sparser than that of 2 weeks .The spatial learning and memory ability of the HIE-hMSCs group were improved. The average escape latency of Morris water maze in HIE-hMSCs group (45.5±16.5) s was significantly shorter than that in HIE group(74.5±7.5)s(P<0.05).The swimming time spent in the target quadrant in HIE-hMSCs group(47±10)s was obviously longer than that in HIE group(36±8)s(P<0.01). The survival neurons of hippocamal CA1 zone in HIE-hMSCs group(94±23)neuron/mm were more than those in HIE group(61±12) neuron/mm(P<0.05). Conclusions The implanted hMSCs can survive at least for 5 weeks,and migrate in the brain of neonatal rats with HIE. hMSCs transplantation can improve the long-term learning

  8. 多巴胺受体调节对新生大鼠缺氧缺血性脑损伤后焦虑样行为的影响%Impact of dopamine receptor modulation on reduced anxiety-like behavior in neonatal rats after hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    陶惠康; 汤琴; 戴津津; 李媛媛; 黑明燕

    2014-01-01

    Objective To observe the long-term changes in anxiety-like behavior and tyrosine hydroxylase (TH) expression in the substantia nigra (SN) after hypoxic-ischemic brain damage (HIBD) in a neonatal rat model and to further explore the relationship between dopamine (DA) level and long-term anxiety-like behavior using the DA receptor (DAR) antagonist. Methods Seven-day-old (P7) neonatal Sprague-Dawley (SD) rats were randomized into normal control, sham-operated, HIBD and HIBD+DAR antagonist groups. HIBD model was prepared by ligating the right common carotid artery and 8%hypoxia exposure. The rats in the sham-operated group were sham-operated and were not subjected to right common carotid artery ligation and hypoxia exposure. The DAR antagonist was injected intraperitoneally before and after inducing HIBD. The same amount of normal saline was given to the other three groups as a control. Anxiety-like behavior was evaluated by elevated plus maze test, and TH expression in the SN was measured by immunohistochemistry on P14, P21, and P28. Results On P21 and P28, the time spent in the open arms and the percentage of open arms entries in the HIBD group were signiifcantly increased compared with those in the normal control, sham-operated and HIBD+DAR antagonist groups (P<0.05);in addition, the HIBD+DAR antagonist group showed a signiifcantly longer time spent in the open arms than the normal control group (P<0.05). On P14, P21, and P28, TH expression in the HIBD and HIBD+DAR antagonist groups was signiifcantly lower than that in the normal control and sham-operated groups, and TH level in the HIBD group was signiifcantly lower than that in the HIBD+DAR antagonist group (P<0.05). Conclusions DAR antagonist allows the restoration of anxiety-like behavior and alleviates the damage to dopaminergic neurons in SD rats after HIBD.%目的:观察缺氧缺血性脑损伤(HIBD)新生大鼠远期黑质酪氨酸羟化酶(TH)的表达及焦虑样行为的变化以及多巴胺

  9. 蛋白激酶R样内质网激酶的磷酸化对缺氧缺血性脑损伤新生大鼠脑神经细胞凋亡的影响%The role of phosphorylated protein kinase R-like ER kinase in brain tissue of hypoxic-ischemic neonatal rats and the following effect on neuronic apoptosis

    Institute of Scientific and Technical Information of China (English)

    顾卉; 纪莲; 黄天楚; 梅妍; 袁正伟

    2015-01-01

    Objective To investigate the effect and mechanism of phosphorylated protein kinase R-like ER kinase(p-PERK) and C/EBP homologous protein(CHOP) after hypoxic-ischemic brain damage ( HIBD) . Methods Neonatal 7-day-old Sprague Dawley rats were divided into sham-operation control group and HIBD group( n=30 per group) . Each group was divided into 0 h,6 h and 24 h subgroup after operation ( n=10 per group) . The ratio of apoptosis of brain cell was measured by flow cytometer and the expression of p-PERK and CHOP were detected by Western blot. Results (1)Apoptosis cell appeared at 6 h in HIBD group,the ratio of cell apoptosis was(2. 17 ± 0. 19)%. The apoptosis cell obvious increased at 24 h,the ratio of cell apoptosis was(13. 42 ± 0. 83)%. There was a significant increase in the ratio of apoptosis after HIBD 6 h and 24 h, as compared with sham-operation control group [ ( 0. 57 ± 0. 06 )%( P 0.05)。与假手术组比较,HIBD组各时间点二者的表达均明显上升,差异有统计学意义(P<0.01)。(3)缺氧缺血后各时间点磷酸化的PERK 的表达和 CHOP 的表达呈正相关(r=0.997,P<0.05)。结论脑缺氧缺血后,随着凋亡的出现,磷酸化的PERK 和 CHOP 表达水平升高,提示 PERK-CHOP通路的活化可能参与了新生大鼠 HIBD 神经细胞凋亡的发生。

  10. Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Parizel, Paul M.; Oezsarlak, Oezkan; Goethem, Johan W. van [Department of Radiology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Ceulemans, Berten; Laridon, Annick [Department of Pediatric Neurology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Jorens, Philippe G. [Department of Pediatric Intensive Care Medicine, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium)

    2003-12-01

    Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury. (orig.)

  11. The effects of cattle encephalon glycoside and ignotin injection combined with citicoline in the treatment of neonates with hypoxic ischemic encephalopathy%脑苷肌肽注射液联合胞二磷胆碱对新生儿缺氧缺血性脑病的影响

    Institute of Scientific and Technical Information of China (English)

    林春雨; 梁锦俊

    2015-01-01

    目的:探讨脑苷肌肽联合胞二磷胆碱对新生儿缺氧缺血性脑病(HIE)临床症状及神经功能的影响。方法选择我院收治的132例 H IE患者为研究对象,采用随机数字表法分为对照组(60例)和观察组(62例),对照组采用胞二磷胆碱治疗,观察组联合脑苷肌肽治疗,比较2组患儿治疗前后临床神经症状恢复时间、神经行为及神经功能评分(NBNA)的变化。结果观察组患者的意识、肌张力、原始反射等临床神经症状恢复时间明显短于对照组(5.32±1.28VS5.32±1.28,4.35±1.59VS6.64±1.58,5.39±1.12VS7.48±1.13);一般状态、原始反射、主动肌张力、被动肌张力、NABA评分方面明显高于对照组(4.78±0.36VS3.33±0.36,5.08±0.68VS3.28±0.62,6.38±1.01VS6.24±1.09,9.34±2.05VS9.27±1.93,39.09±2.01VS 31.69±2.05)。结论脑苷肌肽联合胞二磷胆碱有助于迅速恢复临床神经症状,改善神经功能,提高治疗效果。%Objective To study the effects of cattle encephalon glycoside and ignotin combined with citicoline on the nerve function in the treatment of neonates with hypoxic ischemic encephalopathy(HIE) .Methods 132 HIE patients in our hospital were randomly divided into the control group (60 cases) and the observation group (62 cases) .The control group were given citicoline treatment , observation group given citicoline combined with cattle encephalon glycoside and ignotin injection therapy .The changes of clinical symptom recovery time ,neural behavior ,and neural function score (NBNA) were compared between the two groups before and after treatment .Results The consciousness ,muscle tension ,and primitive reflex clinical neurological symptoms recovery time of the observation group were significantly shorter than the control group (5 .32 ± 1 .28 VS 5 .32 ± 1 .28 ,4 .35 ± 1 .59 VS 6 .64 ± 1 .58 ,5 .39 ± 1 .12 VS 7

  12. Expressions of Per1 and Cry1 in the pineal gland of neonatal rats with hypoxic-ischemic brain damage%缺氧缺血性脑损伤新生大鼠松果体钟基因Per1和Cry1表达的变化

    Institute of Scientific and Technical Information of China (English)

    余剑; 冯星; 孙斌; 王莹; 丁欣; 金美芳; 倪宏; 朱雪明

    2013-01-01

    目的 观察缺氧缺血性脑损伤(HIBD)新生大鼠松果体中Per1 mRNA、Cry1 mRNA表达水平及PER1和CRY1蛋白合成水平的变化,探讨钟基因表达异常在HIBD导致的昼夜节律紊乱中可能扮演的重要角色.方法将7日龄新生SD大鼠72只,随机分为2组(HIBD组36只,对照组36只).HIBD模型按改良Levine法建立.用半定量反转录(RT)-PCR和Western blot法分别测定HIBD模型制备后0、2、12、24、36、48 h2组新生大鼠松果体中Per1 mRNA和Cry1 mRNA以及PER1、CRY1蛋白合成水平,并比较2组之间的差异.结果 1.HIBD组Per1 mRNA的表达水平在HIBD模型制备后24、36、48 h均显著高于对照组(P均<0.05),0、2、12h与对照组相比差异均无统计学意义(P均>0.05);HIBD模型制备后24 h Per1 mRNA水平开始升高,36 h到达高峰,持续至48 h.2.HIBD组Cry1 mRNA的表达水平在HIBD模型制备后12、24、36 h均显著高于对照组(P均<0.05),0、2、48 h与对照组相比差异均无统计学意义(P均>0.05);HIBD模型制备后12 h Cry1 mRNA水平开始升高,24h到达高峰,持续至36 h.3.HIBD组PER1蛋白水平在HIBD模型制备后36 h显著高于对照组(P<0.05),0、2、12、24、48 h与对照组相比差异均无统计学意义(P均>0.05).4.HIBD组CRY1蛋白水平在HIBD模型制备后2、12、24h均显著高于对照组(P均<0.05),0、36、48 h与对照组相比差异均无统计学意义(P均>0.05);HIBD模型制备后2 h CRY1蛋白水平开始升高,24 h到达高峰,36 h降至正常.结论 HIBD对新生大鼠松果体细胞中Per1 mRNA、Cry1 mRNA和PER1、CRY1蛋白水平均有显著影响,生物钟系统的紊乱可能与HIBD的发病有关.%Objective To explore the effects of clock genes on circadian disorder in hypoxic-ischemic brain damage(HIBD) by comparing the level of PER1,CRY1 synthesis and the expression of Per1 mRNA,Cry1 mRNA in pineal gland of neonatal rats with HIBD.Methods Seven-day-old Sprague-Dawley (SD) rats were randomly divided into

  13. Immediate hypothermia reduces cardiac troponin I after hypoxic-ischemic encephalopathy in newborn pigs.

    Science.gov (United States)

    Liu, Xun; Tooley, James; Løberg, Else M; Suleiman, M Saadeh; Thoresen, Marianne

    2011-10-01

    Neonatal hypoxic-ischemic encephalopathy (HIE) is a clinically defined neurological condition after lack of oxygen and often associated with cardiac dysfunction in term infants. Therapeutic hypothermia (HT) after birth is neuroprotective in infants with HIE. However, it is not known whether HT is also cardioprotective. Four newborn pigs were used in the pilot study and a further 18 newborn pigs [randomly assigned to 72 h normothermia (NT) or 24 h HT followed by 48 h NT] were subjected to global HIE insults. Serum cTnI was measured before and post the HIE insult. Blood pressure, inotropic support, blood gases, and heart rate (HR) were recorded throughout. Cardiac pathology was assessed from histological sections. Cooling reduced serum cTnI levels significantly in HT pigs by 6 h (NT, 1.36 ± 0.67; HT, 0.34 ± 0.23 ng/mL; p = 0.0009). After rewarming, from 24 to 30 h postinsult, HR and cTnI increased in the HT group; from HR[24 h] = 117 ± 22 to HR[30 h] = 218 ± 32 beats/min (p = 0.0002) and from cTnI[24 h] = 0.23 ± 0.12 to cTnI[30 h] = 0.65 ± 0.53 ng/mL, (p = 0.05). There were fewer ischemic lesions on cardiac examination (37%) in the HT group compared with the NT group (70%). HT (24 h) pigs did not have the postinsult cTnI increase seen in NT-treated pigs. There was a trend that HT improved cardiac pathology in this 3-d survival model.

  14. Neuroprotective effects of electro acupuncture on hypoxic-ischemic encephalopathy in newborn rats Ass.

    Science.gov (United States)

    Xu, Tao; Li, Wenjie; Liang, Yiqun; Yang, Zhonghua; Liu, Jingdong; Wang, Yejun; Su, Nailun

    2014-11-01

    Hypoxic-ischemic encephalopathy (HIE) is a common and potentially devastating condition in the neonate, associated with high mortality and morbidity. Effective treatment options are limited and therefore alternative therapies such as acupuncture are increasingly used. Previous studies have shown that electro acupuncture promoted proliferation of neural progenitor cell and increased expression of neurotrophic factor in HIE. However, effects of electro acupuncture on downstream signaling pathways have been rarely researched. So, in the present study, we aimed to evaluate the neuroprotective effects of electro acupuncture on HIE and to further investigate the role of GDNF family receptor member RET and its key downstream PI3-K/Akt pathway in the process. A rat HIE model was constructed by the left common carotid artery (LCCA) ligation method in combination with hypoxic treatment. Considering that Baihui (GV20), Dazhui (GV14), Quchi (LI11) and Yongquan (KI1) are commonly used in clinics for stroke treatment and are easy to locate, we chose the above four acupoints as the combination for electro acupuncture treatment which was performed once a day for different time periods. Hematoxylin-eosin (HE) staining and transmission electron microscopy results showed that electro acupuncture could ameliorate neurologic damage and alleviate the degenerative changes of ultra structure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex. These findings suggest that electro acupuncture shows neuroprotective effects in HIE, which at least in part is attributed to activation of PI3-K/Akt signaling pathway.

  15. A Newborn Case of Hypoxic-Ischemic Encephalopathy Accompanied with 46,XX,-21,+t(21;21)%新生儿缺氧性脑病伴46,XX,-21,+t(21;21)罕见核型一例

    Institute of Scientific and Technical Information of China (English)

    付建华; 宁建英; 张青; 付睿婷; 李露霞

    2003-01-01

    This report describes a cytogenetic aberration in one neonatal patient with hypoxic-ischemic encephalopathy. A rare karyotype,46,XX, -21, +t(21;21), was detected. This de nono chromosomal abnormality may be caused by the meiotic non-disjunction of chromosomes during gametogenesis along with the formation of Robertsonian translocation between homologous chromosome 21.

  16. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmanić Šamija, R. [Department of Pediatrics, University Hospital Split, Split (Croatia); Primorac, D. [School of Medicine Split, University of Split, Split (Croatia); Department of Pediatrics, School of Medicine, University of Osijek, Osijek (Croatia); Eberly College of Science, Penn State University, University Park, PA (United States); St. Catherine Speciality Hospital, Zabok (Croatia); Rešić, B. [School of Medicine Split, University of Split, Split (Croatia); Pavlov, V. [Department of Neonatology, University Hospital Split, Split (Croatia); Čapkun, V. [Department of Nuclear Medicine, University Hospital Split, Split (Croatia); Punda, H. [School of Medicine Split, University of Split, Split (Croatia); Lozić, B. [Department of Pediatrics, University Hospital Split, Split (Croatia); Zemunik, T. [Department of Medical Biology, School of Medicine Split, University of Split, Split (Croatia)

    2014-08-15

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  17. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Kuzmanić Šamija, R; Primorac, D; Rešić, B; Pavlov, V; Čapkun, V; Punda, H; Lozić, B; Zemunik, T

    2014-10-01

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  18. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    R. Kuzmani? ?amija

    2014-10-01

    Full Text Available The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  19. Stem cells for brain repair in neonatal hypoxia-ischemia.

    Science.gov (United States)

    Chicha, L; Smith, T; Guzman, R

    2014-01-01

    Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

  20. Amplitude-integrated Electroencephalography in Full-term Newborns without Severe Hypoxic-ischemic Encephalopathy: Case Series

    OpenAIRE

    Osredkar,Damjan; Derganc, Metka; Paro-Panjan, Darja; Neubauer, David

    2006-01-01

    Aim: To assess the diagnostic value of amplitude-integrated electroencephalography (EEG) in comparison to standard EEG in newborns without severe hypoxic-ischemic encephalopathy who were at risk for seizures. Methods: The study included a consecutive series of 18 term newborns without severe hypoxic-ischemic encephalopathy, but with clinical signs suspicious of epileptic seizures, history of loss of social contact, disturbance of muscle tone, hyperirritability, and/or jitteriness. Amplitud...

  1. Birth Injuries and Related Risk Factors in Neonates Born in Emam Sajjad Hospital in Yasuj in 2005 to 2006

    Directory of Open Access Journals (Sweden)

    M Rezaie

    2009-04-01

    Risk factors were included NVD (difficult vaginal delivery, high gestation age, and low Apgar score at first minute of life, shoulder dystocia, vacuum and birth at night. Conclusion: The present study revealed that the incidence of birth injuries in this area is high. Considering the serious complications of birth injuries and hypoxic-ischemic encephalopathy with no treatment for some cases, it seems that using the preventing methods to reduce the prevalence of birth injuries is nessesary

  2. Effects of platelet derived growth factor on brain cell apoptosis rate and serum neuron-specific enolase after hypoxic-ischemic brain damage in neonatal rats%血小板生长因子对缺氧缺血性脑损伤新生鼠脑细胞凋亡率和血清神经元特异性烯醇化酶的影响

    Institute of Scientific and Technical Information of China (English)

    周春清; 许锋; 姜红; 薛永梅

    2011-01-01

    apoptosis rate and serum neuron-specific enolase (NSE) concentration after hypoxic-ischemic brain damage (HIBD) in neonatal rats. Methods Forty-eight HIBD models of 7-day old neonatal Wistar rats were established and then divided into two groups randomly:PDGF group and normal saline control group (n =24 in each).Another 24 neonatal Wistar rats were taken into the sham operation group.The treatment group received intraperitoneal injection of PDGF-BB (50 ng/kg) once,while the other two groups received normal saline at the same time.In each group,rats were randomly sacrificed immediately at 12,24 and 72 hours after injection (n=8).The serum of rats were reserved for NSE concentration determination by enzyme linked immunosorbent assay,and the right brains of the sacrificed rats were used to prepare brain cell suspension for neurocyte apoptosis rate examination by flow cytometry.Mono-variate analysis and q-test were performed for statistical analysis. Results (1) The brain cell apoptotic rates of treatment group [ (6.09 ± 0.70)%,(9.67 ± 1.52) % and (14.15±1.52)%] and control group [(8.00± 1.10)%,(11.45±2.42)% and (22.90±2.03) %] were significantly increased compared to that of sham group [(2.11 ± 0.54)%,(2.34 ±0.46)% and (2.21±0.49)%] at all time points (all P<0.01 or <0.05),the apoptotic rate of treatment group was lower than that of control group (P<0.01 or <0.05).Statistical differences were found among the three groups at 12,24 and 72 hours (F =39.01,66.60 and 194.20respectively; P<0.01).(2) Serum NSE concentration was significantly increased in the treatment group [(8.43 ± 0.17) μg/L,(6.73 ± 0.16) μg/L and (6.12 ± 0.13) μg/L] and control group [(10.04±0.19) μg/L,(9.33 0.15) μg/L and (8.36 ± 0.16) μg/L] than in the sham group [(4.22±0.53) μg/L,(3.96±0.60) μg/L and (3.59±0.55) μg/L] at all time points,and it was significantly lower in treatment group than in control group (P< 0.01).Statistical difference was found among

  3. Nerve protective effect of rhTPO and G-CSF on hypoxic ischemic brain damage in rats

    Institute of Scientific and Technical Information of China (English)

    Hong-Xia Zhou; Chun-Lai Zhang; Yue-Hong Li; Yu-Xin Zhang; Zi-Feng Wei; Xi Wang Meng Ling-Li

    2014-01-01

    Objective:To observe the protection effect of rhTPO and granulocyte colony stimulating factor (G-CSF) on brain nerve after hypoxic ischemic brain damage(HIBD) in neonatal rats, exploring new ways for the laboratory basis of treatment for hypoxic ischemic encephalopathy, and provide for possible.Methods:A total of120 newbornSD rats aging7 d were randomly divided into control group, model group,TPO group andG-CSF group, using the method of blockingleft carotid artery to establishHIBD model.The left carotid artery was only seperated rather than blocked in the control group; after modeling, saline injection, rhTPO treatment andG-CSF treatment were adopted in the model group,TPO group andG-CSF group respectively.Then10 rats of4 groups were executed atDay3,7,14 after modeling, brain tissue was extracted to observe the brain damage;Immunohistochemical method was used to observe the histopathological changes of brain tissue and changes of nest protein(nestin) expression.Results:Injured brain mass of model group,TPO group andG-CSF group were significantly higher than that of control group at corresponding time point(P<0.05).Injured brain mass ofTPO group andG-CSF group were significantly lower than that of model group(P<0.05), and with the increase of age, more significant increasing trend.AtDay3 after modeling, the expression of nestin positive cells in cerebral cortex of model group,TPO group andG-CSF group increased significantly than that of control group(P<0.05); nestin positive cells ofG-CSF group outnumberedTPO group significantly (P<0.05).Conclusions:The earlyTPO,G-CSF treatment ofHIBD rats can improve brain function after hypoxia ischemia by neural protection.G-CSF can promote the differentiation of neural cells proliferation, and reduce degeneration and necrosis of nerve cells.

  4. Influences of Hypoxic-ischemic Brain Damage on Pineal Arylalkylamine-N-acetyltransferase mRNA Expression and Plasma Melatonin Level in Neonatal Rats%缺氧缺血对新生大鼠松果体芳香烷基胺-N-乙酰基转移酶

    Institute of Scientific and Technical Information of China (English)

    丁欣; 姜善雨; 冯星; 何军; 孙斌; 朱雪明

    2011-01-01

    Objective To elucidate the influences of hypoxic-ischemic brain damage (HIBD) on pineal function of melatonin synthesis and explore the possible significance of pineal function alterations in HIBD.Methods Sixty seven-day-old rats were randomly divided into 2 groups: the HIBD group and sham-operated group.Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to measure the melatonin-synthetase-arylalkylamine-N-acetyltransferase (AANAT) mRNA expressions in pineal gland.Radioimmunoassay (RIA) was used to measure the plasma melatonin levels.Results ( 1 ) The AANAT mRNA expression 6 h, 12 h, 24 h after HIBD were lower than those in the corresponding sham-operated groups( P <0.05 or 0.01 ) ,and no significant difference was found among different time points in the sham-operated groups; (2) The plasma melatonin levels 12 h, 24 h after HIBD were lower than those in the corresponding sham-operated groups.The melatonin levels at different time points in the sham-operated group were similar.Conclusions Pineal melatonin-synthesis is impaired on early stage of HIBD.Alternation of the protective process of endogenous MLT might be involved in pathogenic mechanism of early HIBD.%目的 了解缺氧缺血性脑损伤(HIBD)对松果体芳香烷基胺-N-乙酰基转移酶(AANAT)mRNA表达和血浆褪黑素(MLT)含量的影响,探讨松果体功能改变在HIBD中的意义.方法 选取7日龄SD大鼠60只随机分成HIBD模型组和假手术组.HIBD模型组按改良Levine法建立,然后用半定量逆转录聚合酶链反应(RT-PCR)和放免技术分别测定并比较两组缺氧缺血后0 h、6 h、12 h、24h、48 h松果体中AANAT mRNA的表达水平及血浆MLT的浓度.结果 (1)松果体中AANAT mRNA的表达在HIBD后6 h、12 h、24 h低于对应假手术组(P<0.05或<0.01);假手术组各时点之间AANAT mRNA的表达水平无明显变化(P>0.05).(2)血浆MLT浓度在HIBD后12 h、24 h均低于对应假手术组(P<0.01);假手术组

  5. Effects of inter-alpha inhibitor proteins on neonatal brain injury: Age, task and treatment dependent neurobehavioral outcomes.

    Science.gov (United States)

    Threlkeld, Steven W; Gaudet, Cynthia M; La Rue, Molly E; Dugas, Ethan; Hill, Courtney A; Lim, Yow-Pin; Stonestreet, Barbara S

    2014-11-01

    Hypoxic-ischemic (HI) brain injury is frequently associated with premature and/or full term birth related complications. HI injury often results in learning and processing deficits that reflect widespread damage to an extensive range of cortical and sub-cortical brain structures. Further, inflammation has been implicated in the long-term progression and severity of HI injury. Recently, inter-alpha inhibitor proteins (IAIPs) have been shown to attenuate inflammation in models of systemic infection. Importantly, preclinical studies of neonatal HI injury and neuroprotection often focus on single time windows of assessment or single behavioral domains. This approach limits translational validity, given evidence for a diverse spectrum of neurobehavioral deficits that may change across developmental windows following neonatal brain injury. Therefore, the aims of this research were to assess the effects of human IAIPs on early neocortical cell death (72h post-insult), adult regional brain volume measurements (cerebral cortex, hippocampus, striatum, corpus callosum) and long-term behavioral outcomes in juvenile (P38-50) and adult (P80+) periods across two independent learning domains (spatial and non-spatial learning), after postnatal day 7 HI injury in rats. Here, for the first time, we show that IAIPs reduce acute neocortical neuronal cell death and improve brain weight outcome 72h following HI injury in the neonatal rat. Further, these longitudinal studies are the first to show age, task and treatment dependent improvements in behavioral outcome for both spatial and non-spatial learning following systemic administration of IAIPs in neonatal HI injured rats. Finally, results also show sparing of brain regions critical for spatial and non-spatial learning in adult animals treated with IAIPs at the time of injury onset. These data support the proposal that inter-alpha inhibitor proteins may serve as novel therapeutics for brain injury associated with premature birth and

  6. The Association between NOS3 Gene Polymorphisms and Hypoxic-Ischemic Encephalopathy Susceptibility and Symptoms in Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Yongqin Wu

    2016-01-01

    Full Text Available Endothelial NOS (NOS3 has a potential role in the prevention of neuronal injury in hypoxic-ischemic encephalopathy (HIE. Thus, we aimed to explore the association between NOS3 gene polymorphisms and HIE susceptibility and symptoms in a Chinese Han population. Three single nucleotide polymorphisms (SNPs in the NOS3 gene, rs1800783, rs1800779, and rs2070744, were detected in 226 children with HIE and 212 healthy children in a Chinese Han population. Apgar scores and magnetic resonance image scans were used to estimate the symptoms and brain damage. The association analyses were conducted by using SNPStats and SPSS 18.0 software. The genotype and allele distributions of rs1800779 and rs1799983 displayed no significant differences between the patients and the controls, while the rs2070744 allele distribution was significantly different (corrected P=0.009. For clinical characteristics, the rs2070744 genotype distribution was significantly different in patients with different Apgar scores (≤5, TT/TC/CC = 6/7/5; 6~7, TT/TC/CC = 17/0/0; 8~9, TT/TC/CC = 6/2/0; 10, TT/TC/CC = 7/1/0; corrected P=0.006 in the 1001 to 1449 g birth weight subgroup. The haplotype test did not show any associations with the risk and clinical characteristics of HIE. The results suggest that NOS3 gene SNP rs2070744 was significantly associated with HIE susceptibility and symptom expression in Chinese Han population.

  7. The Association between NOS3 Gene Polymorphisms and Hypoxic-Ischemic Encephalopathy Susceptibility and Symptoms in Chinese Han Population.

    Science.gov (United States)

    Wu, Yongqin; Zhu, Zhiling; Fang, Xiaoxia; Yin, Ling; Liu, Yuxia; Xu, Shouxia; Li, Aixue

    2016-01-01

    Endothelial NOS (NOS3) has a potential role in the prevention of neuronal injury in hypoxic-ischemic encephalopathy (HIE). Thus, we aimed to explore the association between NOS3 gene polymorphisms and HIE susceptibility and symptoms in a Chinese Han population. Three single nucleotide polymorphisms (SNPs) in the NOS3 gene, rs1800783, rs1800779, and rs2070744, were detected in 226 children with HIE and 212 healthy children in a Chinese Han population. Apgar scores and magnetic resonance image scans were used to estimate the symptoms and brain damage. The association analyses were conducted by using SNPStats and SPSS 18.0 software. The genotype and allele distributions of rs1800779 and rs1799983 displayed no significant differences between the patients and the controls, while the rs2070744 allele distribution was significantly different (corrected P = 0.009). For clinical characteristics, the rs2070744 genotype distribution was significantly different in patients with different Apgar scores (≤5, TT/TC/CC = 6/7/5; 6~7, TT/TC/CC = 17/0/0; 8~9, TT/TC/CC = 6/2/0; 10, TT/TC/CC = 7/1/0; corrected P = 0.006) in the 1001 to 1449 g birth weight subgroup. The haplotype test did not show any associations with the risk and clinical characteristics of HIE. The results suggest that NOS3 gene SNP rs2070744 was significantly associated with HIE susceptibility and symptom expression in Chinese Han population.

  8. NOC/oFQ and NMDA contribute to piglet hypoxic ischemic hypotensive cerebrovasodilation impairment.

    Science.gov (United States)

    Armstead, William M

    2002-05-01

    Previous studies have observed that hypotensive pial artery dilation was blunted after hypoxia-ischemia. In unrelated studies, the opioid nociceptin/orphanin FQ (NOC/oFQ) was observed to contribute to hypoxic ischemic impairment of N-methyl-D-aspartate (NMDA)-induced pial dilation. This study determined the contribution of NOC/oFQ and NMDA to hypoxic ischemic hypotensive cerebrovasodilation impairment in newborn pigs equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased PO(2) to 33 +/- 3 mm Hg. Topical NOC/oFQ (10(-10) M), the cerebrospinal fluid concentration after hypoxia-ischemia, had no effect on pial artery diameter by itself but attenuated hypotension (mean arterial blood pressure decrease of 44 +/- 2%) -induced pial artery dilation (35 +/- 2% versus 22 +/- 3%). Hypotensive pial artery dilation was blunted by hypoxia-ischemia, but such dilation was partially protected by pretreatment with the putative NOC/oFQ receptor antagonist, [F/G] NOC/oFQ (1-13) NH(2) (10(-6) M; 29 +/- 2%, sham control; 7 +/- 2%, hypoxia-ischemia; and 13 +/- 2%, hypoxia-ischemia and [F/G] NOC/oFQ (1-13) NH(2)). Coadministration of the NMDA antagonist MK801 (10(-5) M) with NOC/oFQ(10(-10) M) partially prevented hypotensive pial dilation impairment. Similarly, pretreatment with MK801 partially protected hypoxic ischemia impairment of hypotensive pial dilation (35 +/- 2%, sham control; 7 +/- 1%, hypoxia-ischemia; 22 +/- 2%, hypoxia-ischemia + MK801). These data show that NOC/oFQ and NMDA contribute to hypoxic ischemic hypotensive cerebrovasodilation impairment. These data suggest that NOC/oFQ modulation of NMDA vascular activity also contributes to such hypotensive impairment.

  9. MRI in paediatric hypoxic-ischemic disease, metabolic disorders and malformations-A review

    Energy Technology Data Exchange (ETDEWEB)

    Beitzke, Dietrich [Department of Radiology, Division of Neuroradiology, Medical University, Graz (Austria)], E-mail: dietrich.beitzke@meduni-graz.at; Simbrunner, Josef [Department of Radiology, Division of Neuroradiology, Medical University, Graz (Austria); Riccabona, Michael [Department of Radiology, Division of Paediatric Radiology, Medical University, Graz (Austria)

    2008-11-15

    MRI has become the most important modality in paediatric neuroimaging. It provides an excellent anatomical overview with good spatial and temporal resolution, allows investigations of the blood vessels, and - using technologies such as diffusion-weighted imaging and magnetic resonance spectroscopy - it allows quick and exact differentiation of ischemic, hypoxic, inflammatory, oncologic, traumatic and metabolic diseases. This review presents an overview of brain MRI in infants and children with suspected hypoxic-ischemic disease, metabolic disorders or (vascular) malformations, illustrating these issues by some MRI findings in selected important conditions and discussing some major clinical and pathophysiological aspects important for imaging.

  10. Plasminogen activator inhibitor-1 mitigates brain injury in a rat model of infection-sensitized neonatal hypoxia-ischemia.

    Science.gov (United States)

    Yang, Dianer; Sun, Yu-Yo; Nemkul, Niza; Baumann, Jessica M; Shereen, Ahmed; Dunn, R Scott; Wills-Karp, Marsha; Lawrence, Daniel A; Lindquist, Diana M; Kuan, Chia-Yi

    2013-05-01

    Intrauterine infection exacerbates neonatal hypoxic-ischemic (HI) brain injury and impairs the development of cerebral cortex. Here we used low-dose lipopolysaccharide (LPS) pre-exposure followed by unilateral cerebral HI insult in 7-day-old rats to study the pathogenic mechanisms. We found that LPS pre-exposure blocked the HI-induced proteolytic activity of tissue-type plasminogen activator (tPA), but significantly enhanced NF-κB signaling, microglia activation, and the production of pro-inflammatory cytokines in newborn brains. Remarkably, these pathogenic responses were all blocked by intracerebroventricular injection of a stable-mutant form of plasminogen activator protein-1 called CPAI. Similarly, LPS pre-exposure amplified, while CPAI therapy mitigated HI-induced blood-brain-barrier damage and the brain tissue loss with a therapeutic window at 4 h after the LPS/HI insult. The CPAI also blocks microglia activation following a brain injection of LPS, which requires the contribution by tPA, but not the urinary-type plasminogen activator (uPA), as shown by experiments in tPA-null and uPA-null mice. These results implicate the nonproteolytic tPA activity in LPS/HI-induced brain damage and microglia activation. Finally, the CPAI treatment protects near-normal motor and white matter development despite neonatal LPS/HI insult. Together, because CPAI blocks both proteolytic and nonproteolytic tPA neurotoxicity, it is a promising therapeutics of neonatal HI injury either with or without infection.

  11. Neuroprotective body hypothermia among newborns with hypoxic ischemic encephalopathy: three-year experience in a tertiary university hospital. A retrospective observational study

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    Mauricio Magalhães

    Full Text Available CONTEXT AND OBJECTIVE:Neonatal hypoxic-ischemic encephalopathy is associated with high morbidity and mortality. Studies have shown that therapeutic hypothermia decreases neurological sequelae and death. Our aim was therefore to report on a three-year experience of therapeutic hypothermia among asphyxiated newborns.DESIGN AND SETTING:Retrospective study, conducted in a university hospital.METHODS:Thirty-five patients with perinatal asphyxia undergoing body cooling between May 2009 and November 2012 were evaluated.RESULTS:Thirty-nine infants fulfilled the hypothermia protocol criteria. Four newborns were removed from study due to refractory septic shock, non-maintenance of temperature and severe coagulopathy. The median Apgar scores at 1 and 5 minutes were 2 and 5. The main complication was infection, diagnosed in seven mothers (20% and 14 newborns (40%. Convulsions occurred in 15 infants (43%. Thirty-one patients (88.6% required mechanical ventilation and 14 of them (45% were extubated within 24 hours. The duration of mechanical ventilation among the others was 7.7 days. The cooling protocol was started 1.8 hours after birth. All patients showed elevated levels of creatine phosphokinase, creatine phosphokinase- MB and lactate dehydrogenase. There was no severe arrhythmia; one newborn (2.9% presented controlled coagulopathy. Four patients (11.4% presented controlled hypotension. Twenty-nine patients (82.9% underwent cerebral ultrasonography and 10 of them (34.5% presented white matter hyper-echogenicity. Brain magnetic resonance imaging was performed on 33 infants (94.3% and 11 of them (33.3% presented hypoxic-ischemic changes. The hospital stay was 23 days. All newborns were discharged. Two patients (5.8% needed gastrostomy.CONCLUSION:Hypothermia as therapy for asphyxiated newborns was shown to be safe.

  12. Influence of hyperbaric oxygen on the differentiation of hypoxic/ischemic brain-derived neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Zhengrong Peng; Sue Wang; Pingtian Xiao

    2009-01-01

    BACKGROUND: It has been previously shown that hyperbaric oxygen may promote proliferation of neural stem cells and reduce death of endogenous neural stem cells (NSCs).OBJECTIVE: To explore the effects of hyperbaric oxygen on the differentiation of hypoxic/ischemic brain-derived NSCs into neuron-like cells and compare with high-concentration oxygen and high pressure.DESIGN, TIME AND SETTING: An in vitro contrast study, performed at Laboratory of Neurology,Central South University between January and May 2006.MATERIALS: A hyperbaric oxygen chamber (YLC 0.5/1A) was provided by Wuhan Shipping Design Research Institute; mouse anti-rat microtubute-associated protein 2 monoclonal antibody by Jingmei Company, Beijing; mouse anti-rat glial fibrillary acidic protein monoclonal antibody by Neo Markers,USA; mouse anti-rat galactocerebroside monoclonal antibody by Santa Cruz Biotechnology Inc.,USA; and goat anti-mouse fluorescein isothiocyanate-labeled secondary antibody by Wuhan Boster Bioengineering Co., Ltd., China.METHODS: Brain-derived NSCs isolated from brain tissues of neonatal Sprague Dawiey rats werecloned and passaged, and assigned into five groups: normal control, model, high-concentration oxygen, high pressure, and hyperbaric oxygen groups. Cells in the four groups, excluding the normal control group, were incubated in serum-containing DMEM/F12 culture medium. Hypoxic/ischemic models of NSCs were established in an incubator comprising 93% N2, 5% CO2, and 2% O2.Thereafter, cells were continuously cultured as follows: compressed air (0.2 MPa, 1 hour, once a day)in the high pressure group, compressed air+a minimum of 80% O2 in the hyperbaric oxygen group,and a minimum of 80% O2 in the high-concentration oxygen group. Cells in the normal control and model groups were cultured as normal.MAIN OUTCOME MEASURES: At day 7 after culture, glial fibrillary acidic protein,microtubule-associated protein 2, and galactocerebroside immunofluorescence staining were examined to

  13. Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns

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    Verónica Chaparro-Huerta

    2017-02-01

    Conclusion: The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models.

  14. Cortical region-specific engraftment of embryonic stem cell-derived neural progenitor cells restores axonal sprouting to a subcortical target and achieves motor functional recovery in a mouse model of neonatal hypoxic-ischemic brain injury

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    Mizuya eShinoyama

    2013-08-01

    Full Text Available Hypoxic–ischemic encephalopathy (HIE at birth could cause cerebral palsy, mental retardation, and epilepsy, which last throughout the individual’s lifetime. However, few restorative treatments for ischemic tissue are currently available. Cell replacement therapy offers the potential to rescue brain damage caused by HI and to restore motor function. In the present study, we evaluated the ability of embryonic stem cell-derived neural progenitor cells (ES-NPCs to become cortical deep layer neurons, to restore the neural network, and to repair brain damage in an HIE mouse model. ES cells stably expressing the reporter gene GFP are induced to a neural precursor state by stromal cell co-culture. Forty-hours after the induction of HIE, animals were grafted with ES-NPCs targeting the deep layer of the motor cortex in the ischemic brain. Motor function was evaluated 3 weeks after transplantation. Immunohistochemistry and neuroanatomical tracing with GFP were used to analyze neuronal differentiation and axonal sprouting. ES-NPCs could differentiate to cortical neurons with pyramidal morphology and expressed the deep layer-specific marker, Ctip2. The graft showed good survival and an appropriate innervation pattern via axonal sprouting from engrafted cells in the ischemic brain. The motor functions of the transplanted HIE mice also improved significantly compared to the sham-transplanted group. These findings suggest that cortical region specific engraftment of preconditioned cortical precursor cells could support motor functional recovery in the HIE model. It is not clear whether this is a direct effect of the engrafted cells or due to neurotrophic factors produced by these cells. These results suggest that cortical region-specific NPC engraftment is a promising therapeutic approach for brain repair.

  15. Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors.

    Science.gov (United States)

    Pazos, M Ruth; Mohammed, Nagat; Lafuente, Hector; Santos, Martin; Martínez-Pinilla, Eva; Moreno, Estefania; Valdizan, Elsa; Romero, Julián; Pazos, Angel; Franco, Rafael; Hillard, Cecilia J; Alvarez, Francisco J; Martínez-Orgado, Jose

    2013-08-01

    The mechanisms underlying the neuroprotective effects of cannabidiol (CBD) were studied in vivo using a hypoxic-ischemic (HI) brain injury model in newborn pigs. One- to two-day-old piglets were exposed to HI for 30 min by interrupting carotid blood flow and reducing the fraction of inspired oxygen to 10%. Thirty minutes after HI, the piglets were treated with vehicle (HV) or 1 mg/kg CBD, alone (HC) or in combination with 1 mg/kg of a CB₂ receptor antagonist (AM630) or a serotonin 5HT(1A) receptor antagonist (WAY100635). HI decreased the number of viable neurons and affected the amplitude-integrated EEG background activity as well as different prognostic proton-magnetic-resonance-spectroscopy (H(±)-MRS)-detectable biomarkers (lactate/N-acetylaspartate and N-acetylaspartate/choline ratios). HI brain damage was also associated with increases in excitotoxicity (increased glutamate/N-acetylaspartate ratio), oxidative stress (decreased glutathione/creatine ratio and increased protein carbonylation) and inflammation (increased brain IL-1 levels). CBD administration after HI prevented all these alterations, although this CBD-mediated neuroprotection was reversed by co-administration of either WAY100635 or AM630, suggesting the involvement of CB₂ and 5HT(1A) receptors. The involvement of CB₂ receptors was not dependent on a CBD-mediated increase in endocannabinoids. Finally, bioluminescence resonance energy transfer studies indicated that CB₂ and 5HT(1A) receptors may form heteromers in living HEK-293T cells. In conclusion, our findings demonstrate that CBD exerts robust neuroprotective effects in vivo in HI piglets, modulating excitotoxicity, oxidative stress and inflammation, and that both CB₂ and 5HT(1A) receptors are implicated in these effects.

  16. 新生儿缺氧缺血性脑病颅脑MRI-Apgar评分、血清NSE相关性研究%Study on brain MRI and its relations to Apgar scores, serum level of NSE in patients with neonatal hypoxic ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    丁燕霞; 李晓春

    2011-01-01

    Objective To invastigate the change of cerebral MRI of neonatal Hypoxic Is-chemic Encephalopathy(HIE), and the relation between the serum neuron - specific enolase(NSE) and Apgar scores. Methods One hundred HIE cases were chosen as experimental group, including 50 preterm cases and 50 term neonates. Based the degree of MRI, the subjects in the experimental group were classified into HIE mild and HIE moderate and severe. Another forty normal ones were chosen as control group. Blood samples were collected in all the research objects for NSE detecting. MRI was performed 3~7 days after birth in the experimental group. Results In full term neonates and preterm neonates, as the aggravation of the degrees of MRI, the serum NSE levels got increased and Apgar scores got decreased. Compared with the control group and the HIE mild group, the NSE levels in the HIE moderate and severe group had significant differences. However, the differences between the mild HIE group and the control group was insignificant. Differences of 5 min Apgar score between any two groups were significant. Conclusion Serum NSE level and Apgar score can be used as the early objective markers for evaluating the prognosis of brain damage in hypoxic is-chemic encephalopathy, and they are concordance with the cerebral MRI degrees. We can perform early diagnosis and evaluation of HIE by utilizing the two indexes.%目的 探讨新生儿缺氧缺血性脑病(HIE)颅脑磁共振成像(MRI)改变与血清神经元特异性烯醇化酶(NSE)及新生儿评分(Apgar评分)之间的关系.方法 选取HIE患儿100例(早产儿50例,足月儿50例)为实验组,依据颅脑MRI表现程度分为轻度HIE和中重度HIE组;另选同期非HIE新生儿40例为对照组,均在其生后行Apgar评分、检测血清NSE浓度,并于生后3~7 d行颅脑MRI检查.结果 HIE足月儿和早产儿随着MRI表现程度加重,血清NSE值逐渐增高,Apgar评分逐渐降低.中重度组与轻度组、对照组相比NSE水平

  17. Hypoxic-ischemic encephalopathy with cystic brain stem necroses and thalamic calcifications in a preterm twin.

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    Peters, B; Walka, M M; Friedmann, W; Stoltenburg-Didinger, G; Obladen, M

    2000-06-01

    A severe and rare ischemic brain lesion in a preterm twin boy is reported. The boy was born after two weeks of anhydramnios and amnionic infection at 24 weeks of gestation. Following a difficult Caesarean section and prolonged umbilical cord compression he developed prenatal acidosis with an umbilical cord pH of 6.96. At the age of 7 h, heart rate variability narrowed due to severely disturbed brain stem function and the patient developed clinical signs of hypoxic-ischemic encephalopathy. Sonography demonstrated extensive symmetrical brain stem and basal ganglia lesions. After a prolonged comatose and apneic state, death occurred at the age of 25 days. Autopsy confirmed columnar bilateral cavitation of basal ganglia, diencephalon, brain stem and spinal gray matter, as well as focal calcifications in the palladium, thalamus, and brain stem. The findings highly resemble those observed after experimental or clinical cardiac arrest.

  18. NEUROGENETIC ASPECTS OF PERINATAL HYPOXIC-ISCHEMIC AFFECTIONS OF THE CENTRAL NERVOUS SYSTEM

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    G. A. Karkashadze

    2016-01-01

    Full Text Available Neurogenetics is a thriving young science greatly contributing to the generally accepted concept of the brain development in health and disease. Thereby; scientists are not only able to highlight new key points in traditional ideas about the origin of diseases; but also to completely rethink their view on the problem of pathology development. In particular; new data on neurogenetics of perinatal affections of the central nervous system (CNS has appeared. Genetic factors in varying degrees affect perinatal hypoxic-ischemic CNS affections. Prematurity determination stays the most studied among them. Nevertheless; there is increasing evidence of significant epigenetic regulations of neuro-expression caused by hypoxia; malnutrition of a pregnant woman; stress; smoking; alcohol; drugs that either directly pathologically affect the developing brain; or form a brain phenotype sensitive to a perinatal CNS affection. New data obliges to change the approaches to prevention of perinatal CNS affections.

  19. The study of Histamine 3 Receptor Antagonist on Treatment and mechanism to Rat Model with Neonatal Hypoxic ischemic Encephalopathy%组胺H3受体拮抗剂对缺血缺氧性脑病新生大鼠神经保护作用及其机制研究

    Institute of Scientific and Technical Information of China (English)

    贾飞勇; 郝云鹏; 姜慧轶; 杜琳; 单玲; 王江涛

    2011-01-01

    0bjective the study on H3 receptor antagonist com pound to the neonatal with Hypoxia ischemia bam dam age animal model therapeutic action mechanism research .By the measurement of brain organization hippocampal area histamine ,MDA , SOD .Methods 7-day old neonatal Wistar rats was divided in to 3group :norm al com parison ,HIE model group and theraputic group .The theraputic group is devided into H3 ,H3 +H1 ,H3 +H2 Group .Rats in H3 group are intraperitoneally injected by 5 mg/kg Thio; Rats in H 2 group are intraperitoneally injected by 5mg/kg Dhp ,and intraperitoneally injected by 5mg/kg Thio 30m iniutes later; Rats in H1 group are intraperitoneally injected by 100mg/kg C in, and intraperitoneally injected by 5mg/kg Thio 30m iniutes later. Rats in normal comparison and HIE model group are intraperitoneally injected by Saline.6 h、24 h and 72 h after injection, getBrain tissue specimens to detect the value of Brain water content, hippocampal area histamine, MDA,SOD .Results 6,24 and 72 hour after the therapy, we find, the compariaon between the result of 24h and 6h in each group shows that the Brain water content, MDA are both increased( P <0.05 ) ,while the hippocampal area histamine and SOD are both decreased( P<0.05 ) .The Brain water content, MDA in each Thiogroup are significantly less than in the NS group( P<0.05 ) ,while the hippocampal area histamine and SOD are significantly more( P <0.05 ) .The Brain water content, MDA in each Thio group are significantly nore than in the NS group( P<0.05 ) ,while the hippocam pal area histamine and SOD are significantly less(P<0.05).Conclusion The histamine H3 receptorantagonist compound has the protective function for the neonatal with Hypoxia ischemia neuron dam age. The histamine H3 receptor antagonist com pound the protective function which dam ages to the neonatal rats with Hypoxia ischemia neuron dam age is mainly realizes through the histamine H2 acceptor.%目的 探讨组胺H3受体拮抗剂硫丙咪

  20. Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia.

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    Shellhaas, Renée A; Ng, Chee M; Dillon, Christina H; Barks, John D E; Bhatt-Mehta, Varsha

    2013-02-01

    Phenobarbital is the first-line treatment for neonatal seizures. Many neonates with hypoxic ischemic encephalopathy are treated with therapeutic hypothermia, and about 40% have clinical seizures. Little is known about the pharmacokinetics of phenobarbital in infants with hypoxic ischemic encephalopathy who undergo therapeutic hypothermia. The objective of this study was to determine the effect of therapeutic hypothermia on phenobarbital pharmacokinetics, taking into account maturational changes. Level 3 neonatal ICU. Infants with hypoxic ischemic encephalopathy and suspected seizures, all treated with phenobarbital. Some of these infants also received treatment with therapeutic hypothermia. None. A retrospective cohort study of 39 infants with hypoxic ischemic encephalopathy treated with phenobarbital (20 were treated with therapeutic hypothermia and 19 were not). Data on phenobarbital plasma concentrations were collected in 39 subjects with hypoxic ischemic encephalopathy with or without therapeutic hypothermia. Using nonlinear mixed-effects modeling, population pharmacokinetics of phenobarbital were developed with a total of 164 plasma concentrations. A one-compartment model best described the pharmacokinetics. The clearance of phenobarbital was linearly related to body weight and matured with increasing age with a maturation half-life of 22.1 days. Therapeutic hypothermia did not influence the pharmacokinetic parameters of phenobarbital. Therapeutic hypothermia does not influence the clearance of phenobarbital after accounting for weight and age. Standard phenobarbital dosing is appropriate for the initial treatment of seizures in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia.

  1. 肿瘤坏死因子α、超敏C反应蛋白在新生儿缺氧缺血性脑病中的变化及临床意义%Changes and clinical significance of tumor necrosis factor-αand high-sensitivity C-reactive protein in neonates with hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    尚云; 石计朋; 杨卫红; 马慧敏; 郭喜霞; 唐成和

    2016-01-01

    Objective To investigate the potential roles of tumor necrosis factorα(TNF-α)and highsensitivity Creactive protein (HsCRP)in the progression and prognosis of neonatal hypoxicischemic encephalopathy(HIE).Methods This study was a clinical ex-perimental study.Totally 74 cases of neonates with HIE diagnosed in the First Affiliated Hospital of Xinxiang Medical University From February 2011 to February 2013 were enrolled as observation group (mild 31 cases,moderate 26 cases,severe 17 cases;32 cases with good prognosis,42 poor prognosis),and another 74 cases of normal healthy neonates were selected as control group.The levels of TNF-αand HsCRP in all samples were measured 48 hours after being born by enzymelinked immunosorbent assay (ELISA)and radio immu-noassay (RIA)method.Results The data revealed significant upregulation of the serum levels of TNF-αand HsCRP in patients with HIE.The increase in the levels of these inflammatory mediators correlated with the severity of the disease and also had a positive corre-lation with the prognosis of the disease.Serum levels of TNF-αand HsCRP in HIE group were significantly higher than those in normal control group.TNF-αlevels were 17.20 ±1.26 vs 97.00 ±5.97 ng·L -1 (P <0.05);HsCRP levels were 0.51 ±0.18 vs 11.93 ± 1.91 mg·L -1 (P <0.05).Serum levels of TNF-αand HsCRP in the moderate and severe patient groups were significantly higher compared with those in the mild group(P <0.05).Furthermore,there was a significant upregulation of the cytokines in the severe group compared with those in the moderate group(P <0.05).The differences among 3 groups were also significant ,and they were the highest with severe HIE,TNF-αlevels(mild group 31.37 ±3.28 vs moderate group 52.59 ±5.19 vs severe group 102.65 ±7.81 ng·L -1 ,P<0.05);HsCRP levels(mild group 4.63 ±0.69 vs moderate group 7.56 ±1.19 vs severe group 12.92 ±3.25 mg·L -1 ,P <0.05).Comparison of the serum levels of TNF-αand HsCRP in patients with different

  2. Inflammatory injury to the neonatal brain – what can we do?

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    Noa eOfek-shlomai

    2014-04-01

    Full Text Available Abstract Perinatal brain damage is one of the leading causes of life long disability. This damage could be hypoxic-ischemic, inflammatory or both.This mini-review discusses different interventions aiming at minimizing inflammatory processes in the neonatal brain, both before and after insult. Current options of anti-inflammatory measures for neonates remain quite limited. We describe current anti-inflammatory intervention strategies such as avoiding perinatal infection and inflammation, and reducing exposure to inflammatory processes. We describe the known effects of anti-inflammatory drugs such as steroids, antibiotics, and indomethacin, and the possible anti-inflammatory role of other substances such as IL-1receptor antagonists, erythropoietin, caffeine, estradiol, insulin like growth factor and melatonin as well as endogenous protectors, and genetic regulation of inflammation. If successful, these may decrease mortality and long term morbidity among term and preterm infants.

  3. 新生儿发生脑损伤的产前危险因素研究%The research of prenatal risk factors of neonatal brain injury

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    臧丽; 王清刚; 李晓华

    2016-01-01

    Objective To evaluate prenatal risk factors of neonatal brain injury.Methods This study was a retrospective study.518 newborn born in our hospital from January 2013 to February 2016 were included,and divided into neonatal brain injury group (n=285) and non-brain injury group (n=233) according to the diagnostic result of neonatal hypoxic-ischemic encephalopathy (HIE).Analyzed prenatal risk factors of neonatal brain injury.Results The shorter the gestational age was,the higher the risk of neonatal brain injury was (trend x2=16.802,P=0.001).The lower neonatal birth weight was,the higher the risk of neonatal brain injury was (trend x2=29.556,P=0.001).The rate of monochorionic twins (MCT) and complex monochorionic twins (CMCT) in brain injury group were higher than those in non-brain injury group.Univariate analysis showed that CMCT,gestational age,birth weight were prenatal risk factors of neonatal brain injury.Binomial classification logistic regression analysis showed that gestational age was prenatal independent protective factor of neonatal brain injury,CMCT was prenatal independent risk factor of neonatal brain injury.Conclusions The shorter the gestational age is,the higher the risk of neonatal brain injury is.The risk of neonatal brain injury significantly increase for newborn with <1500 g birth weight and <30 weeks gestational age.CMCT is another risk factor of neonatal brain injury.%目的 评价新生儿发生脑损伤的产前危险因素.方法 本研究为回顾性研究,选取2013年1月至2016年2月在我院分娩的518例新生儿,根据新生儿缺氧缺血性脑病(HIE)诊断结果将新生儿分为脑损伤组(n=285)与非脑损伤组(n=233),分析评价新生儿发生脑损伤的产前危险因素.结果 新生儿孕周越小,发生脑损伤的风险越高(趋势x2=16.802,P=0.001).新生儿出生体重越小则发生脑损伤的风险越高(趋势x2=29.556,P=0.001).脑损伤组单绒毛膜双胎(MCT)与复杂性单绒毛膜

  4. Acute kidney injury in asphyxiated neonates

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    Roy Amardiyanto

    2013-07-01

    Full Text Available Background Asphyxia neonatorum may result in multiorgan dysfunction including renal involvement. There is no consensus on the determination of acute kidney injury (AKI in neonates making establishment of the diagnosis and its management becomes difficult. The Acute Kidney Injury Network (AKIN recommends AKI criteria based on increased serum creatinine level and reduced urine output. Objectives To identify the prevalence of AKI in asphyxiated neonates using the AKIN criteria, to compare the difference of AKI stages, and the glomerular filtration rates (GFR between moderate and severe asphyxia. Methods This was a cross-sectional analytical study conducted between July 2012 and January 2013. Subjects were all asphyxiated neonates (Apgar score 35 weeks delivered and hospitalized in Cipto Mangunkusumo Hospital and Koja District Hospital, Jakarta, Indonesia. Glomerular filtration rate was calculated using the components of urine creatinine, serum creatinine, and urine output; while AKI stages were determined according to AKIN criteria. Urinary output was measured via urethral catheterization. Results Of 94 subjects, there were 70 neonates with moderate and 24 neonates with severe asphyxia, with the prevalence of AKI was 63%. Twenty one out of 24 neonates with severe asphyxia experienced AKI, while neonates with moderate asphyxia who experienced AKI was 38 out of 70 subjects (54%. Two third of neonates with severe asphyxia who experienced AKI had stage 3 of AKI. More severe AKI stages and lower median GFR were found in neonates with severe compared to moderate asphyxia (P<0.001. Conclusion The prevalence of AKI in neonatal asphyxia is high (63%. The more severe degree of neonatal asphyxia, the more severe AKI stage and the lower median GFR. [Paediatr Indones. 2013;53:232-8.].

  5. Cell therapy for neonatal hypoxia-ischemia and cerebral palsy.

    Science.gov (United States)

    Bennet, Laura; Tan, Sidhartha; Van den Heuij, Lotte; Derrick, Matthew; Groenendaal, Floris; van Bel, Frank; Juul, Sandra; Back, Stephen A; Northington, Frances; Robertson, Nicola J; Mallard, Carina; Gunn, Alistair Jan

    2012-05-01

    Perinatal hypoxic-ischemic brain injury remains a major cause of cerebral palsy. Although therapeutic hypothermia is now established to improve recovery from hypoxia-ischemia (HI) at term, many infants continue to survive with disability, and hypothermia has not yet been tested in preterm infants. There is increasing evidence from in vitro and in vivo preclinical studies that stem/progenitor cells may have multiple beneficial effects on outcome after hypoxic-ischemic injury. Stem/progenitor cells have shown great promise in animal studies in decreasing neurological impairment; however, the mechanisms of action of stem cells, and the optimal type, dose, and method of administration remain surprisingly unclear, and some studies have found no benefit. Although cell-based interventions after completion of the majority of secondary cell death appear to have potential to improve functional outcome for neonates after HI, further rigorous testing in translational animal models is required before randomized controlled trials should be considered. Copyright © 2011 American Neurological Association.

  6. Denver developmental screening test II for early identification of the infants who will develop major neurological deficit as a sequalea of hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Hallioglu, O; Topaloglu, A K; Zenciroglu, A; Duzovali, O; Yilgor, E; Saribas, S

    2001-08-01

    The primary aim of this study was to find widely available, inexpensive, and non-invasive parameters for early identification or prediction of the infants with hypoxic-ischemic encephalopathy (HIE) who will have a severe adverse outcome (classified as death or a major neurological deficit). Fifty-seven full-term or near-term newborn infants with a diagnosis of HIE were consecutively admitted to the neonatal intensive care unit and studied. Occurrence of seizures during the first 24 h, cranial ultrasonography (US) findings within the first 5 days of life, and Denver developmental screening test II (DDST II) at 6 months of age, were analyzed in relation to mortality and neurological status at 2 years of age. Of the 57 infants, 10 were lost to follow-up. Twenty of the remaining 47 infants had a severe adverse outcome. Among the predictors of severe adverse outcome, occurrence of seizures was found to have a poor predictive accuracy. Cranial US had 100% sensitivity, however with a rather low specificity (55%). However, DDST II at 6 months of age, yielded a very high predictive accuracy (sensitivity=100%, specificity=95%). We conclude that DDST II at 6 months of age could be used in predicting severe neurological outcome in infants with HIE.

  7. Phenobarbital and temperature profile during hypothermia for hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Sant'Anna, Guilherme; Laptook, Abbot R; Shankaran, Seetha; Bara, Rebecca; McDonald, Scott A; Higgins, Rosemary D; Tyson, Jon E; Ehrenkranz, Richard A; Das, Abhik; Goldberg, Ronald N; Walsh, Michele C

    2012-04-01

    Data from the whole-body hypothermia trial was analyzed to examine the effects of phenobarbital administration prior to cooling (+PB) on the esophageal temperature (T (e)) profile, during the induction phase of hypothermia. A total of 98 infants were analyzed. At enrollment, +PB infants had a higher rate of severe hypoxic-ischemic encephalopathy and clinical seizures and lower T (e) and cord pH than infants that have not received phenobarbital (-PB). There was a significant effect of phenobarbital itself and an interaction between phenobarbital and time in the T (e) profile. Mean T (e) in the +PB group was lower than in the -PB group, and the differences decreased over time. In +PB infants, the time to surpass target T (e) of 33.5°C and to reach the minimum T (e) during overshoot were shorter. In conclusion, the administration of phenobarbital before cooling was associated with changes that may reflect a reduced thermogenic response associated with barbiturates.

  8. Clinical analysis of the early comprehensive intervention on hypoxic ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Xu-E Li; Yi-MinDu; Yan-JuGuo; Zhi-QingWu; Su-GeHao

    2015-01-01

    Objective:To explore the clinical efficacy of the early comprehensive intervention on hypoxic ischemic encephalopathy (HIE).Methods:HIE children who were admitted in our department from March, 2014 to May, 2015 were included in the study and randomized into the observation group and the control group. The patients in the control group were given routine fluid infusion, electrolyte disturbance correcting, blood sugar maintaining, convulsion controlling, intracranial pressure reducing, hormone, mannitol, vitamins, infection preventing, and other treatments. Based on the treatments given in the control group, the patients in the observation group were given the comprehensive intervention. After treatment, the serum related indicators, NBNA, and DQ in the two groups were observed.Results:The levels of serum AST, LDH, CK, and CK-MB in the observation group were significantly lower than those in the control group (P0.05). NBNA score in the observation group was significantly superior to that in the control group (P<0.05). DQ values at 3, 6, 12, 18, and 24 months in the observation group were significantly higher than those in the control group (P<0.05).Conclusions:Early comprehensive intervention on HIE patients can effectively reduce the serum cardiac enzyme levels, increase the therapeutic effect, improve the intelligence and motor development levels and DQ in order to enhance the living qualities.

  9. Association of NOS3 tag polymorphisms with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Kuzmanić Samija, Radenka; Primorac, Dragan; Resić, Biserka; Lozić, Bernarda; Krzelj, Vjekoslav; Tomasović, Maja; Stoini, Eugenio; Samanović, Ljubo; Benzon, Benjamin; Pehlić, Marina; Boraska, Vesna; Zemunik, Tatijana

    2011-06-01

    To test the association of NOS3 gene with hypoxic-ischemic encephalopathy (HIE). The study included 110 unrelated term or preterm born children (69 boys and 41 girls) with HIE and 128 term and preterm born children (60 boys and 68 girls) without any neurological problems after the second year of life. Children with perinatal HIE fulfilled the diagnostic criteria for perinatal asphyxia. All children were admitted to the Clinical Hospital Split between 1992 and 2008. We analyzed 6 tagging single nucleotide polymorphisms (SNP) within NOS3 gene (rs3918186, rs3918188, rs1800783, rs1808593, rs3918227, rs1799983), in addition to previously confirmed NOS3-associated SNP rs1800779. Genotyping was conducted using real-time polymerase chain reaction (PCR). Association analyses were performed according to allelic and genotypic distribution. Allelic test did not show any SNP association with HIE. SNP rs1808593 showed genotype association (P=0.008) and rs1800783-rs1800779 TG haplotype showed an association with HIE (PNOS3 polymorphisms with HIE.

  10. Molecular Mechanisms of Neonatal Brain Injury

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    Claire Thornton

    2012-01-01

    Full Text Available Fetal/neonatal brain injury is an important cause of neurological disability. Hypoxia-ischemia and excitotoxicity are considered important insults, and, in spite of their acute nature, brain injury develops over a protracted time period during the primary, secondary, and tertiary phases. The concept that most of the injury develops with a delay after the insult makes it possible to provide effective neuroprotective treatment after the insult. Indeed, hypothermia applied within 6 hours after birth in neonatal encephalopathy reduces neurological disability in clinical trials. In order to develop the next generation of treatment, we need to know more about the pathophysiological mechanism during the secondary and tertiary phases of injury. We review some of the critical molecular events related to mitochondrial dysfunction and apoptosis during the secondary phase and report some recent evidence that intervention may be feasible also days-weeks after the insult.

  11. Glucose and Intermediary Metabolism and Astrocyte-Neuron Interactions Following Neonatal Hypoxia-Ischemia in Rat.

    Science.gov (United States)

    Brekke, Eva; Berger, Hester Rijkje; Widerøe, Marius; Sonnewald, Ursula; Morken, Tora Sund

    2017-01-01

    Neonatal hypoxia-ischemia (HI) and the delayed injury cascade that follows involve excitotoxicity, oxidative stress and mitochondrial failure. The susceptibility to excitotoxicity of the neonatal brain may be related to the capacity of astrocytes for glutamate uptake. Furthermore, the neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance for limiting this kind of injury. Also, in the neonatal brain, neurons depend upon de novo synthesis of neurotransmitters via pyruvate carboxylase in astrocytes to increase neurotransmitter pools during normal brain development. Several recent publications describing intermediary brain metabolism following neonatal HI have yielded interesting results: (1) Following HI there is a prolonged depression of mitochondrial metabolism in agreement with emerging evidence of mitochondria as vulnerable targets in the delayed injury cascade. (2) Astrocytes, like neurons, are metabolically impaired following HI, and the degree of astrocytic malfunction may be an indicator of the outcome following hypoxic and hypoxic-ischemic brain injury. (3) Glutamate transfer from neurons to astrocytes is not increased following neonatal HI, which may imply that astrocytes fail to upregulate glutamate uptake in response to the massive glutamate release during HI, thus contributing to excitotoxicity. (4) In the neonatal brain, the activity of the PPP is reduced following HI, which may add to the susceptibility of the neonatal brain to oxidative stress. The present review aims to discuss the metabolic temporal alterations observed in the neonatal brain following HI.

  12. Detection of seizures with amplitude-integrated electroencephalography in a neonate treated with extracorporeal membrane ox%应用振幅整合脑电图监测体外膜肺治疗过程中的新生儿癫癎1例

    Institute of Scientific and Technical Information of China (English)

    李萌; 杨于嘉

    2008-01-01

    Infants with severe cardiorespiratory failure treated with extracorporeal membrane oxygenation are at risk of hypoxic-ischemic injury and infarction of the brain,intracranial hemorrhage,and seizures.Consequently,this can lead to adverse neumdevelopmental outcome. We present a neonate treated with veno-arterial extracorporeal membrane oxygenation due to diaphragmatic hernia.The infant'S brain function was continuously monitored with amplitude-integrated electroencephalography.The child experienced clinical seizures and subclinical seizure discharges,detected by amplitudeintegrated electroencephalography,permitting the opportunity to treat them and adjust the anticonvulsive treatment accordingly.

  13. Docosahexaenoic Acid Reduces Cerebral Damage and Ameliorates Long-Term Cognitive Impairments Caused by Neonatal Hypoxia-Ischemia in Rats.

    Science.gov (United States)

    Arteaga, Olatz; Revuelta, M; Urigüen, L; Martínez-Millán, L; Hilario, E; Álvarez, A

    2016-10-29

    As the interest in the neuroprotective possibilities of docosahexaenoic acid (DHA) for brain injury has grown in the recent years, we aimed to investigate the long-term effects of this fatty acid in an experimental model of perinatal hypoxia-ischemia in rats. To this end, motor activity, aspects of learning, and memory function and anxiety, as well as corticofugal connections visualized by using tracer injections, were evaluated at adulthood. We found that in the hours immediately following the insult, DHA maintained mitochondrial inner membrane integrity and transmembrane potential, as well as the integrity of synaptic processes. Seven days later, morphological damage at the level of the middle hippocampus was reduced, since neurons and myelin were preserved and the astroglial reactive response and microglial activation were seen to be diminished. At adulthood, the behavioral tests revealed that treated animals presented better long-term working memory and less anxiety than non-treated hypoxic-ischemic animals, while no difference was found in the spontaneous locomotor activity. Interestingly, hypoxic-ischemic injury caused alterations in the anterograde corticofugal neuronal connections which were not so evident in rats treated with DHA. Thus, our results indicate that DHA treatment can lead to long-lasting neuroprotective effects in this experimental model of neonatal hypoxia-ischemic brain injury, not only by mitigating axonal changes but also by enhancing cognitive performance at adulthood.

  14. Clinical hypoxic-ischemic encephalopathy score of the Iberoamerican Society of Neonatology (Siben: A new proposal for diagnosis and management

    Directory of Open Access Journals (Sweden)

    José Maria Rodriguez Perez

    Full Text Available Summary Hypoxic ischemic encephalopathy is a major complication of perinatal asphyxia, with high morbidity, mortality and neurologic sequelae as cerebral palsy, mostly in poor or developing countries. The difficulty in the diagnosis and management of newborns in these countries is astonishing, thus resulting in unreliable data on this pathology and bad outcomes regarding mortality and incidence of neurologic sequelae. The objective of this article is to present a new clinical diagnostic score to be started in the delivery room and to guide the therapeutic approach, in order to improve these results.

  15. Infection-related perinatal brain injury: the pathogenic role of impaired fetal cardiovascular control.

    Science.gov (United States)

    Garnier, Yves; Coumans, Audrey B C; Jensen, Arne; Hasaart, Tom H M; Berger, Richard

    2003-12-01

    There is a growing body of evidence from clinical and epidemiologic studies that in utero exposure to infection plays an important role in the genesis of fetal or neonatal injury leading to cerebral palsy and chronic lung disease. Thus, after chorioamnionitis the incidence of immature neonates with periventricular white matter damage and periventricular or intraventricular hemorrhage is significantly elevated. Recent clinical and experimental data support the hypothesis that a fetal inflammatory response links antenatal infection with brain white matter damage and subsequent motor handicap. A variety of studies support the view that cytokines released during intrauterine infection directly cause injury to the immature brain. In this review, we provide evidence that in utero exposure to bacterial infection can severely alter fetal cardiovascular function, resulting in dysregulation of cerebral blood flow and subsequent hypoxic-ischemic brain injury.

  16. Early biochemical indicators of hypoxic-ischemic encephalopathy after birth asphyxia.

    Science.gov (United States)

    Nagdyman, N; Kömen, W; Ko, H K; Müller, C; Obladen, M

    2001-04-01

    Hypoxic-ischemic encephalopathy (HIE) after perinatal asphyxia is a condition in which serum concentrations of brain-specific biochemical markers may be elevated. Neuroprotective interventions in asphyxiated newborns require early indicators of brain damage to initiate therapy. We examined brain-specific creatine kinase (CK-BB), protein S-100, and neuron-specific enolase in cord blood and 2, 6, 12, and 24 h after birth in 29 asphyxiated and 20 control infants. At 2 h after birth, median (quartiles) serum CK-BB concentration was 10.0 U/L (6.0-13.0 U/L) in control infants, 16.0 U/L (13.0-23.5 U/L) in infants with no or mild HIE, and 46.5 U/L (21.4-83.0 U/L) in infants with moderate or severe HIE. Serum protein S-100 was 1.6 microg/L (1.4-2.5 microg/L) in control infants, 2.9 microg/L (1.8-4.7 microg/L) in asphyxiated infants with no or mild HIE, and 17.0 microg/L (3.2-34.1 microg/L) in infants with moderate or severe HIE 2 h after birth. No significant difference was detectable in serum neuron-specific enolase between infants with no or mild and moderate or severe HIE 2 and 6 h after birth. A combination of serum protein S-100 (cutoff value, 8.5 microg/L) and CK-BB (cutoff value, 18.8 U/L) 2 h after birth had the highest predictive value (83%) and specificity (95%) of predicting moderate and severe HIE. Cord blood pH (cutoff value, 17 mM) increase the predictive values of protein S-100 and CK-BB. We conclude that elevated serum concentrations of protein S-100 and CK-BB reliably indicate moderate and severe HIE as early as 2 h after birth.

  17. Role of mixed lineage kinase inhibition in neonatal hypoxia-ischemia.

    Science.gov (United States)

    Carlsson, Ylva; Leverin, Anna-Lena; Hedtjärn, Maj; Wang, Xiaoyang; Mallard, Carina; Hagberg, Henrik

    2009-01-01

    Hypoxic-ischemic brain injury is often delayed and involves both apoptotic and immunoregulatory mechanisms. In this study, we used a neonatal model of hypoxia-ischemia to examine the effect of the mixed lineage kinase (MLK) inhibitor CEP-1347 on brain damage, apoptosis and inflammation. The tissue volume loss was reduced by 28% (p = 0.019) in CEP-1347-treated versus vehicle-treated rats and CEP-1347 significantly attenuated microgliosis at 7 days (p = 0.038). CEP-1347 decreased TUNEL-positive staining as well as cleaved caspase 3 immunoreactivity. CEP-1347 did not affect the expression of pro-inflammatory cytokines IL-1 beta, IL-6 and MCP-1, nor did it affect the expression of OX-42 (CR3) and OX-18 (MHC I) 24 h after the insult. In conclusion, the MLK inhibitor CEP-1347 has protective effects in a neonatal rat model of hypoxia-ischemia, which is mainly related to reduced apoptosis.

  18. Negative regulation of miRNA-9 on oligodendrocyte lineage gene 1 during hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Lijun Yang; Hong Cui; Ting Cao

    2014-01-01

    Oligodendrocyte lineage gene 1 plays a key role in hypoxic-ischemic brain damage and myelin repair. miRNA-9 is involved in the occurrence of many related neurological disorders. Bioin-formatics analysis demonstrated that miRNA-9 complementarily, but incompletely, bound oligodendrocyte lineage gene 1, but whether miRNA-9 regulates oligodendrocyte lineage gene 1 remains poorly understood. Whole brain slices of 3-day-old Sprague-Dawley rats were cultured and divided into four groups:control group;oxygen-glucose deprivation group (treatment with 8% O2+ 92%N2 and sugar-free medium for 60 minutes);transfection control group (after oxygen and glucose deprivation for 60 minutes, transfected with control plasmid) and miRNA-9 transfection group (after oxygen and glucose deprivation for 60 minutes, transfected with miRNA-9 plasmid). From the third day of transfection, and with increasing culture days, oligodendrocyte lineage gene 1 expression increased in each group, peaked at 14 days, and then decreased at 21 days. Real-time quantitative PCR results, however, demonstrated that oligoden-drocyte lineage gene 1 expression was lower in the miRNA-9 transfection group than that in the transfection control group at 1, 3, 7, 14, 21 and 28 days after transfection. Results suggested that miRNA-9 possibly negatively regulated oligodendrocyte lineage gene 1 in brain tissues during hypoxic-ischemic brain damage.

  19. Pharmacotherapeutical reduction of post-hypoxic-ischemic brain injury in the newborn

    NARCIS (Netherlands)

    Peeters, C; van Bel, F

    2001-01-01

    Perinatal hypoxia-ischemia (PHI) is a major cause of morbidity and mortality. A substantial part of PHI-related brain damage occurs upon reperfusion and reoxygenation by the excess production of excitatory amino acids, free (pro)radicals and the release of cytokines, triggering programmed cell death

  20. Prognostic value of brain proton MR spectroscopy and diffusion tensor imaging in newborns with hypoxic-ischemic encephalopathy treated by brain cooling

    Energy Technology Data Exchange (ETDEWEB)

    Ancora, G. [Neonatal Intensive Care Unit, Department of Mother and Infant Infermi Hospital of Rimini, Rimini (Italy); Testa, C.; Tonon, C.; Manners, D.N.; Gramegna, L.L.; Lodi, R. [Department of Biomedical and Neuromotor Sciences University of Bologna, MR Functional Unit, Bologna (Italy); Grandi, S.; Sbravati, F.; Savini, S.; Corvaglia, L.T.; Faldella, G. [University of Bologna, Neonatology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Tani, G. [University of Bologna, Radiology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Malucelli, E. [University of Bologna, Department of Pharmacy and Biotechnologies, Bologna (Italy)

    2013-08-15

    MRI, proton magnetic resonance spectroscopy ({sup 1}H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on {sup 1}H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). Twenty infants treated with BC underwent conventional MRI and {sup 1}H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. Adverse outcome was observed in 6/20 newborns. Both {sup 1}H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100 % PPV and 93 % NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91 %, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. Selective BC in HIE neonates does not affect the early and accurate prognostic value of {sup 1}H-MRS and DTI, which outperform conventional MRI. (orig.)

  1. Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Cavalleri, Francesca; Todeschini, Alessandra [Azienda Unita Sanitaria Locale di Modena, Neuroradiology Unit, Department of Neuroscience, Nuovo Ospedale Civile S. Agostino Estense di Modena, Modena (Italy); Lugli, Licia; Pugliese, Marisa; Della Casa, Elisa; Gallo, Claudio; Frassoldati, Rossella; Ferrari, Fabrizio [Modena University Hospital, Institute of Pediatrics and Neonatal Medicine and NICU, Modena (Italy); D' Amico, Roberto [University of Modena and Reggio Emilia, Department of Clinical and Diagnostic Medicine and Public Health, Modena (Italy)

    2014-09-15

    The diagnostic and prognostic assessment of newborn infants with hypoxic-ischemic encephalopathy (HIE) comprises, among other tools, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. To compare the ability of DWI and ADC maps in newborns with HIE to predict the neurodevelopmental outcome at 2 years of age. Thirty-four term newborns with HIE admitted to the Neonatal Intensive Care Unit of Modena University Hospital from 2004 to 2008 were consecutively enrolled in the study. All newborns received EEG, conventional MRI and DWI within the first week of life. DWI was analyzed by means of summation (S) score and regional ADC measurements. Neurodevelopmental outcome was assessed with a standard 1-4 scale and the Griffiths Mental Developmental Scales - Revised (GMDS-R). When the outcome was evaluated with a standard 1-4 scale, the DWI S scores showed very high area under the curve (AUC) (0.89) whereas regional ADC measurements in specific subregions had relatively modest predictive value. The lentiform nucleus was the region with the highest AUC (0.78). When GMDS-R were considered, DWI S scores were good to excellent predictors for some GMDS-R subscales. The predictive value of ADC measurements was both region- and subscale-specific. In particular, ADC measurements in some regions (basal ganglia, white matter or rolandic cortex) were excellent predictors for specific GMDS-R with AUCs up to 0.93. DWI S scores showed the highest prognostic value for the neurological outcome at 2 years of age. Regional ADC measurements in specific subregions proved to be highly prognostic for specific neurodevelopmental outcomes. (orig.)

  2. Brainstem tegmental lesions in neonates with hypoxicischemic encephalopathy: Magnetic resonance diagnosis and clinical outcome

    Institute of Scientific and Technical Information of China (English)

    Carlo Cosimo Quattrocchi; Giuseppe Fariello; Daniela Longo

    2016-01-01

    Lesions of the brainstem have been reported in the clinical scenarios of hypoxic-ischemic encephalopathy(HIE), although the prevalence of these lesions is probably underestimated. Neuropathologic studies have demonstrated brainstem involvement in severely asphyxiated infants as an indicator of poor outcome. Among survivors to HIE, the most frequent clinical complaints that may be predicted by brainstem lesions include feeding problems, speech, language and communication problems and visual impairments. Clinical series, including vascular and metabolic etiologies, have found selective involvement of the brainstem with the demonstration of symmetric bilateral columnar lesions of the tegmentum. The role of brainstem lesions in HIE is currently a matter of debate, especially when tegmental lesions are present in the absence of supratentorial lesions. Differential diagnosis of tegmental lesions in neonates and infants include congenital metabolic syndromes and drug-related processes. Brainstem injury with the presence of supratentorial lesions is a predictor of poor outcome and high rates of mortality and morbidity. Further investigation will be conducted to identify specific sites of the brainstem that are vulnerable to hypoxic-ischemic and toxic-metabolic insults.

  3. Comparison of selective head cooling therapy and whole body cooling therapy in newborns with hypoxic ischemic encephalopathy: short term results

    Science.gov (United States)

    Atıcı, Aytuğ; Çelik, Yalçın; Gülaşı, Selvi; Turhan, Ali Haydar; Okuyaz, Çetin; Sungur, Mehmet Ali

    2015-01-01

    Aim: In this study, it was aimed to investigate which method was superior by applying selective head cooling or whole body cooling therapy in newborns diagnosed with moderate or severe hypoxic ischemic encephalopathy. Materials and Method: Newborns above the 35th gestational age diagnosed with moderate or severe hypoxic ischemic encephalopathy were included in the study and selective head cooling or whole body cooling therapy was performed randomly. The newborns who were treated by both methods were compared in terms of adverse effects in the early stage and in terms of short-term results. Ethics committee approval was obtained for the study (06.01.2010/35). Results: Fifty three babies diagnosed with hypoxic ischemic encephalopathy were studied. Selective head cooling was applied to 17 babies and whole body cooling was applied to 12 babies. There was no significant difference in terms of adverse effects related to cooling therapy between the two groups. When the short-term results were examined, it was found that the hospitalization time was 34 (7–65) days in the selective head cooling group and 18 (7–57) days in the whole body cooling group and there was no significant difference between the two groups (p=0.097). Four patients in the selective head cooling group and two patients in the whole body cooling group were discharged with tracheostomy because of the need for prolonged mechanical ventilation and there was no difference between the groups in terms of discharge with tracheostomy (p=0.528). Five patients in the selective head cooling group and three patients in the whole body cooling group were discharged with a gastrostomy tube because they could not be fed orally and there was no difference between the groups in terms of discharge with a gastrostomy tube (p=0.586). One patient who was applied selective head cooling and one patient who was applied whole body cooling died during hospitalization and there was no difference between the groups in terms of

  4. Patterns of neonatal hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Linda S. de [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands); Wilhelmina Children' s Hospital, University Medical Centre, Department of Neonatology, KE 04.123.1, P.O. Box 85090, Utrecht (Netherlands); Groenendaal, Floris [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands)

    2010-06-15

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  5. Neonatal encephalopathy: a prospective comparison of head US and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Epelman, Monica [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Children' s Hospital of Philadelphia, Philadelphia, PA (United States); Daneman, Alan; Blaser, Susan [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Kellenberger, Christian J. [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); University Children' s Hospital, Department of Diagnostic Imaging, Zuerich (Switzerland); Aziz, Abdul; Whyte, Hilary [Hospital for Sick Children, Division of Neonatology, Toronto (Canada); Konen, Osnat [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Tel Aviv University, Imaging Department, Schneider Children' s Medical Center, Tel Aviv (Israel); Moineddin, Rahim [University of Toronto, Department of Public Health Sciences, Toronto (Canada)

    2010-10-15

    Head US, the cornerstone neuroimaging modality in neonates, is believed to be less sensitive than MRI for detecting hypoxic ischemic injury (HII). Most reports comparing these modalities are retrospective and have a long interval between the exams. To prospectively characterize the range of abnormalities found in US examinations performed within 2 h of brain MRI in encephalopathic neonates. A total of 76 consecutive exams met our inclusion criteria. Diagnostic performance of the US images was prospectively compared with MRI. MRI was considered positive for HII in 53 neonates. Of the remaining 23, MRI was negative for HII in 9, showed white matter abnormalities unrelated to HII in 8, and was inconclusive in 6. Of the 70 neonates with conclusive examinations, the US exam was regarded as positive in 67. Diagnostic accuracy of US was 95.7%. Our study demonstrates that US should still be regarded as a screening test in neonates. US is more sensitive for the detection of injury than previously reported, and more attention should be paid to proper US technique. MRI shows disease more extensively and should be accomplished as early as possible. (orig.)

  6. Effects of xenon and hypothermia on cerebrovascular pressure reactivity in newborn global hypoxic-ischemic pig model.

    Science.gov (United States)

    Chakkarapani, Elavazhagan; Dingley, John; Aquilina, Kristian; Osredkar, Damjan; Liu, Xun; Thoresen, Marianne

    2013-11-01

    Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between -1 and +1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO2, seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx >0.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as 'severe' or 'mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P=0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P=0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, -0.098 (95% CI (-0.18, -0.01)), independent of the insult severity.

  7. The role of miR-182 in regulating pineal CLOCK expression after hypoxia-ischemia brain injury in neonatal rats.

    Science.gov (United States)

    Ding, Xin; Sun, Bin; Huang, Jian; Xu, Lixiao; Pan, Jian; Fang, Chen; Tao, Yanfang; Hu, Shukun; Li, Ronghu; Han, Xing; Miao, Po; Wang, Ying; Yu, Jian; Feng, Xing

    2015-03-30

    Circadian rhythm disorder is a common neurological deficit caused by neonatal hypoxic-ischemic brain damage (HIBD). However, little is known about its underlying mechanisms. Our previous studies revealed a significant elevation of clock genes at the protein, but not mRNA, levels in the pineal gland after neonatal HIBD. To investigate the mechanisms of post-transcriptional regulation on clock genes, we screened changes of miRNA levels in the pineal gland after neonatal HIBD using high-throughput arrays. Within the miRNAs whose expression was significantly down-regulated, we identified one miRNA (miR182) that targeted the 3'-untranslated region (3'-UTR) of Clock, a key component of clock genes, and played a crucial role in regulating CLOCK expression after oxygen-glucose deprivation in primarily cultured pinealocytes. Our findings therefore provide new insight on studies of therapeutic targets for circadian rhythm disturbance after neonatal HIBD.

  8. Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats.

    Science.gov (United States)

    Arteaga, Olatz; Revuelta, Miren; Urigüen, Leyre; Álvarez, Antonia; Montalvo, Haizea; Hilario, Enrique

    2015-01-01

    Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

  9. Changes in hippocampal neurons and memory function during the developmental stage of newborn rats with hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yue Li; Huiying Gao

    2006-01-01

    BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily.OBJECTTVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult.DESTGN: Completely randomized grouping, controlled experiment.SETTING: Taian Health Center for Women and Children; Taishan Medical College.MATERTALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou.METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability(After test, 5 rats from each group were sacrificed and used for immunohistochemical staining) ② The right common carotid artery of newborn rats of model group was ligated under the sthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③Thalamencephal tissue

  10. Phenobarbital and midazolam increase neonatal seizure-associated neuronal injury.

    Science.gov (United States)

    Torolira, Daniel; Suchomelova, Lucie; Wasterlain, Claude G; Niquet, Jerome

    2017-07-01

    Status epilepticus is common in neonates and infants, and is associated with neuronal injury and adverse developmental outcomes. γ-Aminobutyric acidergic (GABAergic) drugs, the standard treatment for neonatal seizures, can have excitatory effects in the neonatal brain, which may worsen the seizures and their effects. Using a recently developed model of status epilepticus in postnatal day 7 rat pups that results in widespread neuronal injury, we found that the GABAA agonists phenobarbital and midazolam significantly increased status epilepticus-associated neuronal injury in various brain regions. Our results suggest that more research is needed into the possible deleterious effects of GABAergic drugs on neonatal seizures and on excitotoxic neuronal injury in the immature brain. Ann Neurol 2017;82:115-120. © 2017 American Neurological Association.

  11. Prevalence and outcomes of acute kidney injury in term neonates ...

    African Journals Online (AJOL)

    Prevalence and outcomes of acute kidney injury in term neonates with perinatal ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... Background: The kidney is the most damaged organ in asphyxiated full-term infants.

  12. The value of brainstem evoked potential in clinical decision of a patient with hypoxic-ischemic encephalopathy O valor do potencial evocado auditivo em decisão clínica em paciente com síndrome hipóxico-isquêmica

    Directory of Open Access Journals (Sweden)

    Anna Lecticia R. Pinto

    2007-09-01

    Full Text Available Establishing a prognosis for hypoxic-ischemic encephalopathy during the neonatal period is extremely difficult, as the neuroplasticity of the developing brain makes it almost impossible to measure the affected area. This case report describes a newborn with severe perinatal asphyxia and neonatal neurological syndrome including absent suck reflex. Normal brainstem auditory evoked potential led the diagnosis towards a transitory dysfunction of deglutition, and the subject received daily stimulation in the hospital environment. Suck developed satisfactorily by day of life 30 and the patient was released without having to be tube fed. Neurophysiologic tests can be of value in the clinical decisions and analysis of functional prognosis of patients with hypoxic-ischemic encephalopathy.Estabelecer o prognóstico da encefalopatia hipóxico-isquêmica durante o período neonatal é extremamente difícil, devido à neuroplasticidade do cérebro em desenvolvimento que impede a medida exata das áreas afetadas. Este relato descreve um recém-nascido a termo com grave asfixia perinatal e síndrome neurológica pós-natal, incluindo ausência do reflexo de sucção. O potencial evocado auditivo do tronco cerebral foi normal, sugerindo o diagnóstico de disfunção transitória da deglutição. Após estimulação diária no hospital a sucção foi obtida satisfatoriamente, e o paciente recebeu alta sem necessidade de alimentação enteral. Os testes neurofisiológicos podem ser de grande valor em decisões clínicas e análise funcional prognóstica de pacientes com encefalopatia hipóxico-isquêmica.

  13. Intranasal mesenchymal stem cell treatment for neonatal brain damage : long-term cognitive and sensorimotor improvement

    NARCIS (Netherlands)

    Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; van Bel, Frank; Kas, Martien J H; Kavelaars, Annemieke; Heijnen, Cobi J

    2013-01-01

    Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic wi

  14. Hyperbaric oxygen therapy for promoting the intellectual rehabilitation of infants with severe hypoxic-ischemic encephalopathy A 5-year follow-up

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: It has been reported that early intervention of hyperbaric oxygen (HBO) can promote the intellectual rehabilitation of infants with severe hypoxic-ischemic encephalopathy (HIE) and can prevent mental retardation recently. However, the prior observations on the therapeutic effect almost were short-term.How about the observations on prospective efficacy and the following up on systematic intelligence test? OBJECTIVE: To investigate the short-term and long-term effects of HBO therapy on the promotion of the intellectual rehabilitation in infants with severe HIE.DESIGN: A comparative observation.SETTING: Department of Pediatrics, Affiliated Hospital, Qingdao University Medical College.PARTICIPANTS: Forty-seven infants with severe HIE (35 males and 12 females) were treated with HBO in the Department of Pediatrics, the Affiliated Hospital of the Medical College of Qingdao University from October 1996 to July 1999. All of them were consistent with the diagnostic criteria and clinical grading on severe HIE which were designed by Chinese Medical Association pediatrics committee neonate group in Hangzhou, October, 1996. Informed contents were obtained from the relatives of all the infants.METHODS: ① Grouping: The infants were randomly divided into two groups according to the order of admission, those of odd numbers were HBO group (n =24) and those of even numbers were control group(n =23). All the infants were treated with routine therapy for 3 months, in addition to HBO therapy in the HBO group, once a day for 4 courses of 10 days with the interval of 10 - 15 days since 8 to 10 days after birth. HBO chamber produced by the 701 Institute of China Ship Industry Company was used, and the therapy pressure was 0.14 - 0.16 Mpa, and the time of compression and decompression were both 15 minutes while voltage-stabilizing was 30 minutes. ② In order to evaluate the short-term and long-term effects of HBO on intellectual rehabilitation in infants with HIE, neonatal

  15. Advance of progesterone and the signal pathway of phosphatidylinositol 3-kinase/protein kinase B in hypoxic ischemic brian damage%孕酮和 PI3 K/Akt信号通路在缺氧缺血性脑损伤中的研究现状

    Institute of Scientific and Technical Information of China (English)

    徐之良; 陈卫萍; 钟森

    2015-01-01

    磷酸肌醇-3羟激酶/蛋白激酶B( PI3K/Akt)是一种经典的抗凋亡、促存活信号传导通路,在脑梗死、帕金森病、癫痫等神经系统疾病中发挥调节作用。孕酮是一种脂溶性甾体激素,对创伤性脑损伤、卒中、阿尔茨海默病等患者的神经保护有重要作用,其与p-Akt上调有关。本文通过收集讨论新生儿缺氧缺血性脑病( HIE)、孕酮和PI3K/Akt的研究报道,以期为进一步探讨孕酮在HIE中的神经保护作用与 PI3 K/Akt信号通路的关系提供一定的理论依据。%Phosphatidylinositol 3 -kinase /protein kinase B ( PI3 K/Akt) is a classic anti -apoptotic and pro -survival signaling pathway, which plays a role in the regulation of cerebral infarction, Parkinson's dis-ease , epilepsy and other neurological diseases.Progesterone is one of the fat-soluble sex hormones, which has been proved to have neuro-pro-tective effect on nerological disease, such as brain injury, stroke and Alzheimer's disease, and it′s relevant to the up-regulation of p-Akt. Studies about the advance of neonatal hypoxic ischemic encephalopathy ( HIE) , progesterone and PI3K/Akt were collected and reviewed, antici-pating that it will provide theoretical basis for the further research of the relationship between progesterone and the signal pathway of PI3K/Akt in HIE.

  16. Acute kidney injury in the fetus and neonate.

    Science.gov (United States)

    Nada, Arwa; Bonachea, Elizabeth M; Askenazi, David J

    2017-04-01

    Acute kidney injury (AKI) is an under-recognized morbidity of neonates; the incidence remains unclear due to the absence of a unified definition of AKI in this population and because previous studies have varied greatly in screening for AKI with serum creatinine and urine output assessments. Premature infants may be born with less than half of the nephrons compared with term neonates, predisposing them to chronic kidney disease (CKD) early on in life and as they age. AKI can also lead to CKD, and premature infants with AKI may be at very high risk for long-term kidney problems. AKI in neonates is often multifactorial and may result from prenatal, perinatal, or postnatal insults as well as any combination thereof. This review focuses on the causes of AKI, the importance of early detection, the management of AKI in neonates, and long-term sequela of AKI in neonates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Fetal trauma: brain imaging in four neonates

    Energy Technology Data Exchange (ETDEWEB)

    Breysem, Luc; Mussen, E.; Demaerel, P.; Smet, M. [Department of Radiology, University Hospitals, Herestraat 49, 3000, Leuven (Belgium); Cossey, V. [Department of Pediatrics, University Hospitals, Leuven (Belgium); Voorde, W. van de [Department of Forensic Medicine, University Hospitals, Leuven (Belgium)

    2004-09-01

    The purpose of this paper is to describe brain pathology in neonates after major traffic trauma in utero during the third trimester. Our patient cohort consisted of four neonates born by emergency cesarean section after car accident in the third trimester of pregnancy. The median gestational age (n=4) was 36 weeks (range: 30-38). Immediate post-natal and follow-up brain imaging consisted of cranial ultrasound (n=4), computed tomography (CT) (n=1) and post-mortem magnetic resonance imaging (MRI) (n=1). Pathology findings were correlated with the imaging findings (n=3). Cranial ultrasound demonstrated a huge subarachnoidal hemorrhage (n=1), subdural hematoma (n=1), brain edema with inversion of the diastolic flow (n=1) and severe ischemic changes (n=1). In one case, CT demonstrated the presence and extension of the subarachnoidal hemorrhage, a parietal fracture and a limited intraventricular hemorrhage. Cerebellar hemorrhage and a small cerebral frontal contusion were seen on post-mortem MRI in a child with a major subarachnoidal hemorrhage on ultrasound. None of these four children survived (three children died within 2 days and one child died after 1 month). Blunt abdominal trauma during pregnancy can cause fetal cranial injury. In our cases, skull fracture, intracranial hemorrhage and hypoxic-ischemic encephalopathy were encountered. (orig.)

  18. Red photon treatment inhibits apoptosis via regulation of bcl-2 proteins and ROS levels, alleviating hypoxic-ischemic brain damage.

    Science.gov (United States)

    Jiang, W; Chen, L; Zhang, X J; Chen, J; Li, X C; Hou, W S; Xiao, N

    2014-05-30

    Therapeutic options for hypoxic-ischemic brain damage (HIBD) are scarce and inefficient. Recently, many studies have demonstrated that red photon plays an important role in anti-inflammatory processes as well as apoptosis, the main trait of HIBD. In this study, we investigated whether red photon can protect from HIBD in SD rats and oxygen-glucose deprivation (OGD) in PC12 cells. Apoptosis, mitochondrial transmembrane potential (MMP), and reactive oxygen species (ROS) rates were assessed in PC12 cells. We found that 6-h irradiation resulted in decreased MMP, ROS and apoptosis rates, although these changes were reversible with prolonged irradiation. Importantly, these effects were sustained for 2-8h upon quenching of the red photon. Similar trends were observed for protein and mRNA expression of bax and bcl-2, with short-term irradiation (6h) inhibiting apoptosis in PC12 Cells. However, long-term (>6h) irradiation caused cell damage. In vivo experiments, bax mRNA and protein levels were reduced after 7days in HIBD model rats treated with red photon, in contrast to bcl-2. Furthermore, we found that bax and bcl-2 were mainly expressed in pyramidal cells of the hippocampus CA1 and CA3. Importantly, Morris Water Maze test results revealed an improvement in learning ability and spatial memory in rats after irradiation. Overall, our data showed that short-term irradiation with red photon in the acute phase inhibits the mitochondrial apoptotic pathway via regulation of bcl-2-related proteins and reduction of ROS levels, thereby decreasing apoptosis in nerve cells and improving the neurological prognosis of HIBD.

  19. NOC/oFQ PKC-dependent superoxide generation contributes to hypoxic-ischemic impairment of NMDA cerebrovasodilation.

    Science.gov (United States)

    Armstead, W M

    2000-12-01

    This study determined whether nociceptin/orphanin FQ (NOC/oFQ) generates superoxide anion (O(2)(-)) in a protein kinase C (PKC)-dependent manner and whether such production contributes to hypoxic-ischemic (H-I) impairment of N-methyl-D-aspartate (NMDA)-induced pial artery dilation in newborn pigs equipped with closed cranial windows. Superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was an index of O(2)(-) generation. Under non-H-I conditions, topical NOC/oFQ (10(-10) M, concentration present in cerebrospinal fluid after I or H-I) increased SOD-inhibitable NBT reduction from 1 +/- 1 to 20 +/- 3 pmol/mm(2). PKC inhibitors staurosporine and chelerythrine (10(-7) M) blunted NBT reduction (1 +/- 1 to 7 +/- 2 pmol/mm(2) for chelerythrine), whereas the NOC/oFQ receptor antagonist [F/G]NOC/oFQ (1-13)-NH(2) (10(-6) M) blocked NBT reduction. [F/G]NOC/oFQ(1-13)-NH(2) and staurosporine also blunted the NBT reduction observed after I or H-I. NMDA (10(-8), 10(-6) M)-induced pial artery dilation was reversed to vasoconstriction after H-I. The NOC/oFQ antagonist staurosporine and free radical scavengers partially prevented this impaired dilation (sham: 9 +/- 1 and 16 +/- 1; H-I: -5 and -10 +/- 1; H-I staurosporine pretreated: 3 +/- 1 and 6 +/- 1%). These data show that NOC/oFQ increased O(2)(-) production in a PKC-dependent manner and contributed to this production after insult and that NOC/oFQ contributed to impaired NMDA-induced pial artery dilation after H-I, suggesting, therefore, that PKC-dependent O(2)(-) generation by NOC/oFQ links NOC/oFQ release to impaired NMDA dilation after H-I.

  20. Effects of exogenous ganglioside-1 on learning and memory in a neonatal rat model of hypoxia-ischemia brain injury

    Institute of Scientific and Technical Information of China (English)

    Shizhi Li; Nong Xiao; Xiaoping Zhang; Ling Liu; Liyun Lin; Siyuan Chen; Yuxia Chen; Bei Xu

    2008-01-01

    BACKGROUND: Exogenous ganglioside-1 (GM1) can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage. OBJECTIVE: To examine the possible mechanisms of exogenous GM1 protection in hypoxia-ischemia-induced brain damage in a neonatal rat model by measuring changes in brain mass, pathological morphology, growth-associated protein-43 expression, and neurobehavioral manifestations. DESIGN, TIME AND SETTING: A randomized block-design study was performed at the lmmunohistochemistry Laboratory of the Pediatric Research Institute, Children's Hospital of Chongqing Medical University from August 2005 to August 2006. MATERIALS: A total of 36 neonatal, 7-day-old, Sprague Dawley rats were used in this experiment. The hypoxia-ischemia-induced brain damage model was established by permanently occluding the right carotid artery, followed by oxygen inhalation at a low concentration (8% O2, 92% N2) for 2 hours. METHODS: All rats were randomly divided into the following groups: GM1, model, and sham operation, with 12 rats each group. Rats in the GM1 and model groups received hypoxic/ischemic-induced brain damage. Rats in the GM1 group received injections ofGM1 (i.p., 20 mg/kg) at 0, 24, 48, 72, 96, 120, and 144 hours following models established, and rats in the model group were administered (i.p.) the same amount of saline. The right carotid artery was separated, but not ligated, in the sham operation group rats. MAIN OUTCOME MEASURES: At 1 week after surgery, expression of growth-associated protein-43, a marker of neural development and plasticity, was detected in the hippocampal CA3 region by immunohistochemistry. Brain mass was measured, and the pathological morphology was observed. At 4 weeks after surgery, behavioral changes in the remaining rats were tested by Morris water maze, and growth-associated protein-43 expression was measured. RESULTS: (1) In the GM 1 and sham operation groups, growth-associated protein-43 expression was

  1. 缺氧缺血性脑损伤%Hypoxic-Ischemic Brain Damage in Children

    Institute of Scientific and Technical Information of China (English)

    邹峥; 刘小惠; 邹大卫

    2011-01-01

    由于高代谢的需要,脑高度的依赖充分的氧供给,全脑性缺氧/缺血会导致快速的能量丧失,引起一连串的包括兴奋毒性损伤、炎症和凋亡所共同造成的脑损伤.围生期窒息复杂的先天性心脏病开放性手术及意外的捂热综合征均是酿成缺氧/缺血脑损伤的危险因素.缺氧/缺血愈久,损伤愈重,预后也愈差.因而需及早给予积极和恰当的治疗.%Due to its high metabolism demand, the brain is highly dependent on sufficient oxygen supply so that hypoxia - ischemia of the global brain results in a rapid depletion of energy stores that trigger a complex and cascade of celluar events including excitotoxic injury,inflammation and apoptosis of the brain tissue. Perinatal asphyxia complex congenital open heart surgery and muggy disease are risk factors to induce hypoxia - ischemia brain damage. Severity and duration determine the ultimate prognosis,so that the hypoxia - ischemia patients should be early,actively and properly treated.

  2. Research progress in apoptosis and hypoxic - ischemic brain damage%缺氧缺血性脑损伤与凋亡的进展

    Institute of Scientific and Technical Information of China (English)

    陈敏榕; 陈燕惠

    2004-01-01

    Apoptosis is one of the most important causes, which results in the central neuronal system complication in hypoxic- ischemic brain damage (HIBD). Apoptosis occurs in the developing brain more than in the developed brain. Apoptosis can last several weeks and may be inverted its pathology by appropriate therapy. Caspase inhibitor, neurotrophic factors, anti-apoptosis gene Bcl-2, mild hypothermia, and early intervention play important roles in promoting neuronal cell survival and preventing from apoptosis through different mechanisms. It may be a new way for rehabilitation of HIBD.

  3. Brain injuries due to neonatal hypoglycemia: case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Bong; Song, Chang Joon; Chang, Mae Young; Youn, Hyae Won [College of Medicine, Chungram National Univ., Daejeon (Korea, Republic of)

    2003-10-01

    Although hypoglycemia may be common among neonates, brain injuries resulting from isolated neonatal hypoglycemia are rare. The condition may cause neurological symptoms such as stupor, jitteriness, and seizures, though in their absence, diagnosis delayed or difficult. Hypoglycemia was diagnosed in a three-day-old neonate after he visited the emergency department with loose stool, poor oral intake, and decreased activity, first experienced two days earlier. Two days after his visity, several episodes of seizure occurred. T2 and diffusion-weighted magnetic resonance (MR) scanning, performed at 11 days of age, revealed bilateral and symmetrical high signal intensity lesions in occipital, parietal, and temporal lobes. We report the MR findings of hypoglycemic encephalopathy in a neonate.

  4. Iatrogenic skin injury in the neonatal intensive care unit.

    Science.gov (United States)

    Sardesai, Smeeta R; Kornacka, Maria K; Walas, Wojciech; Ramanathan, Rangasamy

    2011-02-01

    Although neonatal care has become more and more meticulous with significant changes in technology in the neonatal intensive care unit (NICU) in the past 50 years, iatrogenic cutaneous injuries continue to occur. Although the incidence of severe injuries is decreasing because the more difficult procedures are being replaced by improved techniques, skin injuries have not yet been completely eliminated. However, the nature and causes of cutaneous injuries have changed, and the injuries are frequent but generally minor. The major risk factors are low birth weight, gestational age, length of stay, a central venous line, mechanical ventilation, and support with continuous positive airway pressure. The rate of iatrogenic events is about 57% at gestational ages of 24-27 weeks, compared with 3% at term. There are no current comprehensive reviews of iatrogenic cutaneous injury. The purpose of this review is to describe the iatrogenic cutaneous injuries that may occur in the newborns as a consequence of perinatal and postnatal medical procedures. With increased survival of extremely-low-birth-weight (ELBW) infants and changing modes of management in the NICU, neonatologists must make every effort to recognize injuries and prevent their occurrence in the NICU.

  5. NOC/oFQ contributes to hypoxic-ischemic impairment of N-methyl-D-aspartate-induced cerebral vasodilation.

    Science.gov (United States)

    Armstead, W M

    2000-06-16

    Previous studies in piglets show that either hypoxia, ischemia-reperfusion (I+R) or combined hypoxia-ischemia-reperfusion (H+I+R) attenuated N-methyl-D-aspartate (NMDA)-induced pial artery dilation. This study was designed to determine the contribution of the newly described opioid nociceptin orphanin FQ (NOC/oFQ) to hypoxic-ischemic impairment of NMDA induced cerebral vasodilation in piglets equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased P(O(2)) to 35+/-3 mmHg with unchanged P(CO(2)). I+R elevated CSF NOC/oFQ from 67+/-4 to 266+/-29 pg/ml ( approximately 10(-10) M) while H+I+R elevated CSF NOC/oFQ to 483+/-67 pg/ml within 1 h of reperfusion. Such elevated NOC/oFQ levels returned to control within 4 h in I+R animals and within 12 h in H+I+R animals. Topical NOC/oFQ (10(-10) M) had no effect on pial artery diameter by itself but attenuated NMDA (10(-8), 10(-6) M) induced pial dilation (control, 9+/-1 and 16+/-1; coadministered NOC/oFQ, 5+/-1 and 10+/-1%). NMDA induced pial artery dilation was attenuated by I+R or H+I+R; but such dilation was partially restored by pretreatment with the putative NOC/oFQ antagonist [F/G] NOC/oFQ (1-13) NH(2) (10(-6) M) (control, 9+/-1 and 16+/-1; I+R, 3+/-1 and 5+/-1; I+R+NOC/oFQ antagonist, 6+/-1 and 11+/-1%) Similar results were obtained for glutamate. These data suggest that NOC/oFQ release contributes to impaired NMDA and glutamate-induced cerebrovasodilation following I+R or H+I+R.

  6. TIMP1 in conditioned media of human adipose stromal cells protects neurons against oxygen-glucose deprivation injury.

    Science.gov (United States)

    Du, Shiwei; Mao, Gengsheng; Zhu, Timothy; Luan, Zuo; Du, Yansheng; Gu, Huiying

    2015-01-01

    Adipose stromal cells (ASC) can protect neurons when administered to brains due to secreted trophic factors. Our previous studies demonstrated that several neurotrophic factors such as brain-derived neurotropic factor (BDNF) and insulin like growth factor-1 (IGF-1) in ASC conditioned media (ASC-CM) can protect brains against hypoxic-ischemic (HI) injury in neonatal rats. In this study, we demonstrated that human ASC-CM potently blockeds caspase-3 mediated cortical neuronal apoptosis under in vitro oxygen-glucose deprivation (OGD). Interestingly, tissue inhibitor of metalloproteinase 1 (TIMP1), a non neurotrophic factor, played a significant role in the ASC-CM-induced neural protection against OGD. Thus, this study establishes the therapeutic potential of TIMP1 together with other neurotrophic factors in ASC-CM for treating cerebral HI disorders.

  7. Electroencephalogram and magnetic resonance imaging comparison as a predicting factor for neurodevelopmental outcome in hypoxic ischemic encephalopathy infant treated with hypothermia

    Directory of Open Access Journals (Sweden)

    Francesca Del Balzo

    2014-10-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is an important cause of acute neurological damage in newborns at (or near term. Several trials in recent years have shown that moderate hypothermia by total body cooling or selective head is an effective intervention to reduce mortality and major disability in infants survived a perinatal hypoxic-ischemic attack. Follow-up in these patients is very important to establish neurodevelopmental outcome, and specific markers can lead us to detect predicting sign for good or poor outcome. We reported a few cases of newborn with HIE treated with hypothermia, in whom the comparison between electroencephalogram (EEG and magnetic resonance imaging (MRI represents the first marker for neurodevelopment outcome prediction. The continuous EEG monitoring showed a depressed EEG activity with diffuse burst depression in 7 patients. No epileptic abnormalities were registered. In 10 out of 20 patients no abnormalities of the background activity and no epileptic abnormalities were observed. We found that a depressed EEG activity during the first 72 h of life and a diffused alteration of basal ganglia at MRI were correlated with a poor neurodevelopmental outcome at 18 months of follow-up.

  8. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants,. Inflammatory markers .... were then moved back to their respective dams and immediately ..... various pro-inflammatory cytokines is stimulated.

  9. Hypoxic preconditioning differentially affects GABAergic and glutamatergic neuronal cells in the injured cerebellum of the neonatal rat.

    Directory of Open Access Journals (Sweden)

    Sergio G Benitez

    Full Text Available In this study we examined cerebellar alterations in a neonatal rat model of hypoxic-ischemic brain injury with or without hypoxic preconditioning (Pc. Between postnatal days 7 and 15, the cerebellum is still undergoing intense cellular proliferation, differentiation and migration, dendritogenesis and synaptogenesis. The expression of glutamate decarboxylase 1 (GAD67 and the differentiation factor NeuroD1 were examined as markers of Purkinje and granule cells, respectively. We applied quantitative immunohistochemistry to sagittal cerebellar slices, and Western blot analysis of whole cerebella obtained from control (C rats and rats submitted to Pc, hypoxia-ischemia (L and a combination of both treatments (PcL. We found that either hypoxia-ischemia or Pc perturbed the granule cells in the posterior lobes, affecting their migration and final placement in the internal granular layer. These effects were partially attenuated when the Pc was delivered prior to the hypoxia-ischemia. Interestingly, whole nuclear NeuroD1 levels in Pc animals were comparable to those in the C rats. However, a subset of Purkinje cells that were severely affected by the hypoxic-ischemic insult--showing signs of neuronal distress at the levels of the nucleus, cytoplasm and dendritic arborization--were not protected by Pc. A monoclonal antibody specific for GAD67 revealed a three-band pattern in cytoplasmic extracts from whole P15 cerebella. A ∼110 kDa band, interpreted as a potential homodimer of a truncated form of GAD67, was reduced in Pc and L groups while its levels were close to the control animals in PcL rats. Additionally we demonstrated differential glial responses depending on the treatment, including astrogliosis in hypoxiated cerebella and a selective effect of hypoxia-ischemia on the vimentin-immunolabeled intermediate filaments of the Bergmann glia. Thus, while both glutamatergic and GABAergic cerebellar neurons are compromised by the hypoxic-ischemic insult

  10. White matter injury detection in neonatal MRI

    Science.gov (United States)

    Cheng, Irene; Hajari, Nasim; Firouzmanesh, Amirhossein; Shen, Rui; Miller, Steven; Poskitt, Ken; Basu, Anup

    2013-02-01

    Early detection of white matter injury in premature newborns can facilitate timely clinical treatments reducing the potential risk of later developmental deficits. It was reported that there were more than 5% premature newborns in British Columbia, Canada, among which 5-10% exhibited major motor deficits and 25-50% exhibited significant developmental and visual deficits. With the advancement of computer assisted detection systems, it is possible to automatically identify white matter injuries, which are found inside the grey matter region of the brain. Atlas registration has been suggested in the literature to distinguish grey matter from the soft tissues inside the skull. However, our subjects are premature newborns delivered at 24 to 32 weeks of gestation. During this period, the grey matter undergoes rapid changes and differs significantly from one to another. Besides, not all detected white spots represent injuries. Additional neighborhood information and expert input are required for verification. In this paper, we propose a white matter feature identification system for premature newborns, which is composed of several steps: (1) Candidate white matter segmentation; (2) Feature extraction from candidates; (3) Validation with data obtained at a later stage on the children; and (4) Feature confirmation for automated detection. The main challenge of this work lies in segmenting white matter injuries from noisy and low resolution data. Our approach integrates image fusion and contrast enhancement together with a fuzzy segmentation technique to achieve promising results. Other applications, such as brain tumor and intra-ventricular haemorrhage detection can also benefit from our approach.

  11. New Antioxidant Drugs for Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Maria Luisa Tataranno

    2015-01-01

    Full Text Available The brain injury concept covers a lot of heterogeneity in terms of aetiology involving multiple factors, genetic, hemodynamic, metabolic, nutritional, endocrinological, toxic, and infectious mechanisms, acting in antenatal or postnatal period. Increased vulnerability of the immature brain to oxidative stress is documented because of the limited capacity of antioxidant enzymes and the high free radicals (FRs generation in rapidly growing tissue. FRs impair transmembrane enzyme Na+/K+-ATPase activity resulting in persistent membrane depolarization and excessive release of FR and excitatory aminoacid glutamate. Besides being neurotoxic, glutamate is also toxic to oligodendroglia, via FR effects. Neuronal cells die of oxidative stress. Excess of free iron and deficient iron/binding metabolising capacity are additional features favouring oxidative stress in newborn. Each step in the oxidative injury cascade has become a potential target for neuroprotective intervention. The administration of antioxidants for suspected or proven brain injury is still not accepted for clinical use due to uncertain beneficial effects when treatments are started after resuscitation of an asphyxiated newborn. The challenge for the future is the early identification of high-risk babies to target a safe and not toxic antioxidant therapy in combination with standard therapies to prevent brain injury and long-term neurodevelopmental impairment.

  12. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    Science.gov (United States)

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  13. Biomarkers of acute kidney injury in neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Sweetman, D U

    2013-03-01

    Acute kidney injury (AKI) is a common complication of neonatal encephalopathy (NE). The accurate diagnosis of neonatal AKI, irrespective of the cause, relies on suboptimal methods such as identification of rising serum creatinine, decreased urinary output and glomerular filtration rate. Studies of AKI biomarkers in adults and children have shown that biomarkers can improve the early diagnosis of AKI. Hypoxia-ischaemia is the proposed aetiological basis of AKI in both NE and cardiopulmonary bypass (CPB). However, there is a paucity of studies examining the role of AKI biomarkers specifically in NE. Urinary cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18, kidney injury molecule-1, liver-type fatty acid-binding protein, serum CysC and serum NGAL all show good ability to predict early AKI in a heterogeneous critically ill neonatal population including infants post-CPB. Moreover, serum and urinary NGAL and urinary CysC are early predictors of AKI secondary to NE. These findings are promising and open up the possibility of biomarkers playing a significant role in the early diagnosis and treatment of NE-related AKI. There is an urgent need to explore the role of AKI biomarkers in infants with NE as establishing the diagnosis of AKI earlier may allow more timely intervention with potential for improving long-term outcome.

  14. Biomarkers of brain injury in the premature infant

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2013-01-01

    Full Text Available The term encephalopathy of prematurity encompasses not only the acute brain injury (such as intraventricular hemorrhage but also complex disturbance on the infant’s subsequent brain development. In premature infants, the most frequent recognized source of brain injury is intraventricular hemorrhage (IVH and periventricular leukomalacia (PVL. Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9 and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after post-hemorrhagic ventricular dilation. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

  15. Biomarkers of brain injury in the premature infant.

    Science.gov (United States)

    Douglas-Escobar, Martha; Weiss, Michael D

    2012-01-01

    The term "encephalopathy of prematurity" encompasses not only the acute brain injury [such as intraventricular hemorrhage (IVH)] but also complex disturbance on the infant's subsequent brain development. In premature infants, the most frequent recognized source of brain injury is IVH and periventricular leukomalacia (PVL). Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury, and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD), and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP, and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9, and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after PHVD. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

  16. MRI for premature neonatal brain injury: a case report.

    Science.gov (United States)

    Langham, Alexander

    2017-06-01

    This case report aims to extend analytical thinking and clinical reasoning of clinicians and radiographers when presented with diagnosing premature neonatal brain injuries (PNBI). The report considers the uses and merit of magnetic resonance imaging (MRI) in the primary assessment of PNBI. The traditional technique of cranial ultrasound as the first modality of choice can have several limitations, which includes a lower temporal resolution in its ability to differentiate grey-white matter distribution patterns, lower spatial resolution in its ability to accurately map white matter fibre tracts and distribution patterns which are critical in white matter injury pathological events. In this specific case report, MRI was useful for the assessment of haemorrhagic brain injury post partum.Therefore, should MRI be considered, the primary imaging modality in these cases when the concerns about PNBI is presented? This case study explores the current trends in MRI neonatal brain imaging and advancements being made in this field. © 2017 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.

  17. Antimicrobial peptides and complement in neonatal hypoxia-ischemia induced brain damage

    Directory of Open Access Journals (Sweden)

    Eridan eRocha-Ferreira

    2015-02-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1-5 per 1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy and cognitive disabilities. Even though the brain is considered an immune-privileged site, it has innate and adaptive immune response and can produce complement (C components and antimicrobial peptides (AMPs. Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain.Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS, including neonatal hypoxia-ischemia (HI, resident microglia and astroglia are the main cells providing immune defence to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI-injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins which can chemoattract and promote maturation of dendritic cells, and can also limit inflammation by controlling the viability of these same dendritic cells. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI-injury and the effect of that balance on the

  18. The Role of Cytokines and Inflammatory Cells in Perinatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Ryan M. McAdams

    2012-01-01

    Full Text Available Perinatal brain injury frequently complicates preterm birth and leads to significant long-term morbidity. Cytokines and inflammatory cells are mediators in the common pathways associated with perinatal brain injury induced by a variety of insults, such as hypoxic-ischemic injury, reperfusion injury, toxin-mediated injury, and infection. This paper examines our current knowledge regarding cytokine-related perinatal brain injury and specifically discusses strategies for attenuating cytokine-mediated brain damage.

  19. Encefalopatia hipóxico-isquêmica em recém-nascidos a termo: aspectos da fase aguda e evolução Perinatal hypoxic-ischemic encephalopathy: acute period and outcome

    Directory of Open Access Journals (Sweden)

    Carolina A. R. Funayama

    1997-01-01

    Full Text Available Noventa e quatro recém-nascidos com encefalopatia hipóxico-isquêmica (EHI, atendidos no Hospital das Clínicas de Ribeirão Preto desde 1982, foram avaliados evolutivamente na fase aguda e por período médio de 47 meses. De 43 casos com EHI 1,40 se recuperaram em 96 horas e 3 faleceram. Dos 40 com EHI II, 37,5% se recuperaram até o sétimo dia e demais permaneceram com alterações. Os 11 casos com grau III faleceram até o segundo mês de vida. As crianças com EHI grau I não apresentaram seqüelas motoras. Do grupo com EHI grau II 34,5% apresentaram paralisia cerebral e 17,7% atraso neuromotor. 80% dos casos com sequela apresentaram exame neurológico anormal além do sétimo dia, na fase aguda da EHI. Epilepsia ocorreu em 17,5% dos casos com EHI grau II e somente no grupo com seqüelas motoras. Teste de QI não evidenciou diferença significativa entre os grupos com grau I, II sem seqüelas motoras e o grupo controle. Com esses dados os autores reafirmaram a importância prognostica da evolução da EHI na fase aguda.Ninety four neonates with hypoxic ischemic encephalopathy HIE attended at the University of Ribeirão Preto since 1982 were studied in terms of the neurological alterations during the acute phase and outcome over a mean period of 47 months. From 43 newborns with HIE I, 40 recovered within 96 hours and 3 died. Among 40 infants with HIE II, 37.5% recovered within the first week, and the others continued abnormal beyond the 7th day. All 11 infants with HIE III died before the second month of life. The HIE I group had no motor sequelae. Among the HIE II group, 34.5% showed cerebral palsy and 17.7% neuromotor retardation. 80.0% of those with sequelae persisted abnormal beyond 7th day of life, during the acute phase of the HIE. Epilepsy occurred in 17.5% of cases with HIE grade II, only among those with neuromotor sequelae. The 1Q test did not show statistically significant difference between the HIE I, II without motor sequelae

  20. 近足月胎兔持续宫内缺氧缺血性脑损伤模型的建立%Establishment of intrauterine hypoxic-ischemic brain damage model in near term fetal rabbits

    Institute of Scientific and Technical Information of China (English)

    王能里; 南燕; 柳艳丽; 林素; 叶伟; 唐震海; 林锦; 林振浪

    2012-01-01

    anesthesia and spinal anesthesia , a 4F Fogarty arterial embolectomy catheter was introduced into the left femoral artery . The blood supply of uterus in experiment group was blocked by inflating the catheter balloon with 0. 3 mL saline for 20 min, 25 min, 28 min, 30 min and 40 min (n = 4 for each experimental time group ). The catheter balloon was not inflated in con -trol group (n = 4). All pregnant rabbits were subject to cesarean section 24 h after the experimental procedure to induce hypoxia - ischemia to the fetus. The general conditions of the newborn rabbits were recorded , and the neurobehavioral dam -age and histology of the brain tissue were assessed. RESULTS: During the entire procedure , the pregnant rabbits had stable vital signs, no hypoxia happened , and had a good tolerance to the anesthesia program . When the balloon was inflated , the pulses of right femoral artery disappeared and the right leg blood pressure became non - detectable in experimental groups. In contrast, no fluctuation of the right leg blood pressure in control group (P > 0. 05 ) was observed. Intrauterine hypoxia - ischemia caused neonatal and fetal rabbit death , neurobehavioral damage and brain cell death . When the balloonwas inflated for 20 min, all fetal rabbits were alive and had no obvious neurologic damage . For 25 ~ 28 min, the stillbirth rates were 12. 9% and 40. 6% , respectively, while the live neonatal rabbits manifested neurobehavioral damage , edema neural cells , activated microglia cells and apoptotic brain cells . When blocking time beyond 30 min, above 80% fetal rabbits died. CONCLUSION: Continuous blockage of uterine blood supply in pregnant rabbits causes neonatal rabbit death , neurobehavioral damage and brain cell death . Different blocking time arouses different levels of brain damage . Continuous blockage of uterine blood supply for 25 -28 min can establish fetal generalize hypoxic - ischemic brain damage rabbit model , which is a good animal model for the

  1. Brain injury in premature neonates: A primary cerebral dysmaturation disorder?

    Science.gov (United States)

    Back, Stephen A; Miller, Steven P

    2014-04-01

    With advances in neonatal care, preterm neonates are surviving with an evolving constellation of motor and cognitive disabilities that appear to be related to widespread cellular maturational disturbances that target cerebral gray and white matter. Whereas preterm infants were previously at high risk for destructive brain lesions that resulted in cystic white matter injury and secondary cortical and subcortical gray matter degeneration, contemporary cohorts of preterm survivors commonly display less severe injury that does not appear to involve pronounced glial or neuronal loss. Nevertheless, these milder forms of injury are also associated with reduced cerebral growth. Recent human and experimental studies support that impaired cerebral growth is related to disparate responses in gray and white matter. Myelination disturbances in cerebral white matter are related to aberrant regeneration and repair responses to acute death of premyelinating late oligodendrocyte progenitors (preOLs). In response to preOL death, early oligodendrocyte progenitors rapidly proliferate and differentiate, but the regenerated preOLs fail to normally mature to myelinating cells required for white matter growth. Although immature neurons appear to be more resistant to cell death from hypoxia-ischemia than glia, they display widespread disturbances in maturation of their dendritic arbors, which further contribute to impaired cerebral growth. These complex and disparate responses of neurons and preOLs thus result in large numbers of cells that fail to fully mature during a critical window in development of neural circuitry. These recently recognized forms of cerebral gray and white matter dysmaturation raise new diagnostic challenges and suggest new therapeutic directions centered on reversal of the processes that promote dysmaturation.

  2. 结合遗传算法的脉冲耦合神经网络在新生儿缺氧缺血性脑病磁共振图像中的应用研究%Application of Pulse-coupled Neural Network Combined with Genetic Algorithm on MR Images of Hypoxic-ischemic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    刘俐; 石海瑛; 霍丽琴; 张峰; 郑崇勋; 尤佳; 何喜宁; 张洁

    2011-01-01

    为收集新生儿缺氧缺血性脑病(HIE)核磁共振图像特征数据,采用基于遗传算法(GA)结合脉冲耦合神经网络(PCNN)的方法,对新生儿HIE磁共振图像进行分割实验和病灶特征提取,结果显示:基于GA的PCNN分割不仅有较好的分割结果,且优于具有固定参数PCNN的分割,可为HIE早期诊断系统建立提供依据,为进一步诊断及研究提供有效的帮助.%This paper is to provide a basis for the establishment of an early diagnostic system for hypoxic-ischemic en-cephalopathy (HIE) by performing segmentation and feature extraction of lesions on the MR images of neonatal babies with HIE. The segmentation on MR images of HIE based on the genetic algorithm (GA) combined with a pulse-coupled neural network (PCNN) were carried out. There were better segmentation results by using PCNN segmentation based on GA than PCNN segmentation with fixed parameters. The data suggested that a PCNN based on GA could provide effective assistance for diagnosis and research.

  3. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury

    Directory of Open Access Journals (Sweden)

    Eridan Rocha-Ferreira

    2016-01-01

    Full Text Available Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity.

  4. The oxygen free radicals originating from mitochondrial complex I contribute to oxidative brain injury following hypoxia-ischemia in neonatal mice

    Science.gov (United States)

    Niatsetskaya, Zoya V.; Sosunov, Sergei A.; Matsiukevich, Dzmitry; Utkina-Sosunova, Irina V.; Ratner, Veniamin I.; Starkov, Anatoly A.; Ten, Vadim S.

    2012-01-01

    Oxidative stress and Ca++ toxicity are mechanisms of hypoxic-ischemic (HI) brain injury. This work investigates if partial inhibition of mitochondrial respiratory chain protects HI-brain by limiting generation of oxidative radicals during reperfusion. HI-insult was produced in p10 mice treated with complex-I (C-I) inhibitor, pyridaben (P), or vehicle. Administration of P significantly decreased extent of HI injury. Mitochondria isolated from the ischemic hemisphere in P-treated animals showed reduced H2O2 emission, less oxidative damage to the mitochondrial matrix, and increased tolerance to Ca++ triggered opening of permeability transition pore. Protective effect of P administration was also observed when the reperfusion-driven oxidative stress was augmented by the exposure to 100% O2 which exacerbated brain injury only in V-treated mice. In vitro, intact brain mitochondria dramatically increased H2O2 emission in response to hyperoxia, resulting in substantial loss of Ca++ buffering capacity. However, in the presence of C-I inhibitor, rotenone, or antioxidant, catalase, these effects of hyperoxia were abolished. Our data suggest that the reperfusion-driven recovery of C-I dependent mitochondrial respiration contributes not only to the cellular survival, but also causes an oxidative damage to the mitochondria, potentiating a loss of Ca++ buffering capacity. This highlights a novel neuroprotective strategy against HI-brain injury where the major therapeutic principle is a pharmacological attenuation, rather than an enhancement of mitochondrial oxidative metabolism during early reperfusion. PMID:22378894

  5. The oxygen free radicals originating from mitochondrial complex I contribute to oxidative brain injury following hypoxia-ischemia in neonatal mice.

    Science.gov (United States)

    Niatsetskaya, Zoya V; Sosunov, Sergei A; Matsiukevich, Dzmitry; Utkina-Sosunova, Irina V; Ratner, Veniamin I; Starkov, Anatoly A; Ten, Vadim S

    2012-02-29

    Oxidative stress and Ca(2+) toxicity are mechanisms of hypoxic-ischemic (HI) brain injury. This work investigates if partial inhibition of mitochondrial respiratory chain protects HI brain by limiting a generation of oxidative radicals during reperfusion. HI insult was produced in p10 mice treated with complex I (C-I) inhibitor, pyridaben, or vehicle. Administration of P significantly decreased the extent of HI injury. Mitochondria isolated from the ischemic hemisphere in pyridaben-treated animals showed reduced H(2)O(2) emission, less oxidative damage to the mitochondrial matrix, and increased tolerance to the Ca(2+)-triggered opening of the permeability transition pore. A protective effect of pyridaben administration was also observed when the reperfusion-driven oxidative stress was augmented by the exposure to 100% O(2) which exacerbated brain injury only in vehicle-treated mice. In vitro, intact brain mitochondria dramatically increased H(2)O(2) emission in response to hyperoxia, resulting in substantial loss of Ca(2+) buffering capacity. However, in the presence of the C-I inhibitor, rotenone, or the antioxidant, catalase, these effects of hyperoxia were abolished. Our data suggest that the reperfusion-driven recovery of C-I-dependent mitochondrial respiration contributes not only to the cellular survival, but also causes oxidative damage to the mitochondria, potentiating a loss of Ca(2+) buffering capacity. This highlights a novel neuroprotective strategy against HI brain injury where the major therapeutic principle is a pharmacological attenuation, rather than an enhancement of mitochondrial oxidative metabolism during early reperfusion.

  6. The establishment of a hypoxic-ischemic brain damage model in preterm fetal rabbits%未成熟胎兔缺氧缺血性脑损伤模型的建立

    Institute of Scientific and Technical Information of China (English)

    南燕; 唐震海; 王能里; 柳艳丽; 叶伟; 林锦; 林振浪

    2014-01-01

    目的:建立合适的早产脑损伤动物模型。方法选择孕25 d的健康新西兰白兔32只,阻断孕兔子宫血供,致胎兔宫内缺氧缺血,阻断时间分别持续30 min、35 min、37 min、40 min,对照组不阻断子宫血供。所有孕兔分别在术后24 h (孕26 d,A组)、5 d(孕30 d,B组)行剖宫产,根据阻断时间共分8亚组,每亚组4只。记录新生兔的一般状况,评估胎龄30 d存活新生兔神经行为学,观察脑组织病理改变。结果 A组新生兔缺氧缺血30 min均存活,随时间延长(35~40 min),死胎率由31.0%升至100%,存活新生兔脑组织含水量、凋亡脑细胞数随时间推移逐渐增加,以上差异均有统计学意义(P均<0.05)。B组新生兔,缺氧缺血35和37 min的死胎率升高为50.0%和65.7%,存活兔的体质量均低于对照组,并有不同程度的神经行为学异常,以上差异均有统计学意义(P<0.05)。脑组织病理检查发现,B组脑白质损伤较A组更明显。结论孕25d持续阻断孕兔子宫血供35~37 min可造成部分死胎和宫内体质量增长迟缓,存活新生兔出现不同程度的神经行为学异常及脑白质损伤,可用于制备早产缺氧缺血性脑损伤动物模型。%Objective To establish an appropriate preterm hypoxic-ischemic brain injury animal model. Methods A total of 32 pregnant New Zealand white rabbits at gestational day 25 were selected. The uterine blood supply in pregnant rabbits was blocked for 30, 35, 37, 40 minutes respectively, while in the control group it was not blocked. Then the pregnant rabbits were subjected to cesarean section 24 hours (at embryonic day 26, A group) or 5 days (at embryonic day 30, B group) after the experimental procedure. The general conditions of the newborn rabbits were recorded. The degree of neurobehavioral impairment in newborn rabbits was evaluated. The histological changes of brain tissue were observed. Results In A group

  7. Neonatal brachial plexus injury: comparison of incidence and antecedents between 2 decades.

    LENUS (Irish Health Repository)

    Walsh, Jennifer M

    2011-04-01

    We sought to compare the incidence and antecedents of neonatal brachial plexus injury (BPI) in 2 different 5-year epochs a decade apart following the introduction of specific staff training in the management of shoulder dystocia.

  8. Chrysophanol attenuates lead exposure-induced injury to hippocampal neurons in neonatal mice

    Institute of Scientific and Technical Information of China (English)

    Ji Zhang; Chunlin Yan; Shu Wang; Yong Hou; Guiping Xue; Li Zhang

    2014-01-01

    Previous studies have shown that chrysophanol protects against learning and memory impairments in lead-exposed adult mice. In the present study, we investigated whether chrys-ophanol can alleviate learning and memory dysfunction and hippocampal neuronal injury in lead-exposed neonatal mice. At the end of lactation, chrysophanol (0.1, 1.0, 10.0 mg/kg) was administered to the neonatal mice by intraperitoneal injection for 15 days. Chrysophanol signifi-cantly alleviated injury to hippocampal neurons and improved learning and memory abilities in the lead-poisoned neonatal mice. Chrysophanol also significantly decreased lead content in blood, brain, heart, spleen, liver and kidney in the lead-exposed neonatal mice. The levels of malondialdehyde in the brain, liver and kidney were significantly reduced, and superoxide dismutase and glutathione peroxidase activities were significantly increased after chrysophanol treatment. Collectively, these findings indicate that chrysophanol can significantly reduce damage to hippocampal neurons in lead-exposed neonatal mice.

  9. Clinically silent preoperative brain injuries do not worsen with surgery in neonates with congenital heart disease.

    Science.gov (United States)

    Block, A J; McQuillen, P S; Chau, V; Glass, H; Poskitt, K J; Barkovich, A J; Esch, M; Soulikias, W; Azakie, A; Campbell, A; Miller, S P

    2010-09-01

    Preoperative brain injury, particularly stroke and white matter injury, is common in neonates with congenital heart disease. The objective of this study was to determine the risk of hemorrhage or extension of preoperative brain injury with cardiac surgery. This dual-center prospective cohort study recruited 92 term neonates, 62 with transposition of the great arteries and 30 with single ventricle physiology, from 2 tertiary referral centers. Neonates underwent brain magnetic resonance imaging scans before and after cardiac surgery. Brain injury was identified in 40 (43%) neonates on the preoperative magnetic resonance imaging scan (median 5 days after birth): stroke in 23, white matter injury in 21, and intraventricular hemorrhage in 7. None of the brain lesions presented clinically with overt signs or seizures. Preoperative brain injury was associated with balloon atrial septostomy (P = .003) and lowest arterial oxygen saturation (P = .007); in a multivariable model, only the effect of balloon atrial septostomy remained significant when adjusting for lowest arterial oxygen saturation. On postoperative magnetic resonance imaging in 78 neonates (median 21 days after birth), none of the preoperative lesions showed evidence of extension or hemorrhagic transformation (0/40 [95% confidence interval: 0%-7%]). The presence of preoperative brain injury was not a significant risk factor for acquiring new injury on postoperative magnetic resonance imaging (P = .8). Clinically silent brain injuries identified preoperatively in neonates with congenital heart disease, including stroke, have a low risk of progression with surgery and cardiopulmonary bypass and should therefore not delay clinically indicated cardiac surgery. In this multicenter cohort, balloon atrial septostomy remains an important risk factor for preoperative brain injury, particularly stroke. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  10. White matter injury following rotavirus infection in neonates: new aspects to a forgotten entity, 'fifth day fits'?

    Science.gov (United States)

    Yeom, Jung Sook; Park, Chan-Hoo

    2016-07-01

    That rotavirus infection can cause neurological symptoms in young children has been well established. However, it is surprising why rotavirus infection has been overlooked as a cause of neonatal seizures for many years, despite significant research interest in neonatal rotavirus infection. Neonates are the age group most vulnerable to seizures, which are typically attributed to a wide range of causes. By contrast, because rotavirus infection is usually asymptomatic, it has been difficult to identify an association between this virus and neonatal seizures. The conventional wisdom has been that, although neonates are commonly infected with rotavirus, neurological complications are rare in this age. However, recent studies using diffusion-weighted imaging (DWI) have suggested a connection between rotavirus infection and neonatal seizures and that rotavirus infection can induce diffuse white matter injury without direct invasion of the central nervous system. The clinical features of white matter injury in rotavirus-infected neonates include the onset of seizures at days 4-6 of life in apparently healthy term infants. The recent findings seem to contradict the conventional wisdom. However, white matter injury might not be a completely new aspect of rotavirus infection in neonates, considering the forgotten clinical entity of neonatal seizures, 'fifth day fits'. With increased use of DWI in neonatal seizures, we are just starting to understand connection between viral infection and white matter injury in neonates. In this review, we discuss the historical aspects of rotavirus infection and neonatal seizures. We also present the clinical features of white matter injury in neonatal rotavirus infection.

  11. The effects of rehabilitation intervention without intermission to infant hypoxic ischemic encephalopathy%不间断康复干预对新生儿缺氧缺血性脑病的影响

    Institute of Scientific and Technical Information of China (English)

    张敬芳; 张瑞玲

    2002-01-01

    Background:With the setting up of the custodial room to infant serious illness,many infant patients with hypoxic ischemic encephalopathy(HIE) has survived.It has been reported that long term prognosis of serious HIE infant patients is bad and its percentage has gone to 73.6% (including sequela and death).Therefore how to improve these infant patients' prognosis are more and more thought highly of.We exerted intervention treatments in 12 months without intermission on 27 infant patients, and got significant effects.

  12. Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats.

    Science.gov (United States)

    Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping

    2015-05-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201

  13. The study of influnce of hypothermia to the expression of P16 and Bcl-2 levels in different brain tissues of the rats with hypoxic-ischemic brain damage%亚低温对新生鼠缺氧缺血性脑损害不同脑区p16和Bcl-2表达的影响研究

    Institute of Scientific and Technical Information of China (English)

    郭亚乐; 李占魁; 李瑞林; 黄绍平; 周戬平

    2011-01-01

    [Objective] To investigate the protective effects of hypothermia to the grey matter and the periventricular white matter of the brains of the neonatal rats with hypoxic-ischemic brain damage(HIBD). [Methods] The 7d neonatal rats got the HIBD model. Hypothermias of 31 ℃, 34 ℃ were given to them for 3 h immediately after the operation. The degrees of grey of apoptosis, p16, bcl-2 of the cerebral cortex, the hippocampi tissue and the periventricular white matter in the brains of rats was used to observe when 24, 72, 168 h after the operation. [ Results] 1 )The degrees of grey of p16:It was higher in the HIBD group than that in the pseuoperation group, the peak was at 24 hours after HI, it was deduced in 31 ℃ group, it was not deduced in 34 ℃group,but the peak was delated. 2) The degrees of grey of apoptosis: It was the same as that of p16. 3) The degrees of grey of bcl-2: It was the same as that of p16,it were deduced 24, 72 hours after HI in the 34 ℃ hypothermia group. 4) Correlation: there were the correlation ships (P<0.01) between either two of the degrees of the greys of p16, apoptosis, bcl-2 in all the brain tissues. [Conclusions] Hypothermia intervention could obviously deduce the express of p16, bcl-2, deduce apoptosis or delate their peaks of neonatal rats, brains with HIBD, so protected their grey matter tissue and the white matter tissue.%[目的]探讨亚低温对新生大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)后脑灰质、室周白质的保护作用.[方法]建立新生大鼠HIBD模型,31℃、34℃亚低温全身干预3 h,观察缺氧缺血(hypoxic-ische-mic,HI)后24 h、72 h、7 d脑皮质、海马、室周白质细胞凋亡、p16、bcl-2表达.[结果]1)p16灰度:模型组表达高于假手术组,HI后24 h达高峰,31℃组表达减少,34℃组总表达不减少,但在HI后24 h表达减少,高峰延迟;2)凋亡细胞灰度:与p16结果一致;3)bcl-2灰度:也与p16结果一致,34℃组术后24 h、HI后72 h

  14. Saline irrigation for the management of skin extravasation injury in neonates.

    Science.gov (United States)

    Gopalakrishnan, P N; Goel, Nitin; Banerjee, Sujoy

    2017-07-19

    Extravasation injury, a complication commonly seen in the neonatal intensive care unit, can result in scarring with cosmetic and functional sequelae. A wide variety of treatments are available, including subcutaneous irrigation with saline (with or without hyaluronidase), liposuction, use of specific antidotes, topical applications, and normal wound care with dry or wet dressings. All such treatments aim to prevent or reduce the severity of complications. Primary objective To compare the efficacy and safety of saline irrigation or saline irrigation with prior hyaluronidase infiltration versus no intervention or normal wound care for tissue healing in neonates with extravasation injury. Secondary objectives To evaluate by subgroup analysis of controlled trials the influence of type of extravasate, timing of irrigation following extravasation, and postmenstrual age (PMA) of the neonate at the time of injury on outcomes and adverse effects.Specifically, we planned to perform subgroup analysis for the primary outcome, if appropriate, by examining:1. time to irrigation from identified extravasation injury (irrigation with or without hyaluronidase infiltration versus no intervention or normal wound care for the management of extravasation injury in neonates. Three review authors independently reviewed and identified articles for possible inclusion in this review. We used the GRADE approach to assess the quality of evidence. We found no eligible studies. Our search revealed 10 case reports or case series describing successful outcomes with different interventions for this condition. To date, no RCTs have examined the effects of saline irrigation with or without prior hyaluronidase infiltration for management of extravasation injury in neonates. Saline irrigation is frequently reported in the literature as an intervention for management of extravasation injury in neonates. Research should focus first on evaluating the efficacy and safety of this intervention through RCTs

  15. Involvement of the JNK/FOXO3a/Bim Pathway in Neuronal Apoptosis after Hypoxic-Ischemic Brain Damage in Neonatal Rats.

    Directory of Open Access Journals (Sweden)

    Deyuan Li

    Full Text Available c-Jun N-terminal kinase (JNK plays a key role in the regulation of neuronal apoptosis. Previous studies have revealed that forkhead transcription factor (FOXO3a is a critical effector of JNK-mediated tumor suppression. However, it is not clear whether the JNK/FOXO3a pathway is involved in neuronal apoptosis in the developing rat brain after hypoxia-ischemia (HI. In this study, we generated an HI model using postnatal day 7 rats. Fluorescence immunolabeling and Western blot assays were used to detect the distribution and expression of total and phosphorylated JNK and FOXO3a and the pro-apoptotic proteins Bim and CC3. We found that JNK phosphorylation was accompanied by FOXO3a dephosphorylation, which induced FOXO3a translocation into the nucleus, resulting in the upregulation of levels of Bim and CC3 proteins. Furthermore, we found that JNK inhibition by AS601245, a specific JNK inhibitor, significantly increased FOXO3a phosphorylation, which attenuated FOXO3a translocation into the nucleus after HI. Moreover, JNK inhibition downregulated levels of Bim and CC3 proteins, attenuated neuronal apoptosis and reduced brain infarct volume in the developing rat brain. Our findings suggest that the JNK/FOXO3a/Bim pathway is involved in neuronal apoptosis in the developing rat brain after HI. Agents targeting JNK may offer promise for rescuing neurons from HI-induced damage.

  16. BDNF Pretreatment of Human Embryonic-Derived Neural Stem Cells Improves Cell Survival and Functional Recovery After Transplantation in Hypoxic-Ischemic Stroke.

    Science.gov (United States)

    Rosenblum, Sahar; Smith, Tenille N; Wang, Nancy; Chua, Joshua Y; Westbroek, Erick; Wang, Kendrick; Guzman, Raphael

    2015-01-01

    Intra-arterial neural stem cell (NSC) therapy has the potential to improve long-term outcomes after stroke. Here we evaluate if pretreatment of NSCs with brain-derived neurotrophic factor (BDNF) prior to transplantation improves cell engraftment and functional recovery following hypoxic-ischemic (HI) stroke. Human embryonic-derived NSCs with or without BDNF pretreatment (1 h, 100 ng/ml) were transplanted 3 days after HI stroke. Functional recovery was assessed using the horizontal ladder test. Cell engraftment was evaluated using bioluminescence imaging (BLI) and histological counts of SC121(+) cells. Fluoro-Jade C (FJC) and NeuN stains were used to evaluate neuroprotection. The effect of BDNF on NSCs was analyzed using a migration assay, immunocytochemistry, Luminex proteomic assay, and RT-qPCR.BLI analysis demonstrated significantly higher photon flux in the BDNF-treated NSC group compared to untreated NSC (p = 0.049) and control groups (p = 0.0021) at 1 week after transplantation. Immunohistochemistry confirmed increased transplanted cell survival in the cortex (p = 0.0126) and hippocampus (p = 0.0098) of animals injected with BDNF-treated NSCs compared to untreated NSCs. Behavioral testing revealed that the BDNF-treated NSC group demonstrated increased sensorimotor recovery compared to the untreated NSC and control groups (p < 0.001) over the 1-month period (p < 0.001) following transplantation. A significant improvement in performance was found in the BDNF-treated NSC group compared to the control group at 14, 21, and 28 (p < 0.05) days after transplantation. The cortex and hippocampus of the BDNF-treated NSC group had significantly more SC121(+) NSCs (p = 0.0125, p = 0.0098), fewer FJC(+) neurons (p = 0.0370, p = 0.0285), and a higher percentage of NeuN(+) expression (p = 0.0354) in the cortex compared to the untreated NSC group. BDNF treatment of NSCs resulted in significantly greater migration to SDF-1, secretion of M-CSF, VEGF, and expression of CXCR4

  17. Flunarizine and lamotngine propnyiaxis effects on neuron-specific enolase,S-100,and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Li He; Jingyi Deng; Wendan He

    2008-01-01

    BACKGROUND:Calcium antagonists may act as neuroprotectants,diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically,they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats.OBJECTIVE:To investigate the neuroprotective effects of flunarizine(FNZ),lamotrigine (LTG)and the combination of both drugs,on hypoxic-ischemic brain damage in fetal rats.DESIGN AND SETTING:This randomized,complete block design was performed at the Department of Pediatrics.Shenzhen Fourth People's Hospital,Guangdong Medical College.MATERIALS:Forty pregnant Wistar rats,at gestational day 20,were selected for the experiment and were randomly divided into FNZ,LTG,FNZ+LTG,and model groups,with 10 rats in each group.METHODS:Rats in the FNZ.LTG,and FNZ+LTG groups received intragastric injections of FNZ (0.5 mg/kg/d),LTG(10 mg/kg/d),and FNZ(0.5 mg/kg/d)+LTG(10 mg/kg/d),respectively.Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia.Rats in the modeJ group were not administered any drugs.Three hours after the final administration,eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats.Cesareans were performed at 6,12,24,and 48 hours later;and 5 fetal rats were removed from each mother and kept warm.Twe fetuses without model establishment were removed by planned cesarean at the same time and served as controls.A total of 0.3 mL serum was collected from fetal rats at 6,12,24,and 48 hours,respectively,following birth.MAIN OUTCOME MEASURES:Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA.Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method.RESULTS:Serum concentrations of neuron-specific enolase,S-100,and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats.compared with the non-hypoxic-ischemic

  18. 新生儿颅脑疾病床边超声的诊断价值%Value of bedside high-frequence ultrasound in diagnosis of neonatal cerebral disease

    Institute of Scientific and Technical Information of China (English)

    葛晖; 丁中; 韩旻; 李社会; 刘浩; 李叶刚; 王君琴

    2009-01-01

    目的:探讨床边高频超声在新生儿颅脑疾病中的诊断价值.方法:应用二维超声高频探头,以新生儿前囟为声窗,对78例新生儿进行床边颅脑检查,并与CT诊断结果作对比.结果:通过颅脑超声观察到颅内出血(intracranial hemorrhage,ICH)33例,缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)41例,脑发育异常1例,脑内钙化灶3例.除蛛网膜下腔出血(subaracheoid hemorrhage,SAH)外,超声对新生儿颅脑疾病的检出与CT基本相符.结论:超声对新生儿颅脑疾病有较好的诊断价值,应用超声诊断可以实现对新生儿颅脑疾病的动态观察,且无放射损伤,简便、易行、无创、价廉,可重复床边检查.%Objective:To study the value of bedside high-frequence ultrasound in diagnosis of neonatal cerebral disease.Methods:Seventy eight cases of neonatal cerebral disease were examined bedside by ultrasound high frequency probe,and the result was compared with that by computer tomography(CT).Results:Intracranial hemorrhage was observed in 33 cases,hypoxic-ischemic encephalopathy in 41 cases,encephalodysplasia in 1 case and intracranial calcification in 3 cases by cerebral ultrasound;The result by ultrasonic examination for cerebral disease coincided with that by computer tomography except subarachnoid hemorrhage,and the changes of the cerebral disease could be monitored by ultrasound.Conclusions:Ultrasound is of high value in diagnosis of neonatal cerebral disease and has the advantages of no radiation injury,convenience,easy application and cost efficacy.

  19. The antiapoptotic effect of insulin against anoxia/reoxygenation injury in cultured cardiomyocyte of neonatal rat

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To study protective effect of insulin against cardiomyocyte apoptosis in anoxia/reoxygenation (A/R)injury of neonatal rat. Methods: The model of A/R injury was finished through receiving anoxia for 2 h and reoxygenation for 4 h in cultured cardiomyocytes of neonatal rat. The cardiomyocytes were divided randomly into 3 groups: control group (CON), anoxia/reoxygenation group (A/R) and insulin-treated group (INS). At the end of reoxygenation of 4 hours, activities of lactate dehydrogenase (LDH),contents of malondialdehyde (MDA) were assessed through spectrophotometric procedures, myocyte apoptosis were detected through TUNEL and DNA Ladder. Results: MDA, LDH, and Apoptosis Index were significantly decreased in INS group compared with A/R group (P<0.01). Conclusion: Insulin has a protective effect against A/R injury in cultured cardiomyocyte of neonatal rat; the protective mechanism may contribute to antiapoptosis of insulin.

  20. Perioperative use of cerebral and renal near-infrared spectroscopy in neonates

    DEFF Research Database (Denmark)

    Koch, Henrik W; Hansen, Tom G

    2016-01-01

    BACKGROUND: Neonates undergoing surgery and intensive care still carry a significant morbidity and mortality often related to hypoxic/ischemic events; some of which may go undetected by conventional monitoring. Near-infrared spectroscopy (NIRS) is a noninvasive, continuous method of measuring...... specific regional cerebral and renal monitoring. Despite some practical and economical limitations, NIRS may be considered a useful supplement to perinatal perioperative intensive care....... regional tissue oxygen saturation, and may be used to supplement conventional monitoring to improve neonatal perioperative care. However, high costs and lack of evidence regarding improved outcomes have minimized wider perinatal use of NIRS. The aim of this study was to investigate the applicability...

  1. Stem cell therapy for neonatal brain injury : Perspectives and Challenges

    NARCIS (Netherlands)

    Titomanlio, Luigi; Kavelaars, Annemieke; Dalous, Jeremie; Mani, Shyamala; El Ghouzzi, Vincent; Heijnen, Cobi; Baud, Olivier; Gressens, Pierre

    2011-01-01

    Cerebral palsy is a major health problem caused by brain damage during pregnancy, delivery, or the immediate postnatal period. Perinatal stroke, intraventricular hemorrhage, and asphyxia are the most common causes of neonatal brain damage. Periventricular white matter damage (periventricular leukoma

  2. Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: Role of oxidative stress and endoplasmic reticulum stress.

    Science.gov (United States)

    Liu, Song; Xin, Danqing; Wang, Lingxiao; Zhang, Tiantian; Bai, Xuemei; Li, Tong; Xie, Yunkai; Xue, Hao; Bo, Shishi; Liu, Dexiang; Wang, Zhen

    2017-10-01

    Neonatal hypoxic-ischemic (HI) injury is a major cause of neonatal death and neurological dysfunction. H2S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS) in the brain and sequentially produces endogenous H2S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H2S. L-Cysteine treatment significantly attenuated brain edema and decreased infarct volume and neuronal cell death, as shown by a decrease in the Bax/Bcl-2 ratio, suppression of caspase-3 activation, and reduced phosphorylation of Akt and ERK at 72h after HI. Additionally, L-Cysteine substantially up-regulated NF-E2-related factor 2 and heme oxygenase-1 expression. L-Cysteine also decreased endoplasmic reticulum (ER) stress-associated pro-apoptotic protein expression. Furthermore, L-Cysteine had long-term effects by protecting against the loss of ipsilateral brain tissue and improving neurobehavioral outcomes. Importantly, pre-treatment with a CBS inhibitor significantly attenuated the neuroprotection of L-Cysteine on HI insult. Thus, L-Cysteine exerts neuroprotection against HI-induced injury in neonates via the CBS/H2S pathway, mediated in part by anti-apoptotic effects and reduced oxidative stress and ER stress. Thus, L-Cysteine may be a promising treatment for HI. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: Role of oxidative stress and endoplasmic reticulum stress

    Directory of Open Access Journals (Sweden)

    Song Liu

    2017-10-01

    Full Text Available Neonatal hypoxic-ischemic (HI injury is a major cause of neonatal death and neurological dysfunction. H2S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS in the brain and sequentially produces endogenous H2S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H2S. L-Cysteine treatment significantly attenuated brain edema and decreased infarct volume and neuronal cell death, as shown by a decrease in the Bax/Bcl-2 ratio, suppression of caspase-3 activation, and reduced phosphorylation of Akt and ERK at 72 h after HI. Additionally, L-Cysteine substantially up-regulated NF-E2-related factor 2 and heme oxygenase-1 expression. L-Cysteine also decreased endoplasmic reticulum (ER stress-associated pro-apoptotic protein expression. Furthermore, L-Cysteine had long-term effects by protecting against the loss of ipsilateral brain tissue and improving neurobehavioral outcomes. Importantly, pre-treatment with a CBS inhibitor significantly attenuated the neuroprotection of L-Cysteine on HI insult. Thus, L-Cysteine exerts neuroprotection against HI-induced injury in neonates via the CBS/H2S pathway, mediated in part by anti-apoptotic effects and reduced oxidative stress and ER stress. Thus, L-Cysteine may be a promising treatment for HI.

  4. 缺氧缺血性脑损害患儿血小板参数变化的临床研究%Changes of platelet parameters in children with hypoxic-ischemic brain damage*

    Institute of Scientific and Technical Information of China (English)

    罗世永; 苏国生; 劳炳焕

    2012-01-01

    Objective To investigate the clinical significance of changes of platelet parameters in children with hypoxic ischemic brain damage. Methods 63 cases of children with hypoxic ischemic encephalopathy were enrolled as experiment group,and 60 cases of asphyxia children without brain damage were enrolled as control group. Changes of platelet parameters in these two groups were compared. Results Platelet counts(PLT) in experiment group in acute stage and convalescent period were significantly lower than that in control group,but mean platelet volume(MPV) and platelet distribution width(PDW) were significantly higher. Conclusion There might be changes of platelet parameters in children with hypoxic ischemic encephalopathy and those asphyxia children without brain damage,and changes might be more obvious in former. Detection of platelet parameters could be helpful for monito ring disease condition.%目的 探讨缺氧缺血性脑损害患儿血小板参数变化的临床意义.方法 选取临床确诊缺氧缺血性脑病患儿63例作为实验组,同时选取同期发生窒息但无脑损害的患儿60例作为对照组,比较两组急性期和恢复期血小板参数的变化情况.结果 实验组血小板计数急性期和恢复期均低于对照组,两组比较差异具有统计学意义(P<0.05);平均血小板体积及血小板分布宽度急性期和恢复期均高于对照组,两组比较差异具有统计学意义(P<0.05).结论 缺氧缺血性脑病和窒息但无脑损害患儿血小板参数均有不同程度的变化,但缺氧缺血性脑病患儿变化程度较明显,临床可作为一个辅助的监测指标.

  5. Effect of dexamethasone on myelin basic protein (MBP) in brain tissues after hypoxic-ischemic brain damage%地塞米松干预对缺氧缺血性脑损伤脑组织髓鞘碱性蛋白的影响

    Institute of Scientific and Technical Information of China (English)

    江莲; 郑伟; 张会芬; 戎小平; 刁玉巧; 陈健

    2008-01-01

    目的 探讨地塞米松(dexamethasone,Dex)在缺氧缺血性脑损伤(hypoxic ischemicbrain damage,HIBD)中的作用及可能机制.方法 通过建立大鼠HIBD模型,分为Dex大剂量预处理组、Dex小剂量预处理组、Dex大剂量治疗组、Dex小剂量治疗组、生理盐水组和正常对照组,检测血清及脑组织髓鞘碱性蛋白(myelin basic protein,MBP)、白介素-1β(interleukin-1β IL-1β)、凋亡细胞计数和脑组织病理改变.结果 (1)与生理盐水组比较,不同剂量Dex干预组和治疗组脑组织病变均减轻,表现神经元树突复旧,尼氏体增多;(2)HIBD后3 d生理盐水组血清、脑组织MBP、IL-1β的含量(5.88±0.46,34.25±4.65;127.97±16.60,1060.33±42.22)及脑组织凋亡细胞计数(13.27±0.90,11.05±1.23)较正常对照组(2.01±0.12,10.24±1.75;41.21±4.02,221.10±30.57及0.75±0.17)显著增加,P0.05;大剂量组较小剂量组作用更明显;(4)Dex预处理组、治疗组的脑组织凋亡细胞计数(7.92±1.64和8.97±0.81)显著低于生理盐水组(13.27±0.90),P<0.05;预处理组较治疗组下降更为明显,P<0.05;大剂量组较小剂量组作用更明显.结论 血清MBP含量的变化可反映脑白质损伤的程度;Dex可能是通过抑制IL-1β的过度表达,减轻炎症级联反应从而起到脑损伤的保护作用.%Objective To explore the possible mechanisms of the neuroprotective effect of dexamethasone(DEX) on neonatal rats with cerebral bypoxia-ischemia. Methods Sprague-Dawley (SD) pregnant rats were made to hypoxic ischemic brain damage (HIBD) model and randomly divided into: pretreatment groups of different doses (L-Dexl group, H-Dexl group); treatment groups of different doses (L-Dex2 group, H-Dex2 group); isotonic saline group (NS group) and normal group (NOR). The expressions of interleukin-1β(IL-1β) and myelin basic protein (MBP) in serum and brain tissue were measured, the number of apoptosis cells in brain tissue was counted, and the pathological changes of brain

  6. Clinical application of transcranial Doppler ultrasonography in premature, very-low-birth-weight neonates

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Marta Lucia [Fundacao Faculdade Regional de Medicina (FUNFARME), Sao Jose do Rio Preto, SP (Brazil). Hospital de Base; Piatto, Vania Belintani [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil); Souza, Antonio Soares, E-mail: depimagem@famerp.b [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. de Diagnostico por Imagem

    2010-07-15

    Objective: the present study was aimed at analyzing the value of the early diagnosis of hemodynamic changes in hemorrhages and hypoxic-ischemic events in premature, very-low-birth-weight neonates through the evaluation of images and resistance index measurement by means of transcranial Doppler ultrasonography. Materials and methods: fifty premature, very-low-birth-weight neonates were submitted to transcranial Doppler ultrasonography with sequential transfontanellar and transtemporal techniques. Results: cerebral abnormalities were detected in 32% of the neonates (22% with intracranial hemorrhage, 8% with periventricular leukomalacia, and 2% with toxoplasmosis). Among the 34 cases (68%) of neonates in whom no brain lesion was detected at transcranial Doppler ultrasonography, 18 (53%) presented changes in the resistance index. Such resistance index varied according to the time of the examination. Conclusion: there is a correlation between the presence of cerebral hemodynamic changes demonstrated by resistance index measurements and the subsequent development of hemorrhages and hypoxic-ischemic lesions. Although not being a death predictor, changes in the resistance index are associated with the severity of the clinical conditions in preterm, very-low-birth-weight neonates. (author)

  7. Functional neuroanatomy of executive function after neonatal brain injury in adults who were born very preterm.

    Directory of Open Access Journals (Sweden)

    Anastasia K Kalpakidou

    Full Text Available Individuals who were born very preterm (VPT; <33 gestational weeks are at risk of experiencing deficits in tasks involving executive function in childhood and beyond. In addition, the type and severity of neonatal brain injury associated with very preterm birth may exert differential effects on executive functioning by altering its neuroanatomical substrates. Here we addressed this question by investigating with functional magnetic resonance imaging (fMRI the haemodynamic response during executive-type processing using a phonological verbal fluency and a working memory task in VPT-born young adults who had experienced differing degrees of neonatal brain injury. 12 VPT individuals with a history of periventricular haemorrhage and ventricular dilatation (PVH+VD, 17 VPT individuals with a history of uncomplicated periventricular haemorrhage (UPVH, 13 VPT individuals with no history of neonatal brain injury and 17 controls received an MRI scan whilst completing a verbal fluency task with two cognitive loads ('easy' and 'hard' letters. Two groups of VPT individuals (PVH+VD; n = 10, UPVH; n = 8 performed an n-back task with three cognitive loads (1-, 2-, 3-back. Results demonstrated that VPT individuals displayed hyperactivation in frontal, temporal, and parietal cortices and in caudate nucleus, insula and thalamus compared to controls, as demands of the verbal fluency task increased, regardless of type of neonatal brain injury. On the other hand, during the n-back task and as working memory load increased, the PVH+VD group showed less engagement of the frontal cortex than the UPVH group. In conclusion, this study suggests that the functional neuroanatomy of different executive-type processes is altered following VPT birth and that neural activation associated with specific aspects of executive function (i.e., working memory may be particularly sensitive to the extent of neonatal brain injury.

  8. DHA对新生大鼠缺氧缺血性脑损伤后远期学习记忆障碍的影响%Effect of docosahexaenoic acid on long-term learning and memory disorders after hypoxic ischemic brain damage in rats

    Institute of Scientific and Technical Information of China (English)

    曾成; 舒斯云; 黄玉莎; 程燕; 陈君; 王斌

    2016-01-01

    Objective To explore the effect of docosahexaenoic acid (DHA) on long-term learning and memory disorders and potential mechanism in rats after hypoxic ischemic brain damage. Methods Sixty neonatal 7-day-old SD rats were ramdonly divided into three groups: group S (sham operation+vehicle treatment), group C (hypoxic-ischemic brain damage [HIBD]+vehicle treatment) and group D (HIBD+DHA treatment). After left common carotid artery was isolated and ligated for 2.5 h, rats of group C and group D were put into a condition which oxygen concentration was about 8%for 2 h;rats in the group S were only isolated the left carotid artery, without ligation or hypoxia treatment;rats in the group D were intraperitoneally injected DHA of 15 mg/kg after modeling, and rats in the group S and group C were intraperitoneally injected equivalent volume of vehcle, once a day for 10 consecutive days. The pathomorphology changes of the hypocampal CA1 area, and marginal division of striatum were observed by Nissl staining 48 h after modling; the apoptosis cells were measured by TUNEL;immunohistochemical method was used to detect the expressions of Bax and Caspase-3 positive cells in the two brain areas. Morris water maza test was used to evaluate the long-term lerning and momory functions of 2-month-old rats, and the expressions of N-methyl-D-aspartate receptor 1 (NMDAR1) positive cells were detected by immunohistochemical method. Results The pathomorphology damage was significantly improved, the expressions of Bax and Caspase-3 positive cells and the neuron apoptosis in hypocampal CA1 areas and marginal division of striatum in group D were all signficantly decreased as compared with those in the group C (P<0.05). Rats in group D had significantly decreased escape latency as compared with those in group C in Morris water maze test (P<0.05), and the expression of NMDAR1 positive cells in the two brain areas of group D was significantly increased as compared with that in the group C (P<0

  9. Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Mesenchymal stem cell (MSC administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI. Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5 × 10(6 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy.

  10. Impaired growth of denervated muscle contributes to contracture formation following neonatal brachial plexus injury.

    Science.gov (United States)

    Nikolaou, Sia; Peterson, Elizabeth; Kim, Annie; Wylie, Christopher; Cornwall, Roger

    2011-03-02

    The etiology of shoulder and elbow contractures following neonatal brachial plexus injury is incompletely understood. With use of a mouse model, the current study tests the novel hypothesis that reduced growth of denervated muscle contributes to contractures following neonatal brachial plexus injury. Unilateral brachial plexus injuries were created in neonatal mice by supraclavicular C5-C6 nerve root excision. Shoulder and elbow range of motion was measured four weeks after injury. Fibrosis, cross-sectional area, and functional length of the biceps, brachialis, and subscapularis muscles were measured over four weeks following injury. Muscle satellite cells were cultured from denervated and control biceps muscles to assess myogenic capability. In a comparison group, shoulder motion and subscapularis length were assessed following surgical excision of external rotator muscles. Shoulder internal rotation and elbow flexion contractures developed on the involved side within four weeks following brachial plexus injury. Excision of the biceps and brachialis muscles relieved the elbow flexion contractures. The biceps muscles were histologically fibrotic, whereas fatty infiltration predominated in the brachialis and rotator cuff muscles. The biceps and brachialis muscles displayed reduced cross-sectional and longitudinal growth compared with the contralateral muscles. The upper subscapularis muscle similarly displayed reduced longitudinal growth, with the subscapularis shortening correlating with internal rotation contracture. However, excision of the external rotators without brachial plexus injury caused no contractures or subscapularis shortening. Myogenically capable satellite cells were present in denervated biceps muscles despite impaired muscle growth in vivo. Injury of the upper trunk of the brachial plexus leads to impaired growth of the biceps and brachialis muscles, which are responsible for elbow flexion contractures, and impaired growth of the subscapularis

  11. Evaluation of an Acute RNAi-Mediated Therapeutic for Visual Dysfunction Associated with Traumatic Brain Injury

    Science.gov (United States)

    2013-10-01

    brain injury (TBI) is the leading cause of death in children and young adults globally. Malignant cerebral edema plays a major role in the...pathophysiology which evolves after severe TBI. Added to this is the significant morbidity and mortality from cerebral edema associated with acute stroke...hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic strategies to prevent cerebral edema are limited and if brain swelling

  12. Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN: Design of a Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Jennifer Garcia Jetton

    2016-07-01

    Full Text Available INTRODUCTION: Acute kidney injury (AKI affects ~30% of hospitalized neonates. Critical to advancing our understanding of neonatal AKI is collaborative research among neonatologists and nephrologists. The Neonatal Kidney Collaborative (NKC is an international, multidisciplinary group dedicated to investigating neonatal AKI. The AWAKEN study (Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates was designed to describe the epidemiology of neonatal AKI, validate the definition of neonatal AKI, identify primary risk factors for neonatal AKI, and investigate the contribution of fluid management to AKI events and short term outcomes. METHODS and ANALYSIS: The NKC was established with at least one pediatric nephrologist and neonatologist from 24 institutions from 4 countries (USA, Canada, Australia, India. A Steering Committee and four subcommittees were created. The database subcommittee oversaw the development of the web-based database (MediData Rave™ that captured all NICU admissions from 1/1/14-3/31/14. Inclusion and exclusion criteria were applied to eliminate babies with a low likelihood of AKI. Data collection includes: 1 baseline demographic information; 2 daily physiologic parameters and care received during the first week of life; 3 weekly snapshots; 4 discharge information including growth parameters, final diagnoses, discharge medications and need for renal replacement therapy; and 5 all serum creatinine values. ETHICS and DISSEMINATION: AWAKEN was proposed as human subjects research. The study design allowed for a waiver of informed consent/parental permission. NKC investigators will disseminate data through peer-reviewed publications and educational conferences. DISCUSSION: The purpose of this publication is to describe the formation of the NKC, the establishment of the AWAKEN cohort and database, future directions and a few lessons learned. The AWAKEN database includes ~325 unique variables and >4 million discrete data

  13. A clinical observation of effect of early intervention for preventing brain palsy of children with hypoxic-ischemic encephalopathy%早期干预对预防HIE患儿脑瘫发生的临床分析

    Institute of Scientific and Technical Information of China (English)

    倪仙玉; 闫红霞; 沈鹏; 赵战绒; 郝荣; 秦红; 王琪; 南娜

    2011-01-01

    Objective To observe therapeutic effect of early intervention for children with hypoxic-ischemic encephalopathy (HIE) and to reduce disability rate of the disease. Methods 67 children with HIE who admitted to department of neonatology of our hospital and were excluded congenital malformations and hereditary and metabolic diseases in a period from Dec. , 2005 to Feb. , 2010 were divided into early intervention group ( n = 39 ) and control group ( n = 28 ). The children with HIE in the early intervention group received early intervention from the neonatal period and the children in the cotrol group were just fed conventionally and didn't receive any interventions.At 3 months and 6 months of age, the children in the two groups were assessed with Gesell Developmental Diagnosis Scale (GDDS).Results At 3 months of age, the GDDS scores in person-reacting ability and action ability of the children in the early intervention group were higher than those in the control group and there were significant differences between the two groups ( t = 1.73, 1.80 respectively, both P < 0.05 ), while in GDDS scores in material-reacting ability and language ability there were no significanfi differences between the two groups. At 6 months of age, the GDDS scores in all four domains of the children in the early intervention group were higher than those in the control group and there were significant differences between the two groups (t = 11.58, 5.51, 3.95, 6.53 respectively, ali P <0. 05 ). At 1 year of age, the number of children with cerebral palsy in the intervention group was significantly less than the control group (X2 = 4.6752, P < 0.05 ). Conclusion Early intervention can improve prognosis of children with HIE and reduce incidence rate of disability.%目的 观察早期干预对缺氧缺血性脑病患儿的疗效、旨在降低残障率.方法 2005年12月~2010年2月在咸阳市儿童医院新生儿科住院治疗并来儿保康复科做早期干预的缺氧缺血性脑

  14. Comparison of detection results of hypoxic-ischemic encephalopathy at different degrees in infant patients between brain electrical activity mapping, transcranial Doppler sonography and computer tomography examinations

    Institute of Scientific and Technical Information of China (English)

    Dongruo He; Xiaoying Xu; Yinghui Zhang; Guochao Han

    2006-01-01

    BACKGROUND; It has been proved that brain electrical activity mapping (BEAM) and transcranial Doppler (TCD) detection can reflect the function of brain cell and its diseased degree of infant patients with moderate to severe hypoxic-ischemic encephalopathy (HIE).OBJECTIVE: To observe the abnormal results of HIE at different degrees detected with BEAM and TCD in infant patients, and compare the detection results at the same time point between BEAM, TCD and computer tomography (CT) examinations.DESTGN: Contrast observation.SETTING: Departments of Neuro-electrophysiology and Pediatrics, Second Affiliated Hospital of Qiqihar Medical College.PARTICTPANTS: Totally 416 infant patients with HIE who received treatment in the Department of Newborn Infants, Second Affiliated Hospital of Qiqihar Medical College during January 2001 and December 2005. The infant patients, 278 male and 138 female, were at embryonic 37 to 42 weeks and weighing 2.0 to 4.1 kg, and they were diagnosed with CT and met the diagnostic criteria of HIE of newborn infants compiled by Department of Neonatology, Pediatric Academy, Chinese Medical Association. According to diagnostic criteria, 130patients were mild abnormal, 196 moderate abnormal and 90 severe abnormal. The relatives of all the infant patients were informed of the experiment.METHODS: BEAM and TCD examinations were performed in the involved 416 infant patients with HIE at different degrees with DYD2000 16-channel BEAM instrument and EME-2000 ultrasonograph before preliminary diagnosis treatment (within 1 month after birth) and 1,3,6,12 and 24 months after birth, and detected results were compared between BEAM, TCD and CT examinations.MATN OUTCOME MEASURES: Comparison of detection results of HIE at different time points in infant patients between BEAM, TCD and CT examinations. RESULTS: All the 416 infant patients with HIE participated in the result analysis. ① Comparison of the detected results in infant patients with mild HIE at different

  15. Regulation of Toll-like receptor 1 and -2 in neonatal mice brains after hypoxia-ischemia

    Directory of Open Access Journals (Sweden)

    Naylor Andrew S

    2011-05-01

    Full Text Available Abstract Background Hypoxic-ischemic (HI brain injury remains a major problem in newborns, resulting in increased risk of neurological disorders. Neonatal HI triggers a broad inflammatory reaction in the brain, including activation of the innate immune system. Toll-like receptors (TLRs, which are key components of the innate immune system, are believed to play a role in adult cerebral ischemic injury. The expression of TLRs in the neonatal brain and their regulation after HI is unknown. Methods Wild type C57BL/6, TLR 1 knockout (KO and TLR 2 KO mice were subjected to HI at postnatal day 9 and sacrificed 30 min, 6 h, 24 h or 5 days after HI. TLR mRNA expression was determined by RT-qPCR and protein and cell type localisation by immunohistochemistry (IHC. To evaluate brain injury, infarct volume was measured in the injured hemisphere. Results mRNA expression was detected for all investigated TLRs (TLR1-9, both in normal and HI exposed brains. After HI, TLR-1 was down-regulated at 30 min and up-regulated at 6 h and 24 h. TLR-2 was up-regulated at 6 h and 24 h, and TLR-7 at 24 h. Both TLR-5 and TLR-8 were down-regulated at 24 h and 30 min respectively. IHC showed an increase of TLR-1 in neurons in the ipsilateral hemisphere after HI. TLR-2 was constitutively expressed in astrocytes and in a population of neurons in the paraventricular nucleus in the hypothalamus. No changes in expression were detected following HI. Following HI, TLR-2 KO mice, but not TLR-1 KO, showed a decreased infarct volume compared to wild type (p = 0.0051. Conclusions This study demonstrates that TLRs are regulated after HI in the neonatal brain. TLR-1 protein was up-regulated in injured areas of the brain but TLR-1 KO animals were not protected from HI. In contrast, TLR-2 was constitutively expressed in the brain and TLR-2 deficiency reduced HI injury. These data suggest that TLR-2, but not TLR-1, plays a role in neonatal HI brain injury.

  16. 超声诊断在新生儿颅脑疾病中的运用%Application of ultrasound diagnosis in neonatal craniocerebral diseases

    Institute of Scientific and Technical Information of China (English)

    王涛; 伊春花; 魏芳; 刘维佳; 饶莉莉

    2015-01-01

    目的:对超声诊断在新生儿颅脑疾病中的应用价值进行分析。方法:2010年3月-2014年3月收治疑为颅脑损伤新生儿50例,采取彩色多普勒超声检查,并进行前囟冠状面探查、前囟矢状面探查以及侧囟探查。结果:1例检出脑发育异常;27例检出缺氧缺血性脑病,其中基底节与颅脑损伤3例,脑室旁白质软化型3例,脑水肿型21例;22例检出颅内出血,其中脑实质出血8例,脑室内出血9例,脉络丛出血5例。结论:对于新生儿颅脑疾病采取超声检查,能对新生儿血流动力学变化以及新生儿颅脑实质结构进行观察,对于新生儿颅脑疾病的诊断有着重要的作用。在新生儿缺氧缺血性脑病以及颅内出血的诊断与治疗中有着重要的作用。%Objective:To analyze the application value of ultrasound diagnosis in neonatal craniocerebral diseases.Methods:50 newborns with suspected craniocerebral injury were selected from March 2010 to March 2014.Takeing the color doppler ultrasound,they were given the anterior coronal plane exploration,the anterior sagittal plane exploration and lateral fontanel exploration.Results:1 case was detected abnormal brain development.27 cases were detected hypoxic ischemic encephalopathy, including 3 cases of basal ganglia and brain injury,3 cases of periventricular leukomalacia type,21 cases of brain edema type.22 cases was detected intracranial hemorrhage,including 8 cases of intracerebral hemorrhage,9 cases of intraventricular hemorrhage, 5 cases of choroid plexus hemorrhage.Conclusion:Taking ultrasonography in neonatal craniocerebral diseases can observe the neonatal hemodynamic change and neonatal craniocerebral substance structure.It plays an important role in the diagnosis of neonatal craniocerebral diseases.It plays an important role in the diagnosis and treatment of neonatal hypoxic ischemic encephalopathy and intracranial hemorrhage.

  17. CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility.

    Science.gov (United States)

    Awad, Hisham A E; Tantawy, Azza A G; El-Farrash, Rania A; Ismail, Eman A; Youssif, Noha M

    2014-04-01

    ABO antigens are expressed on the surfaces of red blood cells and the vascular endothelium. We studied circulating endothelial microparticles (EMP) in ABO haemolytic disease of the newborn (ABO HDN) as a marker of endothelial activation to test a hypothesis of possible endothelial injury in neonates with ABO HDN, and its relation with the occurrence and severity of haemolysis. Forty-five neonates with ABO HDN were compared with 20 neonates with Rhesus incompatibility (Rh HDN; haemolytic controls) and 20 healthy neonates with matched mother and infant blood groups (healthy controls). Laboratory investigations were done for markers of haemolysis and von Willebrand factor antigen (vWF Ag). EMP (CD144(+)) levels were measured before and after therapy (exchange transfusion and/or phototherapy). vWF Ag and pre-therapy EMP levels were higher in infants with ABO HDN or Rh HDN than in healthy controls, and were significantly higher in babies with ABO HDN than in those with Rh HDN (pABO HDN, pre-therapy EMP levels were higher in patients with severe hyperbilirubinaemia than in those with mild and moderate disease or those with Rh HDN (pABO HDN and Rh HDN groups; however, the decline in EMP levels was particularly evident after exchange transfusion in ABO neonates with severe hyperbilirubinaemia (pABO HDN. Elevated EMP levels in ABO HDN may reflect an IgG-mediated endothelial injury parallel to the IgG-mediated erythrocyte destruction and could serve as a surrogate marker of vascular dysfunction and disease severity in neonates with this condition.

  18. Acute Kidney Injury and Fluid Overload in Neonates Following Surgery for Congenital Heart Disease.

    Science.gov (United States)

    Piggott, Kurt D; Soni, Meshal; Decampli, William M; Ramirez, Jorge A; Holbein, Dianna; Fakioglu, Harun; Blanco, Carlos J; Pourmoghadam, Kamal K

    2015-07-01

    Acute kidney injury (AKI) and fluid overload have been shown to increase morbidity and mortality. The reported incidence of AKI in pediatric patients following surgery for congenital heart disease is between 15% and 59%. Limited data exist looking at risk factors and outcomes of AKI or fluid overload in neonates undergoing surgery for congenital heart disease. Neonates aged 6 to 29 days who underwent surgery for congenital heart disease and who were without preoperative kidney disease were included in the study. The AKI was determined utilizing the Acute Kidney Injury Network criteria. Ninety-five neonates were included in the study. The incidence of neonatal AKI was 45% (n = 43), of which 86% had stage 1 AKI. Risk factors for AKI included cardiopulmonary bypass time, selective cerebral perfusion, preoperative aminoglycoside use, small kidneys by renal ultrasound, and risk adjustment for congenital heart surgery category. There were eight mortalities (five from stage 1 AKI group, three from stage 2, and zero from stage 3). Fluid overload and AKI both increased hospital length of stay and postoperative ventilator days. To avoid increased risk of morbidity and possibly mortality, every attempt should be made to identify and intervene on those risk factors, which may be modifiable or identifiable preoperatively, such as small kidneys by renal ultrasound. © The Author(s) 2015.

  19. Short and Long-Term Analysis and Comparison of Neurodegeneration and Inflammatory Cell Response in the Ipsilateral and Contralateral Hemisphere of the Neonatal Mouse Brain after Hypoxia/Ischemia

    Directory of Open Access Journals (Sweden)

    Kalpana Shrivastava

    2012-01-01

    Full Text Available Understanding the evolution of neonatal hypoxic/ischemic is essential for novel neuroprotective approaches. We describe the neuropathology and glial/inflammatory response, from 3 hours to 100 days, after carotid occlusion and hypoxia (8% O2, 55 minutes to the C57/BL6 P7 mouse. Massive tissue injury and atrophy in the ipsilateral (IL hippocampus, corpus callosum, and caudate-putamen are consistently shown. Astrogliosis peaks at 14 days, but glial scar is still evident at day 100. Microgliosis peaks at 3–7 days and decreases by day 14. Both glial responses start at 3 hours in the corpus callosum and hippocampal fissure, to progressively cover the degenerating CA field. Neutrophils increase in the ventricles and hippocampal vasculature, showing also parenchymal extravasation at 7 days. Remarkably, delayed milder atrophy is also seen in the contralateral (CL hippocampus and corpus callosum, areas showing astrogliosis and microgliosis during the first 72 hours. This detailed and long-term cellular response characterization of the ipsilateral and contralateral hemisphere after H/I may help in the design of better therapeutic strategies.

  20. Peripheral nerve injury sensitizes neonatal dorsal horn neurons to tumor necrosis factor-α

    OpenAIRE

    2009-01-01

    Abstract Background Little is known about whether peripheral nerve injury during the early postnatal period modulates synaptic efficacy in the immature superficial dorsal horn (SDH) of the spinal cord, or whether the neonatal SDH network is sensitive to the proinflammatory cytokine TNFα under neuropathic conditions. Thus we examined the effects of TNFα on synaptic transmission and intrinsic membrane excitability in developing rat SDH neurons in the absence or presence of sciatic nerve damage....

  1. Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury.

    Science.gov (United States)

    Endesfelder, Stefanie; Weichelt, Ulrike; Strauß, Evelyn; Schlör, Anja; Sifringer, Marco; Scheuer, Till; Bührer, Christoph; Schmitz, Thomas

    2017-01-18

    Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28-32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

  2. Isolated acute non-cystic white matter injury in term infants presenting with neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Barrett, Michael Joseph

    2013-03-01

    We discuss possible aetiological factors, MRI evolution of injury and neuro-developmental outcomes of neonatal encephalopathy (NE). Thirty-six consecutive infants diagnosed with NE were included. In this cohort, four infants (11%) were identified with injury predominantly in the deep white matter on MRI who were significantly of younger gestation, lower birthweight with higher Apgars at one and five minutes compared to controls. Placental high grade villitis of unknown aetiology (VUA) was identified in all four of these infants. Our hypothesis states VUA may induce white matter injury by causing a local inflammatory response and\\/or oxidative stress during the perinatal period. We underline the importance of continued close and systematic evaluation of all cases of NE, including examination of the placenta, in order to come to a better understanding of the clinical presentation, the patterns of brain injury and the underlying pathophysiological processes.

  3. Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups.

    Science.gov (United States)

    Yazdani, Armin; Khoja, Zehra; Johnstone, Aaron; Dale, Laura; Rampakakis, Emmanouil; Wintermark, Pia

    2016-01-01

    Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations.

  4. RAGE/NF-κB signaling mediates lipopolysaccharide induced acute lung injury in neonate rat model.

    Science.gov (United States)

    Li, Yuhong; Wu, Rong; Tian, Yian; Yu, Min; Tang, Yun; Cheng, Huaipin; Tian, Zhaofang

    2015-01-01

    Lipopolysaccharide (LPS) is known to induce acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Accumulating data suggest the crucial role of RAGE in the pathogenesis of ALI/ARDS. However, the mechanism by which RAGE mediates inflammatory lung injury in the neonates remains elusive. In this study we established LPS-induced ALI model in neonate rats, and investigated the role of RAGE/NF-κB signaling in mediating ALI. We found that RAGE antibody or bortezomib reduced LPS-induced histopathological abnormalities in the lung and lung damage score. RAGE antibody or bortezomib also reduced TNF-α level in both serum and BALF of the rats. Furthermore, RAGE antibody or bortezomib significantly reduced LPS-induced upregulation of RAGE and NF-κB expression in the lung. In conclusion, we established ALI model in neonate rats to demonstrate that LPS induced inflammatory lung injury via RAGE/NF-κB signaling. Interference with RAGE/NF-κB signaling is a potential approach to prevent and treat sepsis-related ALI/ARDS.

  5. Dendritic development of hippocampal CA1 pyramidal cells in a neonatal hypoxia-ischemia injury model.

    Science.gov (United States)

    Zhao, Yan Dong; Ou, Shan; Cheng, Sai Yu; Xiao, Zhi; He, Wen Juan; Zhang, Jin Hai; Ruan, Huai Zhen

    2013-09-01

    It is believed that neonatal hypoxia-ischemia (HI) brain injury causes neuron loss and brain functional defects. However, the effect of HI brain injury on dendritic development of the remaining pyramidal cells of the hippocampus and the reaction of contralateral hippocampal neurons require further studies. The Morris water maze and Golgi-Cox staining were used to evaluate the learning and memory and dendritic morphology of pyramidal cells. The results of Golgi-Cox staining showed CA1 pyramidal neurons of HI injury models with fewer bifurcations and shorter dendrite length than the naive control group. The density of dendritic spines of hippocampal CA1 pyramidal neurons was significantly lower in the HI brain injury group than in controls. With respect to hippocampal function, the HI brain injury group presented cognitive deficits in the reference memory task and probe trail. In the HI group, the pyramidal cells of left hippocampus that did not experienced ischemia but did experience hypoxia had more complex dendrites and higher density of spine than the HI injury side and control. The functional implementation of injured hippocampus might depend mainly on the hypertrophy of contralateral hippocampus after HI brain injury. Corticosterone can partially prevent the hippocampal pyramidal cells from HI injury and reduce the difference of the bilateral hippocampus pyramidal cells, but there was no improvement in learning and memory.

  6. 42d龄婴儿脑外间隙与新生儿缺氧缺血性脑病关系的CT分析%CT analysis of the relationship between extracerebral space and newborn hypoxic ischemic encephalopathy in 42 days old infants

    Institute of Scientific and Technical Information of China (English)

    陶可伟; 徐中华; 邢伟; 蒯烨斌; 李杰

    2012-01-01

    Objective To study the relationship between extracerebral space and newborn hypoxic ischemic cnccphalopathyf HIE) in 42 days old infants by CT. Methods CT findings of two groups were analyzed,including experimental group: 38 infants of mild HIE and control group:28 infants with respiratory descascs caused fever, convulsion and trauma who were underwent head CT examination with negative CT results. All the patients were 42 days old. Their extracerebral space widths, including frontal gap, anterior longitudinal gap and rolandic gap were measured. Statistical significance was inferred at P0. 05). Conclusion The measurement analysis of frontal gap and anterior longitudinal gap width of 42 days baby may be a useful tool in neonatal HIE diagnosis.%目的 研究42d龄婴儿脑外间隙与新生儿期缺氧缺血性脑病的关系,回顾性评价新生儿期缺氧缺血性脑病的诊断并及时指导临床给予适当治疗改善预后.方法 将38例新生儿期患轻度缺氧缺血性脑病的42 d龄婴儿作为一组,将28例因呼吸道引起发热、惊厥以及外伤而行CT头颅检查,并且结果 为阴性的同龄婴儿作为对照组,分别测量2组婴儿的脑外间隙宽度并进行统计学分析.结果 缺氧缺血性脑病组婴儿的额前间隙及前纵裂间隙宽度明显大于对照组,有显著性差异(P<0.01),而外侧裂间隙宽度的比较无统计学意义(P>0.05).结论 通过对42 d龄婴儿额前间隙及前纵裂间隙宽度的测量分析有助于新生儿期缺氧缺血性脑病的诊断.

  7. Neonatal injury at cephalic vaginal delivery: a retrospective analysis of extent of association with shoulder dystocia.

    Directory of Open Access Journals (Sweden)

    Cantekin Iskender

    Full Text Available PURPOSE: To describe the risk factors and labor characteristics of Clavicular fracture (CF and brachial plexus injury (BPI; and compare antenatal and labor characteristics and prognosis of obstetrical BPI associated with shoulder dystocia with obstetrical BPI not associated with shoulder dystocia. METHODS: This retrospective study consisted of women who gave birth to an infant with a fractured clavicle or BPI between January 2009 and June 2013. Antenatal and neonatal data were compared between groups. The control group (1300 was composed of the four singleton vaginal deliveries that immediately followed each birth injury. A multivariable logistic regression model, with backward elimination, was constructed in order to find independent risk factors associated with BPI and CF. A subgroup analysis involved comparison of features of BPI cases with or without associated shoulder dystocia. RESULTS: During the study period, the total number of vaginal deliveries was 44092. The rates of CF, BPI and shoulder dystocia during the study period were 0,6%, 0,16% and 0,29%, respectively. In the logistic regression model, shoulder dystocia, GDM, multiparity, gestational age >42 weeks, protracted labor, short second stage of labor and fetal birth weight greater than 4250 grams increased the risk of CF independently. Shoulder dystocia and protracted labor were independently associated with BPI when controlled for other factors. Among neonates with BPI whose injury was not associated with shoulder dystocia, five (12.2% sustained permanent injury, whereas one neonate (4.5% with BPI following shoulder dystocia sustained permanent injury (p = 0.34. CONCLUSION: BPI not associated with shoulder dystocia might have a higher rate of concomitant CF and permanent sequelae.

  8. 个性化护理对新生儿缺氧缺血性脑病21例的护理效果体会%Nursing experience of personalized nursing on 21 cases of hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    王素芹; 郭丽

    2014-01-01

    Objective To investigate the effect of personalized nursing on hypoxic-ischemic encephalopathy(HIE). Methods Divided 42 patients with hypoxic-ischemic encephalopathy into nursing group and control group. Traditional nursing was given to control group. Personalized nursing was given to nursing group. Therapeutic effect and sequela rate was observed. Results Mental development index(MDI) and motor development index(PDI) in nursing group were higher than in control group. By contrast, the variation in scores had statistical significance. (P<0.05). Follow-up 6 months to 2 years, there were 1 mentally retarded, 2 cerebral palsy in the nursing group, the sequela rate was 9.5%. There were 2 mentally retarded, 2 visual impairment and 2 cerebral palsy in the control group, the sequela rate was 28.6%. By contrast, the variation in scores had statistical significance. (P<0.05). Conclusion Personalized nursing on patient with hypoxic-ischemic encephalopathy can improve their living quality and decrease the sequela rate. It can also reduce the economic burden for the patients’family, so it is worthy of clinical promotion.%目的:观察个性化护理对新生儿缺氧缺血性脑病(HIE)的护理效果。方法42例HIE患者随机分为护理组和对照组,每组21例。对照组患者予以常规护理,护理组患者在此基础上予以针对性个性化护理,观察两组患者的疗效和后遗症发生情况。结果护理组患者在出生后6个月和24个月的智力发育指数(MDI)和运动发育指数(PDI)得分均高于对照组患者,差异有统计学意义(P<0.05)。随访时间从6个月~2年。护理组患者发生智力低下1例,脑瘫1例,后遗症发生率9.5%;对照组患者发生智力低下2例,视力障碍2例,脑瘫2例,后遗症发生率28.6%。两组比较差异有统计学意义(P<0.05)。结论针对新生儿缺氧缺血性脑病患者的具体情况制定个性化护理方案,对于提高患者生活质量、降低后

  9. CT影像在新生儿缺氧缺血性脑病的价值及预后%The Value and Prognosis of CT Image in Hypoxic-ischemic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    侯文光; 陈晓明; 林铁华

    2013-01-01

    Objective:To explore the clinical value and significance of CT image in hypoxic-ischemic encephalopathy,and to evaluate its prognosis and outcome situation.Methods:The data of 138 patients with hypoxic-ischemic encephalopathy from January 2006 to December 2011 were analyzed retrospectively, there were 77 males and 61 females,aged ranged from 2 h to 40 days[(8.00±1.25)d].All patients were followed up 18 to 24 months.Results:138 cases,according to the CT image results pointed mild in 78 cases,accounting for 56.52%;Moderate 29 cases,accounting for 21.04%;Severe 31 cases,accounting for 22.46%;Follow-up review showed mild group CT check all returned to normal,moderate group limited brain atrophy or brain atrophy performance,severe group had a wide range of softening of the brain,brain atrophy and residual sequelae.Conclusion:CT image for hypoxic-ischemic encephalopathy(HIE) is highly sensitive, especially HIE early indispensable preferred inspection methods,in combination with clinical manifestations of the make the right dividing,the clinical treatment on certain guiding significance,to evaluate the prognosis and outcome is active.%  目的:探讨CT影像在新生儿缺氧缺血性脑病(HIE)的临床价值及意义,进而评价其预后及转归情况。方法:回顾性分析2006年1月-2011年12月138例新生儿缺氧缺血性脑病患儿的临床资料,其中男77例,女61例,年龄最小为出生2 h,最大40 d,平均(8.00±1.25)d。所有患儿定期随访时间为18~24个月。结果:根据CT影像检查结果,138例患儿,轻度78例,占56.52%;中度29例,占21.01%;重度31例,占22.46%。随访复查显示:78轻度患儿CT检查全部恢复正常,29例中度患儿有局限性脑萎缩或脑萎缩表现;31重度患儿有较大范围脑软化、脑萎缩等后遗症残留。结论:CT影像检查对新生儿缺氧缺血性脑病高度敏感,特别是HIE早期不可缺少的首选检查方法,同时结合临床表

  10. Stem cell therapy for neonatal brain injury: perspectives and challenges.

    Science.gov (United States)

    Titomanlio, Luigi; Kavelaars, Annemieke; Dalous, Jeremie; Mani, Shyamala; El Ghouzzi, Vincent; Heijnen, Cobi; Baud, Olivier; Gressens, Pierre

    2011-11-01

    Cerebral palsy is a major health problem caused by brain damage during pregnancy, delivery, or the immediate postnatal period. Perinatal stroke, intraventricular hemorrhage, and asphyxia are the most common causes of neonatal brain damage. Periventricular white matter damage (periventricular leukomalacia) is the predominant form in premature infants and the most common antecedent of cerebral palsy. Stem cell treatment has proven effective in restoring injured organs and tissues in animal models. The potential of stem cells for self-renewal and differentiation translates into substantial neuroprotection and neuroregeneration in the animal brain, with minimal risks of rejection and side effects. Stem cell treatments described to date have used neural stem cells, embryonic stem cells, mesenchymal stem cells, umbilical cord stem cells, and induced pluripotent stem cells. Most of these treatments are still experimental. In this review, we focus on the efficacy of stem cell therapy in animal models of cerebral palsy, and discuss potential implications for current and future clinical trials. Copyright © 2011 American Neurological Association.

  11. Influence of early intervention on intelligence development of infant with hypoxic-ischemic encephalopathy.%早期干预对新生儿缺氧缺血性脑病智能发育的影响

    Institute of Scientific and Technical Information of China (English)

    栗绪娥; 郭月香; 于菊梅

    2011-01-01

    Objective:To discuss the effect of early nursing intervention on intelligence development of infant with hypoxic - ischemic encephalopathy. Methods: 168 children patients were divided into intervention group( n =88 ) and control group( n =80 ) at random. The patients in the control group received normal treatment and feeding guidance,while the patients in the intervention group received support nursing ,at the same time given health education and family nursing guidance for the parents. To test the intelligence development for the children patients at difference times , such as 3 months, six months and 12 months. To observe the occur of cerebral palsy. Results:The occur rate of cerebral palsy in intervention group was lower than in control group( P <0.01 ). The adaptability, gross motor, fine motor, language and behavior of patients in intervention group has significant sense compared with control group( P <0.01 or P <0.05 ). Conclusion:Early nursing intervention could promote behabior and intelligence development of infant with hypoxic - ischemic encephalopathy.%目的:探讨早期护理干预对新生儿缺氧缺血性脑病行为智能发育的影响.方法:将168例缺氧缺血性脑病患儿分为干预组(88例)和对照组(80例).对照组在常规的治疗基础上给予一般的喂养知识指导;干预组患儿住院后即提供发育支持护理,同时对家长进行健康宣教,出院时给予家庭护理指导.在3个月、6个月、12个月时对两组患儿进行智能测试,并统计两组患儿脑瘫发生情况.结果:干预组脑瘫发生率低于对照组,差异有显著性意义(P<0.01);在适应性、大运动、精细运动、语言和行为动作5个方面与对照组比,差异有统计学意义(P<0.05).结论:早期护理干预可促进缺氧缺血性脑病患儿的行为智能发育.

  12. 谷氨酸受体阻滞剂对缺氧缺血性脑病神经细胞凋亡的影响%Influence of glutamate receptor blocker on the apoptosis of hypoxic ischemic encephalopathy nerve cells

    Institute of Scientific and Technical Information of China (English)

    阎娜; 安丽; 王平; 郑媛

    2013-01-01

    [目的] 探讨谷氨酸受体阻滞剂(GYKI52466)对缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)新生大鼠脑细胞凋亡的抑制作用. [方法] 体内实验:将新生大鼠随机分为空白对照组(N组)、缺氧缺血性脑损伤组(H组)与GYKI52466干预组(G组).造模后给药,观察各组大鼠的神经行为学异常及超微结构变化.体外实验:将各组新生大鼠的脑细胞制成单细胞悬液,培养4d后,N组给予正常环境培养,H组给予缺氧缺糖环境,G组给予缺氧缺糖环境后添加GYKI52466培养,6h后比较各组细胞生长状态,采用流式细胞仪进行脑细胞凋亡分析. [结果] 体内实验:神经行为学观察,G组与H组相比,异常神经行为学有所改善;电镜下观察,H组神经元细胞核结构破坏,核膜破裂、核仁轻度皱缩,而G组结构趋向完整.体外实验:与模型组相比,G组的细胞凋亡数明显减少,数值差异有高度统计学意义(P<0.001). [结论] 谷氨酸受体阻滞剂GYKI25466有效的减轻新生大鼠缺氧缺血性脑病时异常的神经行为学表现和病理学改变,抑制神经细胞细胞凋亡,证实GYKI25466具有一定的神经保护作用.%[Objective] To evaluate the inhibition of the glutamate receptor blocker(GYKI52466) on the apoptosis of hypoxic ischemic encephalopathy(HIE) newborn rats' nerve cells. [Methods

  13. Incidence of acute kidney injury in the neonatal intensive care unit.

    Science.gov (United States)

    Youssef, Doaa; Abd-Elrahman, Hadeel; Shehab, Mohamed M; Abd-Elrheem, Mohamed

    2015-01-01

    The aim of this work is to study the incidence of acute kidney injury (AKI) in neonates admitted to the neonatal intensive care unit (NICU) over a six-month period from September 2011 to March 2012. This prospective study was performed on 250 neonates admitted to the NICU at the Children's Hospital, Faculty of Medicine, Zagazig University. All neonates were subjected to detailed history taking, including pre-natal, natal and post-natal history, with stress on symptoms suggestive of AKI. All neonates were examined thoroughly and the following investigations were performed: Blood urea nitrogen (BUN), serum creatinine, sodium, potassium, calcium, complete blood count, C-reactive protein, arterial blood gases, urine sodium and urine creatinine. AKI was diagnosed in 27 cases (10.8%), including 12 females and 15 males. 40.7% of the AKI cases were born after full-term pregnancy while 59.3% were pre-term babies. 29.6% of the AKI cases had oliguria, and there was male sex predominance, with a male-female ratio of 1.3:1. The cause of AKI was pre-renal in 96.3% and intrinsic renal in 3.7% of the cases. The predisposing factors for AKI were sepsis in 63% of the cases, respiratory distress syndrome in 55.6%, mechanical ventilation in 51.9%, peri-natal asphyxia in 18.5%, dehydration in 14.8%, surgical operation in 11.1%, congenital heart disease in 7.4%, sub-galeal hematoma in 3.7%, polycythemia in 3.7% and intra-ventricular hemorrhage in 3.7% of the cases. Our data suggest that pre-renal failure was the most common form of AKI in our patients. Early recognition of risk factors such as sepsis, peri-natal asphyxia or peri-operative problems and rapid effective treatment of contributing conditions will reduce the incidence of AKI in the neonatal period.

  14. Free Radicals: Emerging Challenge in Environmental Health Research in Childhood and Neonatal Disorders

    Directory of Open Access Journals (Sweden)

    B. Sharda

    2006-09-01

    Full Text Available Infants and children may undergo severe oxidative stress due to disease state, pre-existing nutritional status, frequent use of oxygen, and lower levels of antioxidant defenses. Antioxidant defenses, made up of intracellular and extra-cellular components, work synergistically to prevent oxidative damage. Total antioxidant activity (TAA was analyzed by method of ferric reducing antioxidant power assay (FRAP. Patients admitted in Pediatric Dept, RNT Medical College, Udaipur, India were selected for these studies. TAA level in neonates with hypoxic-ischemic-encephalopathy (HIE stage III and in poor outcome cases was significantly low. Erythrocyte SOD activity level was low in pre-term neonates. TAA level in severely malnourished children at the time of hospital admission was low. This low antioxidant level in severely malnourished children could be multi-factorial viz. low zinc, selenium, vitamin A and C deficiency, recurrent infections, elevated free iron and chronic starvation stage. Delayed recovery of oxidant injury may lead to delayed incomplete recovery at cellular level. In a study of 29 tuberculosis patients TAA level was found to be low in tubercular patients compared with control. TAA level decreased more in CNS tuberculosis compared with other system tuberculosis. In a study of nutritional tremor syndrome TAA, ascorbic acid and α-tocopherol levels were low during pre-tremor phase compared with tremor phase (ATS. Pre-term neonates have incompletely developed antioxidant defenses and are deficient in vitamin E, which is normally derived from maternal circulation at the end of 3rd trimester. Therefore, decreased TAA level in HIE with poor outcome indicates addition of antioxidants in therapeutic strategy. Since rise in TAA in antioxidant supplemented group of severely malnutrition children was higher with good outcome compared with nonsupplemented group it would be prudent to supplement antioxidant during nutritional management

  15. Lack of evidence for a causal relationship between hypoxic-ischemic encephalopathy and subdural hemorrhage in fetal life, infancy, and early childhood

    DEFF Research Database (Denmark)

    Byard, Roger W; Blumbergs, Peter; Rutty, Guy

    2013-01-01

    to cause injury in certain cases of inflicted head injury in infancy, clarification is required. A retrospective study of 82 fetuses, infants, and toddlers with proven HIE and no trauma was undertaken from forensic institutes in Australia, the United Kingdom, Germany, Denmark, and the United States...

  16. Altered thymocyte and T cell development in neonatal mice with hyperoxia-induced lung injury.

    Science.gov (United States)

    Angusamy, Sowmya; Mansour, Tamer; Abdulmageed, Mohammed; Han, Rachel; Schutte, Brian C; LaPres, John; Harkema, Jack R; Omar, Said A

    2017-08-19

    The adaptive immune system of neonates is relatively underdeveloped. The thymus is an essential organ for adaptive T cell development and might be affected during the natural course of oxygen induced lung injury. The effect of prolonged hyperoxia on the thymus, thymocyte and T cell development, and its proliferation has not been studied extensively. Neonatal mice were exposed to 85% oxygen (hyperoxia) or room air (normoxia) up to 28 days. Flow cytometry using surface markers were used to assay for thymocyte development and proliferation. Mice exposed to prolonged hyperoxia had evidence of lung injury associated alveolar simplification, a significantly lower mean weight, smaller thymic size, lower mean thymocyte count and higher percentage of apoptotic thymocytes. T cells subpopulation in the thymus showed a significant reduction in the count and proliferation of double positive and double negative T cells. There was a significant reduction in the count and proliferation of single positive CD4+ and CD8+ T cells. Prolonged hyperoxia in neonatal mice adversely affected thymic size, thymocyte count and altered the distribution of T cells sub-populations. These results are consistent with the hypothesis that prolonged hyperoxia causes defective development of T cells in the thymus.

  17. Long-lasting neonatal inflammation enhances pain responses to subsequent inflammation, but not peripheral nerve injury in adult rats.

    Science.gov (United States)

    Lim, Eun Jeong; Back, Seung Keun; Kim, Myung Ah; Li, Chengjin; Lee, Jaehee; Jeong, Keun Yeong; Na, Heung Sik

    2009-05-01

    The early postnatal period has been suggested to be the vulnerable time for structural and functional reorganization of sensory systems, and painful stimuli at this time may alter neuronal circuits, thereby leading to changes in an individual's response to pain later in life. In the present study, we examined whether inflammatory experience in the early life can affect pain responses to subsequent noxious insults later in life. The two groups of neonatal rats, treated with an inflammatory irritant and untreated, were subjected to inflammation and peripheral nerve injury in adulthood. Neonatal inflammation was induced by injection of complete Freund's adjuvant (CFA, 25 microl) into the hindpaw or tail of newborn rat pups. Adult rats which had suffered from neonatal paw inflammation at P0 were subjected to re-injection of CFA into the paw neonatally exposed to CFA or L5 spinal nerve ligation. Paw thickness and histology of inflamed paw were examined to assess the neonatal inflammation. Adult animals whose tail had been subjected to CFA injection on P3 received tail-innervating nerve injury. The results showed that the neonatal CFA-treated rats suffered from chronic inflammation, confirmed by persistent increase of paw thickness and histological result of inflamed paw. These animals showed enhanced pain responses to re-inflammatory challenge by injection of CFA (200 microl) into the neonatally inflamed paw 8 weeks after birth compared with the neonatally untreated animals. However, neuropathic pain on the hindpaw and the tail which had been induced by peripheral nerve injury in the neonatal CFA-treated group were not different from those of the untreated group. The present data suggest that early neonatal long-lasting inflammation differentially affects pain responses later in life, depending on the types of subsequent noxious insults.

  18. Early magnetic resonance detection of cortical necrosis and acute network injury associated with neonatal and infantile cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Okabe, Tetsuhiko; Aida, Noriko; Nozawa, Kumiko [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); Niwa, Tetsu [Kanagawa Children' s Medical Center, Department of Radiology, Yokohama (Japan); Tokai University School of Medicine, Department of Radiology, Isehara (Japan); Shibasaki, Jun [Kanagawa Children' s Medical Center, Department of Neonatology, Yokohama (Japan); Osaka, Hitoshi [Kanagawa Children' s Medical Center, Department of Neurology, Yokohama (Japan)

    2014-05-15

    Knowledge of MRI findings in pediatric cerebral infarction is limited. To determine whether cortical necrosis and network injury appear in the acute phase in post-stroke children and to identify anatomical location of acute network injury and the ages at which these phenomena are seen. Images from 12 children (age range: 0-9 years; neonates [<1 month], n=5; infants [1 month-12 months], n=3; others [≥1 year], n=4) with acute middle cerebral artery (MCA) cortical infarction were retrospectively analyzed. Cortical necrosis was defined as hyperintense cortical lesions on T1-weighted imaging that lacked evidence of hemorrhage. Acute network injury was defined as hyperintense lesions on diffusion-weighted imaging that were not in the MCA territory and had fiber connections with the affected cerebral cortex. MRI was performed within the first week after disease onset. Cortical necrosis was only found in three neonates. Acute network injury was seen in the corticospinal tract (CST), thalamus and corpus callosum. Acute network injury along the CST was found in five neonates and one 7-month-old infant. Acute network injury was evident in the thalamus of four neonates and two infants (ages 4 and 7 months) and in the corpus callosum of five neonates and two infants (ages 4 and 7 months). The entire thalamus was involved in three children when infarction of MCA was complete. In acute MCA cortical infarction, MRI findings indicating cortical necrosis or acute network injury was frequently found in neonates and early infants. Response to injury in a developing brain may be faster than that in a mature one. (orig.)

  19. 多探头联合应用在新生儿颅脑疾病中的临床价值%Clinical value of Multi- probe combination in neonatal brain diseases

    Institute of Scientific and Technical Information of China (English)

    张欣荣; 张丽娜

    2011-01-01

    Objective To evaluate the clinical value of Multi - probe combination in the neonatal brain disease. Methods Muliti - slice scanning from the neonatal anterior fontanel with vaginal probe, the heart of the probe and superficial organ probe respectively. Analyze and compare to the three sono-graphic features. Results Three hundred and sixty -one newborns were included,67 brain diseases cases were found by ultrasound,34 hypoxic -ischemic brain injury,21 intracranial hemorrhage,6 ventricular dilatation and hydrocephalus,4 purulent meninggitis and 2 intracranial space occupying. Conclusions Multi - probe combination examination can improve the detection rate of neonatal brain disease , combined with ultrasound follow - up clinical outcome for the newborn to provide a reasonable basis for the diagnosis and treatment.%目的 评价多探头联合应用在新生儿颅脑疾病中的临床应用价值.方法 应用腔探头,心脏探头,浅表器官探头经新生儿前囟做多切面扫查,对三种超声探头扫查的声像图特点进行比较分析.结果 超声检查新生儿共361例,检出颅脑疾病共67例,其中缺氧缺血性脑损伤34例,颅内出血27例,其中伴脑室扩张4例,化脓性脑膜炎4例,颅内占位2例.结论 多探头联合应用检查可提高新生儿颅脑疾病的检出率,结合超声随访为新生儿的临床预后提供合理的诊断治疗依据.

  20. Effect of Ganglioside on hypoxia injury of neonatal and its mechanism

    Institute of Scientific and Technical Information of China (English)

    Hong Zhao

    2015-01-01

    Objective:To explore the effect and mechanism of ganglioside for hypoxia injury in newborn.Methods:A total of 200 cases of newborn patients in our hospital were analyzed. All the patients were divided into 4 groups, control and ganglioside groups with low, medium and high dose. The neonatal behavioral neurological assessment scores were counted in each group and the serum inflammatory factors and transforming growth factor-β (TGFβ)/Smad parameters were detected.Results:The neonatal behavioral neurological assessment scores were increased after ganglioside treatment and the serum interleukin (IL) 2/10, hypoxia inducible factorαand Smad1, Smad3 as well as TGFβ was decreased dramatically when compared with control group.Conclusions:Ganglioside exerts an effective effect on cerebral hypoxia in newborn mainly by inhibiting the TGFβ/Smad signaling pathway.

  1. Baby STEPS: a giant leap for cell therapy in neonatal brain injury.

    Science.gov (United States)

    Borlongan, Cesar V; Weiss, Michael D

    2011-07-01

    We advance Baby STEPS or Stem cell Therapeutics as an Emerging Paradigm in Stroke as a guide in facilitating the critical evaluation in the laboratory of the safety and efficacy of cell therapy for neonatal encephalopathy. The need to carefully consider the clinical relevance of the animal models in mimicking human neonatal brain injury, selection of the optimal stem cell donor, and the application of functional outcome assays in small and large animal models serve as the foundation for preclinical work and beginning to understand the mechanism of this cellular therapy. The preclinical studies will aid our formulation of a rigorous human clinical trial that encompasses not only efficacy testing but also monitoring of safety indices and demonstration of mechanisms of action. This schema forms the basis of Baby STEPS. Our goal is to resonate the urgent call to enhance the successful translation of cell therapy from the laboratory to the clinic.

  2. Therapeutic effect evaluation of hyperbaric oxygen combined with cerebrolysin in treating hypoxic-ischemic encephalopathy%高压氧加脑活素治疗新生儿缺氧缺血性脑病的疗效评价

    Institute of Scientific and Technical Information of China (English)

    罗珍

    2012-01-01

    目的 探讨高压氧结合脑活素治疗新生儿缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)的治疗效果.方法 213例HIE患儿随机分为两组.对照组108例,采用脑活素治疗;观察组105例,采用高压氧结合脑活素治疗.结果 观察组总有效率93.3%,对照组总有效率80.6%,观察组高于对照组(P<0.01);患儿第14、21、28天NBNA评分,观察组均高于对照组(P<0.01).结论 高压氧结合脑活素治疗HIE安全、有效.

  3. Effects of Nimodipine and Cerebrolysin on Prognosis of Newborn with Hypoxic-Ischemic Encephalopathy%尼莫地平、脑活素对缺氧缺血性脑病新生儿预后的影响

    Institute of Scientific and Technical Information of China (English)

    张梅英; 张丽慧; 吴洪轩

    2005-01-01

    目的:探讨尼莫地平、脑活素对缺氧缺血性脑病(Hypoxic-Ischemic Encephalopathy ,HIE)新生儿预后的改善及保护作用.方法:将146例HIE患儿随机分为观察组(76例)和对照组(70例).对照组行常规治疗,观察组在常规治疗的基础上于生后48h内加用尼莫地平、脑活素治疗.所有患儿日龄12~14d和26~28d行新生儿行为神经评分(NBNA);3、6个月龄时行智测检查.结果:中、重度HIE,观察组两次NBNA评分和智能发育评估均优于对照组(P<0.05,P<0.01).结论:早期应用尼莫地平、脑活素能明显改善中、重度HIE患儿预后.

  4. Neonatal asphyxia and forensic medicine.

    Science.gov (United States)

    d'Aloja, E; Müller, M; Paribello, F; Demontis, R; Faa, A

    2009-01-01

    In the last decades, the scientific literature addressing neonatal encephalopathy has grown in a logarithmic way and malpractice claims in obstetrics and neonatology have become a major threat to the health service. At the moment, scientific evidence are insufficient to clearly identify in each single case whether the hypoxic insult has developed in the course of labor or in the first few hours after the birth or, otherwise, whether the damage has to recognize a remote and long-lasting cause acting during pregnancy. Several authors feel that this scientific uncertainty leads to a higher percentage of civil suit decisions prone to recognizing a guilty medical behavior, and they wish a more in-depth analysis of all these cases to clearly identify all the data either in favor or in contrary to the assumption of the existence of a causal correlation between neonatal encephalopathy and medical misbehavior. This article will focus on the medico-legal approach to a hypoxic-ischemic event in the perinatal period, addressing the relevant data to be collected in order to establish the medical and juridical cause of the neonatal damage.

  5. 牛磺酸对哺乳动物大脑发育及抗缺氧缺血性脑损伤的作用%Effects of taurine on the development of the mammalian brain and anti-hypoxic ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    罗济璇; 舒斯云; 马林; 吴升

    2014-01-01

    As an inhibitory amino acid similar to gama-aminobutyric acid,taurine can activate the corticostriatal pathway as an endogenous ligand for glycine receptors,establishing equilibrium between the excitatory and inhibitory processes in the brain.In mammalian brains,taurine concentrations increase during the developmental period of the brain until weaning,and subsequently decline reaching stable concentrations in adulthood.With abilities of anti-oxidative stress,anti-inflammatory and anti-apoptosis,taurine can improve the hypoxic-ischemic brain injury,promote the proliferation and differentiation of neurons and affect brain development,It needs more investigations to prove when and how taurine supplementation during gestation,baby,children or adult can assist the development of the brain and prevent the damage of the brain from hypoxic and ischemic damage.%牛磺酸是存在于哺乳动物大脑中类似γ-氨基丁酸的抑制性氨基酸,可与甘氨酸受体结合激活皮质纹状体通路,发挥着平衡大脑兴奋性和抑制性过程的重要作用.它的浓度在哺乳动物大脑发育过程中持续升高至断奶期,到成年后达到稳定水平.牛磺酸具有强大的抗氧化应激、抗炎和抗凋亡作用,并且可以改善缺氧缺血性脑损伤,促进神经细胞增殖分化,影响胎儿脑发育.动物实验表明补充牛磺酸可促进新生儿脑发育,有保护或减轻脑缺氧缺血性和氧化应激脑损伤的作用.但对于人类能否补充牛磺酸来促进脑发育保护脑损伤,以及在何时补充、补充的剂量和途径的研究资料并不充分,有待于进一步深入研究.

  6. CXCR4 Blockade Attenuates Hyperoxia Induced Lung Injury in Neonatal Rats

    Science.gov (United States)

    Drummond, Shelley; Ramachandran, Shalini; Torres, Eneida; Huang, Jian; Hehre, Dorothy; Suguihara, Cleide; Young, Karen C.

    2015-01-01

    Background Lung inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Stromal derived factor-1 (SDF-1) and its receptor chemokine receptor 4 (CXCR4) modulate the inflammatory response. Whether antagonism of CXCR4 will alleviate lung inflammation in neonatal hyperoxia-induced lung injury is unknown. Objective To determine whether CXCR4 antagonism would attenuate lung injury in rodents with experimental BPD by decreasing pulmonary inflammation. Methods Newborn rats exposed to normoxia (RA) or hyperoxia (FiO2=0.9) from postnatal day 2 (P2)-P16 were randomized to receive the CXCR4 antagonist, AMD3100 or placebo (PL) from P5 to P15. Lung alveolarization, angiogenesis, and inflammation were evaluated at P16. Results As compared to RA, hyperoxic-PL pups had a decrease in alveolarization, reduced lung vascular density and increased lung inflammation. In contrast, AMD3100-treated hyperoxic pups had improved alveolarization and increased angiogenesis. This improvement in lung structure was accompanied by a decrease in bronchoalveolar lavage fluid macrophage and neutrophil count and reduced lung myeloperoxidase activity. Conclusion CXCR4 antagonism decreases lung inflammation and improves alveolar as well as vascular structure in neonatal rats with experimental BPD. These findings suggest a novel therapeutic strategy to alleviate lung injury in preterm infants with BPD. PMID:25825119

  7. Bone Marrow-Derived c-kit+ Cells Attenuate Neonatal Hyperoxia-Induced Lung Injury

    Science.gov (United States)

    Ramachandran, Shalini; Suguihara, Cleide; Drummond, Shelley; Chatzistergos, Konstantinos; Klim, Jammie; Torres, Eneida; Huang, Jian; Hehre, Dorothy; Rodrigues, Claudia O.; McNiece, Ian K.; Hare, Joshua M.; Young, Karen C.

    2016-01-01

    Recent studies suggest that bone marrow (BM)-derived stem cells have therapeutic efficacy in neonatal hyperoxia-induced lung injury (HILI). c-kit, a tyrosine kinase receptor that regulates angiogenesis, is expressed on several populations of BM-derived cells. Preterm infants exposed to hyperoxia have decreased lung angiogenesis. Here we tested the hypothesis that administration of BM-derived c-kit+ cells would improve angiogenesis in neonatal rats with HILI. To determine whether intratracheal (IT) administration of BM-derived c-kit+ cells attenuates neonatal HILI, rat pups exposed to either normobaric normoxia (21% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to P15 were randomly assigned to receive either IT BM-derived green fluorescent protein (GFP)+ c-kit− cells (PL) or BM-derived GFP+ c-kit+ cells on P8. The effect of cell therapy on lung angiogenesis, alveolarization, pulmonary hypertension, vascular remodeling, cell proliferation, and apoptosis was determined at P15. Cell engraftment was determined by GFP immunostaining. Compared to PL, the IT administration of BM-derived c-kit+ cells to neonatal rodents with HILI improved alveolarization as evidenced by increased lung septation and decreased mean linear intercept. This was accompanied by an increase in lung vascular density, a decrease in lung apoptosis, and an increase in the secretion of proangiogenic factors. There was no difference in pulmonary vascular remodeling or the degree of pulmonary hypertension. Confocal microscopy demonstrated that 1% of total lung cells were GFP+ cells. IT administration of BM-derived c-kit+ cells improves lung alveolarization and angiogenesis in neonatal HILI, and this may be secondary to an improvement in the lung angiogenic milieu. PMID:23759597

  8. The neuroprotective effect of astaxanthin on newborn rat models of hypoxic-ischemic brain damage%虾青素对缺氧缺血性脑损伤新生大鼠模型的神经保护作用

    Institute of Scientific and Technical Information of China (English)

    林良烽

    2015-01-01

    背景:研究发现虾青素有良好的神经保护作用,但是对于其在新生儿缺氧缺血性损伤中的治疗作用,目前尚无相关报道。目的:构建缺氧缺血性脑损伤新生大鼠模型,观察虾青素对其产生的神经保护作用及作用的途径。方法:从98只7 d龄的SD乳鼠中随机取30只作为假手术组,其余大鼠结扎左颈总动脉2 h后,置于体积分数92%的特种标准气体、8%的氧气缺氧舱2 h建立缺血缺氧性脑损伤模型。假手术组仅分离颈总动脉,不予缺血缺氧处理。将造模成功的大鼠随机分为脑缺血缺氧组和虾青素治疗组,各30只。虾青素治疗组大鼠在脑缺血缺氧模型建成后立即通过腹腔注射80 mg/kg虾青素。结果与结论:与假手术组相比,脑缺血缺氧组大鼠缺血损伤区顶叶皮质中p-Akt、p-GSK3β、cleaved-caspase3蛋白的表达水平显著增加,Bcl-2蛋白的表达水平显著减少(P <0.05);与脑缺血缺氧组相比,虾青素治疗可以显著减少凋亡相关蛋白cleaved-caspase3蛋白的表达水平(P <0.05),显著上调Bcl-2蛋白的表达水平(P <0.05),明显减少凋亡细胞的数量(P <0.05)。提示虾青素可以显著改善新生大鼠缺氧缺血性脑损伤的预后及作用途径与上调Akt/GSK3β信号通路相关。%BACKGROUND:Several studies have demonstrated that astaxanthin has a good neuroprotective effect; however, the treatment effects of astaxanthin on newborns with hypoxic-ischemic brain damage have not been reported. OBJECTIVE: To build newborn rat models of hypoxic-ischemic brain damage, and investigate the neuroprotective effects of astaxanthin and the ways of action. METHODS: Thirty newborn Sprague-Dawley rats aged 7 days out of 98 were randomly taken as sham-operated group. The rest of rats were subjected to ligature of the left carotid artery for 2 hours and then placed in the hypoxic box containing 92% special standard gas and 8% oxygen to establish

  9. Current perspectives on neonatal hypoglycemia, its management, and cerebral injury risk

    Directory of Open Access Journals (Sweden)

    Chandran S

    2015-02-01

    Full Text Available Suresh Chandran,1–4 Victor Samuel Rajadurai,1–3 Abdul Alim Abdul Haium,1–3 Khalid Hussain5,6 1Department of Neonatology, KK Women’s and Children’s Hospital, Singapore; 2Duke-NUS Graduate School of Medicine, Singapore; 3Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 4Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 5Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, 6The Institute of Child Health, University College London, London, UK Abstract: Glucose is an essential substrate for mammalian cells; in particular, the brain needs glucose continuously as a primary source of energy. Hypoglycemia is the most common biochemical finding in the neonatal period. However, despite the common occurrence, there is still controversy on the definition of hypoglycemia in the newborn period. This has led to the development of guidelines designed to identify infants “at-risk” and the implementation of an “operational threshold” for physicians to consider intervention. In healthy term infants, the optimal hormonal and metabolic adaptations during the immediate neonatal period ensure an adequate energy substrate for the vital organs, whereas the abnormal glucose homeostasis observed in preterm and growth-retarded infants is multifactorial in origin. For these high-risk infants, it is important to identify, screen, and prevent significant hypoglycemia. Detailed investigations are warranted in infants with severe and persistent hypoglycemia. Neonatal hypoglycemia is a major cause of brain injury. The speculated mechanisms of cellular injury include excitatory neurotoxins active at N-methyl-D-aspartate receptors, increased mitochondrial free radical generation with initiation of apoptosis and altered cerebral energetic characteristics. This hypoglycemic brain injury predominantly affects parieto-occipital regions causing

  10. Systematic review and meta-analysis of therapeutic hypothermia in animal models of spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Peter E Batchelor

    Full Text Available Therapeutic hypothermia is a clinically useful neuroprotective therapy for cardiac arrest and neonatal hypoxic ischemic encephalopathy and may potentially be useful for the treatment of other neurological conditions including traumatic spinal cord injury (SCI. The pre-clinical studies evaluating the effectiveness of hypothermia in acute SCI broadly utilise either systemic hypothermia or cooling regional to the site of injury. The literature has not been uniformly positive with conflicting studies of varying quality, some performed decades previously.In this study, we systematically review and meta-analyse the literature to determine the efficacy of systemic and regional hypothermia in traumatic SCI, the experimental conditions influencing this efficacy, and the influence of study quality on outcome. Three databases were utilised; PubMed, ISI Web of Science and Embase. Our inclusion criteria consisted of the (i reporting of efficacy of hypothermia on functional outcome (ii number of animals and (iii mean outcome and variance in each group.Systemic hypothermia improved behavioural outcomes by 24.5% (95% CI 10.2 to 38.8 and a similar magnitude of improvement was seen across a number of high quality studies. The overall behavioural improvement with regional hypothermia was 26.2%, but the variance was wide (95% CI -3.77 to 56.2. This result may reflect a preponderance of positive low quality data, although a preferential effect of hypothermia in ischaemic models of injury may explain some of the disparate data. Sufficient heterogeneity was present between studies of regional hypothermia to reveal a number of factors potentially influencing efficacy, including depth and duration of hypothermia, animal species, and neurobehavioural assessment. However, these factors could reflect the influence of earlier lower quality literature.Systemic hypothermia appears to be a promising potential method of treating acute SCI on the basis of meta-analysis of the

  11. Stem cell factor improves lung recovery in rats following neonatal hyperoxia-induced lung injury

    Science.gov (United States)

    Miranda, Luis F.; Rodrigues, Claudia O.; Ramachandran, Shalini; Torres, Eneida; Huang, Jian; Klim, Jammie; Hehre, Dorothy; McNiece, Ian; Hare, Joshua M.; Suguihara, Cleide Y.; Young, Karen C.

    2016-01-01

    BACKGROUND Stem cell factor (SCF) and its receptor, c-kit, are modulators of angiogenesis. Neonatal hyperoxia-induced lung injury (HILI) is characterized by disordered angiogenesis. The objective of this study was to determine whether exogenous SCF improves recovery from neonatal HILI by improving angiogenesis. METHODS Newborn rats assigned to normoxia (RA: 20.9% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to 15, received daily injections of SCF 100 µg/kg or placebo (PL) from P15 to P21. Lung morphometry was performed at P28. Capillary tube formation in SCF-treated hyperoxia-exposed pulmonary microvascular endothelial cells (HPMECs) was determined by Matrigel assay. RESULTS As compared with RA, hyperoxic-PL pups had decrease in alveolarization and in lung vascular density, and this was associated with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and vascular remodeling. In contrast, SCF-treated hyperoxic pups had increased angiogenesis, improved alveolarization, and attenuation of pulmonary hypertension as evidenced by decreased RVSP, right ventricular hypertrophy, and vascular remodeling. Moreover, in an in vitro model, SCF increased capillary tube formation in hyperoxia-exposed HPMECs. CONCLUSION Exogenous SCF restores alveolar and vascular structure in neonatal rats with HILI by promoting neoangiogenesis. These findings suggest a new strategy to treat lung diseases characterized by dysangiogenesis. PMID:24153399

  12. Metformin attenuates hyperoxia-induced lung injury in neonatal rats by reducing the inflammatory response.

    Science.gov (United States)

    Chen, Xueyu; Walther, Frans J; Sengers, Rozemarijn M A; Laghmani, El Houari; Salam, Asma; Folkerts, Gert; Pera, Tonio; Wagenaar, Gerry T M

    2015-08-01

    Because therapeutic options are lacking for bronchopulmonary dysplasia (BPD), there is an urgent medical need to discover novel targets/drugs to treat this neonatal chronic lung disease. Metformin, a drug commonly used to lower blood glucose in type 2 diabetes patients, may be a novel therapeutic option for BPD by reducing pulmonary inflammation and fibrosis and improving vascularization. We investigated the therapeutic potential of daily treatment with 25 and 100 mg/kg metformin, injected subcutaneously in neonatal Wistar rats with severe experimental BPD, induced by continuous exposure to 100% oxygen for 10 days. Parameters investigated included survival, lung and heart histopathology, pulmonary fibrin and collagen deposition, vascular leakage, right ventricular hypertrophy, and differential mRNA expression in the lungs of key genes involved in BPD pathogenesis, including inflammation, coagulation, and alveolar development. After daily metformin treatment rat pups with experimental BPD had reduced mortality, alveolar septum thickness, lung inflammation, and fibrosis, demonstrated by a reduced influx of macrophages and neutrophils and hyperoxia-induced collagen III and fibrin deposition (25 mg/kg), as well as improved vascularization (100 mg/kg) compared with control treatment. However, metformin did not ameliorate alveolar enlargement, small arteriole wall thickening, vascular alveolar leakage, and right ventricular hypertrophy. In conclusion metformin prolongs survival and attenuates pulmonary injury by reducing pulmonary inflammation, coagulation, and fibrosis but does not affect alveolar development or prevent pulmonary arterial hypertension and right ventricular hypertrophy in neonatal rats with severe hyperoxia-induced experimental BPD.

  13. Neonatal sensory nerve injury-induced synaptic plasticity in the trigeminal principal sensory nucleus.

    Science.gov (United States)

    Lo, Fu-Sun; Erzurumlu, Reha S

    2016-01-01

    Sensory deprivation studies in neonatal mammals, such as monocular eye closure, whisker trimming, and chemical blockade of the olfactory epithelium have revealed the importance of sensory inputs in brain wiring during distinct critical periods. But very few studies have paid attention to the effects of neonatal peripheral sensory nerve damage on synaptic wiring of the central nervous system (CNS) circuits. Peripheral somatosensory nerves differ from other special sensory afferents in that they are more prone to crush or severance because of their locations in the body. Unlike the visual and auditory afferents, these nerves show regenerative capabilities after damage. Uniquely, damage to a somatosensory peripheral nerve does not only block activity incoming from the sensory receptors but also mediates injury-induced neuro- and glial chemical signals to the brain through the uninjured central axons of the primary sensory neurons. These chemical signals can have both far more and longer lasting effects than sensory blockade alone. Here we review studies which focus on the consequences of neonatal peripheral sensory nerve damage in the principal sensory nucleus of the brainstem trigeminal complex.

  14. The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury

    Directory of Open Access Journals (Sweden)

    Vega-Avelaira David

    2012-04-01

    Full Text Available Abstract Background Peripheral nerve injuries can trigger neuropathic pain in adults but cause little or no pain when they are sustained in infancy or early childhood. This is confirmed in rodent models where neonatal nerve injury causes no pain behaviour. However, delayed pain can arise in man some considerable time after nerve damage and to examine this following early life nerve injury we have carried out a longer term follow up of rat pain behaviour into adolescence and adulthood. Results Spared nerve injury (SNI or sham surgery was performed on 10 day old (P10 rat pups and mechanical nociceptive reflex thresholds were analysed 3, 7, 14, 21, 28, 38 and 44 days post surgery. While mechanical thresholds on the ipsilateral side are not significantly different from controls for the first 2–3 weeks post P10 surgery, after that time period, beginning at 21 days post surgery (P31, the SNI group developed following early life nerve injury significant hypersensitivity compared to the other groups. Ipsilateral mechanical nociceptive threshold was 2-fold below that of the contralateral and sham thresholds at 21 days post surgery (SNI-ipsilateral 28 (±5 g control groups 69 (±9 g, p Conclusions We report a novel consequence of early life nerve injury whereby mechanical hypersensitivity only emerges later in life. This delayed adolescent onset in mechanical pain thresholds is accompanied by neuroimmune activation and NMDA dependent central sensitization of spinal nociceptive circuits. This delayed onset in mechanical pain sensitivity may provide clues to understand the long term effects of early injury such as late onset phantom pain and the emergence of complex adolescent chronic pain syndromes.

  15. Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury

    Science.gov (United States)

    Jablonska, Beata; Gierdalski, Marcin; Chew, Li-Jin; Hawley, Teresa; Catron, Mackenzie; Lichauco, Arturo; Cabrera-Luque, Juan; Yuen, Tracy; Rowitch, David; Gallo, Vittorio

    2016-01-01

    Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown in culture and its targeted ablation in vivo suppresses basal and HX-induced OPC proliferation. Inhibition of Sirt1 also promotes OPC differentiation after HX. Our results indicate that Sirt1 is an essential regulator of OPC proliferation and OL regeneration after neonatal brain injury. Therefore, enhancing Sirt1 activity may promote OL recovery after DWMI. PMID:27991597

  16. Incidence of acute kidney injury in the neonatal intensive care unit

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    Doaa Youssef

    2015-01-01

    Full Text Available The aim of this work is to study the incidence of acute kidney injury (AKI in neonates admitted to the neonatal intensive care unit (NICU over a six-month period from September 2011 to March 2012. This prospective study was performed on 250 neonates admitted to the NICU at the Children′s Hospital, Faculty of Medicine, Zagazig University. All neonates were subjected to detailed history taking, including pre-natal, natal and post-natal history, with stress on symptoms suggestive of AKI. All neonates were examined thoroughly and the following investigations were performed: Blood urea nitrogen (BUN, serum creatinine, sodium, potassium, calcium, complete blood count, C-reactive protein, arterial blood gases, urine sodium and urine creatinine. AKI was diagnosed in 27 cases (10.8%, including 12 females and 15 males. 40.7% of the AKI cases were born after full-term pregnancy while 59.3% were pre-term babies. 29.6% of the AKI cases had oliguria, and there was male sex predominance, with a male-female ratio of 1.3:1. The cause of AKI was pre-renal in 96.3% and intrinsic renal in 3.7% of the cases. The predisposing factors for AKI were sepsis in 63% of the cases, respiratory distress syndrome in 55.6%, mechanical ventilation in 51.9%, peri-natal asphyxia in 18.5%, dehydration in 14.8%, surgical operation in 11.1%, congenital heart disease in 7.4%, sub-galeal hematoma in 3.7%, polycythemia in 3.7% and intra-ventricular hemorrhage in 3.7% of the cases. Our data suggest that pre-renal failure was the most common form of AKI in our patients. Early recognition of risk factors such as sepsis, peri-natal asphyxia or peri-operative problems and rapid effective treatment of contributing conditions will reduce the incidence of AKI in the neonatal period.

  17. Peripheral nerve injury sensitizes neonatal dorsal horn neurons to tumor necrosis factor-α

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    Baccei Mark L

    2009-03-01

    Full Text Available Abstract Background Little is known about whether peripheral nerve injury during the early postnatal period modulates synaptic efficacy in the immature superficial dorsal horn (SDH of the spinal cord, or whether the neonatal SDH network is sensitive to the proinflammatory cytokine TNFα under neuropathic conditions. Thus we examined the effects of TNFα on synaptic transmission and intrinsic membrane excitability in developing rat SDH neurons in the absence or presence of sciatic nerve damage. Results The spared nerve injury (SNI model of peripheral neuropathy at postnatal day (P6 failed to significantly alter miniature excitatory (mEPSCs or inhibitory (mIPSCs postsynaptic currents in SDH neurons at P9-11. However, SNI did alter the sensitivity of excitatory synapses in the immature SDH to TNFα. While TNFα failed to influence mEPSCs or mIPSCs in slices from sham-operated controls, it significantly increased mEPSC frequency and amplitude following SNI without modulating synaptic inhibition onto the same neurons. This was accompanied by a significant decrease in the paired-pulse ratio of evoked EPSCs, suggesting TNFα increases the probability of glutamate release in the SDH under neuropathic conditions. Similarly, while SNI alone did not alter action potential (AP threshold or rheobase in SDH neurons at this age, TNFα significantly decreased AP threshold and rheobase in the SNI group but not in sham-operated littermates. However, unlike the adult, the expression of TNFα in the immature dorsal horn was not significantly elevated during the first week following the SNI. Conclusion Developing SDH neurons become susceptible to regulation by TNFα following peripheral nerve injury in the neonate. This may include both a greater efficacy of glutamatergic synapses as well as an increase in the intrinsic excitability of immature dorsal horn neurons. However, neonatal sciatic nerve damage alone did not significantly modulate synaptic transmission or

  18. A neonatal mouse spinal cord injury model for assessing post-injury adaptive plasticity and human stem cell integration.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Boulland

    Full Text Available Despite limited regeneration capacity, partial injuries to the adult mammalian spinal cord can elicit variable degrees of functional recovery, mediated at least in part by reorganization of neuronal circuitry. Underlying mechanisms are believed to include synaptic plasticity and collateral sprouting of spared axons. Because plasticity is higher in young animals, we developed a spinal cord compression (SCC injury model in the neonatal mouse to gain insight into the potential for reorganization during early life. The model provides a platform for high-throughput assessment of functional synaptic connectivity that is also suitable for testing the functional integration of human stem and progenitor cell-derived neurons being considered for clinical cell replacement strategies. SCC was generated at T9-T11 and functional recovery was assessed using an integrated approach including video kinematics, histology, tract tracing, electrophysiology, and high-throughput optical recording of descending inputs to identified spinal neurons. Dramatic degeneration of axons and synaptic contacts was evident within 24 hours of SCC, and loss of neurons in the injured segment was evident for at least a month thereafter. Initial hindlimb paralysis was paralleled by a loss of descending inputs to lumbar motoneurons. Within 4 days of SCC and progressively thereafter, hindlimb motility began to be restored and descending inputs reappeared, but with examples of atypical synaptic connections indicating a reorganization of circuitry. One to two weeks after SCC, hindlimb motility approached sham control levels, and weight-bearing locomotion was virtually indistinguishable in SCC and sham control mice. Genetically labeled human fetal neural progenitor cells injected into the injured spinal cord survived for at least a month, integrated into the host tissue and began to differentiate morphologically. This integrative neonatal mouse model provides opportunities to explore early

  19. Music therapy on infant hypoxic ischemic encephalopathy recovery hearing affect curative effect observation%音乐疗法对幼儿缺氧缺血性脑病恢复期听力影响的疗效观察

    Institute of Scientific and Technical Information of China (English)

    孔令莉; 卢璐

    2016-01-01

    Objective To observe music therapy to treat infant hypoxic ischemic encephalopathy re-covery the curative effect of hearing.Methods In June 2013 to June 201 5 Zhongxiang Maternal and Child Health Care of Family Planning Service Center of hypoxic ischemic encephalopathy is admitted in pediatric recovering from significant hearing impairment of children with 228 cases,1 14 cases were randomly divided into observation group and control group each.Control group using hyperbaric oxygen joint muscle injection of single silica acid has four sugar ganglioside treatment,observation group in the control group therapy based on join music therapy,and listen to music every day 4 times,each time for 20 min,1 month compared two groups of children listening to improve the situation.Results the observation group treatment the total effec-tive rate was 92.1%(105/114),significantly higher than that of control group 69.3%(79/1 14),the difference was statistically significant(P <0.05).All the children in the process of music therapy without any resist-ance,exclusion,pain and other adverse reactions.Conclusion compared with conventional treatment meth-ods,combination of music therapy can significantly improve hypoxia ischemic encephalopathy recovery has children with hearing impairment of hearing recovery effect,and gentle treatment is simple,treatment con-tents,easily accepted by children,no side effects.%目的:观察音乐疗法治疗幼儿缺氧缺血性脑病恢复期听力的疗效。方法2013年6月至2015年6月钟祥市妇幼保健计划生育服务中心儿科收治的缺氧缺血性脑病正处于恢复期有明显听力障碍的患儿228例,随机分为观察组和对照组各114例。对照组采用高压氧联合肌内注射单唾液酸四己糖神经节苷脂进行治疗,观察组对照组治疗基础上加入音乐疗法,每天听音乐4次,每次20 min,治疗1个月对比两组患儿听力改善情况。结果观察组治疗总有效率为92.1%(105/114),

  20. 神经生长因子对缺氧缺血性脑损伤患者闪光视觉诱发电位的影响%Impact of nerve growth factor on flash-visual evoked potential in patients with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    黄杰; 周艳

    2004-01-01

    BACKGROUND: Flash-visual evoked potential(F-VEP) is a new easy practicable method in the clinical evaluation of the functional status of central nervous system in paediatrics at present.OBJECTIVE: To investigate the sensitivity of F-VEP in the reflection of hypoxic-ischemic brain damage(HIBD) in neonatal rats for studying the protective effect of nerve growth factor(NGF) on neonatal HIBD rats, which is aimed to provide a theoretical gist in early diagnosis and intervention in neonatal HIBD.DESIGN: A complete randomised controlled trial.SETTING and PARTICIPANTS: Study was conducted in the Department of Paediatrics of the Second Affiliated Hospital of Nanjing Medical University. A total of 60 7-day old SD rats in either gender with a mass from 14 g to 18 g were obtained from the experimental animal centre of Nanjing Medical University, which were SPF experimental animals fed in barrier environment.INTERVENTIONS: A total of 40 rats were randomly allocated into two groups after the establishment of HIBD animal model: HIBD model without treatment group(HIBD group, n=20) and HIBD model NGF treatment group(NGF group, n = 20) and another 20 rats were set in normal control group (control group).MAIN OUTCOME MEASURES: To observe the alteration of F-VEP in control group as well as after HIBD, and the impact of NGF on the increase of mass, mortality, brain weight of left and right side and F-VEP wave in neonatal HIBD rats.RESULTS: Rats in NGF group had an increase of( 11.9 ± 3.5) g in mass, the mortality rate was 5% during the study, and the brain weight of the HIBD side (left side) was(0. 59 ±0.02), which all had signiticant differences compared with that of HIBD group( P < 0. 01). There was no significant difference of the brain weight between right and left side in NGF group but there was significance in HIBD group, which were[(3.39 ±0. 10) g and(0. 57 ±0.05) g] respectively(P < 0.01) . The F-VEP latencies immediately after HIBD in both NGF group and HIBD group[(36

  1. Afferent Innervation, Muscle Spindles, and Contractures Following Neonatal Brachial Plexus Injury in a Mouse Model.

    Science.gov (United States)

    Nikolaou, Sia; Hu, Liangjun; Cornwall, Roger

    2015-10-01

    We used an established mouse model of elbow flexion contracture after neonatal brachial plexus injury (NBPI) to test the hypothesis that preservation of afferent innervation protects against contractures and is associated with preservation of muscle spindles and ErbB signaling. A model of preganglionic C5 through C7 NBPI was first tested in mice with fluorescent axons using confocal imaging to confirm preserved afferent innervation of spindles despite motor end plate denervation. Preganglionic and postganglionic injuries were then created in wild-type mice. Four weeks later, we assessed total and afferent denervation of the elbow flexors by musculocutaneous nerve immunohistochemistry. Biceps muscle volume and cross-sectional area were measured by micro computed tomography. An observer who was blinded to the study protocol measured elbow flexion contractures. Biceps spindle and muscle fiber morphology and ErbB signaling pathway activity were assessed histologically and immunohistochemically. Preganglionic and postganglionic injuries caused similar total denervation and biceps muscle atrophy. However, after preganglionic injuries, afferent innervation was partially preserved and elbow flexion contractures were significantly less severe. Spindles degenerated after postganglionic injury but were preserved after preganglionic injury. ErbB signaling was inactivated in denervated spindles after postganglionic injury but ErbB signaling activity was preserved in spindles after preganglionic injury with retained afferent innervation. Preganglionic and postganglionic injuries were associated with upregulation of ErbB signaling in extrafusal muscle fibers. Contractures after NBPI are associated with muscle spindle degeneration and loss of spindle ErbB signaling activity. Preservation of afferent innervation maintained spindle development and ErbB signaling activity, and protected against contractures. Pharmacologic modulation of ErbB signaling, which is being investigated as a

  2. Dietary interventions designed to protect the perinatal brain from hypoxic-ischemic encephalopathy--Creatine prophylaxis and the need for multi-organ protection.

    Science.gov (United States)

    Ellery, Stacey J; Dickinson, Hayley; McKenzie, Matthew; Walker, David W

    2016-05-01

    Birth asphyxia or hypoxia arises from impaired placental gas exchange during labor and remains one of the leading causes of neonatal morbidity and mortality worldwide. It is a condition that can strike in pregnancies that have been uneventful until these final moments, and leads to fundamental loss of cellular energy reserves in the newborn. The cascade of metabolic changes that occurs in the brain at birth as a result of hypoxia can lead to significant damage that evolves over several hours and days, the severity of which can be ameliorated with therapeutic cerebral hypothermia. However, this treatment is only applied to a subset of newborns that meet strict inclusion criteria and is usually administered only in facilities with a high level of medical surveillance. Hence, a number of neuropharmacological interventions have been suggested as adjunct therapies to improve the efficacy of hypothermia, which alone improves survival of the post-hypoxic infant but does not altogether prevent adverse neurological outcomes. In this review we discuss the prospect of using creatine as a dietary supplement during pregnancy and nutritional intervention that can significantly decrease the risk of brain damage in the event of severe oxygen deprivation at birth. Because brain damage can also arise secondarily to compromise of other fetal organs (e.g., heart, diaphragm, kidney), and that compromise of mitochondrial function under hypoxic conditions may be a common mechanism leading to damage of these tissues, we present data suggesting that dietary creatine supplementation during pregnancy may be an effective prophylaxis that can protect the fetus from the multi-organ consequences of severe hypoxia at birth. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Influence of lung injury on cardiac output measurement using transpulmonary ultrasound dilution: a validation study in neonatal lambs

    NARCIS (Netherlands)

    Vrancken, S.L.A.G.; Boode, W.P. de; Hopman, J.C.W.; Looijen-Salamon, M.G.; Liem, K.D.; Heijst, A.F. van

    2012-01-01

    BACKGROUND: /st> Transpulmonary ultrasound dilution (TPUD) is a promising method for cardiac output (CO) measurement in severely ill neonates. The incidence of lung injury in this population is high, which might influence CO measurement using TPUD because of altered lung perfusion. We evaluated t

  4. Factors related to the psychosocial functioning of youth with neonatal brachial plexus injuries.

    Science.gov (United States)

    Mentrikoski, Janelle M; Duncan, Christina L; Melanson, Andrea; Louden, Emily; Allgier, Allison; Michaud, Linda; Rinaldi, Robert

    2015-04-01

    Owing to the possible visible nature and functional impairments associated with neonatal brachial plexus injuries (NBPI), the current study investigated the relations of injury severity, social support, and coping strategies to social difficulties and self-concept in youth with NBPI. 88 children (aged 10-17 years) with NBPI and their parent(s) were recruited from a national organization and two brachial plexus clinics. Participants completed a variety of questionnaires during their scheduled clinic visits. More social support from classmates was associated with better self-concept and fewer social difficulties. Less frequent use of negative coping strategies was associated with better self-concept and fewer social difficulties and was a significant moderator of the relation between injury severity and self-concept. Clinicians who work with children with NBPI should consider peer support and coping strategies when promoting the psychosocial functioning of these youth. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Non-injurious neonatal hypoxia confers resistance to brain senescence in aged male rats.

    Directory of Open Access Journals (Sweden)

    Nicolas Martin

    Full Text Available Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal "conditioning-like" hypoxia (100% N₂, 5 min on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence. We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP kinase. At 21 days of age, increased thicknesses and cell densities were recorded in various subregions, with strong synapsin activation. During aging, previous exposure to neonatal hypoxia was associated with enhanced memory retrieval scores specifically in males, better preservation of their brain integrity than controls, reduced age-related apoptosis, larger hippocampal cell layers, and higher expression of glutamatergic and GABAergic markers. These changes were accompanied with a marked expression of synapsin proteins, mainly of their phosphorylated active forms which constitute major players of synapse function and plasticity, and with increases of their key regulators, i.e. Erk1/2, the transcription factor EGR-1/Zif-268 and Src kinase. Moreover, the significantly higher interactions between PSD-95 scaffolding protein and NMDA receptors measured in the hippocampus of 720-day-old male animals strengthen the conclusion of increased synaptic functional activity and plasticity associated with neonatal hypoxia. Thus, early non-injurious hypoxia may trigger beneficial long term effects conferring higher resistance to senescence in aged male rats, with a better preservation of cognitive functions.

  6. Matrix metaloproteinases activity during the evolution of hypoxic-ischemic brain damage in the immature rat. The effect of 1-methylnicotinamide (MNA).

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    Dragun, P; Makarewicz, D; Wójcik, L; Ziemka-Nałecz, M; Słomka, M; Zalewska, T

    2008-09-01

    Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the extracellular matrix and carry out key functions during brain development. Apart from a physiological role, excessive activation of MMPs in brain tissue has been postulated to represent a pathway for cell death arising from ischemia. To evaluate the possible involvement of MMPs in the perinatal brain asphyxia, we exposed 7-day-old rats to hypoxia-ischemia (HI). Unilateral HI was administered by ligation of the common carotid artery followed by hypoxia (7.4% O2/92.6% N2) for 65 minutes. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in > 90% of animals. HI resulted in a significant elevation of MMP-2 and MMP-9 activity in the ipsilateral forebrain. The maximum activation was found at 48 hours and 7-14 days after the insult. These results suggest that early and late induction of MMPs may play a role in neuronal death as well as in repair processes. The treatment of animals subjected to HI with 1-methylnicotinamide (MNA), the anti-inflammatory agent, led to the inhibition of MMP-9 in an acute phase of ischemic damage and to the activation of MMP-2 in the later stages after injury. The timing of MMPs modulation by MNA may indicate its possible therapeutic implications.

  7. Role of Antioxidants in Neonatal Hypoxic–Ischemic Brain Injury: New Therapeutic Approaches

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    Arteaga, Olatz; Álvarez, Antonia; Revuelta, Miren; Santaolalla, Francisco; Urtasun, Andoni; Hilario, Enrique

    2017-01-01

    Hypoxic–ischemic brain damage is an alarming health and economic problem in spite of the advances in neonatal care. It can cause mortality or detrimental neurological disorders such as cerebral palsy, motor impairment and cognitive deficits in neonates. When hypoxia–ischemia occurs, a multi-faceted cascade of events starts out, which can eventually cause cell death. Lower levels of oxygen due to reduced blood supply increase the production of reactive oxygen species, which leads to oxidative stress, a higher concentration of free cytosolic calcium and impaired mitochondrial function, triggering the activation of apoptotic pathways, DNA fragmentation and cell death. The high incidence of this type of lesion in newborns can be partly attributed to the fact that the developing brain is particularly vulnerable to oxidative stress. Since antioxidants can safely interact with free radicals and terminate that chain reaction before vital molecules are damaged, exogenous antioxidant therapy may have the potential to diminish cellular damage caused by hypoxia–ischemia. In this review, we focus on the neuroprotective effects of antioxidant treatments against perinatal hypoxic–ischemic brain injury, in the light of the most recent advances. PMID:28134843

  8. Contribution of denervated muscle to contractures after neonatal brachial plexus injury: not just muscle fibrosis.

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    Nikolaou, Sia; Liangjun, Hu; Tuttle, Lori J; Weekley, Holly; Christopher, Wylie; Lieber, Richard L; Cornwall, Roger

    2014-03-01

    We investigated the contribution of muscle fibrosis to elbow flexion contractures in a murine model of neonatal brachial plexus injury (NBPI). Four weeks after NBPI, biceps and brachialis fibrosis were assessed histologically and compared with the timing of contracture development and the relative contribution of each muscle to contractures. Modulus of elasticity and hydroxyproline (collagen) content were measured and correlated with contracture severity. The effect of halofuginone antifibrotic therapy on fibrosis and contractures was investigated. Elbow contractures preceded muscle fibrosis development. The brachialis was less fibrotic than the biceps, yet contributed more to contractures. Modulus and hydroxyproline content increased in both elbow flexors, but neither correlated with contracture severity. Halofuginone reduced biceps fibrosis but did not reduce contracture severity. Contractures after NBPI cannot be explained solely by muscle fibrosis, arguing for investigation of alternate pathophysiologic targets for contracture prevention and treatment. Copyright © 2013 Wiley Periodicals, Inc.

  9. 生后6小时床旁视频脑电图诊断围产期缺氧缺血性脑病及其与近期神经行为发育相关性的研究%Bedside video electroencephalogram within 6 hours after birth in diagnosis of perinatal hypoxic-ischemic encephalopathy and prognosis of short-term neural and behavioral development

    Institute of Scientific and Technical Information of China (English)

    邱甜; 邱鹏玲; 陈天兰; 孙道开; 陈超; 王艺

    2010-01-01

    目的 探讨新生儿生后6 h床旁视频脑电图(video electroencephalogram,VEEG)对缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)的诊断价值以及与早期神经行为发育结局的相关性.方法 采用前瞻性研究方法,连续纳入2009年3月至9月间我院收治的重度窒息新生儿,记录生后6 h床旁VEEG并分度;以HIE标准诊断方案作为临床诊断HIE和分度的金标准.分析生后6 h不同程度VEEG预测相应程度HIE的敏感性和特异性;在观察者盲法的基础上,比较生后6 h、3和7 d异常VEEG预测HIE的敏感性和特异性.生后7~14 d行新生儿行为神经评分(neonatal behavior neurological assessment,NBNA),出院后3月龄门诊随访行脑电图(electroencephalogram,EEG)、全身运动(general movements,GMs)质量评估和0~6岁发育筛查测验(developmental screening test for child under six,DST)评估;6月龄行EEG、贝利婴幼儿发展量表(Bayley scales of infant development,BSID)评估,分析6 h VEEG与近期神经发育结局的相关性.结果 重度窒息新生儿48例纳入分析.诊断为单纯重度窒息12例;HIE 36例,其中轻、中和重度分别为14、12和10例.生后6 h VEEG正常9例;异常39例(81.3%),其中轻、中、重和极重度异常分别为16、11、5和7例.36例HIE新生儿生后6 h VEEG异常32例.异常率88.9%.生后6 h VEEG异常程度与脑损伤程度的等级相关系数为0.849,P85分,3例DST 70~84分且伴有EEG异常,其中1例GMs质量评估示不安运动缺乏,提示脑性瘫痪可能性大.6月龄时14例患儿来院随访,7例EEG异常,4例BSID异常且均伴有EEG异常.结论 生后6 h VEEG预测HIE及其严重程度的敏感性和特异性较高,与早期神经发育结局有较好的相关性.%Objective To evaluate the diagnostic value of bedside video electroencephalogram (VEEG) in neonatal within 6 h after birth in diagnosing hypoxic-ischemic encephalopathy ( HIE) and the correlation of bedside VEEG results and early neural and

  10. Complement Component C1q Mediates Mitochondria-Driven Oxidative Stress in Neonatal Hypoxic–Ischemic Brain Injury

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    Ten, Vadim S.; Yao, Jun; Ratner, Veniamin; Sosunov, Sergey; Fraser, Deborah A.; Botto, Marina; Baalasubramanian, Sivasankar; Morgan, B. Paul; Silverstein, Samuel; Stark, Raymond; Polin, Richard; Vannucci, Susan J.; Pinsky, David; Starkov, Anatoly A.

    2010-01-01

    Hypoxic–ischemic (HI) brain injury in infants is a leading cause of lifelong disability. We report a novel pathway mediating oxidative brain injury after hypoxia–ischemia in which C1q plays a central role. Neonatal mice incapable of classical or terminal complement activation because of C1q or C6 deficiency or pharmacologically inhibited assembly of membrane attack complex were subjected to hypoxia–ischemia. Only C1q−/− mice exhibited neuroprotection coupled with attenuated oxidative brain injury. This was associated with reduced production of reactive oxygen species (ROS) in C1q−/− brain mitochondria and preserved activity of the respiratory chain. Compared with C1q+/+ neurons, cortical C1q−/− neurons exhibited resistance to oxygen– glucose deprivation. However, postischemic exposure to exogenous C1q increased both mitochondrial ROS production and mortality of C1q−/− neurons. This C1q toxicity was abolished by coexposure to antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). Thus, the C1q component of complement, accelerating mitochondrial ROS emission, exacerbates oxidative injury in the developing HI brain. The terminal complement complex is activated in the HI neonatal brain but appeared to be nonpathogenic. These findings have important implications for design of the proper therapeutic interventions against HI neonatal brain injury by highlighting a pathogenic priority of C1q-mediated mitochondrial oxidative stress over the C1q deposition-triggered terminal complement activation. PMID:20147536

  11. Upregulation of Shh and Ptc1 in hyperoxia‑induced acute lung injury in neonatal rats.

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    Dang, Hongxing; Wang, Shaohua; Yang, Lin; Fang, Fang; Xu, Feng

    2012-08-01

    The aim of the present study was to observe the expression of sonic hedgehog (Shh) and Ptc signaling molecules in the lungs of newborn rats exposed to prolonged hyperoxia, and to explore the role of the SHH signaling pathway in hyperoxia‑induced lung injury. Newborn Sprague-Dawley rat pups were placed in chambers containing room air or oxygen above 95% for 14 days following birth. The rats were sacrificed after 3, 7 or 14 days and their lungs were removed. Sections were fixed and subjected to hematoxylin and eosin (H&E) staining. Shh and Ptc1 were quantitated by immunohistochemistry. The total RNA and protein were also extracted from lung tissue; real-time PCR (RT-PCR) and western blot analysis were utilized to assess the mRNA and protein expression of Shh and Ptc1. H&E staining demonstrated significant histomorphological changes in the hyperoxia‑exposed lungs at 3, 7 and 14 days of age. The results of the immunohistochemistry, RT-PCR and western blot analysis demonstrated that the expression of Shh was significantly higher in the hyperoxia-exposed lungs at 3, 7 and 14 days, while Ptc1 was significantly elevated at 7 and 14 days. Exposure of the neonatal rat lung to prolonged hyperoxia resulted in acute lung injury and histomorphological changes. Shh and Ptc1 were upregulated in a time-dependent manner in the course of hyperoxia-induced lung injury. The SHH signal pathway may be involved in the pathogenesis of hyperoxia-induced lung injury. This is the first evidence that in vivo hyperoxia induces activation of the SHH signal transduction pathway in newborn lung.

  12. Synergistic protection of combined probiotic conditioned media against neonatal necrotizing enterocolitis-like intestinal injury.

    Directory of Open Access Journals (Sweden)

    Sheng-Ru Shiou

    Full Text Available Balance among the complex interactions of the gut microbial community is important for intestinal health. Probiotic bacteria can improve bacterial balance and have been used to treat gastrointestinal diseases. Neonatal necrotizing enterocolitis (NEC is a life-threatening inflammatory bowel disorder primarily affecting premature infants. NEC is associated with extensive inflammatory NF-κB signaling activation as well as intestinal barrier disruption. Clinical studies have shown that probiotic administration may protect against NEC, however there are safety concerns associated with the ingestion of large bacterial loads in preterm infants. Bacteria-free conditioned media (CM from certain probiotic organisms have been shown to retain bioactivity including anti-inflammatory and cytoprotective properties without the risks of live organisms. We hypothesized that the CM from Lactobacillus acidophilus (La, Bifidobacterium infantis (Bi, and Lactobacillus plantarum (Lp, used separately or together would protect against NEC. A rodent model with intestinal injury similar to NEC was used to study the effect of CM from Lp, La/Bi, and La/Bi/Lp on the pathophysiology of NEC. All the CM suppressed NF-κB activation via preserved IκBα expression and this protected IκBα was associated with decreased liver activity of the proteasome, which is the degrading machinery for IκBα. These CM effects also caused decreases in intestinal production of the pro-inflammatory cytokine TNF-α, a downstream target of the NF-κB pathway. Combined La/Bi and La/Bi/Lp CM in addition protected intestinal barrier function by maintaining tight junction protein ZO-1 levels and localization at the tight junction. Double combined La/Bi CM significantly reduced intestinal injury incidence from 43% to 28% and triple combined La/Bi/Lp CM further reduced intestinal injury incidence to 20%. Thus, this study demonstrates different protective mechanisms and synergistic bioactivity of the CM

  13. Visualization of neonatal lung injury associated with mechanical ventilation using x-ray dark-field radiography

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    Yaroshenko, Andre; Pritzke, Tina; Koschlig, Markus; Kamgari, Nona; Willer, Konstantin; Gromann, Lukas; Auweter, Sigrid; Hellbach, Katharina; Reiser, Maximilian; Eickelberg, Oliver; Pfeiffer, Franz; Hilgendorff, Anne

    2016-04-01

    Mechanical ventilation (MV) and supplementation of oxygen-enriched gas, often needed in postnatal resuscitation procedures, are known to be main risk factors for impaired pulmonary development in the preterm and term neonates. Unfortunately, current imaging modalities lack in sensitivity for the detection of early stage lung injury. The present study reports a new imaging approach for diagnosis and staging of early lung injury induced by MV and hyperoxia in neonatal mice. The imaging method is based on the Talbot-Lau x-ray grating interferometry that makes it possible to quantify the x-ray small-angle scattering on the air-tissue interfaces. This so-called dark-field signal revealed increasing loss of x-ray small-angle scattering when comparing images of neonatal mice undergoing hyperoxia and MV-O2 with animals kept at room air. The changes in the dark field correlated well with histologic findings and provided superior differentiation than conventional x-ray imaging and lung function testing. The results suggest that x-ray dark-field radiography is a sensitive tool for assessing structural changes in the developing lung. In the future, with further technical developments x-ray dark-field imaging could be an important tool for earlier diagnosis and sensitive monitoring of lung injury in neonates requiring postnatal oxygen or ventilator therapy.

  14. Neonatal encephalopathic cerebral injury in South India assessed by perinatal magnetic resonance biomarkers and early childhood neurodevelopmental outcome.

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    Peter J Lally

    Full Text Available Although brain injury after neonatal encephalopathy has been characterised well in high-income countries, little is known about such injury in low- and middle-income countries. Such injury accounts for an estimated 1 million neonatal deaths per year. We used magnetic resonance (MR biomarkers to characterise perinatal brain injury, and examined early childhood outcomes in South India.We recruited consecutive term or near term infants with evidence of perinatal asphyxia and a Thompson encephalopathy score ≥6 within 6 h of birth, over 6 months. We performed conventional MR imaging, diffusion tensor MR imaging and thalamic proton MR spectroscopy within 3 weeks of birth. We computed group-wise differences in white matter fractional anisotropy (FA using tract based spatial statistics. We allocated Sarnat encephalopathy stage aged 3 days, and evaluated neurodevelopmental outcomes aged 3½ years using Bayley III.Of the 54 neonates recruited, Sarnat staging was mild in 30 (56%; moderate in 15 (28% and severe in 6 (11%, with no encephalopathy in 3 (6%. Six infants died. Of the 48 survivors, 44 had images available for analysis. In these infants, imaging indicated perinatal rather than established antenatal origins to injury. Abnormalities were frequently observed in white matter (n = 40, 91% and cortex (n = 31, 70% while only 12 (27% had abnormal basal ganglia/thalami. Reduced white matter FA was associated with Sarnat stage, deep grey nuclear injury, and MR spectroscopy N-acetylaspartate/choline, but not early Thompson scores. Outcome data were obtained in 44 infants (81% with 38 (79% survivors examined aged 3½ years; of these, 16 (42% had adverse neurodevelopmental outcomes.No infants had evidence for established brain lesions, suggesting potentially treatable perinatal origins. White matter injury was more common than deep brain nuclei injury. Our results support the need for rigorous evaluation of the efficacy of rescue hypothermic

  15. Foxg1 mRNA overexpression in neonatal rats following hypoxic brain injury

    Institute of Scientific and Technical Information of China (English)

    Luquan Li; Yi Zheng; Guoliang Mo; Fang Li; Jialin Yu

    2011-01-01

    Forkhead box G1 (Foxg1) is expressed during the embryonic stage and in postnatal brain regions sensitive to hypoxia/ischemia injury,such as the hippocampus and cerebral cortex.To date,very little is known about Foxg 1 expression changes in the brain following hypoxia injury (HI).The present study measured Foxg 1 mRNA expression using reverse-transcription polymerase chain reaction on days 3,7,14,28,and 56 following HI to determine self-restorative features in the injured brain.In addition,mRNA expression of other related layer markers,such as Reelin,RORB,Foxp1,Foxp2,ER81,and Otx-1,was detected following HI.Results revealed significantly decreased Foxg1 mRNA expression at 3 days after HI,which significantly increa