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Sample records for asphyxia induced brain

  1. Could Perinatal Asphyxia Induce a Synaptopathy? New Highlights from an Experimental Model

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    María Inés Herrera

    2017-01-01

    Full Text Available Birth asphyxia also termed perinatal asphyxia is an obstetric complication that strongly affects brain structure and function. Central nervous system is highly susceptible to oxidative damage caused by perinatal asphyxia while activation and maturity of the proper pathways are relevant to avoiding abnormal neural development. Perinatal asphyxia is associated with high morbimortality in term and preterm neonates. Although several studies have demonstrated a variety of biochemical and molecular pathways involved in perinatal asphyxia physiopathology, little is known about the synaptic alterations induced by perinatal asphyxia. Nearly 25% of the newborns who survive perinatal asphyxia develop neurological disorders such as cerebral palsy and certain neurodevelopmental and learning disabilities where synaptic connectivity disturbances may be involved. Accordingly, here we review and discuss the association of possible synaptic dysfunction with perinatal asphyxia on the basis of updated evidence from an experimental model.

  2. Brain pertechnetate SPECT in perinatal asphyxia

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    Sfakianakis, G.; Curless, R.; Goldberg, R.; Clarke, L.; Saw, C.; Sfakianakis, E.; Bloom, F.; Bauer, C.; Serafini, A.

    1984-01-01

    Single photon emission computed tomography of the brain was performed in 6 patients with perinatal asphyxis aged 8-26 days. A single-head (LFOV) commercial SPECT system (Picker) was used and data were acquired 2-3 hr after an IV injection of 1-2 mCi Tc-99m-pertechnetate (360/sup 0/ rotation, 60 views, 64 x 64 matrix, 50K cts/view). Reconstruction in three planes was performed using MDS software (Hanning medium resolution filter, with or without attenuation correction using Sorenson's technique). For each clinical study, a ring type phantom source was used to identify the level of reconstruction noise in the tomographic planes. Abnormalities were found in all patients studied, 3 central (moderate intensity), 2 peripheral (1 severe, 1 moderate) and 1 diffuse (mild intensity). Despite use of oral perchlorate (50 mg) in one patient the choroid plexus was visible. Since attenuation correction tended to amplify noise, the clinical studies were interpreted both with and without this correction. All 3 patients with central lesions were found abnormal on early (1-4 mo) neurologic follow-up examination, whereas the others were normal. No correlation was found between SPECT and 24 hr blood levels of CPK, ammonia, base excess, or the Apgar scores. Ct scans were reported abnormal (3 diffuse, 1 peripheral, 1 central and 1 questionable). Planar scintigrams obtained immediately after SPECT were normal (2), questionable (2) and abnormal (2). Follow-up SPECT brain scintigrams in two of the patients showed partial resolution. SPECT of the brain appears promising in perinatal asphyxia but long-term correlation with patient development is necessary.

  3. [Recurrence plot analysis of HRV for brain ischemia and asphyxia].

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    Chen, Xiaoming; Qiu, Yihong; Zhu, Yisheng

    2008-02-01

    Heart rate variability (HRV) is the tiny variability existing in the cycles of the heart beats, which reflects the corresponding balance between sympathetic and vagus nerves. Since the nonlinear characteristic of HRV is confirmed, the Recurrence Plot method, a nonlinear dynamic analysis method based on the complexity, could be used to analyze HRV. The results showed the recurrence plot structures and some quantitative indices (L-Mean, L-Entr) during asphyxia insult vary significantly as compared to those in normal conditions, which offer a new method to monitor brain asphyxia injury.

  4. Influences on the activities of tissue- type plasminogen activator of mouse brain in asphyxia%窒息对鼠脑分泌组织型纤溶酶原激活物的影响

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    徐剑文; 王玮; 康仲涵; 赵小贞; 张更

    2001-01-01

    Objective To observe the changes of the activity of tissue-type plasminogen activator(TPA) after asphyxia. Methods Asphyxia was induced in mouse pups by performing a‘ delayed cesarean section' . The experiment was designed for a control group and 4 asphyctic groups to detect the activity of TPA. Results TPA activity of brain increased after asphyxia (P<0.01). Conclusion TPA increased after asphyxia might be able to attack the basement membrane of microvessels, then opened the blood-brain barrier and induced neuronal damage.

  5. TIME COURSE MODIFICATIONS INDUCED BY PERINATAL ASPHYXIA IN RAT CNS

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    Francisco Capani

    2015-04-01

    Full Text Available Perinatal asphyxia (PA induced short and long term biochemical, synaptic, cytoskeletal and astrocytes alterations that has been associated with neuronal cell death following hypoxia . The lack of knowledge about the mechanisms underlying this dysfunction prompted us to investigate the changes in the synapse and neuronal cytoskeleton and related structures. For this study we used a well established murine model of PA. Full-term pregnant rats were rapidly decapitated and the uterus horns were placed in a water bath at 37 °C for different time of asphyxia. When their physiological conditions improved, they were given to surrogate mothers. One month, four month, 6 month and 18 month after PA rats were included in this study. Modifications were analyzed using photooxidation with phalloidin-eosin, conventional electron microscopy (EM, inmunocytochemistry and ethanolic phosphotungstic acid (E-PTA staining combining with electron tomography and 3-D reconstruction techniques and molecular biology studies. After one month of the PA insult, an increase in the F-actin staining in neostriatum and hippocampus synapses was observed using correlative fluorescent electron microscopy for phalloidin-eosin. Mushroom-shaped spines showed the most consistent staining. Strong alterations in the dendrite and astroglial cytoskeleton were found at four months of PA (1. After six months of PA, postsynaptic densities (PSDs of the rat neostriatum are highly modified . We observed an increment of PSDs thickness related with the duration and severity of the hypoxic insult. In addition, PSDs showed and increase in the ubiquitination level. Using 3-d reconstruction and electron tomography we observed showed clear signs of damage in the asphyctic PSDs. These changes are correlated with intense staining for ubiquitin (2. Finally, in 18 months old rat was observed a reduction in the number of synapses in the PA animals related with a decrease in BDNF staining.(3 Using protocols

  6. Experimental modelling of the consequences of brief late gestation asphyxia on newborn lamb behaviour and brain structure.

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    Margie Castillo-Melendez

    Full Text Available Brief but severe asphyxia in late gestation or at the time of birth may lead to neonatal hypoxic ischemic encephalopathy and is associated with long-term neurodevelopmental impairment. We undertook this study to examine the consequences of transient in utero asphyxia in late gestation fetal sheep, on the newborn lamb after birth. Surgery was undertaken at 125 days gestation for implantation of fetal catheters and placement of a silastic cuff around the umbilical cord. At 132 days gestation (0.89 term, the cuff was inflated to induce umbilical cord occlusion (UCO, or sham (control. Fetal arterial blood samples were collected for assessment of fetal wellbeing and the pregnancy continued until birth. At birth, behavioral milestones for newborn lambs were recorded over 24 h, after which the lambs were euthanased for brain collection and histopathology assessments. After birth, UCO lambs displayed significant latencies to (i use all four legs, (ii attain a standing position, (iii find the udder, and (iv successfully suckle--compared to control lambs. Brains of UCO lambs showed widespread pathologies including cell death, white matter disruption, intra-parenchymal hemorrhage and inflammation, which were not observed in full term control brains. UCO resulted in some preterm births, but comparison with age-matched preterm non-UCO control lambs showed that prematurity per se was not responsible for the behavioral delays and brain structural abnormalities resulting from the in utero asphyxia. These results demonstrate that a single, brief fetal asphyxic episode in late gestation results in significant grey and white matter disruption in the developing brain, and causes significant behavioral delay in newborn lambs. These data are consistent with clinical observations that antenatal asphyxia is causal in the development of neonatal encephalopathy and provide an experimental model to advance our understanding of neuroprotective therapies.

  7. 25 years of research on global asphyxia in the immature rat brain.

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    Barkhuizen, M; van den Hove, D L A; Vles, J S H; Steinbusch, H W M; Kramer, B W; Gavilanes, A W D

    2017-02-01

    Hypoxic-ischemic encephalopathy remains a common cause of brain damage in neonates. Preterm infants have additional complications, as prematurity by itself increases the risk of encephalopathy. Currently, therapy for this subset of asphyxiated infants is limited to supportive care. There is an urgent need for therapies in preterm infants - and for representative animal models for preclinical drug development. In 1991, a novel rodent model of global asphyxia in the preterm infant was developed in Sweden. This method was based on the induction of asphyxia during the birth processes itself by submerging pups, still in the uterine horns, in a water bath followed by C-section. This insult occurs at a time-point when the rodent brain maturity resembles the brain of a 22-32 week old human fetus. This model has developed over the past 25 years as an established model of perinatal global asphyxia in the early preterm brain. Here we summarize the knowledge gained on the short- and long-term neuropathological and behavioral effects of asphyxia on the immature central nervous system.

  8. Environmental Enrichment Decreases Asphyxia-Induced Neurobehavioral Developmental Delay in Neonatal Rats

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    Kiss, Peter; Vadasz, Gyongyver; Kiss-Illes, Blanka; Horvath, Gabor; Tamas, Andrea; Reglodi, Dora; Koppan, Miklos

    2013-01-01

    Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia. PMID:24232451

  9. Environmental Enrichment Decreases Asphyxia-Induced Neurobehavioral Developmental Delay in Neonatal Rats

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    Peter Kiss

    2013-11-01

    Full Text Available Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia.

  10. Immediate Remote Ischemic Postconditioning Reduces Brain Nitrotyrosine Formation in a Piglet Asphyxia Model.

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    Rocha-Ferreira, Eridan; Rudge, Brogan; Hughes, Michael P; Rahim, Ahad A; Hristova, Mariya; Robertson, Nicola J

    2016-01-01

    Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention that could be administered as an alternative to cooling in cases of perinatal hypoxia-ischemia (HI). In the current study we hypothesized that RIPostC in the piglet model of birth asphyxia confers protection by reducing nitrosative stress and subsequent nitrotyrosine formation, as well as having an effect on glial immunoreactivity. Postnatal day 1 (P1) piglets underwent HI brain injury and were randomised to HI (control) or HI + RIPostC. Immunohistochemistry assessment 48 hours after HI revealed a significant decrease in brain nitrotyrosine deposits in the RIPostC-treated group (p = 0.02). This was accompanied by a significant increase in eNOS expression (p piglet model of neonatal asphyxia, which appears to be mediated by modulation of nitrosative stress, despite glial activation.

  11. Predictive value of brain-specific proteins in serum for neurodevelopmental outcome after birth asphyxia.

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    Nagdyman, Nicole; Grimmer, Ingrid; Scholz, Tristess; Muller, Christian; Obladen, Michael

    2003-08-01

    Brain-specific proteins have been used to detect cerebral injury after birth asphyxia. Previous investigations suggest that serum protein S-100beta, brain-specific creatine kinase (CK-BB), and neuron-specific enolase (NSE) are capable of identifying patients with a risk of developing hypoxic-ischemic encephalopathy. Whether detection of elevated serum concentrations of these proteins reflects long-term neurodevelopmental impairment remains to be investigated. We examined serum protein S-100beta, NSE, and CK-BB at 2, 6, 12, and 24 h after birth in 29 asphyxiated infants and 20 control infants. Neurodevelopmental follow-up examinations were performed at 20 mo of age using the German revision of the Griffiths scales for developmental assessment. Elevated concentrations of serum protein S-100beta, NSE, and CK-BB within 24 h after asphyxia did not correlate with long-term neurodevelopmental delay. We conclude that serum protein S-100beta, NSE, and CK-BB, sampled on the first day of life, is of limited value in predicting severe brain damage after birth asphyxia.

  12. CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia.

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    Fiedorowicz, Michał; Makarewicz, Dorota; Stańczak-Mrozek, Kinga I; Grieb, Paweł

    2008-01-01

    To estimate protective potential of citicoline in a model of birth asphyxia, the drug was given to 7-day old rats subjected to permanent unilateral carotid artery occlusion and exposed for 65 min to a hypoxic gas mixture. Daily citicoline doses of 100 or 300 m/kg, or vehicle, were injected intraperitoneally for 7 consecutive days beginning immediately after the end of the ischemic-hypoxic insult, and brain damage was assessed by gross zorphology score and weight deficit two weeks after the insult. Caspase-3, alpha-fodrin, Bcl-2, and Hsp70 levels were assessed at 0, 1, and 24 h after the end of the hypoxic insult in another group of rat pups subjected to the same insult and given a single dose of 300 m/kg of citicoline or the vehicle. Citicoline markedly reduced caspase-3 activation and Hsp70 expression 24 h after the insult, and dose-dependently attenuated brain damage. In the context of the well-known excellent safety profile of citicoline, these data suggest that clinical evaluation of the efficacy of the drug in human birth asphyxia may be warranted.

  13. Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

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    R.L. Figueira

    2016-01-01

    Full Text Available Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC. This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group: 1 preterm control (PTC, 2 preterm ventilated (PTV, 3 preterm asphyxiated (PTA, 4 preterm asphyxiated and ventilated (PTAV, 5 term control (TC, 6 term ventilated (TV, 7 term asphyxiated (TA, and 8 term asphyxiated and ventilated (TAV. We measured body, brain, and intestine weights and respective ratios [(BW, (BrW, (IW, (BrW/BW and (IW/BW]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus and intestine (jejunum/ileum tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP. IW was lower in the TA than in the other terms (P<0.05, and the IW/BW ratio was lower in the TA than in the TAV (P<0.005. PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex and TA (cortex/hippocampus (P<0.005. I-FABP was higher in PTAV (P<0.005 and TA (ileum (P<0.05. I-FABP expression was increased in PTAV subgroup (P<0.0001. Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

  14. ASPHYXIA, INTRACRANIAL HEMORRHAGES AND BRAIN EDEMA OF RISK CHILDREN IN THE ADVISORY INSTITUTE IN BITOLA FROM 1989-1994

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    M. ILIEVSKA,

    1997-09-01

    Full Text Available 3986 files have been examined in the Advisory Institute for a five year period in relation to the present risk factors in the pre, peri and postnatal period, the occurrence of asphyxia, I.H. (intracranial hemorrhages and brain edema and their outcome for the children. There were 958 or 32% risk children, out of them 206 or 22% were with asphyxia, 25 or 3% were with brain edema and 14 or 1,5% were with intracranial hemorrhages.The analysis for the risk factors shows that 119 of them were abortive , and from them 15% were born with asphyxia; 124 were SFD and 21% of them with asphyxia; 272 children weighed over 4500 gr., 7% of them with asphyxia and 0.4% with I.H., there were 68 twins, 12% of them with asphyxia. Out of the children with no risk registered, 6 were born with I.H., or 0,2%.Mothers under the age of 18 gave birth to 13% children with asphyxia; treated for sterility and anemia during pregnancy 15%; with increased blood pressure 14%; and 5% with maintained pregnancy.The highest delivery risk is present with children born with vacuum extraction (30% or every third child is with asphyxia and 3% with I.H. and with children delivered by caesarean section (14% with asphyxia.As for the position of the fetus-Citus pedalicus gave 55% children with asphyxia, and Situs pelvicus 12%.The worst damage is suffered by infants with premature amnion disruption (62% are with asphyxia; with the umbilical cord round the neck-56% with asphyxia and 6% with I.H.; and with muddled amniotic fluid and placenta pelvia-50%.The order of risk factors related to asphyxia, I.H. and brain edema is as follows: the first is premature amnion disruption, then follows the umbilical cord round the neck, the muddled amniotic fluid, and placenta previa and Citus pedalicus-which are obstetric problems. The next are the vacuum extraction and S.C. As for the gestatory period the order is as follows: first the abortive, then the twins and hypertrofic infants. The outcome of the

  15. The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia

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    van Doormaal, Pieter Jan; Meiners, Linda C.; ter Horst, Hendrik J.; van der Veere, Christa N.; Sijens, Paul E.

    2012-01-01

    Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and

  16. Atrial fibrillation in rats induced by rapid transesophageal atrial pacing during brief episodes of asphyxia: A new in vivo model

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    Haugan, K.; Lam, Henrik Rye; Knudsen, C. B.;

    2004-01-01

    Non-pharmacological in vivo models of atrial fibrillation (AF) have been developed in large animals only. We aimed to develop and characterize a new small animal non-pharmacological in vivo model of AF. AF was induced by transesophageal atrial burst pacing during 35 seconds periods of asphyxia...... was associated with a marked profibrillatory effect. Increasing gap junction intracellular communication using the antiarrhythmic peptide analogue AAP 10 did not affect AF duration. Basal plasma level of epinephrine and norepinephrine were increased 5- to 20-fold relative to values reported by others......, but unchanged following 35 seconds of asphyxia. The results from our study demonstrate that the rat model shares several clinical key characteristics with human AF: (1) hemodynamic response to AF; (2) increased autonomic tone; (3) antiarrhythmic effects of clinically used drugs; (4) profibrillatory effect...

  17. Atrial fibrillation in rats induced by rapid transesophageal atrial pacing during brief episodes of asphyxia: a new in vivo model.

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    Haugan, Ketil; Lam, Henrik Rye; Knudsen, Carsten Boye; Petersen, Jørgen Søberg

    2004-07-01

    Non-pharmacological in vivo models of atrial fibrillation (AF) have been developed in large animals only. We aimed to develop and characterize a new small animal non-pharmacological in vivo model of AF. AF was induced by transesophageal atrial burst pacing during 35 seconds periods of asphyxia in anesthetized male Sprague-Dawley rats. AF was reproducibly induced in 81% of the rats. The presence of AF was associated with an increased heart rate, and a decreased blood pressure. Treatment with amiodarone, D,L-sotalol, flecainide, and propranolol all reduced duration of AF, whereas verapamil treatment was associated with a marked profibrillatory effect. Increasing gap junction intracellular communication using the antiarrhythmic peptide analogue AAP10 did not affect AF duration. Basal plasma level of epinephrine and norepinephrine were increased 5- to 20-fold relative to values reported by others, but unchanged following 35 seconds of asphyxia. The results from our study demonstrate that the rat model shares several clinical key characteristics with human AF: (1) hemodynamic response to AF; (2) increased autonomic tone; (3) antiarrhythmic effects of clinically used drugs; (4) profibrillatory effect of verapamil. Relative to existing models of AF in larger animals, this model offers rapid, predictive, and inexpensive testing of antiarrhythmic/profibrillatory effects of new drugs.

  18. Perinatal asphyxia: CNS development and deficits with delayed onset

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    Mario eHerrera-Marschitz

    2014-03-01

    Full Text Available Perinatal asphyxia constitutes a prototype of obstetric complications occurring when pulmonary oxygenation is delayed or interrupted. The primary insult relates to the duration of the period lacking oxygenation, leading to death if not re-established. Re-oxygenation leads to a secondary insult, related to a cascade of biochemical events required for restoring proper function. Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated to mental and neurological diseases with delayed clinical onset, by mechanisms not yet clarified.In the experimental scenario, the effects observed long after perinatal asphyxia have been explained by over expression of sentinel proteins, such as poly(ADP-ribose polymerase-1 (PARP-1, competing for NAD+ during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a suitable therapeutic strategy. Asphyxia induces transcriptional activation of pro-inflammatory factors, in tandem with PARP-1 overactivation, and pharmacologically induced PARP-1 inhibition also down-regulates the expression of proinflammatory cytokines. Nicotinamide has been proposed as a suitable PARP-1 inhibitor. Its effect has been studied in an experimental model of global hypoxia in rats. In that model, the insult is induced by immersing rat foetuses into a water bath for various periods of time. Following asphyxia, the pups are delivered, treated, and nursed by surrogate dams, pending further experiments. Nicotinamide rapidly distributes into the brain following systemic administration, reaching steady state concentrations sufficient to inhibit PARP-1 activity for several hours, preventing several of the long-term consequences of perinatal asphyxia, supporting the idea that it constitutes a lead for exploring compounds with similar or better pharmacological profiles.

  19. The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia

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    Doormaal, Pieter Jan van [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands); Meander Medical Center Amersfoort, Department of Radiology, PO Box 1502, Amersfoort (Netherlands); Meiners, Linda C.; Sijens, Paul E. [University Medical Center Groningen and University of Groningen, Department of Radiology, Groningen (Netherlands); Horst, Hendrik J. ter; Veere, Christa N. van der [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands)

    2012-04-15

    Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and grey matter metabolites in a slab cranial to the ventricles and relate these to the outcome. A standard 2D-chemical shift imaging protocol was used for measuring a transverse volume of interest located cranial to the ventricles allowing for direct comparison of the metabolites in white and grey matter brain tissue in 24 term asphyxiated newborns aged 3 to 16 days. Cho, NAA and Lact showed significant differences between four subgroups of asphyxiated infants with more and less favourable outcomes. High levels of Cho and Lact in the grey matter differentiated non-survivors from survivors (P = 0.003 and P = 0.017, respectively). In perinatal asphyxia the levels of Cho, NAA and Lact in both white and grey matter brain tissue are affected. The levels of Cho and Lact measured in the grey matter are the most indicative of survival. It is therefore advised to include grey matter brain tissue in the region of interest examined by multivoxel MR spectroscopy. (orig.)

  20. Pressure passive cerebral blood flow and breakdown of the blood-brain barrier in experimental fetal asphyxia

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    Lou, H C; Lassen, N A; Tweed, W A

    1979-01-01

    Cerebral blood flow (CBF) was studied in non-exteriorized near-term sheep fetuses using the radioactive microsphere technique. By partially occluding the umbilical vessels for a period of 1--1 1/2 hours a progressive and severe asphyxia with a final arterial pH of 6.90 was achieved. Varying...

  1. Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.

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    Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín, Luis Javier; De Fonseca, Fernando Rodríguez; Capani, Francisco; Blanco, Eduardo

    2013-09-01

    Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction.

  2. Connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal sheep.

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    Joanne O Davidson

    Full Text Available Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete umbilical cord occlusion in preterm fetal sheep (103-104 d gestational age. Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic peptide starting 90 min after asphyxia at a concentration of 50 µM/h for one hour followed by 50 µM/24 hour for 24 hours (occlusion-peptide group, n = 6 or vehicle infusion for controls (occlusion-vehicle group, n = 7. Peptide infusion was associated with earlier recovery of electroencephalographic power after asphyxia compared to occlusion-vehicle (p<0.05, with reduced neuronal loss in the caudate and putamen (p<0.05, but not in the hippocampus. In the intragyral and periventricular white matter, peptide administration was associated with an increase in total oligodendrocyte numbers (p<0.05 and immature/mature oligodendrocytes compared to occlusion-vehicle (p<0.05, with a significant increase in proliferation (p<0.05. Connexin hemichannel blockade was neuroprotective and reduced oligodendrocyte death and improved recovery of oligodendrocyte maturation in preterm fetuses after asphyxia.

  3. Serum cortisol concentrations during induced hypothermia for perinatal asphyxia are associated with neurological outcome in human infants.

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    Scaramuzzo, Rosa T; Giampietri, Matteo; Fiorentini, Erika; Bartalena, Laura; Fiori, Simona; Guzzetta, Andrea; Ciampi, Mariella; Boldrini, Antonio; Ghirri, Paolo

    2015-01-01

    Birth asphyxia is a cause of neonatal death or adverse neurological sequelae. Biomarkers can be useful to clinicians in order to optimize intensive care management and communication of prognosis to parents. During perinatal adverse events, increased cortisol secretion is due to hypothalamo-pituitary-adrenal axis activation. We aimed to investigate if cortisol variations during therapeutic hypothermia are associated with neurodevelopmental outcome. We compared 18 cases (neonates with birth asphyxia) with 18 controls (healthy term newborns) and confirmed increased serum cortisol concentrations following the peri-partum adverse event. Among cases, we stratified patients according to neurological outcome at 18 months (group A - good; group B - adverse) and found that after 24 h of therapeutic hypothermia serum cortisol concentration was significantly lower in group A vs group B (28.7 ng/mL vs 344 ng/mL, *p = 0.01). In group B serum, cortisol concentration decreased more gradually during therapeutic hypothermia. We conclude that monitoring serum cortisol concentration during neonatal therapeutic hypothermia can add information to clinical evaluation of neonates with birth asphyxia; cortisol values after the first 24 h of hypothermia can be a biomarker associated with neurodevelopmental outcome at 18 months of age.

  4. ASPHYXIA AND DEVELOPMENTAL OUTCOME IN HIGH RISK INFANTS

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    Valentina DUKOVSKA

    2010-04-01

    Full Text Available Asphyxia is a risk factor that is very often related to neuro-developmental issues in high risk infants and equally affects preterm and term infants, however its outcome on the developed brain differs from the outcome on the preterm brain.In preterm infants, asphyxia usually exerts a hemorrhagic or ischaemic event and periventricular leukomalacia.In term infants, asphyxia leads to cerebral edema and atrophy of the brain, which may later lead to hypoxic ischaemic encephalopathy (HIE.The number of term infants with HIE who have survived is lower than those of preterm infants, while the percentage of term infants with HIE who have neuro-developmental issues is higher. Preemies face more problems in their motor development as a result of the brain damage, while term infants suffer from encephalopathy and their cognitive abilities are more affected.We have conducted a study about the effects that asphyxia has on the developmental outcomes in high risk infants. In our study, we did a longitudinal developmental follow-up of 30 high risk infants and an evaluation of their developmental outcome using the Griffiths Mental Development Scales, from the 4th month of life until the end of the 36th month. First, we found that high risk infants had a much lower developmental outcome than the control group during the trial. Finally, we found that asphyxia makes a difference in the developmental outcome of preterm infants without asphyxia who have a very low birth weight, the preterm infants with asphyxia, and the term infants with HIE-II.

  5. Magnesium for neuroprotection in birth asphyxia

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    Geeta Gathwala

    2010-01-01

    Full Text Available Background : Magnesium ion gates the N-methyl-D-aspartate (NMDA receptor and may protect the brain from NMDA receptor-mediated asphyxial injury. The present study evaluated the neuroprotective role of magnesium in birth asphyxia. Material and Methods : Forty term neonates with severe birth asphyxia were randomized to either the study group or the control group. Neonates in the study group received magnesium sulfate in a dose of 250 mg/kg initially within half an hour of birth followed by 125 mg/kg at 24 and 48 h of birth. Cranial computed tomography (CT scan and electroencephalography (EEG were performed for all the babies. Denver II was used for developmental assessment at the age of 6 months. Results : Two babies in each group died of severe hypoxic ischemic encephalopathy. EEG abnormalities occurred in 43.75% of the cases in the control group compared with 31.25% in the study group. CT scan abnormalities were present in 62.5% of the control group compared with 37.5% of the cases in the study group. The Denver II assessment at 6 months revealed that there were five babies that were either abnormal or suspect in the control group compared with three in the study group. Conclusion : Magnesium is well tolerated and does appear to have beneficial effects in babies with severe asphyxia. More data is however needed and a large multicenter trial should be conducted.

  6. Clinicoradiological correlation in birth asphyxia

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    Basavaraj Patil

    2015-06-01

    Full Text Available Background: Hypoxic Ischemic Encephalopathy (HIE is the most dreaded neurological disease of the new-born. Assessment of severity of HIE would help proper parent counseling and early institution of stimulation therapy for better development of the infant. Methods: This study was conducted between December 2012 and May 2014. 37 term neonates with perinatal asphyxia were the subjects. The cranial ultrasound, EEG and MRI findings of these babies are analysed and correlated with each other and with clinical staging and the neurological condition of the babies at discharge. Results: Among the 37 neonates, 21 were of HIE stage 2 and 16 were of stage 3. Sensitivity of EEG in detecting abnormality in the neurological condition according to our study is 76.9%, specificity 87.5%, positive predictive value 76.9%, negative predictive value 87.5%. Sensitivity of severe pattern of injury in MRI brain in detecting abnormality in neurological condition according to our study is 76.9%, specificity 91.6%, positive predictive value 83.3%, negative predictive value 88%. Involvement of both basal ganglia and cortex in MRI brain had statistically significant correlation with abnormal neurological condition at discharge in our study (P = 0.04. Conclusion: An abnormal EEG and MRI brain in a term new-born with Hypoxic Ischemic Encephalopathy (HIE is associated with poor neurological outcome. Involvement of basal ganglia/thalamus and cortex together in the MRI are predictors of abnormal outcome. [Int J Res Med Sci 2015; 3(3.000: 560-567

  7. Radio-induced brain lesions

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    Gorgan Mircea Radu

    2014-03-01

    Full Text Available Introduction : Radiotherapy, an important tool in multimodal oncologic treatment, can cause radio-induced brain lesion development after a long period of time following irradiation.

  8. Quality of general movements in term infants with asphyxia

    NARCIS (Netherlands)

    van Iersel, Patricia A. M.; Bakker, Saskia C. M.; Jonker, Arnold J. H.; Hadders-Algra, Mijna

    2009-01-01

    Background: Perinatal asphyxia may result in a developmental disorder. A recently developed non-invasive toot to investigate brain function at an early age is the assessment of general movements (GMs). Aim: To evaluate relationships between perinatal risk factors and the quality of GMs in the neonat

  9. Shenfu injection provides protection for perinatal asphyxia in neonates

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    Yu Jiang

    2016-03-01

    Full Text Available This study aimed to investigate the efficacy of shenfu injection for the protection of neonates with asphyxia. Eighty neonates with asphyxia were randomly divided into two groups, treatment group and control group (n=40. Both groups received interventions such as ventilation, oxygen, and circulation support. Treatment group was administrated with shenfu injection additionally. Serum levels of creatine kinase, alanine aminotransferase, aspartate aminotransferase, creatinine, and neuron-specific enolase were significantly lower but the oxygenation index was significantly higher in treatment group on day 7 and day 14. The neurobehavioral score was significantly higher in treatment group than in control group. On the 14th day, the survival rate of treatment group (77.5% was higher than that of control group (55%. Shenfu injection could protect the function of the brain, heart, lung, liver and kidney by attenuating ischemia reperfusion after severe asphyxia resuscitation, improve neurobehavioral ability and increase the survival of neonates.

  10. 围生期窒息新生儿脑损伤早期超声的临床诊断价值%Diagnostic value of cerebral ultrasound in early brain damage of asphyxia children in perinatal period

    Institute of Scientific and Technical Information of China (English)

    李静波; 王建荣; 张海峰

    2015-01-01

    目的:对围生期窒息病史的新生儿,72h内行床旁颅脑超声检查,观察脑组织结构及血流动力学改变,探讨此类患儿早期常见脑损伤类型及超声表现。方法方患儿出生后72h内行首次颅脑超声检查,多普勒技术经颞囟检测大脑前动脉、中动脉血流动力学变化,主要参数:收缩期峰值血流速度(Vs)、舒张末期血流速度(Vd)、阻力指数(RI)。结果生后72h内超声检查,60例患儿中47例表现不同程度的脑损伤,阳性率78.3%。结论围生期窒息患儿易造成缺氧缺血性脑损伤,颅脑超声可早期发现脑组织结构改变及血流动力学变化,72h内检查阳性率高,对NICU中的重症患儿,超声具有床旁检查的优势。%Objective In this work ,the newborn babies with the history of asphyxia in the perinatal period were subjec‐ted to the bedside cerebral ultrasound examination within 72 h .The brain structure and hemodynamic changes were ob‐served so as to early explore the the common type of brain injury and sonographic findings in these children .Methods Children born within 72 h underwent the bedeside cerebral ultrasound examination for the first time .The main parame‐ters ,which reflected the blood flow dynamic changes in anterior cerebral artery and middle cerebral artery ,in terms of the peak systolic blood flow velocity (Vs) ,end‐diastolic velocity (Vd) ,and resistance index (RI) ,were detected with doppler technique via temporal fontanelle .Results By the Ultrasound test within 72 h after birth ,47 out of 60 cases were shown brain injury at different extent .The positive rate was 78 .3% .Conclusion Children with asphyxia in the perinatal period are prone to hypoxic ischemic brain damage .Cerebral ultrasound can early detect the changes of brain tissue structure and hemodynamics .Checking within 72 h ,the positive rate is high .For the severe patients in NICU ,ultrasound has the ad‐vantages for

  11. Neuroprotective properties of melatonin in a model of birth asphyxia in the spiny mouse (Acomys cahirinus).

    Science.gov (United States)

    Hutton, Lisa C; Abbass, Mahila; Dickinson, Hayley; Ireland, Zoe; Walker, David W

    2009-01-01

    Birth asphyxia is associated with disturbed development of the neonatal brain. In this study, we determined if low-dose melatonin (0.1 mg/kg/day), administered to the mother over 7 days at the end of pregnancy, could protect against the effects of birth asphyxia in a precocial species - the spiny mouse (Acomys cahirinus). At 37 days of gestation (term is 38-39 days), pups were subjected to birth asphyxia (7.5 min uterine ischemia) and compared to Cesarean section-delivered controls. At 24 h of age, birth asphyxia had increased markers of CNS inflammation (microglia, macrophage infiltration) and apoptosis (activated caspase-3, fractin) in cortical gray matter, which were reduced to control levels by prior maternal melatonin treatment. Melatonin may be an effective prophylactic agent for use in late pregnancy to protect against hypoxic-ischemic brain injury at birth.

  12. Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn rat model of acute severe asphyxia.

    Science.gov (United States)

    Martínez-Orgado, José; Fernández-Frutos, Beatriz; González, Rita; Romero, Eva; Urigüen, Leire; Romero, Julián; Viveros, M Paz

    2003-06-10

    This study was designed to evaluate the neuroprotective effect of the cannabinoid agonist WIN-55212 after inducing acute severe asphyxia in newborn rats. The left common carotid artery was ligated in anaesthetised 7-day-old Wistar rats, which were then asphyxiated by inhaling 100% nitrogen for 10 min. Pups recovering from asphyxia were s.c. administered vehicle (n=23), WIN-55212 (0.1 mg/kg, n=18), or WIN-55212 plus the CB1 receptor antagonist SR141716 (3 mg/kg, n=10). Pups undergoing a sham operation served as controls (n=12). Coronal sections of the brain were obtained on the 14th day after surgery and observed under light microscope after Nissl or Fluoro-Jade B (FJB) staining, to respectively quantify surviving or degenerating neurones in the CA1 area of the hippocampus and parietal cortex. Acute asphyxia led to early neurone loss amounting to 19% in the hippocampus and 29% in the cortex (both ANOVA P<0.05 vs. control). Delayed neurone loss occurred in the proportions 13% in the hippocampus and 20% in the cortex (both ANOVA P<0.05 vs. control). Neuronal loss was fully prevented by WIN-55212 administration. Co-administration of SR141716 failed to modify the protective effect of WIN-55212 on early neuronal death, but abolished the WIN-55212-induced prevention of delayed neuronal death. We conclude that when administered after acute severe asphyxia in newborn rats, WIN-55212 shows a neuroprotective effect, reducing both early and delayed neurone loss. This effect is achieved through two parallel CB1-dependent and -independent mechanisms.

  13. 血清NSE对晚期早产儿窒息脑损伤早期评价的意义%Significance of serum neuron-specific enolase in the early evaluation of brain damage of late preterm with perinatal asphyxia

    Institute of Scientific and Technical Information of China (English)

    王士杰; 李晓春; 孔少云

    2013-01-01

    Objective To investigate the value of serum neuron-specific enolase ( NSE )levels in the diagnosis of neonatal asphyxia Methods 154 late- preterm neonates were enrolled in the study, including 94 with neonatal asphyxia for experimental group,52 with perinatal asphyxia,42 without brain damage and 60 normal ones for control group. For all the research objects blood samples were obtained for NSE detecting and Apgar scores were evaluated on proper time. MRI was performed 3 ~ 7 days after birth in experimental group. Results The levels of serum NSE in 52 with perinatal asphyxia were significantly higher than those in ones without brain damage and in control group. There were no significant difference between the levels in ones without brain damage and in control group. Conclusion Serum NSE level can be used as the early objective markers for evaluating the prognosis of brain damage due to late preterm perinatal asphyxia.%目的 探讨新生儿窒息后血清神经元特异性烯醇化酶(NSE)水平变化对判断晚期早产儿脑损伤的价值.方法 选取154例晚期早产儿为研究对象,其中出生时有窒息的患儿94例为实验组,于出生后3~7 d行颅脑MRI检查,依据颅脑MRI分为无脑损伤组42例和脑损伤组52例;正常的60例为对照组,所有患儿均在其出生后24 h内检测血清NSE浓度.结果 窒息脑损伤组血清NSE值较窒息无脑损伤组和对照组增高,差异具有统计学意义(P0.05).结论 外周血清NSE值可作为临床早期评价晚期早产儿窒息后脑损伤的参考指标.

  14. Electroencephalogram abnormalities in full term infants with history of severe asphyxia

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    Susanti Halim

    2015-11-01

    Full Text Available Background An electroencephalogram (EEG is an electroimaging tool used to determine developmental and electrical problems in the brain. A history of severe asphyxia is a risk factor for these brain problems in infants. Objective To evaluate the prevalence of abnormal EEGs infull term neonates and to assess for an association with severe asphyxia, hypoxic ischemic encephalopathy (HIE, and spontaneous delivery. Methods This cross-sectional study was conducted at the Pediatric Outpatient Department of Sanglah Hospital, Denpasar, from November 2013 to January 2014. Subjects were fullterm infants aged 1 month who were delivered and/or hospitalized at Sanglah Hospital. All subjects underwent EEG. The EEGs were interpreted by a pediatric neurology consultant, twice, with a week interval between readings. Clinical data were obtained from medical records. Association between abnormal ECG and severe asphyxia were analyzed by Chi-square and multivariable logistic analyses. Results Of 55 subjects, 27 had a history of severe asphyxia and 28 were vigorous babies. Forty percent (22/55 of subjects had abnormal EEG findings, 19/22 of these subjects having history of severe asphyxia, 15/22 had history of hypoxic-ischemic encephalopathy (HIE, and 20/22 were delievered vaginally. There were strong correlations between the prevalence of abnormal EEG and history of severe asphyxia, HIE, and spontaneous delivery. Conclusion Prevalence of abnormal EEG among full-term neonates referred to neurology/growth development clinic is around 40%, with most of them having a history of severe asphyxia. Abnormal EEG is significantly associated to severe asphyxia, HIE, and spontaneous delivery.

  15. Neonatal asphyxia: A study of 210 cases

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    Hülya Üzel

    2012-06-01

    Full Text Available Objectives: Perinatal asphyxia remains an importantcause of neonatal morbidity and mortality. The aim of thisstudy was to investigate antenatal, natal, and postnatalrisk factors of neonatal asphyxia, relationship with knownrisk factors and stage of Sarnat and Sarnat scores, theeffect of risk factors on hospital discharge and survival forneonates with perinatal asphyxia.Materials and methods: In this study, we retrospectivelyanalyzed the hospital records of 210 patients diagnosedas perinatal asphyxia. The patients’ demographic characteristics,antepartum, intrapartum, and postpartum riskfactors and Sarnat and Sarnat clinical staging criteria ofnewborns were analyzed.Results: The risk factors for asphyxia were detectedantepartum period in 67.7% of newborns, intrapartum in91% and potpartum in of 29.5% of neonates. When caseswere examined according to the studied years, perinatalasphyxia ratio was the most frequent in 2007 as 28.1%.With a decline over the years, frequency dropped to %21in 2010. The number of patients with stage 3 and mortalityrate were significantly decreased over the years (p<0.05.Conclusions: Less preventable intrapartum causes ofbirth asphyxia are seen more frequently. Early detectionof risk factors together with appropriate prenatal, nataland postnatal care provision, reduced emergency caesareansections and will decrease considerably decreasefrequency of perinatal asphyxia. We think that followingup neonates who needed intensive care in neonatal unitssufficiently equipped will decrease complications due toasphyxia. J Clin Exp Invest 2012; 3(2: 194-198

  16. Long lasting cerebellar alterations after perinatal asphyxia in rats.

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    Campanille, Verónica; Saraceno, G Ezequiel; Rivière, Stéphanie; Logica, Tamara; Kölliker, Rodolfo; Capani, Francisco; Castilla, Rocío

    2015-07-01

    The developing brain may be particularly vulnerable to injury before, at and after birth. Among possible insults, hypoxia suffered as a consequence of perinatal asphyxia (PA) exhibits the highest incidence levels and the cerebellar circuitry appears to be particularly susceptible, as the cellular makeup and the quantity of inputs change quickly during days and weeks following birth. In this work, we have used a murine model to induce severe global PA in rats at the time of birth. Short-term cerebellar alterations within this PA model have been previously reported but whether such alterations remain in adulthood has not been conclusively determined yet. For this reason, and given the crucial cerebellar role in determining connectivity patterns in the brain, the aim of our work is to unveil long-term cerebellum histomorphology following a PA insult. Morphological and cytological neuronal changes and glial reaction in the cerebellar cortex were analyzed at postnatal 120 (P120) following injury performed at birth. As compared to control, PA animals exhibited: (1) an increase in molecular and granular thickness, both presenting lower cellular density; (2) a disarrayed Purkinje cell layer presenting a higher number of anomalous calbindin-stained cells. (3) focal swelling and marked fragmentation of microtubule-associated protein 2 (MAP-2) in Purkinje cell dendrites and, (4) an increase in glial fibrillary acidic protein (GFAP) expression in Bergmann cells and the granular layer. In conclusion, we demonstrate that PA produces long-term damage in cellular histomorphology in rat cerebellar cortex which could be involved in the pathogenesis of cognitive deficits observed in both animals and humans.

  17. Electroencephalogram abnormalities in full term infants with history of severe asphyxia

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    Susanti Halim

    2016-11-01

    Full Text Available ingtool used to determine developmental and electrical problemsin the brain. A history of severe asphyxia is a risk factor for thesebrain problems in infants.Objective To evaluate the prevalence of abnormal EEGs infull term neonates and to assess for an association with severeasphyxia, hypoxic ischemic encephalopathy (HIE, and spontaneousdelivery.Methods This cross-sectional study was conducted at thePediatric Outpatient Department of Sanglah Hospital, Denpasar,from November 2013 to January 2014. Subjects were fullterminfants aged 1 month who were delivered and/or hospitalized atSanglah Hospital. All subjects underwent EEG. The EEGs wereinterpreted by a pediatric neurology consultant, twice, with aweek interval between readings. Clinical data were obtainedfrom medical records. Association between abnormal ECG andsevere asphyxia were analyzed by Chi-square and multivariablelogistic analyses.Results Of 55 subjects, 27 had a history of severe asphyxia and 28were vigorous babies. Forty percent (22/55 of subjects had abnormalEEG findings, 19/22 of these subjects having history of severeasphyxia, 15/22 had history of hypoxic-ischemic encephalopathy(HIE, and 20/22 were delievered vaginally. There were strongcorrelations between the prevalence of abnormal EEG and historyof severe asphyxia, HIE, and spontaneous delivery.Conclusion Prevalence of abnormal EEG among full-term neonatesreferred to neurology/growth development clinic is around40%, with most of them having a history of severe asphyxia. AbnormalEEG is significantly associated to severe asphyxia, HIE, andspontaneous delivery.

  18. Polyuria and impaired renal blood flow after asphyxia in preterm fetal sheep.

    Science.gov (United States)

    Quaedackers, J S; Roelfsema, V; Hunter, C J; Heineman, E; Gunn, A J; Bennet, L

    2004-03-01

    Renal impairment is common in preterm infants, often after exposure to hypoxia/asphyxia or other circulatory disturbances. We examined the hypothesis that this association is mediated by reduced renal blood flow (RBF), using a model of asphyxia induced by complete umbilical cord occlusion for 25 min (n = 13) or sham occlusion (n = 6) in chronically instrumented preterm fetal sheep (104 days, term is 147 days). During asphyxia there was a significant fall in RBF and urine output (UO). After asphyxia, RBF transiently recovered, followed within 30 min by a secondary period of hypoperfusion (P preterm fetus was associated with evolving renal tubular dysfunction, as shown by transient polyuria and natriuresis. Despite a prolonged increase in RVR, there was only a modest effect on glomerular function.

  19. Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia

    Science.gov (United States)

    Galeano, Pablo; Blanco, Eduardo; Logica Tornatore, Tamara M. A.; Romero, Juan I.; Holubiec, Mariana I.; Rodríguez de Fonseca, Fernando; Capani, Francisco

    2015-01-01

    Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia. PMID:25601829

  20. Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    Pablo eGaleano

    2015-01-01

    Full Text Available Continuous environmental stimulation induced by exposure to enriched environment (EE has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL, by cesarean section (C+, or by C+ following 19 min of asphyxia at birth (PA. At weaning, rats were assigned to standard (SE or enriched environment (EE for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM. Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia.

  1. Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia.

    Science.gov (United States)

    Galeano, Pablo; Blanco, Eduardo; Logica Tornatore, Tamara M A; Romero, Juan I; Holubiec, Mariana I; Rodríguez de Fonseca, Fernando; Capani, Francisco

    2014-01-01

    Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia.

  2. Compression asphyxia from a human pyramid.

    Science.gov (United States)

    Tumram, Nilesh Keshav; Ambade, Vipul Namdeorao; Biyabani, Naushad

    2015-12-01

    In compression asphyxia, respiration is stopped by external forces on the body. It is usually due to an external force compressing the trunk such as a heavy weight on the chest or abdomen and is associated with internal injuries. In present case, the victim was trapped and crushed under the falling persons from a human pyramid formation for a "Dahi Handi" festival. There was neither any severe blunt force injury nor any significant pathological natural disease contributing to the cause of death. The victim was unable to remove himself from the situation because his cognitive responses and coordination were impaired due to alcohol intake. The victim died from asphyxia due to compression of his chest and abdomen. Compression asphyxia resulting from the collapse of a human pyramid and the dynamics of its impact force in these circumstances is very rare and is not reported previously to the best of our knowledge.

  3. Pharmacological neuroprotection after perinatal asphyxia

    NARCIS (Netherlands)

    Fan, Xiyong; van Bel, Frank

    2010-01-01

    Recent progress has provided us with several promising neuroprotective compounds to reduce perinatal hypoxic-ischemic (HI) brain injury. In the early post HI phase, therapies can be concentrated on ion channel blockage (Xenon), anti-oxidation (allopurinol, 2-iminobiotin, and indomethacin), anti-infl

  4. Tau protein as a biomarker for asphyxia: A possible forensic tool?

    Science.gov (United States)

    Salama, Mohamed; Mohamed, Wael M Y

    2016-06-01

    Asphyxial death has been a problem for forensic investigations due to the absence of a validated biomarker for the diagnosis of this event. Recently, research on brain affection by asphyxia raised hopes on the possible use of CNS markers for asphyxia. The cytoskeletal proteins seem to be attractive targets as they are vulnerable to hypoxia and can be affected in asphyxial deaths. Tau, an important cytoskeletal protein, showed affection in many neurodegenerative disorders and recently in some acute incidences like trauma and brain ischemia. In this report we show the affection of the normal pattern of tau and pathological aggregates of tau in the case of brain hypoxia. This may give new clues to asphyxial death investigations.

  5. Radiation-induced brain injury: A review

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    Michael eRobbins

    2012-07-01

    Full Text Available Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (> 6 months to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses > 30 Gy; white matter necrosis occurs at fractionated doses > 60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain

  6. Neuropathology and functional deficits in a model of birth asphyxia in the precocial spiny mouse (Acomys cahirinus).

    Science.gov (United States)

    Hutton, Lisa C; Ratnayake, Udani; Shields, Amy; Walker, David W

    2009-01-01

    Birth asphyxia can result in sensory impairment, learning and memory deficits without gross brain injury and severe motor deficits. We developed a model of birth asphyxia resulting in mild neurological injury and cognitive impairment using a long-gestation species with precocial fetal development. Spiny mice (Acomys cahirinus) underwent caesarean-section delivery or 7.5 min of asphyxia at 37 days gestational age (term is 39 days). Brain histology was examined at 1 and 7 days of age, and behaviour was evaluated to 28 days of age. Asphyxiated offspring showed significant impairment in non-spatial memory and learning tasks, accompanied by central nervous system inflammation and increased apoptotic cell death but without the presence of large necrotic or cystic lesions.

  7. Intranasal pyrrolidine dithiocarbamate decreases brain inflammatory mediators and provides neuroprotection after brain hypoxia-ischemia in neonatal rats.

    Science.gov (United States)

    Wang, Zhi; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2013-11-01

    Brain injury due to birth asphyxia is the major cause of death and long-term disabilities in newborns. We determined whether intranasal pyrrolidine dithiocarbamate (PDTC) could provide neuroprotection in neonatal rats after brain hypoxia-ischemia (HI). Seven-day old male and female Sprague-Dawley rats were subjected to brain HI. They were then treated with intranasal PDTC. Neurological outcomes were evaluated 7 or 30 days after the brain HI. Brain tissues were harvested 6 or 24 h after the brain HI for biochemical analysis. Here, PDTC dose-dependently reduced brain HI-induced brain tissue loss with an effective dose (ED)50 at 27 mg/kg. PDTC needed to be applied within 45 min after the brain HI for this neuroprotection. This treatment reduced brain tissue loss and improved neurological and cognitive functions assessed 30 days after the HI. PDTC attenuated brain HI-induced lipid oxidative stress, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells, and various inflammatory mediators in the brain tissues. Inhibition of inducible nitric oxide synthase after brain HI reduced brain tissue loss. Our results suggest that intranasal PDTC provides neuroprotection possibly via reducing inflammation and oxidative stress. Intranasal PDTC may have a potential to provide neuroprotection to human neonates after birth asphyxia.

  8. 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.

    Directory of Open Access Journals (Sweden)

    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.

  9. Polwarth and Texel ewe parturition duration and its association with lamb birth asphyxia.

    Science.gov (United States)

    Dutra, F; Banchero, G

    2011-10-01

    The objective of the present study was to test the hypothesis that parturition duration is related to birth asphyxia in lambs and that asphyxia affects newborn lamb viability and vigor. Two sire and dam genotypes (Texel: TX; Polwarth: PW) and their crosses were represented in the study. Eighty lambs (25 PW sire × PW dam, 13 TX × TX, 25 TX × PW, and 17 PW × TX) born to 69 grazing ewes were used. At birth, the log₁₀ length of the second stage of parturition, birth weight, placental weight, and several body measurements were recorded on all lambs, and jugular blood samples were analyzed with the i-Stat Portable Clinical Analyzer (Abbott, Montevideo, Uruguay). A modified Apgar viability score at birth and lamb behavior during their first hour of life were recorded. Brain weight, muscle:bone ratio, and bone density were recorded in 20 male lambs (5 from each breed group) that were euthanized and dissected 24 h after birth. Data were analyzed by linear regression, least squares ANOVA, and ordinal and binary logistic regressions. Mean blood gas and acid-base variables were 7.21 ± 0.09 for pH, 18.4 ± 9.8 mmHg for partial pressure of oxygen, 53 ± 12.5 mmHg for partial pressure of carbon dioxide, and -4 ± 5.1 mmol/L for extracellular fluid base excess. Parturition duration increased with birth weight (P lambs (P lambs were born asphyxiated (pO₂ risk of asphyxia (P lambs presented at birth a 16-fold greater risk of asphyxia (P lambs appeared immature at birth, with less bone density (P lambs, suggesting that birth asphyxia is an important risk factor in perinatal lamb mortality.

  10. Positional Asphyxia: Death Due to Unusual Head-Down Position in a Narrow Space.

    Science.gov (United States)

    Chaudhari, Vinod Ashok; Ghodake, Dattatray G; Kharat, Rajesh D

    2016-06-01

    Death due to a head-down position with hyperflexion of the neck is a rare event. A person accidentally falling into a narrow space and remaining in an upside-down position with no timely recovery may experience positional or postural asphyxia. It is a critical condition arising out of particular body positions, leading to mechanical obstruction of respiration. The precipitating factors are intoxication due to alcohol, drugs, obesity, psychiatric illnesses, and injuries. A 30-year-old unmarried woman, weighing 82 kg and with a body mass index of 31.24, was found in a narrow space between the bed and the wall in a naked state and in a head-down position with hyperflexion of the neck. The distribution of lividity was consistent with the position of the body at the scene. Blood was oozing from the mouth and nostrils, and signs of asphyxia were present. The toxicological analyses of viscera, blood, and urine were negative for alcohol, drugs, and poisons. Glucose levels in the blood (86 mg/dL) as well as urine and vitreous humor levels (68 mg/dL) were within normal limits. On microscopic examination, there were no findings of coronary atherosclerosis, whereas the brain and lung were edematous. After meticulous examination, we ruled out sexual assault, autoerotic asphyxia, epilepsy, psychiatric illness, diabetes, toxicity, and coronary artery disease. Death was attributed to the accidental fall of the obese individual being stuck in a narrow space, resulting in positional asphyxia. It is imperative to recognize the precipitating or risk factors before labeling positional asphyxia as a cause of death.

  11. Maternal Creatine Supplementation during Pregnancy Prevents Long-Term Changes in Diaphragm Muscle Structure and Function after Birth Asphyxia.

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    Domenic A LaRosa

    Full Text Available Using a model of birth asphyxia, we previously reported significant structural and functional deficits in the diaphragm muscle in spiny mice, deficits that are prevented by supplementing the maternal diet with 5% creatine from mid-pregnancy. The long-term effects of this exposure are unknown. Pregnant spiny mice were fed control or 5% creatine-supplemented diet for the second half of pregnancy, and fetuses were delivered by caesarean section with or without 7.5 min of in-utero asphyxia. Surviving pups were raised by a cross-foster dam until 33±2 days of age when they were euthanized to obtain the diaphragm muscle for ex-vivo study of twitch tension and muscle fatigue, and for structural and enzymatic analyses. Functional analysis of the diaphragm revealed no differences in single twitch contractile parameters between any groups. However, muscle fatigue, induced by stimulation of diaphragm strips with a train of pulses (330 ms train/sec, 40 Hz for 300 sec, was significantly greater for asphyxia pups compared with controls (p<0.05, and this did not occur in diaphragms of creatine + asphyxia pups. Birth asphyxia resulted in a significant increase in the proportion of glycolytic, fast-twitch fibres and a reduction in oxidative capacity of Type I and IIb fibres in male offspring, as well as reduced cross-sectional area of all muscle fibre types (Type I, IIa, IIb/d in both males and females at 33 days of age. None of these changes were observed in creatine + asphyxia animals. Thus, the changes in diaphragm fatigue and structure induced by birth asphyxia persist long-term but are prevented by maternal creatine supplementation.

  12. 戊巴比妥钠和水合氯醛对窒息性心跳骤停大鼠心肺复苏后脑损伤的影响%Influence of pentobarbital and chloral hydrate on cerebral injury after cardiopulmonary resuscitation in a rat model of cardiac arrest induced by asphyxia

    Institute of Scientific and Technical Information of China (English)

    李章平; 陈寿权; 程俊彦; 章杰; 李惠萍; 黄唯佳; 王万铁

    2009-01-01

    Objective To investigate the influence of choral hydrate and pentobarbital on cerebral injury after cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest induced by asphyxia.Methods One hundred and sixty male 70-95 day old SD rats weighing 300-400 g were randomly divided into 2 anesthetic groups ( n = 80 each) : chloral hydrate group (CH) and pentobarbital group (PB).Each group was further divided into 2 subgroups ( n = 40 each) : control subgroup underwent no cardiac arrest and CPR subgroup.Anesthesia was induced with intraperitoneal (IP) 5% chloral hydrate 0.35 g/kg followed by intermittent IP 5% chloral hydrate 0.1 g/kg every hour in group CH and with IP 0.35% pentobarbital 35 mg/kg followed by intermittent IP 0.35% pentobarbital 10 mg/kg every hour in group PB.Left femoral vein and right carotid artery were cunnulated for drug and fluid administration and BP monitoring.The animals were tracheostomized and mechanically ventilated.Cardiac arrest was induced by occlusion of tracheal tube and verified by disappearance of pulse wave on BP tracing and asystole/ventricular fibrillation/systolic BP 60 mm Hg lasting for more than 10 min were used as criteria for recovery of spontaneous circulation (ROSC).Eight animals were decapitated and their brains were immediately removed at 0.5,3,6,9 and 24 h (T1-5) after BOSC respectively.2% Evans blue 2 ml/kg was injected Ⅳ 15 min before each time point.Brain water content (wet weight dry weight/wet weight × 100% ) and Evan's brain content in the brain tissue were determined.Results The two groups were comparable with respect to body weight,amount of adrenaline given,duration of precordial cardiac massage and BOSC time.The brain water content and Evan's blue content in the brain tissue were significantly increased after ROSC in beth groups.The cerebral water content was significantly higher after BOSC in group CH than in group PB.There was no significant difference in Evan's blue content in the brain tissue

  13. Movement disorders induced by deep brain stimulation.

    Science.gov (United States)

    Baizabal-Carvallo, José Fidel; Jankovic, Joseph

    2016-04-01

    Deep brain stimulation represents a major advance in the treatment of several types of movement disorders. However, during stimulation new movement disorders may emerge, thus limiting the positive effects of this therapy. These movement disorders may be induced by: 1) stimulation of the targeted nucleus, 2) stimulation of surrounding tracts and nuclei, and 3) as a result of dose adjustment of accompanying medications, such as reduction of dopaminergic drugs in patients with Parkinson's disease. Various dyskinesias, blepharospasm, and apraxia of eyelid opening have been described mainly with subthalamic nucleus stimulation, whereas hypokinesia and freezing of gait have been observed with stimulation of the globus pallidus internus. Other deep brain stimulation-related movement disorders include dyskinesias associated with stimulation of the globus pallidus externus and ataxic gait as a side effect of chronic bilateral stimulation of the ventral intermediate nucleus of thalamus. These movement disorders are generally reversible and usually resolved once the stimulation is reduced or turned off. This, however, typically leads to loss of benefit of the underlying movement disorder which can be re-gained by using different contacts, changing targets or stimulation parameters, and adjusting pharmacological therapy. New and innovative emerging technologies and stimulation techniques may help to prevent or overcome the various deep brain stimulation-induced movement disorders. In this review we aim to describe the clinical features, frequency, pathophysiology, and strategies for treatment of these iatrogenic movement disorders.

  14. Age, transvestism, bondage, and concurrent paraphilic activities in 117 fatal cases of autoerotic asphyxia.

    Science.gov (United States)

    Blanchard, R; Hucker, S J

    1991-09-01

    Autoerotic asphyxia is the practice of self-inducing cerebral anoxia, usually by hanging, strangulation, or suffocation, during masturbation. This study investigated the relationships between: asphyxiators' ages; two paraphilias commonly accompanying autoerotic asphyxia, bondage and transvestism; and various other types of simultaneous sexual behaviour. Subjects were two concurrent series totalling 117 males aged 10-56 who died accidentally during autoerotic asphyxial activities. Data concerning sexual paraphernalia at the scene of death or among the deceased's effects were extracted from coronors' files using standardised protocols. Anal self-stimulation with dildos, etc., and self-observation with mirrors or cameras were correlated with transvestism. Older asphyxiators were more likely to have been simultaneously engaged in bondage or transvestism, suggesting elaboration of the masturbatory ritual over time. The greatest degree of transvestism was associated with intermediate rather than high levels of bondage, suggesting that response competition from bondage may limit asphyxiators' involvement in a third paraphilia like transvestism.

  15. Local brain heavy ion irradiation induced Immunosuppression

    Science.gov (United States)

    Lei, Runhong; Deng, Yulin; Huiyang Zhu, Bitlife.; Zhao, Tuo; Wang, Hailong; Yu, Yingqi; Ma, Hong; Wang, Xiao; Zhuang, Fengyuan; Qing, Hong

    Purpose: To investigate the long term effect of acute local brain heavy ion irradiation on the peripheral immune system in rat model. Methodology: Only the brain of adult male Wistar rats were radiated by heavy ions at the dose of 15 Gy. One, two and three months after irradiation, thymus and spleen were analyzed by four ways. Tunel assay was performed to evaluate the percentage of apoptotic cells in thymus and spleen, level of Inflammatory cytokines (IL-2, IL-6, SSAO, and TNF-α) was detected by ELISA assay, the differentiation of thymus T lymphocyte subsets were measured by flow cytometry and the relative expression levels of genes related to thymus immune cell development were measured by using quantitative real-time PCR. Results: Thymus and spleen showed significant atrophy from one month to three months after irradiation. A high level of apoptosis in thymus and spleen were obtained and the latter was more vulnerable, also, high level of inflammatory cytokines were found. Genes (c-kit, Rag1, Rag2 and Sca1) related to thymus lymphocytes’ development were down-regulated. Conclusion: Local area radiation in the rat brain would cause the immunosuppression, especially, the losing of cell-mediated immune functions. In this model, radiation caused inflammation and then induced apoptosis of cells in the immune organs, which contributed to immunosuppression.

  16. Rosiglitazone induces mitochondrial biogenesis in mouse brain.

    Science.gov (United States)

    Strum, Jay C; Shehee, Ron; Virley, David; Richardson, Jill; Mattie, Michael; Selley, Paula; Ghosh, Sujoy; Nock, Christina; Saunders, Ann; Roses, Allen

    2007-03-01

    Rosiglitazone was found to simulate mitochondrial biogenesis in mouse brain in an apolipoprotein (Apo) E isozyme-independent manner. Rosiglitazone induced both mitochondrial DNA (mtDNA) and estrogen-stimulated related receptor alpha (ESRRA) mRNA, a key regulator of mitochondrial biogenesis. Transcriptomics and proteomics analysis suggested the mitochondria produced in the presence of human ApoE3 and E4 were not as metabolically efficient as those in the wild type or ApoE knockout mice. Thus, we propose that PPARgamma agonism induces neuronal mitochondrial biogenesis and improves glucose utilization leading to improved cellular function and provides mechanistic support for the improvement in cognition observed in treatment of Alzheimer's patients with rosiglitazone.

  17. Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study

    NARCIS (Netherlands)

    Kaandorp, Joepe J.; Benders, Manon J. N. L.; Rademaker, Carin M. A.; Torrance, Helen L.; Oudijk, Martijn A.; de Haan, Timo R.; Bloemenkamp, Kitty W. M.; Rijken, Monique; van Pampus, Maria G.; Bos, Arie F.; Porath, Martina M.; Oetomo, Sidarto Bambang; Willekes, Christine; Gavilanes, A. W. Danilo; Wouters, Maurice G. A. J.; van Elburg, Ruurd M.; Huisjes, Anjoke J. M.; Bakker, Saskia C. M. J. E. R.; van Meir, Claudia A.; von Lindern, Jeannette; Boon, Janine; de Boer, Inge P.; Rijnders, Robbert J. P.; Jacobs, Corrie J. W. F. M.; Uiterwaal, Cuno S. P. M.; Mol, Ben Willem J.; Visser, Gerard H. A.; van Bel, Frank; Derks, Jan B.

    2010-01-01

    Background: Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limi

  18. Long-term sequelae of perinatal asphyxia in the aging rat

    DEFF Research Database (Denmark)

    Weitzdoerfer, R; Gerstl, N; Hoeger, H;

    2002-01-01

    Information on the consequences of perinatal asphyxia (PA) on brain morphology and function in the aging rat is missing although several groups have hypothesized that PA may be responsible for neurological and psychiatric deficits in the adult. We therefore decided to study the effects of PA...... on the central nervous system (CNS) in terms of morphology, immunohistochemistry, neurology and behavior in the aging animal. Hippocampus and cerebellum were evaluated morphologically by histological, immunohistochemical and magnetic resonance imaging and cerebellum also by stereological tests. Neurological...... for understanding CNS pathology in the aging subject, animal or human....

  19. Effect of Marine Collagen Peptides on Physiological and Neurobehavioral Development of Male Rats with Perinatal Asphyxia

    Directory of Open Access Journals (Sweden)

    Linlin Xu

    2015-06-01

    Full Text Available Asphyxia during delivery produces long-term deficits in brain development. We investigated the neuroprotective effects of marine collagen peptides (MCPs, isolated from Chum Salmon skin by enzymatic hydrolysis, on male rats with perinatal asphyxia (PA. PA was performed by immersing rat fetuses with uterine horns removed from ready-to-deliver rats into a water bath for 15 min. Caesarean-delivered pups were used as controls. PA rats were intragastrically administered with 0.33 g/kg, 1.0 g/kg and 3.0 g/kg body weight MCPs from postnatal day 0 (PND 0 till the age of 90-days. Behavioral tests were carried out at PND21, PND 28 and PND 90. The results indicated that MCPs facilitated early body weight gain of the PA pups, however had little effects on early physiological development. Behavioral tests revealed that MCPs facilitated long-term learning and memory of the pups with PA through reducing oxidative damage and acetylcholinesterase (AChE activity in the brain, and increasing hippocampus phosphorylated cAMP-response element binding protein (p-CREB and brain derived neurotrophic factor (BDNF expression.

  20. Somatostatin modulates generation of inspiratory rhythms and determines asphyxia survival.

    Science.gov (United States)

    Ramírez-Jarquín, Josué O; Lara-Hernández, Sergio; López-Guerrero, Juan J; Aguileta, Miguel A; Rivera-Angulo, Ana J; Sampieri, Alicia; Vaca, Luis; Ordaz, Benito; Peña-Ortega, Fernando

    2012-04-01

    Breathing and the activity of its generator (the pre-Bötzinger complex; pre-BötC) are highly regulated functions. Among neuromodulators of breathing, somatostatin (SST) is unique: it is synthesized by a subset of glutamatergic pre-BötC neurons, but acts as an inhibitory neuromodulator. Moreover, SST regulates breathing both in normoxic and in hypoxic conditions. Although it has been implicated in the neuromodulation of breathing, neither the locus of SST modulation, nor the receptor subtypes involved have been identified. In this study, we aimed to fill in these blanks by characterizing the SST-induced regulation of inspiratory rhythm generation in vitro and in vivo. We found that both endogenous and exogenous SST depress all preBötC-generated rhythms. While SST abolishes sighs, it also decreases the frequency and increases the regularity of eupnea and gasping. Pharmacological experiments showed that SST modulates inspiratory rhythm generation by activating SST receptor type-2, whose mRNA is abundantly expressed in the pre-Bötzinger complex. In vivo, blockade of SST receptor type-2 reduces gasping amplitude and consequently, it precludes auto-resuscitation after asphyxia. Based on our findings, we suggest that SST functions as an inhibitory neuromodulator released by excitatory respiratory neurons when they become overactivated in order to stabilize breathing rhythmicity in normoxic and hypoxic conditions.

  1. Asphyxia from the eyes of the neonatologist

    Directory of Open Access Journals (Sweden)

    Paolo Gancia

    2014-06-01

    Full Text Available The perinatal asphyxia occurs at a frequency of 4-6‰ in developed countries The hypoxic-ischemic encephalopathy (HIE has an incidence of 0.5-2‰, and is a frequent cause of death and severe disability. Cerebral hypothermia is a well-established therapy of HIE, and its benefits have been described by systematic reviews and meta-analyses of numerous controlled clinical trials. Authors describe their experience in implementation of cerebral hypotermia in a Neonatal Intensive Care Unit, the creation of a network to perform neurophysiologic study of asphyxiated infants ≥ 35 weeks gestation, potential hypothermia candidates. Neurodevelopmental prognosis of HIE infants is of paramount importance for parents. To improve the quality of prognosis and communication with the parents, two studies have been undertaken. First, EEG and magnetic resonance imaging (MRI relationships analysis showed that the severity of the background EEG is associated with the severity and location of MRI lesion patterns in infants treated with hypothermia because of HIE. The second study aims to elucidate the relationships between MRI patterns and neurodevelopmental assessment by Griffiths scales. We found that neuroimaging findings correlate significantly with overall neurodevelopmental assessment at 12 and 24 months of life; in particular, this correlation is significant for the loco-motor and psycho-social sides. These instrumental data, with the EEG evaluation and clinical data, allow the neonatologist to predict quite precisely the neurological outcome of an infant. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  2. Metabolic effects of perinatal asphyxia in the rat cerebral cortex.

    Science.gov (United States)

    Souza, Samir Khal; Martins, Tiago Leal; Ferreira, Gustavo Dias; Vinagre, Anapaula Sommer; Silva, Roselis Silveira Martins da; Frizzo, Marcos Emilio

    2013-03-01

    We reported previously that intrauterine asphyxia acutely affects the rat hippocampus. For this reason, the early effects of this injury were studied in the cerebral cortex, immediately after hysterectomy (acute condition) or following a recovery period at normoxia (recovery condition). Lactacidemia and glycemia were determined, as well as glycogen levels in the muscle, liver and cortex. Cortical tissue was also used to assay the ATP levels and glutamate uptake. Asphyxiated pups exhibited bluish coloring, loss of movement, sporadic gasping and hypertonia. However, the appearance of the controls and asphyxiated pups was similar at the end of the recovery period. Lactacidemia and glycemia were significantly increased by asphyxia in both the acute and recovery conditions. Concerning muscle and hepatic glycogen, the control group showed significantly higher levels than the asphyxic group in the acute condition and when compared with groups of the recovery period. In the recovery condition, the control and asphyxic groups showed similar glycogen levels. However, in the cortex, the control groups showed significantly higher glycogen levels than the asphyxic group, in both the acute and recovery conditions. In the cortical tissue, asphyxia reduced ATP levels by 70 % in the acute condition, but these levels increased significantly in asphyxic pups after the recovery period. Asphyxia did not affect glutamate transport in the cortex of both groups. Our results suggest that the cortex uses different energy resources to restore ATP after an asphyxia episode followed by a reperfusion period. This strategy could sustain the activity of essential energy-dependent mechanisms.

  3. A Study on Birth Asphyxia at Tertiary Health Centre

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    Ekta A Dalal

    2013-08-01

    Methodology: This was the cross sectional study conducted in the tertiary care centre of Ahmedabad on the full term babies with birth asphyxia. The maternal, fetal and newborn correlates were recorded according to predesigned proforma. Results: There were total 401 (6.6% babies born with apgar score of less than 7 at one minute and among them, 320 (79.8% were full term babies and 81 (20.2% were preterm babies. Among the babies 52.5% were male, 56.9% were primigravida, and only 41.9% had antenatal care present, 42.2% had MSL and 47.2% were small for date babies. Conclusion: Birth asphyxia is common the babies of the mother who had not received proper antenatal care. Maternal anaemia, primipara, meconium stained liquor babies have more chances of getting birth asphyxia. [Natl J Med Res 2013; 3(4.000: 374-376

  4. Circulatory responses to asphyxia differ if the asphyxia occurs in utero or ex utero in near-term lambs.

    Directory of Open Access Journals (Sweden)

    Kristina S Sobotka

    Full Text Available A cornerstone of neonatal resuscitation teaching suggests that a rapid vagal-mediated bradycardia is one of the first signs of perinatal compromise. As this understanding is based primarily on fetal studies, we investigated whether the heart rate and blood pressure response to total asphyxia is influenced by whether the animal is in utero or ex utero.Fetal sheep were instrumented at ∼ 139 days of gestation and then asphyxiated by umbilical cord occlusion until mean arterial blood pressure decreased to ∼ 20 mmHg. Lambs were either completely submerged in amniotic fluid (in utero; n = 8 throughout the asphyxia or were delivered and then remained ex utero (ex utero; n = 8 throughout the asphyxia. Heart rate and arterial blood pressure were continuously recorded.Heart rate was higher in ex utero lambs than in utero lambs. Heart rates in in utero lambs rapidly decreased, while heart rates in ex utero lambs initially increased following cord occlusion (for ∼ 1.5 min before they started to decrease. Mean arterial pressure initially increased then decreased in both groups.Heart rate response to asphyxia was markedly different depending upon whether the lamb was in utero or ex utero. This indicates that the cardiovascular responses to perinatal asphyxia are significantly influenced by the newborn's local environment. As such, based solely on heart rate, the stage and severity of a perinatal asphyxic event may not be as accurate as previously assumed.

  5. Correlation between clinical and histologic findings in the human neonatal hippocampus after perinatal asphyxia.

    Science.gov (United States)

    Schiering, Irene A M; de Haan, Timo R; Niermeijer, Jikke-Mien F; Koelman, Johannes H; Majoie, Charles B L M; Reneman, Liesbeth; Aronica, Eleonora

    2014-04-01

    Hypoxic ischemic encephalopathy after perinatal asphyxia is a major cause of mortality and morbidity in infants. Here, we evaluated pathologic changes in the hippocampi of a cohort of 16 deceased full-term asphyxiated infants who died from January 2000 to January 2009. Histochemical and immunocytochemical results for glial and neuronal cells were compared between cases with or without seizures and to adult and sudden infant death syndrome cases (n = 3 each). All asphyxiated infants displayed neuronal cell damage and reactive glial changes. Strong aquaporin-4 immunoreactivity was seen on astroglial cells within hippocampi in 50% of cases. In patients with seizures, the expression of metabotropic glutamate receptors was increased in glial cells. Cases with seizures displayed increased microglial activation and greater expression of the inflammatory markers interleukin 1β and complement 1q compared with those in cases without seizures. All cases with seizures displayed alterations in the blood-brain barrier, as assessed by immunohistochemistry for albumin. These findings confirm the complex cascade of cellular and molecular changes occurring in the human neonatal hippocampus after perinatal asphyxia. These changes may contribute to seizure development leading to secondary brain damage. These data may aid in the development of therapeutic targets for neonatal seizures.

  6. Adenoid Cystic Carcinoma of the Trachea Resulting in Fatal Asphyxia.

    Science.gov (United States)

    Huston, Butch; Froloff, Victor; Mills, Kelly; McGee, Michael

    2017-01-01

    Primary malignant tumors of the trachea are uncommon. The authors report a case of a 72-year-old female who died from asphyxia due to an undiagnosed obstructing adenoid cystic carcinoma of the trachea. The decedent became unresponsive while eating cereal and was pronounced upon arrival at the local hospital. The autopsy revealed a near occlusive tumor mass just superior to the bifurcation of the distal trachea. There was no evidence of aspiration. The death was the result of asphyxia due to obstruction of the trachea by an adenoid cystic carcinoma. This case demonstrates that an obstructive tumor mass may remain undiagnosed until an obstructive episode results in a sudden death.

  7. Obstetric interventions and perinatal asphyxia in growth retarded term infants

    DEFF Research Database (Denmark)

    Langhoff-Roos, J; Lindmark, G

    1997-01-01

    BACKGROUND: The monitoring of fetal growth during pregnancy is usually justified because of the increased perinatal risk of these babies. METHODS: In 1552 infants from the Scandinavian Small for Gestational Age Study the need for obstetric interventions, risk of fetal asphyxia and immediate...... neonatal outcome at term have been studied in relation to different types of fetal growth retardation, including sub-groups with low ponderal index or low amount of subcutaneous fat. RESULTS: The need for obstetric intervention indicated by suspected fetal asphyxia before or during labor was increased 3...

  8. Radiosurgery-induced brain tumor. Case report.

    Science.gov (United States)

    Kaido, T; Hoshida, T; Uranishi, R; Akita, N; Kotani, A; Nishi, N; Sakaki, T

    2001-10-01

    The authors describe a case of glioblastoma multiforme (GBM) associated with previous gamma knife radiosurgery for a cerebral arteriovenous malformation (AVM). A 14-year-old boy had undergone radiosurgery for an AVM, which was performed using a 201-source 60Co gamma knife system at another institution. The maximum and margin radiation doses used in the procedure were 40 and 20 Gy, respectively. One year after radiosurgery, the patient noticed onset of mild left hemiparesis due to radiation necrosis. Six and one-half years after radiosurgery, at the age of 20 years, the patient experienced an attack of generalized tonic-clonic seizure. Magnetic resonance (MR) imaging revealed the existence of a brain tumor in the right parietal lobe. The patient underwent an operation and the histological diagnosis of the lesion was GBM. Ten months following the operation, that is, 99 months postradiosurgery, this patient died. To the best of the authors' knowledge, this is the first reported case of a neoplasm induced by radiosurgery for an AVM and the second case in which it occurred following radiosurgery for intracranial disease.

  9. Asphyxia: a rare cause of death for motor vehicle crash occupants.

    Science.gov (United States)

    Conroy, Carol; Stanley, Christina; Eastman, A Brent; Vaughan, Teresa; Vilke, Gary M; Hoyt, David B; Pacyna, Sharon; Smith, Alan

    2008-03-01

    Motor vehicle related trauma is one of the leading causes of traumatic death. Although most of these deaths are because of severe blunt force trauma, there are people without severe injury who die of asphyxia related to the motor vehicle collision. There were 37 deaths because of motor vehicle related asphyxia in San Diego County during 1995-2004. Almost half (48.6%) of these deaths were because of compression asphyxia, 29.7% were positional asphyxia deaths, and 16.2% died of a combination of compression and positional asphyxia. We were unable to classify the mechanism of asphyxia for the remaining 5.4% of asphyxia deaths. Almost all occupants dying from asphyxia were involved in rollover crashes and may have been incapacitated by obesity, drug or alcohol intoxication, or blunt force trauma. Compression asphyxia deaths occurred both from vehicle crush with intrusion into the passenger compartment and from ejection of the occupant and subsequent crushing by the vehicle. Positional asphyxia occurred in positions interfering with normal respiration, including inversion. None of the occupants had injury severe enough to result in death at the scene if they had not first died of asphyxia. This study suggests classifying the mechanism of asphyxia for these fatalities may be a challenge to forensic pathologists who seldom see these rare deaths.

  10. Analysis of Obstetric Factors of Neonatal Asphyxia%新生儿窒息的产科因素分析

    Institute of Scientific and Technical Information of China (English)

    庞正钰; 杨妹; 孙艳萍; 林怡; 黄蓉

    2015-01-01

    目的:探讨新生儿窒息的产科危险因素,分析如何有效降低新生儿窒息发生率和病死率,提高人口素质。方法对2011~2012年间在我院住院分娩的病历、统计资料进行回顾性分析,对新生儿不同性别、产式、孕周、产妇产龄等新生儿窒息影响因素进行比较,找出新生儿窒息的主要原因。结果新生儿窒息率为5.09%;男、女新生儿窒息发生率和病死率无显著性差异;新生儿窒息的前三位原因是:早产、脐带绕颈、妊娠高血压疾病,分别占56.23%、19.15%和12.46%;早产是新生儿窒息和死亡的首位原因;阴道助产、高龄分娩都会增加新生儿窒息的风险。结论加强围产保健,积极预防早产,是降低新生儿窒息的关键。为了母婴健康,应鼓励适龄婚育,才是提高人口素质的有效措施。%Objective To explore the factors of neonatal asphyxia obstetric risk, to reduce the incidence and mortality rate of neonatal asphyxia, and to improve the quality of the population.Methods Medical records and statistical data of hospitalization and delivery from 2011 to 2012 in the hospital were retrospectively analyzed.The newborns′different genders, birth type, gestational age, maternal age and asphyxia were compared, to find out the main causes of neonatal asphyxia.Results The rate of neonatal asphyxia was 5.09%;male and female, the incidence of neonatal asphyxia and mortality had no significant difference;the first three causes of neonatal asphyxia were pre-mature birth, umbilical cord around the neck, pregnancy induced hypertension, accounting for 56.23%, 19.15%and 12.46%;premature was the first cause of neonatal asphyxia and death;vaginal instrumental delivery and advanced age delivery can increase neonatal asphyxia.Conclusion Strengthening perinatal health care and preventing premature delivery is the key to reduce neonatal asphyxia.For maternal and child health, marriage and

  11. Risk factors and prognostic models for perinatal asphyxia at term

    NARCIS (Netherlands)

    Ensing, S.

    2015-01-01

    This thesis will focus on the risk factors and prognostic models for adverse perinatal outcome at term, with a special focus on perinatal asphyxia and obstetric interventions during labor to reduce adverse pregnancy outcomes. For the majority of the studies in this thesis we were allowed to use data

  12. PHENOBARBITAL FOR THE PREVENTION OF INTRACRANIAL DAMAGE IN CHINESE NEONATES WITH SEVERE ASPHYXIA

    Institute of Scientific and Technical Information of China (English)

    陈惠金; 吴圣楣; 黄萍; 孙建华; 陈冠仪; 储凇雯

    2000-01-01

    Objective To evaluate the effect of phenobarbital on preventing intracranial damage and seizure in Chinese neonates with severe asphyxia. Methods A control trial was carried out in 60 Chinese neonates with severe asphyxia. 30 neonates received loading dose of phenobarbital on an average of 5.6h of age. Results The mean value of phenobarbital serum level obtained at the 4th day after birth was 21.9μg/ml. No significant difference was observed in the two groups in terms of birth weight, gestational age, Apgar scores, sex, etc. The imaging diagnosis within 3d of age in all subjects showed normal brain in 14, brain edema in 9 and intraventricular hemorrhage (IVH) in 7 in the treated group with a 53.3% of total complication rate, and normal brain in 5, brain edema in 15, IVH in 9 and subarachnoid hemorrhage (SAH) in 1 in the untreated group with a 83.3% of total complication rate. The incidence of intracranial damage in the untreated group was significantly higher than that in the treated group (83.3% vs 53.3%, P<0.05). In the treated group, 4 neonates with seizure symptom were effectively controlled soon, and none of the other 26 developed seizure. The period of seizure in the treated group was significantly shorter than that in the untreated group (P<0. 05). Other clinical symptoms were also sooner improved and no side effects were observed among the neonates treated with phenobarbital. Conclusion The incidence of postasphyxiated intracranial damage was obviously decreased, and seizure could be prophylactically intervened by phenobarbital. It is recommended that early application of preventive phenobarbitalin severely asphyxiated neonates is reasonable in reducing the incidence of intracranial lesions and subsequent seizures.

  13. Traumatic brain injury-induced sleep disorders

    Directory of Open Access Journals (Sweden)

    Viola-Saltzman M

    2016-02-01

    Full Text Available Mari Viola-Saltzman, Camelia Musleh Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA Abstract: Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%–70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. Keywords: traumatic brain injury, insomnia, hypersomnia, sleep apnea, periodic limb movement disorder, fatigue

  14. Arterial blood gas analysis and electrolyte determination in neonates with asphyxia

    Institute of Scientific and Technical Information of China (English)

    Zi-Mei Sun

    2015-01-01

    Objective:To explore the value of arterial blood gas analysis and electrolyte determination in the diagnosis of neonatal asphyxia.Methods: A total of 100 neonates with asphyxia who were admitted in our department from March, 2013 to March, 2014 were included in the study and divided into the mild asphyxia group and the severe asphyxia group according to Apgar scoring. Moreover, 50 normal neonates were served as the control group and used for comparative analysis. AVL blood-gas analyzer was used to detect the levels of pH, PaO2, HCO3-, BE, PaCO2, K+, Na+, Cl-, and Ca2+.Results:The concentrations of pH, PaO2, HCO3-, and BE in the severe asphyxia group were significantly lower than those in the mild asphyxia group and the control group, while PaCO2 level was significantly higher than that in the mild asphyxia group and the control group. The comparison of the various indicators between the control group and the mild asphyxia group was not statistically significant. The comparison of serum K+, Na+,and Cl- levels among the control group, the mild asphyxia group, and the severe asphyxia group was not statistically significant. The serum Ca2+ level in the severe asphyxia group was significantly lower than that in the mild asphyxia group and the control group, while the comparison between the mild asphyxia group and the control group was also statistically significant.Conclusions:Blood gas analysis and electrolyte determination to the arterial blood in neonates can compensate for the insufficiency of Apgar scoring and provide an objective evidence for the diagnosis of neonatal asphyxia and the estimation of severity degree. Clinical combination with Apgar scoring is of great significance in enhancing the diagnosis of neonatal asphyxia and the accuracy of severity evaluation.

  15. Fluid-percussion–induced traumatic brain injury model in rats

    OpenAIRE

    2010-01-01

    Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Various attempts have been made to replicate clinical TBI using animal models. The fluid-percussion model (FP) is one of the oldest and most commonly used models of experimentally induced TBI. Both central (CFP) and lateral (LFP) variations of the model have been used. Developed initially for use in larger species, the standard FP device was adapted more than 20 years ago to induce consistent degrees of brain injury in ...

  16. Blood-brain interfaces and bilirubin-induced neurological diseases.

    Science.gov (United States)

    Ghersi-Egea, J F; Gazzin, S; Strazielle, N

    2009-01-01

    The endothelium of the brain microvessels and the choroid plexus epithelium form highly specialized cellular barriers referred to as blood-brain interfaces through which molecular exchanges take place between the blood and the neuropil or the cerebrospinal fluid, respectively. Within the brain, the ependyma and the pia-glia limitans modulate exchanges between the neuropil and the cerebrospinal fluid. All these interfaces are key elements of neuroprotection and fulfill trophic functions; both properties are critical to harmonious brain development and maturation. By analogy to hepatic bilirubin detoxification pathways, we review the transport and metabolic mechanisms which in all these interfaces may participate in the regulation of bilirubin cerebral bioavailability in physiologic conditions, both in adult and in developing brain. We specifically address the role of ABC and OATP transporters, glutathione-S-transferases, and the potential involvement of glucuronoconjugation and oxidative metabolic pathways. Regulatory mechanisms are explored which are involved in the induction of these pathways and represent potential pharmacological targets to prevent bilirubin accumulation into the brain. We then review the possible alteration of the neuroprotective and trophic barrier functions in the course of bilirubin-induced neurological dysfunctions resulting from hyperbilirubinemia. Finally, we highlight the role of the blood-brain and blood-CSF barriers in regulating the brain biodisposition of candidate drugs for the treatment or prevention of bilirubin-induced brain injury.

  17. Non-invasive optical monitoring of the newborn piglet brain using continuous-wave and frequency-domain spectroscopy

    Science.gov (United States)

    Fantini, Sergio; Hueber, Dennis; Franceschini, Maria Angela; Gratton, Enrico; Rosenfeld, Warren; Stubblefield, Phillip G.; Maulik, Dev; Stankovic, Miljan R.

    1999-06-01

    We have used continuous-wave (CW) and frequency-domain spectroscopy to investigate the optical properties of the newborn piglet brain in vivo and non-invasively. Three anaesthetized, intubated, ventilated and instrumented newborn piglets were placed into a stereotaxic instrument for optimal experimental stability, reproducible probe-to-scalp optical contact and 3D adjustment of the optical probe. By measuring the absolute values of the brain absorption and reduced scattering coefficients at two wavelengths (758 and 830 nm), frequency-domain spectroscopy provided absolute readings (in contrast to the relative readings of CW spectroscopy) of cerebral haemoglobin concentration and saturation during experimentally induced perturbations in cerebral haemodynamics and oxygenation. Such perturbations included a modulation of the inspired oxygen concentration, transient brain asphyxia, carotid artery occlusion and terminal brain asphyxia. The baseline cerebral haemoglobin saturation and concentration, measured with frequency-domain spectroscopy, were about 60% and 42 µM respectively. The cerebral saturation values ranged from a minimum of 17% (during transient brain asphyxia) to a maximum of 80% (during recovery from transient brain asphyxia). To analyse the CW optical data, we have (a) derived a mathematical relationship between the cerebral optical properties and the differential pathlength factor and (b) introduced a method based on the spatial dependence of the detected intensity (dc slope method). The analysis of the cerebral optical signals associated with the arterial pulse and with respiration demonstrates that motion artefacts can significantly affect the intensity recorded from a single optode pair. Motion artefacts can be strongly reduced by combining data from multiple optodes to provide relative readings in the dc slope method. We also report significant biphasic changes (initial decrease and successive increase) in the reduced scattering coefficient measured

  18. Traumatic brain injury and obesity induce persistent central insulin resistance.

    Science.gov (United States)

    Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M

    2016-04-01

    Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI.

  19. 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

  20. Severe myocardial injury and extracorporeal membrane oxygenation following perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    P. Benson Ham

    2015-05-01

    Full Text Available Perinatal asphyxia is a common cause of morbidity and mortality in the newborn and is associated with myocardial injury in a significant proportion of cases. Biomarkers, echocardiography, and rhythm disturbances are sensitive indicators of myocardial ischemia and may predict mortality. We present a case of severe myocardial dysfunction immediately after delivery managed with extracorporeal membrane oxygenation (ECMO and discuss the role of cardiac biomarkers, echocardiography, electrocardiography, and ECMO in the asphyxiated newborn.

  1. Training-induced behavioral and brain plasticity in inhibitory control

    OpenAIRE

    Lucas eSpierer; Camille eChavan; Aurelie Lynn Manuel

    2013-01-01

    Deficits in inhibitory control, the ability to suppress ongoing or planned motor or cognitive processes, contribute to many psychiatric and neurological disorders. The rehabilitation of inhibition-related disorders may therefore benefit from neuroplasticity-based training protocols aiming at normalizing inhibitory control proficiency and the underlying brain networks. Current literature on training-induced behavioral and brain plasticity in inhibitory control suggests that improvements may fo...

  2. Acupuncture stimulation induces neurogenesis in adult brain.

    Science.gov (United States)

    Nam, Min-Ho; Ahn, Kwang Seok; Choi, Seung-Hoon

    2013-01-01

    The discovery of adult neurogenesis was a turning point in the field of neuroscience. Adult neurogenesis offers an enormous possibility to open a new therapeutic paradigm of neurodegenerative diseases and stroke. Recently, several studies suggested that acupuncture may enhance adult neurogenesis. Acupuncture has long been an important treatment for brain diseases in the East Asia. The scientific mechanisms of acupuncture treatment for the diseases, such as Alzheimer's disease, Parkinson's disease, and stroke, have not been clarified yet; however, the neurogenic effect of acupuncture can be a possible reason. Here, we have reviewed the studies on the effect of stimulation at various acupoints for neurogenesis, such as ST36 and GV20. The suggested mechanisms are also discussed including upregulation of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, basic fibroblast growth factor and neuropeptide Y, and activation of the function of primo vascular system.

  3. Prenatal irradiation-induced brain neuropathology and cognitive impairment.

    Science.gov (United States)

    Yang, Bo; Ren, Bo Xu; Tang, Feng Ru

    2017-01-01

    Embryo/fetus is much more radiosensitive than neonatal and adult human being. The main potential effects of pre-natal radiation exposure on the human brain include growth retardation, small head/brain size, mental retardation, neocortical ectopias, callosal agenesis and brain tumor which may result in a lifetime poor quality of life. The patterns of prenatal radiation-induced effects are dependent not only on the stages of fetal development, the sensitivity of tissues and organs, but also on radiation sources, doses, dose rates. With the increased use of low dose radiation for diagnostic or radiotherapeutic purposes in recent years, combined with postnatal negative health effect after prenatal radiation exposure to fallout of Chernobyl nuclear power plant accident, the great anxiety and unnecessary termination of pregnancies after the nuclear disaster, there is a growing concern about the health effect of radiological examinations or therapies in pregnant women. In this paper, we reviewed current research progresses on pre-natal ionizing irradiation-induced abnormal brain structure changes. Subsequent postnatal neuropsychological and neurological diseases were provided. Relationship between irradiation and brain aging was briefly mentioned. The relevant molecular mechanisms were also discussed. Future research directions were proposed at the end of this paper. With limited human data available, we hoped that systematical review of animal data could relight research interests on prenatal low dose/dose rate irradiation-induced brain microanatomical changes and subsequent neurological and neuropsychological disorders.

  4. Methadone-Induced Toxic Brain Damage

    Directory of Open Access Journals (Sweden)

    Jérôme Corré

    2013-01-01

    Full Text Available A 29-year-old man presented with comatose after methadone intoxication. Cerebral tomography only showed cortico-subcortical hypodense signal in the right cerebellar hemisphere. Brain MRI showed a rare imaging of FLAIR and DWI hyperintensities in the two cerebellar hemispheres as well as basal ganglia (globi pallidi, compatible with methadone overdose. To our knowledge this is the first reported case of both cerebellar and basal ganglia involvement in methadone overdose.

  5. Emotion-Induced Topological Changes in Functional Brain Networks.

    Science.gov (United States)

    Park, Chang-Hyun; Lee, Hae-Kook; Kweon, Yong-Sil; Lee, Chung Tai; Kim, Ki-Tae; Kim, Young-Joo; Lee, Kyoung-Uk

    2016-01-01

    In facial expression perception, a distributed network is activated according to stimulus context. We proposed that an interaction between brain activation and stimulus context in response to facial expressions could signify a pattern of interactivity across the whole brain network beyond the face processing network. Functional magnetic resonance imaging data were acquired for 19 young healthy subjects who were exposed to either emotionally neutral or negative facial expressions. We constructed group-wise functional brain networks for 12 face processing areas [bilateral inferior occipital gyri (IOG), fusiform gyri (FG), superior temporal sulci (STS), amygdalae (AMG), inferior frontal gyri (IFG), and orbitofrontal cortices (OFC)] and for 73 whole brain areas, based on partial correlation of mean activation across subjects. We compared the topological properties of the networks with respect to functional distance-based measures, global and local efficiency, between the two types of face stimulus. In both face processing and whole brain networks, global efficiency was lower and local efficiency was higher for negative faces relative to neutral faces, indicating that network topology differed according to stimulus context. Particularly in the face processing network, emotion-induced changes in network topology were attributable to interactions between core (bilateral IOG, FG, and STS) and extended (bilateral AMG, IFG, and OFC) systems. These results suggest that changes in brain activation patterns in response to emotional face stimuli could be revealed as changes in the topological properties of functional brain networks for the whole brain as well as for face processing areas.

  6. Animal models of brain maldevelopment induced by cycad plant genotoxins.

    Science.gov (United States)

    Kisby, Glen E; Moore, Holly; Spencer, Peter S

    2013-12-01

    Cycads are long-lived tropical and subtropical plants that contain azoxyglycosides (e.g., cycasin, macrozamin) and neurotoxic amino acids (notably β-N-methylamino-l-alanine l-BMAA), toxins that have been implicated in the etiology of a disappearing neurodegenerative disease, amyotrophic lateral sclerosis and parkinsonism-dementia complex that has been present in high incidence among three genetically distinct populations in the western Pacific. The neuropathology of amyotrophic lateral sclerosis/parkinsonism-dementia complex includes features suggestive of brain maldevelopment, an experimentally proven property of cycasin attributable to the genotoxic action of its aglycone methylazoxymethanol (MAM). This property of MAM has been exploited by neurobiologists as a tool to study perturbations of brain development. Depending on the neurodevelopmental stage, MAM can induce features in laboratory animals that model certain characteristics of epilepsy, schizophrenia, or ataxia. Studies in DNA repair-deficient mice show that MAM perturbs brain development through a DNA damage-mediated mechanism. The brain DNA lesions produced by systemic MAM appear to modulate the expression of genes that regulate neurodevelopment and contribute to neurodegeneration. Epigenetic changes (histone lysine methylation) have also been detected in the underdeveloped brain after MAM administration. The DNA damage and epigenetic changes produced by MAM and, perhaps by chemically related substances (e.g., nitrosamines, nitrosoureas, hydrazines), might be an important mechanism by which early-life exposure to genotoxicants can induce long-term brain dysfunction.

  7. MRI-induced heating of deep brain stimulation leads

    Energy Technology Data Exchange (ETDEWEB)

    Mohsin, Syed A; Sheikh, Noor M [University of Engineering and Technology, Lahore (Pakistan); Saeed, Usman [Georgia Institute of Technology, Atlanta, GA (United States)], E-mail: syed_alimohsin@uet.edu.pk, E-mail: deanee@uet.edu.pk, E-mail: usaeed@gatech.edu

    2008-10-21

    The radiofrequency (RF) field used in magnetic resonance imaging is scattered by medical implants. The scattered field of a deep brain stimulation lead can be very intense near the electrodes stimulating the brain. The effect is more pronounced if the lead behaves as a resonant antenna. In this paper, we examine the resonant length effect. We also use the finite element method to compute the near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and brain tissues) and (ii) the lead connected to an implantable pulse generator. Electric field, specific absorption rate and induced temperature rise distributions have been obtained in the brain tissue surrounding the electrodes. The worst-case scenario has been evaluated by neglecting the effect of blood perfusion. The computed values are in good agreement with in vitro measurements made in the laboratory.

  8. Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

    Directory of Open Access Journals (Sweden)

    Saldanha Colin J

    2011-07-01

    Full Text Available Abstract Background Estrogens from peripheral sources as well as central aromatization are neuroprotective in the vertebrate brain. Under normal conditions, aromatase is only expressed in neurons, however following anoxic/ischemic or mechanical brain injury; aromatase is also found in astroglia. This increased glial aromatization and the consequent estrogen synthesis is neuroprotective and may promote neuronal survival and repair. While the effects of estradiol on neuroprotection are well studied, what induces glial aromatase expression remains unknown. Methods Adult male zebra finches (Taeniopygia guttata were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA, an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test. Results Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression. Conclusions These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.

  9. Endogenous control of waking brain rhythms induces neuroplasticity in humans.

    NARCIS (Netherlands)

    Ros, T.; Munneke, M.; Ruge, D.; Gruzelier, J.H.; Rothwell, J.C.

    2010-01-01

    This study explores the possibility of noninvasively inducing long-term changes in human corticomotor excitability by means of a brain-computer interface, which enables users to exert internal control over the cortical rhythms recorded from the scalp. We demonstrate that self-regulation of electroen

  10. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation

    NARCIS (Netherlands)

    Hoeger, S.; Bergstraesser, C.; Selhorst, J.; Fontana, J.; Birck, R.; Waldherr, R.; Beck, G.; Sticht, C.; Seelen, M. A.; van Son, W. J.; Leuvenink, H.; Ploeg, R.; Schnuelle, P.; Yard, B. A.

    2010-01-01

    Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (

  11. Renal sympathetic nerve activity during asphyxia in fetal sheep.

    Science.gov (United States)

    Booth, Lindsea C; Malpas, Simon C; Barrett, Carolyn J; Guild, Sarah-Jane; Gunn, Alistair J; Bennet, Laura

    2012-07-01

    The sympathetic nervous system (SNS) is an important mediator of fetal adaptation to life-threatening in utero challenges, such as asphyxia. Although the SNS is active well before term, SNS responses mature significantly over the last third of gestation, and its functional contribution to adaptation to asphyxia over this critical period of life remains unclear. Therefore, we examined the hypotheses that increased renal sympathetic nerve activity (RSNA) is the primary mediator of decreased renal vascular conductance (RVC) during complete umbilical cord occlusion in preterm fetal sheep (101 ± 1 days; term 147 days) and that near-term fetuses (119 ± 0 days) would have a more rapid initial vasomotor response, with a greater increase in RSNA. Causality of the relationship of RSNA and RVC was investigated using surgical (preterm) and chemical (near-term) denervation. All fetal sheep showed a significant increase in RSNA with occlusion, which was more sustained but not significantly greater near-term. The initial fall in RVC was more rapid in near-term than preterm fetal sheep and preceded the large increase in RSNA. These data suggest that although RSNA can increase as early as 0.7 gestation, it is not the primary determinant of RVC. This finding was supported by denervation studies. Interestingly, chemical denervation in near-term fetal sheep was associated with an initial fall in blood pressure, suggesting that by 0.8 gestation sympathetic innervation of nonrenal vascular beds is critical to maintain arterial blood pressure during the rapid initial adaptation to asphyxia.

  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. MOLECULAR MECHANISMS REGULATING LPS-INDUCED INFLAMMATION IN THE BRAIN

    Directory of Open Access Journals (Sweden)

    Olena eLykhmus

    2016-03-01

    Full Text Available Neuro-inflammation, one of the pathogenic causes of neurodegenerative diseases, is regulated through the cholinergic anti-inflammatory pathway via the 7 nicotinic acetylcholine receptor (7 nAChR. We previously showed that either bacterial lipopolysaccharide (LPS or immunization with the 7(1-208 nAChR fragment decrease 7 nAChRs density in the mouse brain, exacerbating chronic inflammation, beta-amyloid accumulation and episodic memory decline, which mimic the early stages of Alzheimer’s disease. To study the molecular mechanisms underlying the LPS and antibody effects in the brain, we employed an in vivo model of acute LPS-induced inflammation and an in vitro model of cultured glioblastoma U373 cells. Here, we report that LPS challenge decreased the levels of 7 nAChR RNA and protein and of acetylcholinesterase (AChE RNA and activity in distinct mouse brain regions, sensitized brain mitochondria to the apoptogenic effect of Ca2+ and modified brain microRNA profiles, including the cholinergic-regulatory CholinomiRs-132/212, in favor of anti-inflammatory and pro-apoptotic ones. Adding 7(1-208-specific antibodies to the LPS challenge prevented elevation of both the anti-inflammatory and pro-apoptotic miRNAs while supporting the resistance of brain mitochondria to Ca2+ and maintaining 7 nAChR/AChE decreases. In U373 cells, 7-specific antibodies and LPS both stimulated interleukin-6 production through the p38/Src-dependent pathway. Our findings demonstrate that acute LPS-induced inflammation induces the cholinergic anti-inflammatory pathway in the brain, that 7 nAChR down-regulation limits this pathway, and that 7-specific antibodies aggravate neuroinflammation by inducing the pro-inflammatory interleukin-6 and dampening anti-inflammatory miRNAs; however, these antibodies may protect brain mitochondria and decrease the levels of pro-apoptotic miRNAs, preventing LPS-induced neurodegeneration.

  14. Molecular Mechanisms Regulating LPS-Induced Inflammation in the Brain

    Science.gov (United States)

    Lykhmus, Olena; Mishra, Nibha; Koval, Lyudmyla; Kalashnyk, Olena; Gergalova, Galyna; Uspenska, Kateryna; Komisarenko, Serghiy; Soreq, Hermona; Skok, Maryna

    2016-01-01

    Neuro-inflammation, one of the pathogenic causes of neurodegenerative diseases, is regulated through the cholinergic anti-inflammatory pathway via the α7 nicotinic acetylcholine receptor (α7 nAChR). We previously showed that either bacterial lipopolysaccharide (LPS) or immunization with the α7(1–208) nAChR fragment decrease α7 nAChRs density in the mouse brain, exacerbating chronic inflammation, beta-amyloid accumulation and episodic memory decline, which mimic the early stages of Alzheimer’s disease (AD). To study the molecular mechanisms underlying the LPS and antibody effects in the brain, we employed an in vivo model of acute LPS-induced inflammation and an in vitro model of cultured glioblastoma U373 cells. Here, we report that LPS challenge decreased the levels of α7 nAChR RNA and protein and of acetylcholinesterase (AChE) RNA and activity in distinct mouse brain regions, sensitized brain mitochondria to the apoptogenic effect of Ca2+ and modified brain microRNA profiles, including the cholinergic-regulatory CholinomiRs-132/212, in favor of anti-inflammatory and pro-apoptotic ones. Adding α7(1–208)-specific antibodies to the LPS challenge prevented elevation of both the anti-inflammatory and pro-apoptotic miRNAs while supporting the resistance of brain mitochondria to Ca2+ and maintaining α7 nAChR/AChE decreases. In U373 cells, α7-specific antibodies and LPS both stimulated interleukin-6 production through the p38/Src-dependent pathway. Our findings demonstrate that acute LPS-induced inflammation induces the cholinergic anti-inflammatory pathway in the brain, that α7 nAChR down-regulation limits this pathway, and that α7-specific antibodies aggravate neuroinflammation by inducing the pro-inflammatory interleukin-6 and dampening anti-inflammatory miRNAs; however, these antibodies may protect brain mitochondria and decrease the levels of pro-apoptotic miRNAs, preventing LPS-induced neurodegeneration. PMID:27013966

  15. Acupuncture inhibits cue-induced heroin craving and brain activation

    Institute of Scientific and Technical Information of China (English)

    Xinghui Cai; Xiaoge Song; Chuanfu Li; Chunsheng Xu; Xiliang Li; Qi Lu

    2012-01-01

    Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues.Craving is an important trigger of heroin relapse,and acupuncture may inhibit craving.In this study,we performed functional MRI in heroin addicts and control subjects.We compared differences in brain activation between the two groups during heroin cue exposure,heroin cue exposure plus acupuncture at the Zusanli point(ST36)without twirling of the needle,and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle.Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri.Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure,but significantly changed the extent of the activation in the heroin addicts group.Acupuncture at the Zusanli.point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle.These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions,which are involved in reward,learning and memory,cognition and emotion.Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving,supporting its potential as an intervention for drug craving.

  16. Superior neuroprotective effects of cerebrolysin in nanoparticle-induced exacerbation of hyperthermia-induced brain pathology.

    Science.gov (United States)

    Sharma, Aruna; Muresanu, Dafin Fior; Mössler, Herbert; Sharma, Hari Shanker

    2012-02-01

    In recent years, the incidence of heat stroke and associated brain pathology are increasing Worldwide. More than half of the world's population are living in areas associated with high environmental heat especially during the summer seasons. Thus, new research is needed using novel drug targets to achieve neuroprotection in heat-induced brain pathology. Previous research from our laboratory showed that the pathophysiology of brain injuries following heat stroke are exacerbated by chronic intoxication of engineered nanoparticles of small sizes (50-60 nm) following identical heat exposure in rats. Interestingly, in nanoparticle-intoxicated animals the known neuroprotective agents in standard doses failed to induce effective neuroprotection. This suggests that the dose-response of the drugs either requires modification or new therapeutic agents are needed to provide better neuroprotection in nanoparticle-intoxicated animals after heat stroke. This review is focused on the use of cerebrolysin, a mixture of several neurotrophic factors and active peptide fragments, in relation to other neuroprotective agents normally used to treat ischemic stroke in clinics in nanoparticle-induced exacerbation of brain damage in heat stroke. It appears that cerebrolysin exerts the most superior neuroprotective effects in heat stress as compared to other neuroprotective agents on brain pathology in normal rats. Interestingly, to induce effective neuroprotection in nanoparticle-induced exacerbation of brain pathology a double dose of cerebrolysin is needed. On the other hand, double doses of the other drugs were quite ineffective in reducing brain damage. These observations suggest that the drug type and doses are important factors in attenuating nanoparticle-induced exacerbation of brain pathology in heat stroke. The functional significance and possible mechanisms of drug-induced neuroprotection in nanoparticle-treated, heat-stressed rats are discussed.

  17. Effect of therapeutic hypothermia on chromosomal aberration in perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    Bahubali D Gane

    2016-01-01

    Full Text Available Introduction: Perinatal asphyxia is a major cause for neonatal mortality and morbidity around the world. The reduction of O2results in the generation of reactive oxygen species which interact with nucleic acid and make alteration in the structure and functioning of the genome. We studied the effect of therapeutic hypothermia on chromosomes with karyotyping. Subjects and Methods: Babies in the hypothermia group were cooled for the first 72 h, using gel packs. Rectal temperature of 33–34°C was maintained. Blood sample was collected after completion of therapeutic hypothermia for Chromosomal analysis. It was done with IKAROS Karyotyping system, Metasystems, based on recommendations of International system of human cytogenetic nomenclature. Results: The median chromosomal aberration was lower in hypothermia [2(0-5] than control group [4(1-7] and chromatid breakage was commonest aberration seen. Chromosomal aberration was significantly higher in severe encephalopathy group than moderate encephalopathy group. Conclusion: We conclude that the TH significantly reduces DNA damage in perinatal asphyxia.

  18. Perinatal asphyxia and medical professional liability: A case series

    Directory of Open Access Journals (Sweden)

    Andrea Verzeletti

    2016-12-01

    Full Text Available In the context of medical professional liability, obstetrics is one of the most involved medical specialties because the unfavorable outcome of a pregnancy is difficult to accept for parents, who tend to reduce it to inappropriate care that occurred during pregnancy or birth. 32 cases of perinatal asphyxia were evaluated by the Institute of Forensic Medicine in Brescia during the period between 1999 and 2014 (13 in Civil Court and 19 in Penal Court. 9 out of the 32 pregnancies were twins, so the considerations were carried out on a total of 41 fetuses/newborns. Profiles of inadequacy were identified in 66% of cases (85% of the cases evaluated in Civil Court; 53% of the cases evaluated in Penal Court. The existence of a causal relationship between the medical conduct and the onset of asphyxia was recognized in 79% of civil cases and in 38% of penal cases. There is a “greater rigor” in the verification of causal relationship and malpractice profiles in penal cases compared to civil ones: this is in harmony with the most recent Italian Court decisions, characterized by compelling suspect’s protection in the presence of a reasonable doubt in criminal matters and by victim’s protection in civil ones.

  19. Persimmon leaf flavonoid induces brain ischemic tolerance in mice

    Institute of Scientific and Technical Information of China (English)

    Mingsan Miao; Xuexia Zhang; Linan Wang

    2013-01-01

    The persimmon leaf has been shown to improve cerebral ischemic outcomes; however, its mechanism of action remains unclear. In this study, mice were subjected to 10 minutes of ischemic preconditioning, and persimmon leaf flavonoid was orally administered for 5 days. Results showed that the persimmon leaf flavonoid significantly improved the content of tissue type plasminogen activator and 6-keto prostaglandin-F1 α in the cerebral cortex, decreased the content of thromboxane B2, and reduced the content of plasminogen activator inhibitor-1 in mice. Following optical microscopy, persimmon leaf flavonoid was also shown to reduce cell swelling and nuclear hyperchromatism in the cerebral cortex and hippocampus of mice. These results suggested that persimmon leaf flavonoid can effectively inhibit brain thrombosis, improve blood supply to the brain, and relieve ischemia-induced pathological damage, resulting in brain ischemic tolerance.

  20. Carbofuran-induced oxidative stress in mammalian brain.

    Science.gov (United States)

    Rai, Devendra K; Sharma, Bechan

    2007-09-01

    Chronic exposure to carbofuran, a carbamate pesticide, via oral administration has been reported to generate reactive oxygen species (ROS) in rat brain. However, information regarding the effect of short-term intraperitoneal (i.p.) carbofuran intoxication on oxidative stress is lacking. In the present study, the effect of carbofuran on oxidative indices in brain of Wistar rats has been determined by exposing the animals to three subacute concentrations (0.2, 0.4 and 0.8 mg/kg body weight) equivalent to 10, 20, and 40%, respectively, of its LD50 (i.p.) for 24 h. Rat liver has been used as a positive control. The results demonstrated that carbofuran treatment at the 3 concentrations tested caused significant increase in lipid peroxidation (LPO) by 12.50, 34.38, and 59.38%, respectively. The increased oxidative stress at same pesticide concentrations significantly induced activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase in rat brain; the impact on catalase being more marked only at high-pesticide doses (0.4 and 0.8 mg/kg body weight). Carbofuran also caused reduction in protein content of rat tissues tested. Rat brain was more severely affected by carbofuran than liver. The results clearly demonstrated that i.p. administration of carbofuran accelerated oxidative stress in rat brain in a dose-dependent manner.

  1. 心肺复苏后大鼠皮质区凋亡相关性微小RNA的表达变化%Expression changes in apoptosis-related microRNA in cerebral cortex after cardiopulmonary resuscitation in rat models of cardiac arrest induced by asphyxia

    Institute of Scientific and Technical Information of China (English)

    任妙丹; 何爱文; 陈寿权; 李章平; 乔江华; 李东芳; 李惠萍; 黄唯佳; 程俊彦

    2014-01-01

    Objective To observe the expression changes in apoptosis-related microRNA(miRNA) in cerebral cortex after cardiac arrest-cardiopulmonary resuscitation(CA-CPR)in rats and explore the factors that may affect the mechanism of CPR. Methods 24 clean male Sprague-Dawley(SD)rats were randomly divided into three groups,the normal control group,sham operation group and CA-CPR group(each n=8). The animal model of CA induced by asphyxia was established and CPR was performed. In the normal control group,no special management was performed. In the sham operation group,only abdominal cavity anesthesia,tracheotomy,vascular puncture and electrocardiogram(ECG)were performed without clamping the trachea and resuscitating. Normal feeding in normal control group and 24 hours after tracheotomy in sham operation group,at 24 hours after recovery of spontaneous circulation(ROSC)in CA-CPR group,cerebral cortex specimens were obtained for detection of the expression of miRNA by using real time fluorescence quantitative reverse transcription - polymerase chain reaction(RT-PCR). Flow cytometry(FCM)was used to detect the neurocyte apoptotic rate. Results Compared between normal control and sham operation groups,there were no significant differences in the expression of apoptosis-related miRNA and neurocyte apoptosis rate of cerebral cortex(both P>0.05). Compared with sham operation group,in CA-CPR group, 16 miRNA expressions were up-regulated,including Let-7c,miR-15a,miR-21,miR-24,miR-29,miR-29b, miR-34a, miR-103, miR-200a, miR-200b, miR-200c, miR-210, miR-326, miR-338-3p, miR-494 and miR-497,and there were 22 down-regulated,being Let-7a,Let-7b,Let-7d,Let-7e,miR-19a,miR-19b-1, miR-20a,miR-20b,miR-23a,miR-23b,miR-25,miR-98,miR-107,miR-122a,miR-125a,miR-125b, miR-145,miR-181a,miR-181c,miR-335,miR-384-5p and miR-422a. Eight miRNA had significant changes at 24 hours after ROSC,in which miR-15a,miR-21,miR-34a,miR-497 were up-regulated respectively for 6.831±2.625,8.122±3.442,5.349±2.010,6.590±3

  2. Quinolinic acid induces oxidative stress in rat brain synaptosomes.

    Science.gov (United States)

    Santamaría, A; Galván-Arzate, S; Lisý, V; Ali, S F; Duhart, H M; Osorio-Rico, L; Ríos, C; St'astný, F

    2001-03-26

    The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.

  3. Peripheral nerve injury induces adult brain neurogenesis and remodelling.

    Science.gov (United States)

    Rusanescu, Gabriel; Mao, Jianren

    2017-02-01

    Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI has been shown to induce spinal cord adult neurogenesis, which may contribute to the chronic increase in nociceptive sensitivity. Here, we show that CCI also induces rapid and profound asymmetrical anatomical rearrangements in the adult rodent cerebellum and pons. This remodelling occurs throughout the hindbrain, and in addition to regions involved in pain processing, also affects other sensory modalities. We demonstrate that these anatomical changes, partially reversible in the long term, result from adult neurogenesis. Neurogenic markers Mash1, Ngn2, doublecortin and Notch3 are widely expressed in the rodent cerebellum and pons, both under normal and injured conditions. CCI-induced hindbrain structural plasticity is absent in Notch3 knockout mice, a strain with impaired neuronal differentiation, demonstrating its dependence on adult neurogenesis. Grey matter and white matter structural changes in human brain, as a result of pain, injury or learned behaviours have been previously detected using non-invasive neuroimaging techniques. Because neurogenesis-mediated structural plasticity is thought to be restricted to the hippocampus and the subventricular zone, such anatomical rearrangements in other parts of the brain have been thought to result from neuronal plasticity or glial hypertrophy. Our findings suggest the presence of extensive neurogenesis-based structural plasticity in the adult mammalian brain, which may maintain a memory of basal sensory levels, and act as an adaptive mechanism to changes in sensory inputs.

  4. Induction by mercury compounds of brain metallothionein in rats: Hg{sup 0} exposure induces long-lived brain metallothionein

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, Akira; Nakano, Atsuhiro [Biochemistry Section, National Institute for Minamata Disease, Kumamoto (Japan); Hirayama, Kimiko [Kumamoto University, College of Medical Science (Japan)

    1998-03-01

    Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 {mu}mol/kg per day x 5 days, p.o.) showed brain Hg levels as high as 18 {mu}g/g with slight neurological signs 10 days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7-8 {mu}g Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for >2 weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT. (orig.) With 4 figs., 1 tab., 27 refs.

  5. Brain tumors induced in rats by human adenovirus type 12

    Directory of Open Access Journals (Sweden)

    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  6. Brain endocannabinoid system is involved in fluoxetine-induced anorexia.

    Science.gov (United States)

    Zarate, Jon; Churruca, Itziar; Pascual, Jesús; Casis, Luis; Sallés, Joan; Echevarría, Enrique

    2008-06-01

    In order to describe the effects of chronic fluoxetine administration on the brain endocannabinoid system in lean and obese Zucker rats, brain immunostaining for the CB1 and CB1-phosphorylated cannabinoid receptors was carried out. Obese Zucker rats showed significantly increased the numbers of neural cells positively immunostained for the CB1-phosphorylated receptor in the striatum, compared to their lean litter-mates. Chronic fluoxetine administration decreased the number of neural cells immunostained for CB1-phosphorylated receptor in several striatal and hippocampal regions of obese Zucker rats, compared to controls treated with saline. In contrast, no change in CB1-phosphorylated receptor immunostaining was observed in fluoxetine-treated lean rats, with respect to controls. Taken together, these results suggest the involvement of the hippocampal and striatal endocannabinoid receptor system in fluoxetine-induced anorexia in lean and obese Zucker rats.

  7. A Rare and Serious Syndrome That Requires Attention in Emergency Service: Traumatic Asphyxia

    Directory of Open Access Journals (Sweden)

    Gultekin Gulbahar

    2015-01-01

    Full Text Available Traumatic asphyxia is a rare syndrome caused by blunt thoracoabdominal trauma and characterized by cyanosis, edema, and subconjunctival and petechial hemorrhage on the face, neck, upper extremities, and the upper parts of the thorax. Traumatic asphyxia is usually diagnosed by history and inspection; however, the patient should be monitored more closely due to probable complications of thoracoabdominal injuries. Treatment is conservative, but the prognosis depends on the severity of the associated injuries. Herein we present a traumatic asphyxia due to an elevator accident in a 32-year-old male patient and discuss the diagnosis, treatment, and prognosis by reviewing the relevant literature.

  8. Cortical spreading depression-induced preconditioning in the brain

    Institute of Scientific and Technical Information of China (English)

    Ping-ping Shen; Shuai Hou; Di Ma; Ming-ming Zhao; Ming-qin Zhu; Jing-dian Zhang; Liang-shu Feng; Li Cui; Jia-chun Feng

    2016-01-01

    Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. Howev-er, the underlying mechanism for this phenomenon remains relatively unclear. To date, numerous issues exist regarding the experimental model used to precondition the brain with cortical spreading depression, such as the administration route, concentration of potassium chloride, induction time, duration of the protection provided by the treatment, the regional distribution of the protective effect, and the types of neurons responsible for the greater tolerance. In this review, we focus on the mechanisms underlying cor-tical spreading depression-induced tolerance in the brain, considering excitatory neurotransmission and metabolism, nitric oxide, genomic reprogramming, inlfammation, neurotropic factors, and cellular stress response. Speciifcally, we clarify the procedures and detailed information regarding cortical spreading de-pression-induced preconditioning and build a foundation for more comprehensive investigations in the ifeld of neural regeneration and clinical application in the future.

  9. Serotonin-induced brain glycogenolysis in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Pérez-Maceira, Jorge J; Mancebo, María J; Aldegunde, Manuel

    2012-09-01

    In this study, we evaluated the serotonin-mediated control of cerebral glycogen levels in the rainbow trout, Oncorhynchus mykiss. Intracerebroventricular (i.c.v.) administration of serotonin (5-HT) to normoglycemic trout (time and dose response) decreased glycogen levels in the brain and increased brain glycogen phosphorylase activity (time response). In hypoglycemic fish (that had been fasted for 5 and 10 days), there was a time-dependent decrease in brain glycogen levels; under these conditions, i.c.v. administration of 5-HT also reduced the brain glycogen content in fish that had been fasted for 5 days. In fish with local cerebral hypoglycemia (induced by 2-DG administration), the glycogen levels decreased and, as above, i.c.v. administration of 5-HT also lowered the glycogen content. In hyperglycemic fish, 5-HT did not affect glycogen levels. Administration of receptor agonists 5-HT1A (8-OH-DPAT), 5-HT1B (anpirtoline and CP93129) or 5-HT2 (α-m-5-HT) decreased the brain glycogen levels. This effect was antagonized by the administration of receptor antagonists 5-HT1A (WAY100135 and NAN190), 5-HT1B (NAS181) and 5-HT2B/C (SB206553). Administration of the receptor agonists (±)-DOI (5-HT2A/2C), m-CPP (5-HT2B/2C), BW723C86 (5-HT2B) and WAY 161503 (5-HT2C) led to decreases in the levels of brain glycogen. We found that 5-HT is involved in the modulation of brain glycogen homeostasis in the rainbow trout, causing a glycogenolytic effect when fish are in a normoglycemic or hypoglycemic state, but not when they are in a hyperglycemic state. 5-HT1A, 5-HT1B, 5HT2B and 5-HT2C-like receptors appeared to be involved in the glycogenolytic action of 5-HT, although the effect mediated by 5-HT1A or 5-HT1B was apparently stronger.

  10. Olive leaf extract inhibits lead poisoning-induced brain injury**

    Institute of Scientific and Technical Information of China (English)

    Yu Wang; Shengqing Wang; Wenhui Cui; Jiujun He; Zhenfu Wang; Xiaolu Yang

    2013-01-01

    Olive leaves have an antioxidant capacity, and olive leaf extract can protect the blood, spleen and hippocampus in lead-poisoned mice. However, little is known about the effects of olive leaf extract on lead-induced brain injury. This study was designed to determine whether olive leaf extract can inhibit lead-induced brain injury, and whether this effect is associated with antioxidant capacity. First, we established a mouse model of lead poisoning by continuous intragastric administration of lead acetate for 30 days. Two hours after successful model establishment, lead-poisoned mice were given olive leaf extract at doses of 250, 500 or 1 000 mg/kg daily by intragastric administration for 50 days. Under the transmission electron microscope, olive leaf extract attenuated neuronal and capil ary injury and reduced damage to organel es and the matrix around the capil aries in the frontal lobe of the cerebral cortex in the lead-poisoned mice. Olive leaf extract at a dose of 1 000 mg/kg had the greatest protective effect. Spectrophotometry showed that olive leaf extract significantly in-creased the activities of superoxide dismutase, catalase, alkaline phosphatase and acid phospha-tase, while it reduced malondialdehyde content, in a dose-dependent manner. Furthermore, im-munohistochemical staining revealed that olive leaf extract dose-dependently decreased Bax pro-tein expression in the cerebral cortex of lead-poisoned mice. Our findings indicate that olive leaf extract can inhibit lead-induced brain injury by increasing antioxidant capacity and reducing apop-tosis.

  11. Bacoside A: Role in Cigarette Smoking Induced Changes in Brain

    Directory of Open Access Journals (Sweden)

    G. Vani

    2015-01-01

    Full Text Available Cigarette smoking (CS is a major health hazard that exerts diverse physiologic and biochemical effects mediated by the components present and generated during smoking. Recent experimental studies have shown predisposition to several biological consequences from both active and passive cigarette smoke exposure. In particular, passive smoking is linked to a number of adverse health effects which are equally harmful as active smoking. A pragmatic approach should be considered for designing a pharmacological intervention to combat the adverse effects of passive smoking. This review describes the results from a controlled experimental condition, testing the effect of bacoside A (BA on the causal role of passive/secondhand smoke exposure that caused pathological and neurological changes in rat brain. Chronic exposure to cigarette smoke induced significant changes in rat brain histologically and at the neurotransmitter level, lipid peroxidation states, mitochondrial functions, membrane alterations, and apoptotic damage in rat brain. Bacoside A is a neuroactive agent isolated from Bacopa monnieri. As a neuroactive agent, BA was effective in combating these changes. Future research should examine the effects of BA at molecular level and assess its functional effects on neurobiological and behavioral processes associated with passive smoke.

  12. Bacoside A: Role in Cigarette Smoking Induced Changes in Brain.

    Science.gov (United States)

    Vani, G; Anbarasi, K; Shyamaladevi, C S

    2015-01-01

    Cigarette smoking (CS) is a major health hazard that exerts diverse physiologic and biochemical effects mediated by the components present and generated during smoking. Recent experimental studies have shown predisposition to several biological consequences from both active and passive cigarette smoke exposure. In particular, passive smoking is linked to a number of adverse health effects which are equally harmful as active smoking. A pragmatic approach should be considered for designing a pharmacological intervention to combat the adverse effects of passive smoking. This review describes the results from a controlled experimental condition, testing the effect of bacoside A (BA) on the causal role of passive/secondhand smoke exposure that caused pathological and neurological changes in rat brain. Chronic exposure to cigarette smoke induced significant changes in rat brain histologically and at the neurotransmitter level, lipid peroxidation states, mitochondrial functions, membrane alterations, and apoptotic damage in rat brain. Bacoside A is a neuroactive agent isolated from Bacopa monnieri. As a neuroactive agent, BA was effective in combating these changes. Future research should examine the effects of BA at molecular level and assess its functional effects on neurobiological and behavioral processes associated with passive smoke.

  13. Food-induced brain responses and eating behaviour.

    Science.gov (United States)

    Smeets, Paul A M; Charbonnier, Lisette; van Meer, Floor; van der Laan, Laura N; Spetter, Maartje S

    2012-11-01

    The brain governs food intake behaviour by integrating many different internal and external state and trait-related signals. Understanding how the decisions to start and to stop eating are made is crucial to our understanding of (maladaptive patterns of) eating behaviour. Here, we aim to (1) review the current state of the field of 'nutritional neuroscience' with a focus on the interplay between food-induced brain responses and eating behaviour and (2) highlight research needs and techniques that could be used to address these. The brain responses associated with sensory stimulation (sight, olfaction and taste), gastric distension, gut hormone administration and food consumption are the subject of increasing investigation. Nevertheless, only few studies have examined relations between brain responses and eating behaviour. However, the neural circuits underlying eating behaviour are to a large extent generic, including reward, self-control, learning and decision-making circuitry. These limbic and prefrontal circuits interact with the hypothalamus, a key homeostatic area. Target areas for further elucidating the regulation of food intake are: (eating) habit and food preference formation and modification, the neural correlates of self-control, nutrient sensing and dietary learning, and the regulation of body adiposity. Moreover, to foster significant progress, data from multiple studies need to be integrated. This requires standardisation of (neuroimaging) measures, data sharing and the application and development of existing advanced analysis and modelling techniques to nutritional neuroscience data. In the next 20 years, nutritional neuroscience will have to prove its potential for providing insights that can be used to tackle detrimental eating behaviour.

  14. Gastroesophageal manometry and 24-hour double pH monitoring in neonates with birth asphyxia

    Institute of Scientific and Technical Information of China (English)

    Mei Sun; Wei-Lin Wang; Wei Wang; De-Liang Wen; Hui Zhang; Yu-Kun Han

    2001-01-01

    @@ INTRODUCTION Birth asphyxia may lead to disturbances of gastroenteric motility of newborn infants[1.2] . The change of gut pressure and reflux are the major manifestations of the motor disturbance [3-9] . To evaluate the effects of perinatal asphyxia on the gastroenteric motility, gastric and esophageal pressure and double pH were measured in a group of asphyxiated newborns. And. their pathophysiological and anatomical effects on gastroenteric function were discussed.

  15. Detection of electroporation-induced membrane permeabilization states in the brain using diffusion-weighted MRI

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Hansen, Rasmus H; Agerholm-Larsen, Birgit

    2015-01-01

    (DW-MRI) as a quantitative method for detecting EP-induced membrane permeabilization of brain tissue using a rat brain model. MATERIAL AND METHODS: Fifty-four anesthetized Sprague-Dawley male rats were electroporated in the right hemisphere, using different voltage levels to induce no permeabilization......-induced permeabilization of brain tissue and to some extent of differentiating NP, TMP and PMP using appropriate scan timing....

  16. Hypoxic preconditioning induces neuroprotective stanniocalcin-1 in brain via IL-6 signaling

    DEFF Research Database (Denmark)

    Westberg, Johan A; Serlachius, Martina; Lankila, Petri

    2007-01-01

    . Increased expression of IL-6 is evident, particularly in the lungs of animals subjected to hypoxic preconditioning. Stanniocalcin-1 (STC-1) is a 56-kDa homodimeric glycoprotein originally discovered in bony fish, where it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. We...... mRNA levels in brains of wild-type and IL-6 deficient mice. Furthermore, we monitored the Stc-1 response in brains of wild-type and transgenic mice, overexpressing IL-6 in the astroglia, before and after induced brain injury. RESULTS: Hypoxic preconditioning induced an upregulated expression of Stc......-1 in brains of wild-type but not of IL-6-deficient mice. Induced brain injury elicited a stronger STC-1 response in brains of transgenic mice, with targeted astroglial IL-6 expression, than in brains of wild-type mice. Moreover, IL-6 induced STC-1 expression via MAPK signaling in neural Paju cells...

  17. Inducible gene manipulations in brain serotonergic neurons of transgenic rats.

    Directory of Open Access Journals (Sweden)

    Tillmann Weber

    Full Text Available The serotonergic (5-HT system has been implicated in various physiological processes and neuropsychiatric disorders, but in many aspects its role in normal and pathologic brain function is still unclear. One reason for this might be the lack of appropriate animal models which can address the complexity of physiological and pathophysiological 5-HT functioning. In this respect, rats offer many advantages over mice as they have been the animal of choice for sophisticated neurophysiological and behavioral studies. However, only recently technologies for the targeted and tissue specific modification of rat genes - a prerequisite for a detailed study of the 5-HT system - have been successfully developed. Here, we describe a rat transgenic system for inducible gene manipulations in 5-HT neurons. We generated a Cre driver line consisting of a tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2 regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was detected in four transgenic TPH2-CreERT2 rat founder lines. For functional analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG-loxP.EGFP, in which EGFP is expressed after Cre-mediated removal of a loxP-flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre reporter line and demonstrate its applicability for monitoring Cre-mediated recombination in all major neuronal subpopulations of the rat brain. Upon tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen administration, EGFP is only expressed in few 5-HT neurons which confirms minimal background recombination. This 5-HT neuron specific CreERT2 line allows Cre-mediated, inducible gene deletion or gene overexpression in transgenic rats which provides new opportunities to decipher the complex functions of the mammalian serotonergic system.

  18. Signal Transduction Pathways Involved in Brain Death-Induced Renal Injury

    NARCIS (Netherlands)

    Bouma, H. R.; Ploeg, R. J.; Schuurs, T. A.

    2009-01-01

    Kidneys derived from brain death organ donors show an inferior survival when compared to kidneys derived from living donors. Brain death is known to induce organ injury by evoking an inflammatory response in the donor. Neuronal injury triggers an inflammatory response in the brain, leading to endoth

  19. Training-induced behavioral and brain plasticity in inhibitory control

    Directory of Open Access Journals (Sweden)

    Lucas eSpierer

    2013-08-01

    Full Text Available Deficits in inhibitory control, the ability to suppress ongoing or planned motor or cognitive processes, contribute to many psychiatric and neurological disorders. The rehabilitation of inhibition-related disorders may therefore benefit from neuroplasticity-based training protocols aiming at normalizing inhibitory control proficiency and the underlying brain networks. Current literature on training-induced behavioral and brain plasticity in inhibitory control suggests that improvements may follow either from the development of automatic forms of inhibition or from the strengthening of top-down, controlled inhibition. Automatic inhibition develops in conditions of consistent and repeated associations between inhibition-triggering stimuli and stopping goals. Once established, the stop signals directly elicit inhibition, thereby bypassing slow, top-down executive control and accelerating stopping processes. In contrast, training regimens involving varying stimulus-response associations or frequent inhibition failures prevent the development of automatic inhibition and thus strengthen top-down inhibitory processes rather than bottom-up ones. We discuss these findings in terms of developing optimal inhibitory control training regimens for rehabilitation purposes.

  20. [Cellular and molecular mechanisms of radiation-induced brain injury: can peripheral markers be detected?].

    Science.gov (United States)

    Piskunov, A K; Nikitin, K V; Potapov, A A

    2015-01-01

    Investigation of the mechanisms of radiation-induced brain injury is a relevant fundamental objective of radiobiology and neuroradiology. Damage to the healthy brain tissue is the key factor limiting the application of radiation therapy in patients with nervous systems neoplasms. Furthermore, postradiation brain injury can be clinically indiscernible from continued tumor growth and requires differential diagnosis. Thus, there exists high demand for biomarkers of radiation effects on the brain in neurosurgery and radiobiology. These markers could be used for better understanding and quantifying the effects of ionizing radiation on brain tissues, as well as for elaborating personalized therapy. Despite the high demand, biomarkers of radiation-induced brain injury have not been identified thus far. The cellular and molecular mechanisms of the effect of ionizing radiation on the brain were analyzed in this review in order to identify potential biomarkers of radiation-induced injury to nervous tissue.

  1. Ultrasound-induced blood-brain barrier opening.

    Science.gov (United States)

    Konofagou, Elisa E; Tung, Yao-Sheng; Choi, James; Deffieux, Thomas; Baseri, Babak; Vlachos, Fotios

    2012-06-01

    Over 4 million U.S. men and women suffer from Alzheimer's disease; 1 million from Parkinson's disease; 350,000 from multiple sclerosis (MS); and 20,000 from amyotrophic lateral sclerosis (ALS). Worldwide, these four diseases account for more than 20 million patients. In addition, aging greatly increases the risk of neurodegenerative disease. Although great progress has been made in recent years toward understanding of these diseases, few effective treatments and no cures are currently available. This is mainly due to the impermeability of the blood-brain barrier (BBB) that allows only 5% of the 7000 small-molecule drugs available to treat only a tiny fraction of these diseases. On the other hand, safe and localized opening of the BBB has been proven to present a significant challenge. Of the methods used for BBB disruption shown to be effective, Focused Ultrasound (FUS), in conjunction with microbubbles, is the only technique that can induce localized BBB opening noninvasively and regionally. FUS may thus have a huge impact in trans-BBB brain drug delivery. The primary objective in this paper is to elucidate the interactions between ultrasound, microbubbles and the local microenvironment during BBB opening with FUS, which are responsible for inducing the BBB disruption. The mechanism of the BBB opening in vivo is monitored through the MRI and passive cavitation detection (PCD), and the safety of BBB disruption is assessed using H&E histology at distinct pressures, pulse lengths and microbubble diameters. It is hereby shown that the BBB can be disrupted safely and transiently under specific acoustic pressures (under 0.45 MPa) and microbubble (diameter under 8 μm) conditions.

  2. Neural correlates of induced motion perception in the human brain.

    Science.gov (United States)

    Takemura, Hiromasa; Ashida, Hiroshi; Amano, Kaoru; Kitaoka, Akiyoshi; Murakami, Ikuya

    2012-10-10

    A physically stationary stimulus surrounded by a moving stimulus appears to move in the opposite direction. There are similarities between the characteristics of this phenomenon of induced motion and surround suppression of directionally selective neurons in the brain. Here, functional magnetic resonance imaging was used to investigate the link between the subjective perception of induced motion and cortical activity. The visual stimuli consisted of a central drifting sinusoid surrounded by a moving random-dot pattern. The change in cortical activity in response to changes in speed and direction of the central stimulus was measured. The human cortical area hMT+ showed the greatest activation when the central stimulus moved at a fast speed in the direction opposite to that of the surround. More importantly, the activity in this area was the lowest when the central stimulus moved in the same direction as the surround and at a speed such that the central stimulus appeared to be stationary. The results indicate that the activity in hMT+ is related to perceived speed modulated by induced motion rather than to physical speed or a kinetic boundary. Early visual areas (V1, V2, V3, and V3A) showed a similar pattern; however, the relationship to perceived speed was not as clear as that in hMT+. These results suggest that hMT+ may be a neural correlate of induced motion perception and play an important role in contrasting motion signals in relation to their surrounding context and adaptively modulating our motion perception depending on the spatial context.

  3. Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia.

    Directory of Open Access Journals (Sweden)

    Ting Yang

    Full Text Available It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE. Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon, in reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic levels of sevoflurane (0.35% or xenon (35% were tested in a rat model of intrauterine perinatal asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the number of viable neurons on postnatal day (PND 7. A separate cohort of pups was nurtured by a surrogate mother for 50 days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3 positive (apoptotic neurons and increased cell viability in the hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with neuroprotective properties may be effective in preventing HIE and should be

  4. 5-lipoxygenase expression in a brain damage model induced by chronic oral administration of aluminum

    Institute of Scientific and Technical Information of China (English)

    Yongquan Pan; Peng Zhang; Junqing Yang; Qiang Su

    2010-01-01

    A preliminary study has found that the 5-lipoxygenase inhibitor, caffeic acid, has a marked protective effect on acute brain injury induced by intracerebroventricular microinjection of aluminum.In this experiment, chronic brain injury and neuronal degeneration model was established in rats by chronic oral administration of aluminum, and then intervened using caffeic acid. Results showed that caffeic acid can downregulate chronic aluminum overload-induced 5-lipoxygenase mRNA and protein expression, and repair the aluminum overload-induced hippocampal neuronal damage andspatial orientation impairment. It is suggested that direct intervention of 5-lipoxygenase expression has a neuroprotective role in the degeneration induced by chronic aluminum overload brain injury model.

  5. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

    Science.gov (United States)

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2014-10-03

    Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

  6. 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.

  7. Measuring and Inducing Brain Plasticity in Chronic Aphasia

    Science.gov (United States)

    Fridriksson, Julius

    2011-01-01

    Brain plasticity associated with anomia recovery in aphasia is poorly understood. Here, I review four recent studies from my lab that focused on brain modulation associated with long-term anomia outcome, its behavioral treatment, and the use of transcranial brain stimulation to enhance anomia treatment success in individuals with chronic aphasia…

  8. Increased leakage of brain antigens after traumatic brain injury and effect of immune tolerance induced by cells on traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    YAN Hua; ZHANG Hong-wei; WU Qiao-li; ZHANG Guo-bin; LIU Kui; ZHI Da-shi; HU Zhen-bo; ZENG Xian-wei

    2012-01-01

    control group.IL-10 and TGF-β were elevated compared to the control group.Conclusions Traumatic brain injury can lead to strongerarachnoid granulations (AGs) permeability; umbilical cord mesenchymal stem cells and immature dendritic cells can induce immune tolerance and reduce inflammation and anti-brain antibodies to protect the brain tissue.

  9. Hypoxia-inducible factor-1α contributes to brain edema after stroke by regulating aquaporins and glycerol distribution in brain.

    Science.gov (United States)

    Higashida, Tetsuhiro; Peng, Changya; Li, Jie; Dornbos, David; Teng, Kailing; Li, Xiaohua; Kinni, Harish; Guthikonda, Murali; Ding, Yuchuan

    2011-02-01

    Brain edema following stroke is a critical clinical problem due to its association with increased morbidity and mortality. Despite its significance, present treatment for brain edema simply provides symptomatic relief due to the fact that molecular mechanisms underlying brain edema remain poorly understood. The present study investigated the role of hypoxia-inducible factor-1α (HIF-1α) and aquaporins (AQP-4 and -9) in regulating cerebral glycerol accumulation and inducing brain edema in a rodent model of stroke. Two-hours of middle cerebral artery occlusion (MCAO) followed by reperfusion was performed in male Sprague-Dawley rats (250-280 g). Anti-AQP-4 antibody, anti-AQP-9 antibody, or 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α) was given at the time of MCAO. The rats were sacrificed at 1 and 24 hours after reperfusion and their brains were examined. Extracellular and intracellular glycerol concentration of brain tissue was calculated with an enzymatic glycerol assay. The protein expressions of HIF-1α, AQP-4 and AQP-9 were determined by Western blotting. Brain edema was measured by brain water content. Compared to control, edema (p < 0.01), increased glycerol (p < 0.05), and enhanced expressions of HIF-1α, AQP-4, and AQP-9 (p < 0.05) were observed after stroke. With inhibition of AQP-4, AQP-9 or HIF-1α, edema and extracellular glycerol were significantly (p < 0.01) decreased while intracellular glycerol was increased (p < 0.01) 1 hour after stroke. Inhibition of HIF-1α with 2ME2 suppressed (p < 0.01) the expression of AQP-4 and AQP-9. These findings suggest that HIF-1α serves as an upstream regulator of cerebral glycerol concentrations and brain edema via a molecular pathway involving AQP-4 and AQP-9. Pharmacological blockade of this pathway in stroke patients may provide novel therapeutic strategies.

  10. Perinatal risk factors for neonatal asphyxia in Vali-e-Asr hospital, Tehran-Iran

    Directory of Open Access Journals (Sweden)

    Fatemeh Nayeri

    2012-01-01

    Full Text Available Background: Asphyxia is a medical condition in which placental or pulmonary gas exchange is impaired or they cease all together, typically producing a combination of progressive hypoxemia and hypercapnea. Objective: In addition to regional differences in its etiology; it is important to know its risk factors. Materials and Methods: This is a case-control study, all neonates born from May 2002 to September 2005 in Vali-e-Asr Hospital were studied. 9488 newborns were born of which 6091 of the live patients were hospitalized in NICU. 546 newborns were studied as case and control group. 260 neonates (48% were female and 286 neonates (52% were male. Among the neonates who were admitted, 182 of them were diagnosed with asphyxia and twice of them (364 newborns were selected as a control group. The variables consist of; gestational age, type of delivery, birth weight, prenatal care, pregnancy and peripartum complications and neonatal disorders. Results: Our studies showed that 35 (19.2% patients had mild asphyxia, 107 (58.8% had moderate asphyxia and 40 (22% were diagnosed as severe asphyxia. Mean maternal age was 34.23±4.29yr; (range: 23-38 yr; and mean of parity was 2±1.2; (range: 1-8. Risk factors in our study included emergent Caesarian Section, preterm labor (<37w, low birth weight (<2500g, 5 minute Apgar (less than 6, need for resuscitation, nuchal cord, impaired Biophysical Profile, neonatal anemia, and maternal infertility. Conclusion: All risk factors listed above play a role in asphyxia. The majority of these factors are avoidable by means of good perinatal care

  11. Observations on increased accidental asphyxia deaths in infancy while cosleeping in the state of Maryland.

    Science.gov (United States)

    Li, Ling; Zhang, Yang; Zielke, Ron H; Ping, Yan; Fowler, David R

    2009-12-01

    The Office of the Chief Medical Examiner (OCME) has recorded a significant increase of accidental asphyxia deaths in infancy associated with cosleeping in the state of Maryland in 2003. A total of 102 infants died suddenly and unexpectedly during 2003 in the state of Maryland. Of the 102 infants, 46 (45%) were found cosleeping. The frequency of cosleeping among these 102 infants was 28% (29/102) for black infants and 15% (15/102) for white infants. Ten of the 46 cosleeping infant deaths (20%) were determined to be the result of accidental asphyxia, and 28 cosleeping infant deaths (59%) were classified as "undetermined" because the possibility of asphyxia due to overlay while cosleeping could not be ruled out. Only 21 cases were determined to be Sudden Infant Death Syndrome (SIDS), which is consistent with the continuous decline of SIDS death in Maryland since 1994. The age of asphyxiated cosleeping infants ranged from 15 days to 9 months. Nine out of the 10 asphyxia deaths were black infants. The most common sleeping location of the asphyxia infants was on a couch/sofa, followed by an adult bed. Crib availability was documented in all of the cosleeping cases. A majority (61%) of the cosleeping infants (28/46) had an available crib or bassinet at home and 9 out of 10 asphyxiated cosleeping infants had a crib at home at the time of the incident. This report focuses on the detailed scene investigation findings of infant victims who died of asphyxia while cosleeping. The shift of diagnosis in sudden infant death investigation is also addressed.

  12. Asphyxia-related risk factors and their timing in spastic cerebral palsy

    DEFF Research Database (Denmark)

    Nielsen, Lene F.; Schendel, Diana; Grove, Jakob;

    2008-01-01

    Objective To investigate the association of asphyxia-related conditions (reducing blood flow or blood oxygen levels in the fetus) with spastic cerebral palsy (CP) considering different gestational age groups and the timing of risk. Design Population-based case-control study. Setting Danish Cerebral...... Palsy Register in eastern Denmark and Danish Medical Birth Register. Population or Sample 271 singletons with spastic CP and 217 singleton controls, frequency matched by gestational age group, born 1982-1990 in eastern Denmark. Methods Data were abstracted from medical records, and a priori asphyxia...

  13. Risk Factors for Birth Asphyxia in an Urban Health Facility in Cameroon

    OpenAIRE

    Chiabi, Andreas; Nguefack, Seraphin; Evelyne MAH; NODEM, Sostenne; Mbuagbaw, Lawrence; Mbonda, Elie; TCHOKOTEU, Pierre-Fernand; Anderson DOH

    2013-01-01

    How to Cite This Article: Chiabi A, Nguefack S, Mah E, Nodem S, Mbuagbaw L, Mbonda E, Tchokoteu PF, Doh A. Risk Factors for Birth Asphyxia in an Urban Health Facility in Cameroon. Iran J Child Neurol. 2013 Summer; 7(3):46-54.ObjectiveThe World Health Organization (WHO) estimates that 4 million children are born with asphyxia every year, of which 1 million die and an equal number survive with severe neurologic sequelae. The purpose of this study was to identify the risk factors of birth asphyx...

  14. PERINATAL ASPHYXIA-CLINICAL PROFILE IN M R A MEDICAL COLLEGE AMBEDKAR NAGAR UTTAR PRADESH

    Directory of Open Access Journals (Sweden)

    Bhavana

    2014-10-01

    Full Text Available BACKGROUND: Perinatal asphyxia is a condition during the first and second stage of labour in which impaired gas exchange leads to fetal hypoxia and hypercarbia. Perinatal asphyxia is a common cause of mortality and morbidity in neonatal intensive care units. Although many studies are there but no such study was available from the studied area. So this study was conducted to know the clinical correlations of perinatal asphyxia in this area. AIMS: This study was conducted to study various maternal and neonatal risk factors for perinatal asphyxia and to study the various clinical features of perinatal asphyxia with special reference to central nervous system and to grade the encephalopathy as per Sarnat and Sarnat staging. SETTINGS: Neonatal intensive care unit of MRA Medical College Ambedkar Nagar. DESIGN: Observational study. MATERIAL AND METHODS: Neonates admitted in NICU with history of perinatal asphyxia as per the definition by WHO. RESULTS: Various feto-maternal factors were associated with asphyxiated neonates. Those observed to be significantly associated with asphyxia (in decreasing order of risk included no antenatal check-ups (50%, home delivery (40%,fetal distress (25%, meconium stained liquor (23.3%, prolonged labour (20%, prolonged rupture of membranes(16.7% antepartum haemorrhage (13.3%,severe anemia (10%, eclampsia(8.3%,premature rupture of membrane (6.6%, obstructed labour (5%.In many of the cases more than one risk factor was associated. Of the total 120 asphyxiated neonates 80 (66.6% had encephalopathy. As per Sarnat and Sarnat staging 24(20% were in stage 1, 36(30% were in stage 2 and 20(16.6% were in stage 3 of Hypoxic Ischemic Encephalopathy. Other than neurological dysfunction symptoms which were also associated in asphyxiated newborn were feeding difficulties(75%, respiratory distress (25%, meconium aspiration syndrome(13.3%,acute renal Failure(8.3%,apnea(4.2%. CONCLUSION: Perinatal asphyxia is a common cause of morbidity

  15. Cannabinoid-induced changes in respiration of brain mitochondria.

    Science.gov (United States)

    Fišar, Zdeněk; Singh, Namrata; Hroudová, Jana

    2014-11-18

    Cannabinoids exert various biological effects that are either receptor-mediated or independent of receptor signaling. Mitochondrial effects of cannabinoids were interpreted either as non-receptor-mediated alteration of mitochondrial membranes, or as indirect consequences of activation of plasma membrane type 1 cannabinoid receptors (CB1). Recently, CB1 receptors were confirmed to be localized to the membranes of neuronal mitochondria, where their activation directly regulates respiration and energy production. Here, we performed in-depth analysis of cannabinoid-induced changes of mitochondrial respiration using both an antagonist/inverse agonist of CB1 receptors, AM251 and the cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol (THC), cannabidiol, anandamide, and WIN 55,212-2. Relationships were determined between cannabinoid concentration and respiratory rate driven by substrates of complex I, II or IV in pig brain mitochondria. Either full or partial inhibition of respiratory rate was found for the tested drugs, with an IC50 in the micromolar range, which verified the significant role of non-receptor-mediated mechanism in inhibiting mitochondrial respiration. Effect of stepwise application of THC and AM251 evidenced protective role of AM251 and corroborated the participation of CB1 receptor activation in the inhibition of mitochondrial respiration. We proposed a model, which includes both receptor- and non-receptor-mediated mechanisms of cannabinoid action on mitochondrial respiration. This model explains both the inhibitory effect of cannabinoids and the protective effect of the CB1 receptor inverse agonist.

  16. Modulation of brain dead induced inflammation by vagus nerve stimulation.

    Science.gov (United States)

    Hoeger, S; Bergstraesser, C; Selhorst, J; Fontana, J; Birck, R; Waldherr, R; Beck, G; Sticht, C; Seelen, M A; van Son, W J; Leuvenink, H; Ploeg, R; Schnuelle, P; Yard, B A

    2010-03-01

    Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (HRV) was assessed by ECG. The vagus nerve was electrically stimulated (BD + STIM) during BD. Intestine, kidney, heart and liver were recovered after 6 hours. Affymetrix chip-analysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNFalpha concentrations. Renal transplantations were performed to address the influence of vagus nerve stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus nerve stimulation inhibited the increase in serum TNFalpha concentrations and resulted in down-regulation of a multiplicity of pro-inflammatory genes in intestinal tissue. In renal tissue vagal stimulation significantly decreased the expression of E-selectin, IL1beta and ITGA6. Renal function was significantly better in recipients that received a graft from a BD + STIM donor. Our study demonstrates impairment of the parasympathetic nervous system during BD and inhibition of serum TNFalpha through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients.

  17. Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.

    Science.gov (United States)

    Kelpke, Stacey S; Chen, Bo; Bradley, Kelley M; Teng, Xinjun; Chumley, Phillip; Brandon, Angela; Yancey, Brett; Moore, Brandon; Head, Hughston; Viera, Liliana; Thompson, John A; Crossman, David K; Bray, Molly S; Eckhoff, Devin E; Agarwal, Anupam; Patel, Rakesh P

    2012-08-01

    Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.

  18. Treatment of surgical brain injury by immune tolerance induced by intrathymic and hepatic portal vein injection of brain antigens

    Science.gov (United States)

    Yang, Weijian; Liu, Yong; Liu, Baolong; Tan, Huajun; Lu, Hao; Wang, Hong; Yan, Hua

    2016-01-01

    Surgical brain injury (SBI) defines complications induced by intracranial surgery, such as cerebral edema and other secondary injuries. In our study, intrathymic and hepatic portal vein injection of allogeneic myelin basic protein (MBP) or autogeneic brain cell suspensions were administered to a standard SBI model. Serum pro-inflammatory IL-2, anti-inflammatory IL-4 concentrations and the CD4+T/CD8+T ratio were measured at 1, 3, 7, 14 and 21 d after surgery to verify the establishment of immune tolerance. Furthermore, we confirmed neuroprotective effects by evaluating neurological scores at 1, 3, 7, 14 and 21 d after SBI. Anti-Fas ligand (FasL) immunohistochemistry and TUNEL assays of brain sections were tested at 21 d after surgery. Intrathymic injections of MBP or autogeneic brain cell suspensions functioned by both suppressing secondary inflammatory reactions and improving prognoses, whereas hepatic portal vein injections of autogeneic brain cell suspensions exerted a better effect than MBP. Intrathymic and hepatic portal vein injections of MBP had equal effects on reducing secondary inflammation and improving prognoses. Otherwise, hepatic portal vein injections of autogeneic brain cell suspensions had better outcomes than intrathymic injections of autogeneic brain cell suspensions. Moreover, the benefit of injecting antigens into the thymus was outweighed by hepatic portal vein injections. PMID:27554621

  19. Alcohol-induced neuroapoptosis in the fetal macaque brain.

    Science.gov (United States)

    Farber, Nuri B; Creeley, Catherine E; Olney, John W

    2010-10-01

    The ability of brief exposure to alcohol to cause widespread neuroapoptosis in the developing rodent brain and subsequent long-term neurocognitive deficits has been proposed as a mechanism underlying the neurobehavioral deficits seen in fetal alcohol spectrum disorder (FASD). It is unknown whether brief exposure to alcohol causes apoptosis in the fetal primate brain. Pregnant fascicularis macaques at various stages of gestation (G105 to G155) were exposed to alcohol for 8h, then the fetuses were delivered by caesarean section and their brains perfused with fixative and evaluated for apoptosis. Compared to saline control brains, the ethanol-exposed brains displayed a pattern of neuroapoptosis that was widespread and similar to that caused by alcohol in infant rodent brain. The observed increase in apoptosis was on the order of 60-fold. We propose that the apoptogenic action of alcohol could explain many of the neuropathological changes and long-term neuropsychiatric disturbances associated with human FASD.

  20. Measuring and inducing brain plasticity in chronic aphasia

    OpenAIRE

    Fridriksson, Julius

    2011-01-01

    Brain plasticity associated with anomia recovery in aphasia is poorly understood. Here, I review four recent studies from my lab that focused on brain modulation associated with long-term anomia outcome, its behavioral treatment, and the use of transcranial brain stimulation to enhance anomia treatment success in individuals with chronic aphasia caused by left hemisphere stroke. In a study that included 15 participants with aphasia who were compared to a group of 10 normal control subjects, w...

  1. Tunicamycin-induced unfolded protein response in the developing mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Haiping; Wang, Xin [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-Ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203 (China); Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Zhang, Zhuo; Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

    2015-03-15

    Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.

  2. Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain.

    Science.gov (United States)

    Daniel, Sheril; Limson, Janice L; Dairam, Amichand; Watkins, Gareth M; Daya, Santy

    2004-02-01

    Curcumin, the major constituent of turmeric is a known, naturally occurring antioxidant. The present study examined the ability of this compound to protect against lead-induced damage to hippocampal cells of male Wistar rats, as well as lipid peroxidation induced by lead and cadmium in rat brain homogenate. The thiobarbituric assay (TBA) was used to measure the extent of lipid peroxidation induced by lead and cadmium in rat brain homogenate. The results show that curcumin significantly protects against lipid peroxidation induced by both these toxic metals. Coronal brain sections of rats injected intraperitoneally with lead acetate (20 mg/kg) in the presence and absence of curcumin (30 mg/kg) were compared microscopically to determine the extent of lead-induced damage to the cells in the hippocampal CA1 and CA3 regions, and to establish the capacity of curcumin to prevent such damage. Lead-induced damage to the neurons was significantly curtailed in the rats injected with curcumin. Possible chelation of lead and cadmium by curcumin as its mechanism of neuroprotection against such heavy metal insult to the brain was investigated using electrochemical, ultraviolet spectrophotometric and infrared spectroscopic analyses. The results of the study show that there is an interaction between curcumin and both cadmium and lead, with the possible formation of a complex between the metal and this ligand. These results imply that curcumin could be used therapeutically to chelate these toxic metals, thus potentially reducing their neurotoxicity and tissue damage.

  3. Fatores associados à asfixia perinatal Factors associated with perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    Alfredo de Almeida Cunha

    2004-12-01

    stepwise logistic regression model. RESULTS: there were 39 (14% depressed newborns which were compared to 238 (86% not depressed babies. The final analysis (multivariate showed an association between low Apgar score and previous case of stillbirth (OR=52.6, preterm labor threat (OR=33.8, low birth weight, less than 2,500 g body weight (OR=11.2 and previous cesarean section (OR=7.4. Some factors acted as a protection, including birth weight, in grams (OR=0.9, female sex of the newborn (OR=0.1, medical complications (OR=0.4 and prematurity (gestational age < 37 weeks, OR=0.1. CONCLUSION: the study may help in the identification of fetuses at great risk of asphyxia, allowing proper reference within the health system and planning of effective assistance in neonatal intensive care units.

  4. The Role of Exercise-Induced Cardiovascular Adaptation in Brain Health.

    Science.gov (United States)

    Tarumi, Takashi; Zhang, Rong

    2015-10-01

    Regular aerobic exercise improves brain health; however, a potential dose-response relationship and the underling physiological mechanisms remain unclear. Existing data support the following hypotheses: 1) exercise-induced cardiovascular adaptation plays an important role in improving brain perfusion, structure, and function, and 2) a hormetic relation seems to exist between the intensity of exercise and brain health, which needs to be further elucidated.

  5. Blood-brain barrier dysfunction-induced inflammatory signaling in brain pathology and epileptogenesis.

    Science.gov (United States)

    Kim, Soo Young; Buckwalter, Marion; Soreq, Hermona; Vezzani, Annamaria; Kaufer, Daniela

    2012-11-01

    The protection of the brain from blood-borne toxins, proteins, and cells is critical to the brain's normal function. Accordingly, a compromise in the blood-brain barrier (BBB) function accompanies many neurologic disorders, and is tightly associated with brain inflammatory processes initiated by both infiltrating leukocytes from the blood, and activation of glial cells. Those inflammatory processes contribute to determining the severity and prognosis of numerous neurologic disorders, and can both cause, and result from BBB dysfunction. In this review we examine the role of BBB and inflammatory responses, in particular activation of transforming grown factor β (TGFβ) signaling, in epilepsy, stroke, and Parkinson's disease.

  6. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions.

  7. Functional MRI of food-induced brain responses

    NARCIS (Netherlands)

    Smeets, P.A.M.

    2006-01-01

    The ultimate goal of this research was to find central biomarkers of satiety, i.e., physiological measures in the brain that relate to subjectively rated appetite, actual food intake, or both. This thesis describes the changes in brain activity in response to food stimuli as measured by functional M

  8. Correlation between clinical and histologic findings in the human neonatal hippocampus after perinatal asphyxia

    NARCIS (Netherlands)

    Schiering, I.A.M.; de Haan, T.R.; Niermeijer, J.M.F.; Koelman, J.H.; Majoie, C.B.L.M.; Reneman, L.; Aronica, E.

    2014-01-01

    Hypoxic ischemic encephalopathy after perinatal asphyxia is a major cause of mortality and morbidity in infants. Here, we evaluated pathologic changes in the hippocampi of a cohort of 16 deceased full-term asphyxiated infants who died from January 2000 to January 2009. Histochemical and immunocytoch

  9. Cerebellar cytokine expression in a rat model for fetal asphyctic preconditioning and perinatal asphyxia

    DEFF Research Database (Denmark)

    Vlassaks, Evi; Brudek, Tomasz; Pakkenberg, Bente

    2014-01-01

    in saline for 19 min. Pro- and anti-inflammatory cytokine expression were assessed by real-time PCR and immunohistochemistry in cerebella of newborn rats. We found that tumor necrosis factor alpha and interleukin-10 mRNA were increased 12 h after fetal asphyxia, while the inflammatory cytokine response...

  10. Long-lasting effects of perinatal asphyxia on exploration, memory and incentive downshift.

    Science.gov (United States)

    Galeano, Pablo; Blanco Calvo, Eduardo; Madureira de Oliveira, Diêgo; Cuenya, Lucas; Kamenetzky, Giselle Vanesa; Mustaca, Alba Elisabeth; Barreto, George Emilio; Giraldez-Alvarez, Lisandro Diego; Milei, José; Capani, Francisco

    2011-10-01

    Perinatal asphyxia remains as one of the most important causes of death and disability in children, without an effective treatment. Moreover, little is known about the long-lasting behavioral consequences of asphyxia at birth. Therefore, the main aim of the present study was to investigate the motor, emotional and cognitive functions of adult asphyctic rats. Experimental subjects consisted of rats born vaginally (CTL), by cesarean section (C+), or by cesarean section following 19 min of asphyxia (PA). At three months of age, animals were examined in a behavioral test battery including elevated plus maze, open field, Morris water maze, and an incentive downshift procedure. Results indicated that groups did not differ in anxiety-related behaviors, although a large variability was observed in the asphyctic group and therefore, the results are not completely conclusive. In addition, PA and C+ rats showed a deficit in exploration of new environments, but to a much lesser extent in the latter group. Spatial reference and working memory impairments were also found in PA rats. Finally, when animals were downshifted from a 32% to a 4% sucrose solution, an attenuated suppression of consummatory behavior was observed in PA rats. These results confirmed and extended those reported previously about the behavioral alterations associated with acute asphyxia around birth.

  11. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

    Science.gov (United States)

    Banerjee, Soumyabrata; Poddar, Mrinal K

    2015-03-01

    Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats.

  12. Maternal vitamin D deficiency and fetal distress/birth asphyxia: a population-based nested case–control study

    Science.gov (United States)

    Lindqvist, Pelle G; Silva, Aldo T; Gustafsson, Sven A; Gidlöf, Sebastian

    2016-01-01

    Objective Vitamin D deficiency causes not only skeletal problems but also muscle weakness, including heart muscle. If the fetal heart is also affected, it might be more susceptible to fetal distress and birth asphyxia. In this pilot study, we hypothesised that low maternal vitamin D levels are over-represented in pregnancies with fetal distress/birth asphyxia. Design and setting A population-based nested case–control study. Patients Banked sera of 2496 women from the 12th week of pregnancy. Outcome measures Vitamin D levels were analysed using a direct competitive chemiluminescence immunoassay. Vitamin D levels in early gestation in women delivered by emergency caesarean section due to suspected fetal distress were compared to those in controls. Birth asphyxia was defined as Apgar caesarean section due to suspected fetal distress (n=53, 43.6±18 nmol/L) compared to controls (n=120, 48.6±19 nmol/L, p=0.04). Birth asphyxia was more common in women with vitamin D deficiency (n=95) in early pregnancy (OR 2.4, 95% CI 1.1 to 5.7). Conclusions Low vitamin D levels in early pregnancy may be associated with emergency caesarean section due to suspected fetal distress and birth asphyxia. If our findings are supported by further studies, preferably on severe birth asphyxia, vitamin D supplementation/sun exposure in pregnancy may lower the risk of subsequent birth asphyxia. PMID:27660312

  13. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death.

    Directory of Open Access Journals (Sweden)

    Julie Y H Chan

    Full Text Available BACKGROUND: One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM. RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death. METHODOLOGY/PRINCIPAL FINDINGS: A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1, Ubc9 (the only known conjugating enzyme for the sumoylation pathway or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase. CONCLUSIONS

  14. Fluctuations in Brain Temperature Induced by Lypopolysaccharides: Central and Peripheral Contributions

    Directory of Open Access Journals (Sweden)

    Jeremy S. Tang

    2010-01-01

    Full Text Available In this study, we examined changes in central (anterior-preoptic hypothalamus and peripheral (temporal muscle and facial skin temperatures in freely moving rats following intravenous administration of bacterial lipopolysaccharides (LPS at low doses (1 and 10 μg/kg at thermoneutral conditions (28˚C. Recordings were made with high temporal resolution (5-s bin and the effects of LPS were compared with those induced by a tail-pinch, a standard arousing somato-sensory stimulus. At each dose, LPS moderately elevated brain, muscle and skin temperatures. In contrast to rapid, monophasic and relatively short hyperthermic responses induced by a tail-pinch, LPS-induced increases in brain and muscle temperatures occurred with ~40 min onset latencies, showed three not clearly defined phases, were slightly larger with the 10 μm/kg dose and maintained for the entire 4-hour post-injection recording duration. Based on dynamics of brain-muscle and skin-muscle temperature differentials, it appears that the hyperthermic response induced by LPS at the lowest dose originates from enhanced peripheral heat production, with no evidence of brain metabolic activation and skin vasoconstriction. While peripheral heat production also appears to determine the first phase of brain and body temperature elevation with LPS at 10 μg/kg, a further prolonged increase in brain-muscle differentials (onset at ~100 min suggests metabolic brain activation as a factor contributing to brain and body hyperthermia. At this dose, skin temperature increase was weaker than in temporal muscle, suggesting vasoconstriction as another contributor to brain/ body hyperthermia. Therefore, although both LPS at low doses and salient sensory stimuli moderately increase brain and body temperatures, these hyperthermic responses have important qualitative differences, reflecting unique underlying mechanisms.

  15. Endotoxin-induced lung alveolar cell injury causes brain cell damage

    Science.gov (United States)

    Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia RM; Pelosi, Paolo

    2015-01-01

    Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. PMID:25135986

  16. [Molecular-cellular and hormonal mechanisms of induced brain tolerance of extreme factors].

    Science.gov (United States)

    Samoĭlov, M O; Rybnikova, E A

    2012-01-01

    This review includes results of own studies and literature data on the topical problem of neurobiology and medicine: discovery of the mechanisms of increased brain resistance to extreme exposures. The emphasis is made on the molecular-cellular and hormonal mechanisms of hypoxic preconditioning-induced brain tolerance to injurious hypoxia, psychoemotional and traumatic stress. A role of basic hormonal and intracellular cascade pro-adaptive processes mediating the neuroprotective action of hypoxic preconditioning is reviewed. A dynamics of the mechanisms of development of induced susceptible brain areas (hippocampus, neocortex) tolerance which includes phases of induction, transformation and expression, is presented. New data on preconditioning-induced cross-tolerance providing increased brain resistance not only to hypoxia but also to other stresses are reported. For the first time neuroprotective effects of hypoxic postconditioning are described.

  17. Training your brain to be more creative: brain functional and structural changes induced by divergent thinking training.

    Science.gov (United States)

    Sun, Jiangzhou; Chen, Qunlin; Zhang, Qinglin; Li, Yadan; Li, Haijiang; Wei, Dongtao; Yang, Wenjing; Qiu, Jiang

    2016-10-01

    Creativity is commonly defined as the ability to produce something both novel and useful. Stimulating creativity has great significance for both individual success and social improvement. Although increasing creative capacity has been confirmed to be possible and effective at the behavioral level, few longitudinal studies have examined the extent to which the brain function and structure underlying creativity are plastic. A cognitive stimulation (20 sessions) method was used in the present study to train subjects and to explore the neuroplasticity induced by training. The behavioral results revealed that both the originality and the fluency of divergent thinking were significantly improved by training. Furthermore, functional changes induced by training were observed in the dorsal anterior cingulate cortex (dACC), dorsal lateral prefrontal cortex (DLPFC), and posterior brain regions. Moreover, the gray matter volume (GMV) was significantly increased in the dACC after divergent thinking training. These results suggest that the enhancement of creativity may rely not only on the posterior brain regions that are related to the fundamental cognitive processes of creativity (e.g., semantic processing, generating novel associations), but also on areas that are involved in top-down cognitive control, such as the dACC and DLPFC. Hum Brain Mapp 37:3375-3387, 2016. © 2016 Wiley Periodicals, Inc.

  18. An animal-to-human scaling law for blast-induced traumatic brain injury risk assessment.

    Science.gov (United States)

    Jean, Aurélie; Nyein, Michelle K; Zheng, James Q; Moore, David F; Joannopoulos, John D; Radovitzky, Raúl

    2014-10-28

    Despite recent efforts to understand blast effects on the human brain, there are still no widely accepted injury criteria for humans. Recent animal studies have resulted in important advances in the understanding of brain injury due to intense dynamic loads. However, the applicability of animal brain injury results to humans remains uncertain. Here, we use advanced computational models to derive a scaling law relating blast wave intensity to the mechanical response of brain tissue across species. Detailed simulations of blast effects on the brain are conducted for different mammals using image-based biofidelic models. The intensity of the stress waves computed for different external blast conditions is compared across species. It is found that mass scaling, which successfully estimates blast tolerance of the thorax, fails to capture the brain mechanical response to blast across mammals. Instead, we show that an appropriate scaling variable must account for the mass of protective tissues relative to the brain, as well as their acoustic impedance. Peak stresses transmitted to the brain tissue by the blast are then shown to be a power function of the scaling parameter for a range of blast conditions relevant to TBI. In particular, it is found that human brain vulnerability to blast is higher than for any other mammalian species, which is in distinct contrast to previously proposed scaling laws based on body or brain mass. An application of the scaling law to recent experiments on rabbits furnishes the first physics-based injury estimate for blast-induced TBI in humans.

  19. Protection of the blood-brain barrier by pentosan against amyloid-β-induced toxicity.

    Science.gov (United States)

    Deli, Mária A; Veszelka, Szilvia; Csiszár, Boglárka; Tóth, Andrea; Kittel, Agnes; Csete, Mária; Sipos, Aron; Szalai, Anikó; Fülöp, Lívia; Penke, Botond; Abrahám, Csongor S; Niwa, Masami

    2010-01-01

    Endothelial cells of brain capillaries forming the blood-brain barrier play an important role in the pathogenesis and therapy of Alzheimer's disease. Amyloid-β (Aβ) peptides are key pathological elements in the development of the disease. A blood-brain barrier model, based on primary rat brain endothelial cells was used in which the barrier properties were induced by glial cells. The effects of amyloid peptides have been tested on cell viability and barrier functions. Aβ showed toxic effects on primary rat brain endothelial cells measured by MTT dye conversion and the lactate dehydrogenase release. Morphologically cytoplasmic vacuolization, disruption of the structure of cytoplasmic organelles and tight junctions could be observed in brain endothelial cells. Treatment with Aβ1-42 decreased the electrical resistance, and increased the permeability of brain endothelial cell monolayers for both fluorescein and albumin. Serum amyloid P component which stabilizes Aβ fibrils in cortical amyloid plaques and cerebrovascular amyloid deposits significantly potentiated the barrier-weakening effect of Aβ1-42. Sulfated polysaccharide pentosan could decrease the toxic effects of Aβ peptides in brain endothelial cells. It could also significantly protect the barrier integrity of monolayers from damaging actions of peptides. Pentosan modified the size, and significantly decreased the number of amyloid aggregates demonstrated by atomic force microscopy. The present data further support the toxic effects of amyloid peptides on brain endothelial cells, and can contribute to the development of molecules protecting the blood-brain barrier in Alzheimer's disease.

  20. Blood Brain Barrier Dysfunction and Delayed Neurological Deficits in Mild Traumatic Brain Injury Induced by Blast Shock Waves

    Directory of Open Access Journals (Sweden)

    Ashok K Shetty

    2014-08-01

    Full Text Available Mild traumatic brain injury (mTBI resulting from exposure to blast shock waves (BSWs is one of the most predominant causes of illnesses among veterans who served in the recent Iraq and Afghanistan wars. Such mTBI can also happen to civilians if exposed to shock waves of bomb attacks by terrorists. While cognitive problems, memory dysfunction, depression, anxiety and diffuse white matter injury have been observed at both early and/or delayed time-points, an initial brain pathology resulting from exposure to BSWs appears to be the dysfunction or disruption of the blood-brain barrier (BBB. Studies in animal models suggest that exposure to relatively milder BSWs (123 kPa initially induces free radical generating enzymes in and around brain capillaries, which enhances oxidative stress resulting in loss of tight junction proteins, edema formation, and leakiness of BBB with disruption or loss of its components pericytes and astrocyte end-feet. On the other hand, exposure to more intense BSWs (145-323 kPa causes acute disruption of the BBB with vascular lesions in the brain. Both of these scenarios lead to apoptosis of endothelial and neural cells and neuroinflammation in and around capillaries, which may progress into chronic traumatic encephalopathy and/or a variety of neurological impairments, depending on brain regions that are afflicted with such lesions. This review discusses studies that examined alterations in the brain milieu causing dysfunction or disruption of the BBB and neuroinflammation following exposure to different intensities of BSWs. Furthermore, potential of early intervention strategies capable of easing oxidative stress, repairing the BBB or blocking inflammation for minimizing delayed neurological deficits resulting from exposure to BSWs is conferred.

  1. Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria.

    Science.gov (United States)

    Cunha-Oliveira, Teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J; Oliveira, Catarina R; Santos, Maria S

    2013-06-07

    Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand their specific effects in each tissue. Upon energization with complex I substrates, cocaine decreased state-3 respiration in brain (but not in liver) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues, through a direct effect on complex I. Morphine presented only slight effects on brain and liver mitochondria, and the combination cocaine+morphine had similar effects to cocaine alone, except for a greater decrease in state-3 respiration. Brain and liver mitochondrial respirations were differentially affected, and liver mitochondria were more prone to proton leak caused by the drugs or their combination. This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues. In summary, cocaine and cocaine+morphine induce mitochondrial complex I dysfunction in isolated brain and liver mitochondria, with specific effects in each tissue.

  2. Enhanced Expression of Aquaporin-9 in Rat Brain Edema Induced by Bacterial Lipopolysaccharides

    Institute of Scientific and Technical Information of China (English)

    Huaili WANG; Runming JIN; Peichao TIAN; Zhihong ZHUO

    2009-01-01

    To investigate the role of AQP9 in brain edema,the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined.Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals.Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection,with maximum value appearing at 12 h,which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals.The further correlation analysis revealed strong positive correlations among the brain water content,the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals.These results suggested that the regulation of AQP9 expression may play important roles in water movement and in brain metabolic homeostasis associated with the pathophysiology of brain edema induced by LPS injection.

  3. Quantitative analysis of cytokine-induced vascular toxicity and vascular leak in the mouse brain.

    Science.gov (United States)

    Irwan, Yetty Y; Feng, Yi; Gach, H Michael; Symanowski, James T; McGregor, John R; Veni, Gopalkrishna; Schabel, Matthias; Samlowski, Wolfram E

    2009-09-30

    A storm of inflammatory cytokines is released during treatment with pro-inflammatory cytokines, such as interleukin-2 (IL-2), closely approximating changes initially observed during sepsis. These signals induce profound changes in neurologic function and cognition. Little is known about the mechanisms involved. We evaluated a number of experimental methods to quantify changes in brain blood vessel integrity in a well-characterized IL-2 treatment mouse model. Measurement of wet versus dry weight and direct measurement of small molecule accumulation (e.g. [(3)H]-H(2)O, sodium fluorescein) were not sensitive or reliable enough to detect small changes in mouse brain vascular permeability. Estimation of brain water content using proton density magnetic resonance imaging (MRI) measurements using a 7T mouse MRI system was sensitive to 1-2% changes in brain water content, but was difficult to reproduce in replicate experiments. Successful techniques included use of immunohistochemistry using specific endothelial markers to identify vasodilation in carefully matched regions of brain parenchyma and dynamic contrast enhanced (DCE) MRI. Both techniques indicated that IL-2 treatment induced vasodilation of the brain blood vessels. DCE MRI further showed a 2-fold increase in the brain blood vessel permeability to gadolinium in IL-2 treated mice compared to controls. Both immunohistochemistry and DCE MRI data suggested that IL-2 induced toxicity in the brain results from vasodilation of the brain blood vessels and increased microvascular permeability, resulting in perivascular edema. These experimental techniques provide us with the tools to further characterize the mechanism responsible for cytokine-induced neuropsychiatric toxicity.

  4. Opiate-induced changes in brain adenosine levels and narcotic drug responses.

    Science.gov (United States)

    Wu, M; Sahbaie, P; Zheng, M; Lobato, R; Boison, D; Clark, J D; Peltz, G

    2013-01-01

    We have very little information about the metabolomic changes that mediate neurobehavioral responses, including addiction. It was possible that opioid-induced metabolomic changes in brain could mediate some of the pharmacodynamic effects of opioids. To investigate this, opiate-induced brain metabolomic responses were profiled using a semi-targeted method in C57BL/6 and 129Sv1 mice, which exhibit extreme differences in their tendency to become opiate dependent. Escalating morphine doses (10-40 mg/kg) administered over a 4-day period selectively induced a twofold decrease (pOpiate-induced changes in brain adenosine levels may explain many important neurobehavioral features associated with opiate addiction and withdrawal.

  5. Glial Fibrillary Acidic Protein is not an early marker of injury in perinatal asphyxia and hypoxic ischaemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Ann-Marie eLooney

    2015-12-01

    Full Text Available Brain specific glial fibrillary acidic protein (GFAP has been suggested as a potential biomarker for hypoxic ischaemic encephalopathy (HIE in newborns (1, 2. Previous studies have shown increased levels in postnatal blood samples. However its ability to guide therapeutic intervention in HIE is unknown. Therapeutic hypothermia for HIE must be initiated within 6 hours of birth, therefore a clinically useful marker of injury would have to be available immediately following delivery. The goal of our study was to examine the ability of GFAP to predict grade of encephalopathy and neurological outcome when measured in umbilical cord blood. Infants with suspected perinatal asphyxia (PA and HIE were enrolled in a single, tertiary maternity hospital, where umbilical cord blood (UCB was drawn, processed and bio-banked at birth. Expression levels of GFAP were measured by ELISA. In total 169 infants (83 controls, 56 PA, 30 HIE were included in the study. GFAP levels were not increased in UCB of case infants (PA/HIE when compared to healthy controls or when divided into specific grades of HIE. Additionally, no correlation was found between UCB levels of GFAP and outcome at 36 months.

  6. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    Science.gov (United States)

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism.

  7. The Effect of Mangiferin Against Brain Damage Caused by Oxidative Stress and Inflammation Induced by Doxorubicin

    Directory of Open Access Journals (Sweden)

    Soni Siswanto

    2016-04-01

    Full Text Available Doxorubicin (DOX is an anthracycline antibiotic used for anticancer therapy. However, this agent can cause various systemic side effects including cognitive impairments in chronic use. Brain damage due to DOX is caused by an increase of tumor necrosis factor-alpha (TNF-α level in the brain. Increased TNF-α can further lead to chronic inflammation which can lead to neuronal deaths or neurodegenerative diseases. Mangiferin (MAG, a compound extracted from Mangifera indica, has been found neuroprotective activities, but its effect on DOX-induced brain damage is unknown. This study aims to determine the effect of MAG on brain damage induced by DOX. Male Sprague-Dawley rats were induced by DOX intraperitoneally. MAG was given orally at the doses of 30 and 60 mg/kg bw for 7 consecutive weeks. The parameters measured were inflammatory and oxidative stress markers in brain tissue. Coadministration of MAG with DOX reduced inflammation which was marked by the reduction of TNF-α mRNA expression, decreased TNF-α level and reduction of oxidative stress marked by increase of superoxide dismutase level and decrease of malondialdehyde level. In conclusion, MAG was shown to have a neuroprotective effect on brain damage induced by DOX, partly due to inhibition of inflammation and oxidative stress.

  8. Tannic acid alleviates lead acetate-induced neurochemical perturbations in rat brain.

    Science.gov (United States)

    Ashafaq, Mohammad; Tabassum, Heena; Vishnoi, Shruti; Salman, Mohd; Raisuddin, Sheikh; Parvez, Suhel

    2016-03-23

    Oxidative stress has been projected as a promising mechanism involved in lead exposure. The lead predisposition catalyzes oxidative reactions and generates reactive oxygen species. The present study was carried out to investigate the effect of oral administration of tannic acid (TA) on behavioral deficit, antioxidative deterioration induced by lead acetate (LA) exposure on experimental rat brain. Male Wistar rats were treated with 50mg/kg body weight of LA and TA for three times a week for two weeks. Our data showed LA-induced profound elevation of ROS production and oxidative stress, as evidenced by increased levels of oxidative stress markers such as lipid peroxidation and protein carbonyl observed in LA treated rats, whereas significant depletion in the activity of non-enzymatic antioxidants, enzymatic antioxidants, neurotoxicity biomarker and histological changes were observed in LA treated rat brain. However, TA administration restored antioxidant status of brain significantly when compared to control. Our results demonstrate that TA exhibits potent antioxidant properties and suppresses oxidative damages in rat brain induced by LA treatment. These findings were further supported by the neurotoxicity biomarker and histopathological findings in the brain tissue showed that TA protected tissue from deleterious effects of LA exposure. It is concluded, these data suggest that LA induces oxidative stress and supplementation of TA has a powerful antioxidant effect, and it protected rat brain from poisonous effect of LA exposure in experimental rat.

  9. Changes in reward-induced brain activation in opiate addicts

    NARCIS (Netherlands)

    Martin-Soelch, C; Chevalley, AF; Kunig, G; Missimer, J; Magyar, S; Mino, A; Schultz, W; Leenders, KL

    2001-01-01

    Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with (H2O)

  10. Modafinil-Induced Increases in Brain Dopamine Levels

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-04-01

    Full Text Available The acute effects of modafinil on extracellular dopamine and on dopamine transporters in the male human brain were measured by PET study in 10 healthy subjects at Brookhaven National Laboratory and National Institute on Drug Abuse, Bethesda, MD.

  11. Reversible Altered Consciousness and Brain Atrophy Induced by Valproic Acid

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-08-01

    Full Text Available A 5-year-old female child with valproic acid (VPA-related alteration of consciousness and brain atrophy that progressed over a 3 day period and resolved within 12 hours of discontinuing VPA is reported from Dokkyo University School of Medicine and Shimotsuga General Hospital, Tochigi, Japan.

  12. Practice induces function-specific changes in brain activity.

    Directory of Open Access Journals (Sweden)

    Tamar R van Raalten

    Full Text Available BACKGROUND: Practice can have a profound effect on performance and brain activity, especially if a task can be automated. Tasks that allow for automatization typically involve repeated encoding of information that is paired with a constant response. Much remains unknown about the effects of practice on encoding and response selection in an automated task. METHODOLOGY: To investigate function-specific effects of automatization we employed a variant of a Sternberg task with optimized separation of activity associated with encoding and response selection by means of m-sequences. This optimized randomized event-related design allows for model free measurement of BOLD signals over the course of practice. Brain activity was measured at six consecutive runs of practice and compared to brain activity in a novel task. PRINCIPAL FINDINGS: Prompt reductions were found in the entire cortical network involved in encoding after a single run of practice. Changes in the network associated with response selection were less robust and were present only after the third run of practice. CONCLUSIONS/SIGNIFICANCE: This study shows that automatization causes heterogeneous decreases in brain activity across functional regions that do not strictly track performance improvement. This suggests that cognitive performance is supported by a dynamic allocation of multiple resources in a distributed network. Our findings may bear importance in understanding the role of automatization in complex cognitive performance, as increased encoding efficiency in early stages of practice possibly increases the capacity to otherwise interfering information.

  13. Food-induced brain responses and eating behaviour

    NARCIS (Netherlands)

    Smeets, P.A.M.; Charbonnier, L.; Meer, van der F.; Laan, van der L.N.; Spetter, M.S.

    2012-01-01

    The brain governs food intake behaviour by integrating many different internal and external state and trait-related signals. Understanding how the decisions to start and to stop eating are made is crucial to our understanding of (maladaptive patterns of) eating behaviour. Here, we aim to (1) review

  14. Hyperbaric oxygen therapy ameliorates local brain metabolism, brain edema and inflammatory response in a blast-induced traumatic brain injury model in rabbits.

    Science.gov (United States)

    Zhang, Yongming; Yang, Yanyan; Tang, Hong; Sun, Wenjiang; Xiong, Xiaoxing; Smerin, Daniel; Liu, Jiachuan

    2014-05-01

    Many studies suggest that hyperbaric oxygen therapy (HBOT) can provide some clinically curative effects on blast-induced traumatic brain injury (bTBI). The specific mechanism by which this occurs still remains unknown, and no standardized time or course of hyperbaric oxygen treatment is currently used. In this study, bTBI was produced by paper detonators equivalent to 600 mg of TNT exploding at 6.5 cm vertical to the rabbit's head. HBO (100% O2 at 2.0 absolute atmospheres) was used once, 12 h after injury. Magnetic resonance spectroscopy was performed to investigate the impact of HBOT on the metabolism of local injured nerves in brain tissue. We also examined blood-brain barrier (BBB) integrity, brain water content, apoptotic factors, and some inflammatory mediators. Our results demonstrate that hyperbaric oxygen could confer neuroprotection and improve prognosis after explosive injury by promoting the metabolism of local neurons, inhibiting brain edema, protecting BBB integrity, decreasing cell apoptosis, and inhibiting the inflammatory response. Furthermore, timely intervention within 1 week after injury might be more conducive to improving the prognosis of patients with bTBI.

  15. Brain activity correlates with emotional perception induced by dynamic avatars.

    Science.gov (United States)

    Goldberg, Hagar; Christensen, Andrea; Flash, Tamar; Giese, Martin A; Malach, Rafael

    2015-11-15

    An accurate judgment of the emotional state of others is a prerequisite for successful social interaction and hence survival. Thus, it is not surprising that we are highly skilled at recognizing the emotions of others. Here we aimed to examine the neuronal correlates of emotion recognition from gait. To this end we created highly controlled dynamic body-movement stimuli based on real human motion-capture data (Roether et al., 2009). These animated avatars displayed gait in four emotional (happy, angry, fearful, and sad) and speed-matched neutral styles. For each emotional gait and its equivalent neutral gait, avatars were displayed at five morphing levels between the two. Subjects underwent fMRI scanning while classifying the emotions and the emotional intensity levels expressed by the avatars. Our results revealed robust brain selectivity to emotional compared to neutral gait stimuli in brain regions which are involved in emotion and biological motion processing, such as the extrastriate body area (EBA), fusiform body area (FBA), superior temporal sulcus (STS), and the amygdala (AMG). Brain activity in the amygdala reflected emotional awareness: for visually identical stimuli it showed amplified stronger response when the stimulus was perceived as emotional. Notably, in avatars gradually morphed along an emotional expression axis there was a parametric correlation between amygdala activity and emotional intensity. This study extends the mapping of emotional decoding in the human brain to the domain of highly controlled dynamic biological motion. Our results highlight an extensive level of brain processing of emotional information related to body language, which relies mostly on body kinematics.

  16. Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation.

    Directory of Open Access Journals (Sweden)

    Salil R Rajayer

    Full Text Available Binge drinking has been associated with cerebral dysfunction. Ethanol induced microglial activation initiates an inflammatory process that causes upregulation of proinflammatory cytokines which in turn creates neuronal inflammation and damage. However, the molecular mechanism is not fully understood. We postulate that cold-inducible RNA-binding protein (CIRP, a novel proinflammatory molecule, can contribute to alcohol-induced neuroinflammation. To test this theory male wild-type (WT mice were exposed to alcohol at concentrations consistent to binge drinking and blood and brain tissues were collected. At 5 h after alcohol, a significant increase of 53% in the brain of CIRP mRNA was observed and its expression remained elevated at 10 h and 15 h. Brain CIRP protein levels were increased by 184% at 10 h and remained high at 15 h. We then exposed male WT and CIRP knockout (CIRP(-/- mice to alcohol, and blood and brain tissues were collected at 15 h post-alcohol infusion. Serum levels of tissue injury markers (AST, ALT and LDH were significantly elevated in alcohol-exposed WT mice while they were less increased in the CIRP(-/- mice. Brain TNF-α mRNA and protein expressions along with IL-1β protein levels were significantly increased in WT mice, which was not seen in the CIRP(-/- mice. In cultured BV2 cells (mouse microglia, ethanol at 100 mM showed an increase of CIRP mRNA by 274% and 408% at 24 h and 48 h respectively. Corresponding increases in TNF-α and IL-1β were also observed. CIRP protein levels were markedly increased in the medium, suggesting that CIRP was secreted by the BV2 cells. From this we conclude that alcohol exposure activates microglia to produce and secrete CIRP and possibly induce pro-inflammatory response and thereby causing neuroinflammation. CIRP could be a novel mediator of alcohol-induced brain inflammation.

  17. Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism

    DEFF Research Database (Denmark)

    Tanriverdi, F; Agha, A; Aimaretti, G

    2011-01-01

    Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered...... and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here....

  18. Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism.

    LENUS (Irish Health Repository)

    Tanriverdi, F

    2011-01-01

    Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here.

  19. Spontaneous and light-induced photon emission from intact brains of chick embryos

    Institute of Scientific and Technical Information of China (English)

    张锦珠; 于文斗; 孙彤

    1997-01-01

    Photon emission (PE) and light-induced photon emission(LPE) of intact brains isolated from chick embryos have been measured by using the single photon counting device. Experimental results showed that the intensi-ty level of photon emission was detected to be higher from intact brain than from the medium in which the brain was immerged during measuring, and the emission intensity was related to the developmental stages, the healthy situation of the measured embryos, and the freshness of isolated brains as well. After white light illumination, a short-life de-layed emission from intact brains was observed, and its relaxation behavior followed a hyperbolic rather than an expo-nential law. According to the hypothesis of biophoton emission originating from a delocalized coherent electromagnetic field and Frohlich’s idea of coherent long-range interactions in biological systems, discussions were made on the signifi-cance of photon emission in studying cell communication, biological regulation, living system’

  20. Anesthesia for deep brain stimulation in traumatic brain injury-induced hemidystonia

    OpenAIRE

    Jani, Jill M; Oluigbo, Chima O; Reddy, Srijaya K

    2015-01-01

    Key Clinical Message Deep brain stimulation in an awake patient presents several unique challenges to the anesthesiologist. It is important to understand the various stages of the procedure and the complexities of anesthetic management in order to have a successful surgical outcome and provide a safe environment for the patient.

  1. Anesthesia for deep brain stimulation in traumatic brain injury-induced hemidystonia.

    Science.gov (United States)

    Jani, Jill M; Oluigbo, Chima O; Reddy, Srijaya K

    2015-06-01

    Deep brain stimulation in an awake patient presents several unique challenges to the anesthesiologist. It is important to understand the various stages of the procedure and the complexities of anesthetic management in order to have a successful surgical outcome and provide a safe environment for the patient.

  2. Application of a classification system focusing on potential asphyxia for cases of sudden unexpected infant death.

    Science.gov (United States)

    Randall, Brad; Donelan, Kent; Koponen, Mark; Sens, Mary Ann; Krous, Henry F

    2012-03-01

    Current classification schemes for sudden unexpected infant death (SUID) may not be optimal for capturing scene events that potentially predispose to asphyxia. (1) To compare causes of death in a group of SUID cases assigned by multiple reviewers using our recently published classification scheme for SUID that is based on asphyxial risk at the death scene, and (2) To compare these newly assigned causes of death to that originally assigned by the medical examiners of record who performed the autopsies. Five reviewers independently assigned causes of death for 117 cases of SUID, including 83 originally diagnosed as sudden infant death syndrome (SIDS), accessioned into the San Diego SIDS/SUDC Research Project from the San Diego County Medical Examiner's Office. The diagnostic categories are: A: SIDS; B: Unexplained-Potentially Asphyxia; C: Unexplained-Other Potential Causes of Death; D: Unclassified-Other; E: Unclassified; and F: Known Cause of Death. The reviewers collectively opined that conditions at the death scene contributed to or caused death in 32-50% of all of the 117 cases as well as in 40-59% of the 83 originally diagnosed SIDS cases. Another cause of death was considered plausible in 2-12% of the SIDS cases. Application of this new classification system resulted in 55-69% decrease in SIDS diagnoses. Asphyxia as a potential contributor to, or as the specific cause of death, appears to exist in a large percentage of cases designated as SIDS using other classification schemes. When certifiers use a classification system that focuses upon potential asphyxia in determining the cause of death the incidence of SIDS dramatically declines.

  3. The "Bermuda triangle" of neonatal neurology: cerebral palsy, neonatal encephalopathy, and intrapartum asphyxia.

    Science.gov (United States)

    Shevell, Michael I

    2004-03-01

    The terms "cerebral palsy," "neonatal encephalopathy," and "intrapartum asphyxia" are frequently used in pediatric neurology. This article presents concise, verifiable definitions for each of these entities based on our current understanding and formulates the nature of the interrelationships between them. The aim is to provide a level of clarity that will enhance diagnostic and pathogenetic precision and minimize conceptual misunderstanding. This should aid future therapeutic and research efforts in this important area.

  4. Cavitation Induced Structural and Neural Damage in Live Brain Tissue Slices: Relevance to TBI

    Science.gov (United States)

    2014-09-29

    the value of this experimental platform to investigate the single bubble cavitation- induced damage in a biological tissue is illustrated with an...Lei Wu, Malisa Sarntinoranont, Huikai Xie1. Refractive index measurement of acute rat brain tissue slices using optical coherence tomography, Optics...b-TBI, i.e. what is “broken”, in the brain during exposure to shock loading is currently unknown. While blast waves are well known to have negative

  5. An Animal-to-Human Scaling Law for Blast-Induced Traumatic Brain Injury Risk Assessment

    Science.gov (United States)

    2014-10-28

    injury biomechanics (13–15, 17), the peak intra- cranial pressure was chosen as a characteristic metric of blast intensity transmitted to the brain tissue...Management, and Rehabilitation ( Springer , Berlin), pp 1–13. 7. Magnuson J, Leonessa F, Ling GSF (2012) Neuropathology of explosive blast traumatic brain...Front Neurol 3:70. 17. Sundaramurthy A, et al. (2012) Blast-induced biomechanical loading of the rat: An experimental and anatomically accurate

  6. Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

    Directory of Open Access Journals (Sweden)

    Petra eSántha

    2016-01-01

    Full Text Available Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1 and astroglia (GFAP. Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes

  7. Discussion on Therapeutic Effect of Intratracheal Intubation on Asphyxia Neonatorum in Plateau Tibetans( Attached Reports of 48 Cases)

    Institute of Scientific and Technical Information of China (English)

    DEJI Meiduo; ZHOU Cuojie

    2002-01-01

    Objective To discuss the indications for intratracheal intubation in plateau tibetans with asphyxia neonatorum, clinical therapeutic effect relationship, changes of beta2- microglobulin( β2-MC) and creatinine( Cr). Methods 48 cases of asphyxia neonatorum were divided into several groups and underwent intratracheal intubation. Radioimmunoassay was used to determined plasmaβ2- MC level in different groups which were divided according to the severity and onset time of asphyxia neonatorum.And their serum Cr level was also determined by using HTT- ACHI7060 automatic biochemical analyzer.The results were compared with those of 20 healthy mature neonates. Results The incidence of complications of the second group with asphyxia neonatorum was higher than that of the first group. The changing degrees ofβ2 - MC and Cr were parallel with the degree of asphyxia and hypoxia. Conclusion Serumβ2- MC and Cr are the sensitive indications reflecting glomerular filtration function in asphyxia neonatorum. Popularizing novel resuscitation is the key to decrease prevalence and mortality.

  8. Light and Electron Microscopic Evaluation of Hydrogen Ion-Induced Brain Necrosis

    OpenAIRE

    Petito, C. K.; Kraig, R.P.; Pulsinelli, W. A.

    1987-01-01

    Excessive accumulation of hydrogen ions in the brain may play a pivotal role in initiating the necrosis seen in infarction and following hyperglycemic augmentation of ischemic brain damage. To examine possible mechanisms involved in hydrogen ion-induced necrosis, sequential structural changes in rat brain were examined following intracortical injection of sodium lactate solution (pH 4.5), as compared with injections at pH 7.3. Following pH 7.3 injection, neuronal swelling developed between 1 ...

  9. Copeptin concentration in cord blood in infants with early-onset sepsis, chorioamnionitis and perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    Aebi Christoph

    2011-05-01

    Full Text Available Abstract Background Vasopressin is one of the most important physiological stress and shock hormones. Copeptin, a stable vasopressin precursor, is a promising sepsis marker in adults. In contrast, its involvement in neonatal diseases remains unknown. The aim of this study was to establish copeptin concentrations in neonates of different stress states such as sepsis, chorioamnionitis and asphyxia. Methods Copeptin cord blood concentration was determined using the BRAHMS kryptor assay. Neonates with early-onset sepsis (EOS, n = 30, chorioamnionitis (n = 33 and asphyxia (n = 25 were compared to a control group of preterm and term (n = 155 neonates. Results Median copeptin concentration in cord blood was 36 pmol/l ranging from undetectable to 5498 pmol/l (IQR 7 - 419. Copeptin cord blood concentrations were non-normally distributed and increased with gestational age (p Conclusions Copeptin concentrations were strongly related to factors associated with perinatal stress such as birth acidosis, asphyxia and vaginal delivery. In contrast, copeptin appears to be unsuitable for the diagnosis of EOS.

  10. Brain oxidative stress induced by obstructive jaundice in rats.

    Science.gov (United States)

    Chroni, Elisabeth; Patsoukis, Nikolaos; Karageorgos, Nikolaos; Konstantinou, Dimitris; Georgiou, Christos

    2006-02-01

    The effect of experimental obstructive jaundice on the oxidative status of brain tissues in rats was examined. Twenty-four male Wistar rats were divided into 4 groups: Group I was the control, group II was the sham operated, and groups III and IV were bile duct ligated and killed on the 5th and the 10th day, respectively. Oxidative stress was assessed by measuring the thiol redox state (protein and nonprotein components) and lipid peroxidation level variations in samples from the cerebral cortex, midbrain, and cerebellar tissue in all animals. Results indicated the presence of oxidative stress in the jaundiced animals that was more pronounced on the 10th day as indicated by a decrease in reduced glutathione and protein thiol and an increase in protein disulphide and lipid peroxidation. A dramatic elevation of the level of total nonprotein mixed disulphide level was found specifically in the midbrain in the 10th day group. This suggests an accumulation of nonprotein disulfides other than oxidized glutathione, which remained unchanged, in this particular brain area. This study showed a correlation between experimental obstructive jaundice and the oxidative stress in the rats' brain, implying that a similar pathogenetic mechanism may play a key role in cholestatic liver disease, resulting in hepatic encephalopathy in humans.

  11. Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia

    NARCIS (Netherlands)

    Benders, MJNL; Bos, AF; Radernaker, CMA; Rijken, M; Torrance, HL; Groenendaal, F; van Bel, F

    2006-01-01

    Objective: To investigate whether postnatal allopurinol would reduce free radical induced reperfusion/reoxygenation injury of the brain in severely asphyxiated neonates. Method: In an interim analysis of a randomised, double blind, placebo controlled study, 32 severely asphyxiated infants were given

  12. Traumatic asphyxia--fatal accident in an automatic revolving door.

    Science.gov (United States)

    Cortis, J; Falk, J; Rothschild, M A

    2015-09-01

    Due to continuing modernisation, the number of automatic doors in routine use, including powered revolving doors, has increased in recent years. Automatic revolving doors are found mostly in department stores, airports, railway stations and hospitals. Although safety arrangements and guidelines concerning the installation of automatic doors are in existence, their disregard in conjunction with obsolete or incorrect installation can lead to fatal accidents. In this report, a 19-month-old boy is described whose right arm was caught between the elements of an automatic revolving door. As a direct result of rescue attempts, the child's body was drawn further into the narrow gap between elements of the door. To get the boy's body out of the 4-cm-wide gap between the fixed outer wall of the revolving door and the revolving inner, back-up batteries had to be disconnected so as to stop the electrical motor powering the door. Cardiopulmonary resuscitation was begun immediately after the rescue but was unsuccessful; the child was declared dead at the hospital he was taken to. The cause of death was a combination of compression-related skull and brain injury together with thoracic compression. This case shows an outstanding example of the preventive aspect as a special task of forensic medicine. Additionally, it serves as a warning for the correct installation and use of automatic revolving doors. Even so, small children should not use these doors on their own, but only with an alert companion, so as to prevent further fatal accidents of this sort.

  13. Exercise induces autophagy in peripheral tissues and in the brain.

    Science.gov (United States)

    He, Congcong; Sumpter, Rhea; Levine, Beth

    2012-10-01

    We recently identified physical exercise as a newly defined inducer of autophagy in vivo. Exercise induced autophagy in multiple organs involved in metabolic regulation, such as muscle, liver, pancreas and adipose tissue. To study the physiological role of exercise-induced autophagy, we generated mice with a knock-in nonphosphorylatable mutation in BCL2 (Thr69Ala, Ser70Ala and Ser84Ala) (BCL2 AAA) that are defective in exercise- and starvation-induced autophagy but not in basal autophagy. We found that BCL2 AAA mice could not run on a treadmill as long as wild-type mice, and did not undergo exercise-mediated increases in skeletal glucose muscle uptake. Unlike wild-type mice, the BCL2 AAA mice failed to reverse high-fat diet-induced glucose intolerance after 8 weeks of exercise training, possibly due to defects in signaling pathways that regulate muscle glucose uptake and metabolism during exercise. Together, these findings suggested a hitherto unknown important role of autophagy in mediating exercise-induced metabolic benefits. In the present addendum, we show that treadmill exercise also induces autophagy in the cerebral cortex of adult mice. This observation raises the intriguing question of whether autophagy may in part mediate the beneficial effects of exercise in neurodegeneration, adult neurogenesis and improved cognitive function.

  14. Effect of naloxone on level of plasma beta-endorphin in neonates with severe asphyxia

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: β-endorphin is the most actively endogenous substance of cerebral endorphin. When combined with opiate receptor specially, it manifests a strong morphine-like activity and can decrease sensitivity of central nervous system to carbon dioxide so as to inhibit breath.OBJECTIVE: To observe the changes of content of plasma β -endorphin in neonates with severe asphyxia after naloxone treatment in a large dosage.DESIGN: Randomized controlled observation.SETTINGS: Department of Pediatrics, Shenzhen Shajing People's Hospital; Center of Pediatrics,Guangzhou Zhujiang Hospital.PARTICIPANTS: A total of 97 neonates with severe asphyxia including 57 boys and 40 girls were selected from Neonatal Intensive Care Unit, Department of Pediatrics, Shenzhen Shajing People's Hospital from January 2004 to November 2005. Their gestational age was (38 ±3) weeks, body mass was (3.2± 1.7) kg,and hospitalization duration was (2.8±2.3) hours. All neonates met the diagnostic criteria of with severe asphyxia and all their parents provided the confirmed consent.METHODS: All neonates were treated with inspired oxygen, sedation, stopping terror, decreasing cranial pressure, maintaining a well blood perfusion and normal level of blood glucose (about 5.0 mmol/L). After hospitalization, 0.1 mg/(kg ·d) naloxone hydrochloride (Beijing Sihuan Pharmaceutical Technology Co., Ltd.;certification: H10900021; bullet preparation; 0.4 mg/ampoule) was intravenously dribbled into neonates for 4 - 6 hours, 14 days in total. 2 mL blood was collected from radial artery in neonates at the beginning of hospitalization and at 3 days after naloxone treatment, put in aprotinin-pre-cool tube, mixed evenly, and centrifuged at hypothermia. Plasma was maintained in refrigerator at - 70 ℃. The kit was provided by Neurobiology Department of Shanghai Second Military Medical University of Chinese PLA. Concentration of plasma β -endorphin was measured by using radio-immunity assay.All data were expressed as Mean

  15. Combined Effects of Primary and Tertiary Blast on Rat Brain: Characterization of a Model of Blast-induced Mild Traumatic Brain Injury

    Science.gov (United States)

    2014-03-01

    R) asymmetry . Since none of the brain regions exhibited a significant Blast x No. of Events x Side (L/R) interaction, the effect of side was...AD Award Number: W81XWH-11-2-0127 TITLE: Combined Effects of Primary and Tertiary Blast on Rat Brain : Characterization of a Model of...Blast-induced Mild Traumatic Brain Injury PRINCIPAL INVESTIGATOR: Dr. Joseph Long CONTRACTING ORGANIZATION: The Geneva Foundation, Tacoma, WA

  16. Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Mariko Saito

    2016-08-01

    Full Text Available Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD. While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy. Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7 mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain.

  17. Concentrations of Nitric Oxide in Rat Brain Tissues after Diffuse Brain Injury and Neuroprotection by the Selective Inducible Nitric Oxide Synthase Inhibitor Aminoguanidine

    Institute of Scientific and Technical Information of China (English)

    Yi-bao Wang; Shao-wu Ou; Guang-yu Li; Yun-hui Liu

    2005-01-01

    @@ To investigate the effects of nitric oxide (NO) and the selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) on trauma, we explored the concentrations of nitric oxide in rat brain tissues at different time stamps after diffuse brain injury (DBI) with or without AG treatment.

  18. Protective effects of selenium on cadmium-induced brain damage in chickens.

    Science.gov (United States)

    Liu, Li-Li; Li, Cheng-Ming; Zhang, Zi-Wei; Zhang, Jiu-Li; Yao, Hai-Dong; Xu, Shi-Wen

    2014-05-01

    Selenium (Se) is an important dietary micronutrient with antioxidative roles. Cadmium (Cd), a ubiquitous environmental pollutant, is known to cause brain lesion in rats and humans. However, little is reported about the deleterious effects of subchronic Cd exposure on the brain of poultry and the protective roles on the brain by Se against Cd. The aim of this study was to investigate the protective effects of Se on Cd-induced brain damage in chickens. One hundred twenty 100-day-old chickens were randomly assigned to four groups and were fed a basal diet, or Se (as 10 mg Na2SeO3/kg dry weight of feed), Cd (as 150 mg CdCl2/kg dry weight of feed), or Cd + Se in their basic diets for 60 days. Then, concentrations of Cd and Se, production of nitric oxide (NO), messenger RNA (mRNA) level and activity of inducible NO synthase (iNOS), level of oxidative stress, and histological and ultrastructural changes of the cerebrum and cerebellum were examined. The results showed that Cd exposure significantly increased Cd accumulation, NO production, iNOS activities, iNOS mRNA level, and MDA content in the cerebrum and cerebellum. Cd treatment obviously decreased Se content and antioxidase activities and caused histopathological changes in the cerebrum and cerebellum. Se supplementation during dietary Cd obviously reduced Cd accumulation, NO production, mRNA level and activity of iNOS, oxidative stress, and histopathological damage in the cerebrum and cerebellum of chickens. It indicated that Se ameliorates Cd-induced brain damage in chickens by regulating iNOS-NO system changes, and oxidative stress induced by Cd and Se can serve as a potential therapeutic for Cd-induced brain lesion of chickens.

  19. Complications induced by decompressive craniectomies after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    杨学军; 洪国良; 苏少波; 杨树源

    2003-01-01

    Objective: To find out the optimal approach to decompress externally the severe injured brain and to avoid possible complications caused by external decompression.Methods: 68 patients who underwent external decompression after traumatic brain injury were admitted into Tianjin Medical University General Hospital for cranioplasty from 1995 to 2001. Complications were retrospectively investigated and analyzed in all patients. The findings were compared between the patients who accepted the decompressive craniectomy in our hospital and in local hospitals. Χ2-test was employed for statistical analysis and complication evaluation. Results: Large craniectomy definitely caused some side effects to patients. Among various complications, several of them showed significantly high incidence (P0.05) between the two groups including dilation or/and migration of lateral ventricle underlying the cranial defect, skin flap concavity, encephalomalacia of the decompressive area, seizure and infection.Conclusions: To reduce the incidence of iatrogenic side effects, surgical craniectomy should be performed according to the strict indication and standard and any abuse should be avoided.

  20. NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation

    Science.gov (United States)

    He, Hao; Geng, Tingting; Chen, Piyun; Wang, Meixiang; Hu, Jingxia; Kang, Li; Song, Wengang; Tang, Hua

    2016-01-01

    Sepsis could affect the central nervous system and thus induces neuroinflammation, which subsequently leads to brain damage or dysfunction. However, the mechanisms of generation of neuroinflammation during sepsis remain poorly understood. By administration of lipopolysaccharides (LPS) in mice to mimic sepsis, we found that shortly after opening the blood–brain barrier, conventional CD11b+CD27+ NK subset migrated into the brain followed by subsequent neutrophil infiltration. Interestingly, depletion of NK cells prior to LPS treatment severely impaired neutrophil recruitment in the inflamed brain. By in vivo recruitment assay, we found that brain-infiltrated NK cells displayed chemotactic activity to neutrophils, which depended on the higher expression of chemokines such as CXCL2. Moreover, microglia were also responsible for neutrophil recruitment, and their chemotactic activity was significantly impaired by ablation of NK cells. Furthermore, depletion of NK cells could significantly ameliorate depression-like behavior in LPS-treated mice. These data indicated a NK cell-regulated neutrophil recruitment in the blamed brain, which also could be seen on another sepsis model, cecal ligation and puncture. So, our findings revealed an important scenario in the generation of sepsis-induced neuroinflammation. PMID:27270556

  1. Chronic hypertension aggravates heat stress-induced brain damage: possible neuroprotection by cerebrolysin.

    Science.gov (United States)

    Muresanu, Dafin Fior; Zimmermann-Meinzingen, Sibilla; Sharma, Hari Shanker

    2010-01-01

    Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees C in a biological oxygen demand (BOD) incubator showed breakdown of the blood-brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier.

  2. Endomorphins and morphine limit anoxia-reoxygenation-induced brain mitochondrial dysfunction in the mouse.

    Science.gov (United States)

    Feng, Yun; Lu, Yingwei; Lin, Xin; Gao, Yanfeng; Zhao, Qianyu; Li, Wei; Wang, Rui

    2008-03-26

    The protection of brain mitochondria from oxidative stress is an important therapeutic strategy against ischemia-reperfusion injury and neurodegenerative disorders. Isolated brain mitochondria subjected to a 5 min period of anoxia followed by 5 min reoxygenation mirrored the effect of oxidative stress in the brain. The present study attempts to evaluate the protective effects of endomorphin 1 (EM1), endomorphin 2 (EM2), and morphine (Mor) in an in vitro mouse brain mitochondria anoxia-reoxygenation model. Endomorphins (EM1/2) and Mor were added to mitochondria prior to anoxia or reoxygenation. EM1/2 and Mor markedly improved mitochondrial respiratory activity with a decrease in state 4 and increases in state 3, respiratory control ratio (RCR) and the oxidative phosphorylation efficiency (ADP/O ratio), suggesting that they may play a protective role in mitochondria. These drugs inhibited alterations in mitochondrial membrane fluidity, lipoperoxidation, and cardiolipin (CL) release, which indicates protection of the mitochondrial membranes from oxidative damage. The protective effects of these drugs were concentration-dependent. Furthermore, these drugs blocked the enhanced release of cytochrome c (Cyt c), and consequently inhibited the cell apoptosis induced by the release of Cyt c. Our results suggest that EM1/2 and Mor effectively protect brain mitochondria against oxidative stresses induced by in vitro anoxia-reoxygenation and may play an important role in the prevention of deleterious effects during brain ischemia-reperfusion and neurodegenerative diseases.

  3. MLKL inhibition attenuates hypoxia-ischemia induced neuronal damage in developing brain.

    Science.gov (United States)

    Qu, Yi; Shi, Jing; Tang, Ying; Zhao, Fengyan; Li, Shiping; Meng, Junjie; Tang, Jun; Lin, Xuemei; Peng, Xiaodong; Mu, Dezhi

    2016-05-01

    Mixed lineage kinase domain-like protein (MLKL) is a critical molecule mediating cell necroptosis. However, its role in brain injury remains obscure. We first investigated the functions and mechanisms of MLKL in mediating neuronal damage in developing brain after hypoxia-ischemia. Neuronal necroptosis was induced by oxygen-glucose deprivation (OGD) plus caspase inhibitor zVAD treatment (OGD/zVAD). We found that two important necroptosis related proteins, receptor-interacting protein 1 and 3 (RIP1, RIP3) were upregulated. Furthermore, the interaction of RIP1-RIP3 with MLKL increased. Inhibition of MLKL through siRNA diminished RIP1-RIP3-MLKL interaction and attenuated neuronal death induced by OGD/zVAD. The translocation of oligomerized MLKL to the neuronal membrane leading to the injury of cellular membrane is the possible new mechanism of neuronal necroptosis. Animal experiment with neonatal rats further proved that MLKL inhibition attenuated brain damage induced by hypoxia-ischemia. These findings suggest that MLKL is a target to attenuate brain damage in developing brain.

  4. Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia.

    Science.gov (United States)

    Wang, Wenqing; Wang, Aihui; Yu, Limin; Han, Xuesong; Jiang, Guiyun; Weng, Changshui; Zhang, Hongwei; Zhou, Zhiqiang

    2012-11-15

    Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia.

  5. Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

    Institute of Scientific and Technical Information of China (English)

    Wenqing Wang; Aihui Wang; Limin Yu; Xuesong Han; Guiyun Jiang; Changshui Weng; Hongwei Zhang; Zhiqiang Zhou

    2012-01-01

    Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia.

  6. Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity.

    Science.gov (United States)

    Parikh, Neil U; Aalinkeel, R; Reynolds, J L; Nair, B B; Sykes, D E; Mammen, M J; Schwartz, S A; Mahajan, S D

    2015-10-22

    Methamphetamine (Meth) abuse can lead to the breakdown of the blood-brain barrier (BBB) integrity leading to compromised CNS function. The role of Galectins in the angiogenesis process in tumor-associated endothelial cells (EC) is well established; however no data are available on the expression of Galectins in normal human brain microvascular endothelial cells and their potential role in maintaining BBB integrity. We evaluated the basal gene/protein expression levels of Galectin-1, -3 and -9 in normal primary human brain microvascular endothelial cells (BMVEC) that constitute the BBB and examined whether Meth altered Galectin expression in these cells, and if Galectin-1 treatment impacted the integrity of an in-vitro BBB. Our results showed that BMVEC expressed significantly higher levels of Galectin-1 as compared to Galectin-3 and -9. Meth treatment increased Galectin-1 expression in BMVEC. Meth induced decrease in TJ proteins ZO-1, Claudin-3 and adhesion molecule ICAM-1 was reversed by Galectin-1. Our data suggests that Galectin-1 is involved in BBB remodeling and can increase levels of TJ proteins ZO-1 and Claudin-3 and adhesion molecule ICAM-1 which helps maintain BBB tightness thus playing a neuroprotective role. Galectin-1 is thus an important regulator of immune balance from neurodegeneration to neuroprotection, which makes it an important therapeutic agent/target in the treatment of drug addiction and other neurological conditions.

  7. MRI-detectable changes in mouse brain structure induced by voluntary exercise.

    Science.gov (United States)

    Cahill, Lindsay S; Steadman, Patrick E; Jones, Carly E; Laliberté, Christine L; Dazai, Jun; Lerch, Jason P; Stefanovic, Bojana; Sled, John G

    2015-06-01

    Physical exercise, besides improving cognitive and mental health, is known to cause structural changes in the brain. Understanding the structural changes that occur with exercise as well as the neuroanatomical correlates of a predisposition for exercise is important for understanding human health. This study used high-resolution 3D MR imaging, in combination with deformation-based morphometry, to investigate the macroscopic changes in brain structure that occur in healthy adult mice following four weeks of voluntary exercise. We found that exercise induced changes in multiple brain structures that are involved in motor function and learning and memory including the hippocampus, dentate gyrus, stratum granulosum of the dentate gyrus, cingulate cortex, olivary complex, inferior cerebellar peduncle and regions of the cerebellum. In addition, a number of brain structures, including the hippocampus, striatum and pons, when measured on MRI prior to the start of exercise were highly predictive of subsequent exercise activity. Exercise tended to normalize these pre-existing differences between mice.

  8. Involvement of Extracellular Signal Regulated Kinases in Traumatic Brain Injury-Induced Depression in Rodents

    OpenAIRE

    Kuo, Jinn-Rung; Cheng, Yi-Hsuan; Chen, Yi-Shion; Chio, Chung-Ching; Gean, Po-Wu

    2013-01-01

    Traumatic brain injury (TBI) is the most common cause of death and acquired disability among children and young adults in the developed countries. In clinical studies, the incidence of depression is high after TBI, and the mechanisms behind TBI-induced depression remain unclear. In the present study, we subjected rats to a moderate fluid percussion into the closed cranial cavity to induce TBI. After 3 days of recovery, injured rats were given a forced swim test (FST) and novelty-suppressed fe...

  9. Oxidative state and oxidative metabolism in the brain of rats with adjuvant-induced arthritis.

    Science.gov (United States)

    Wendt, Mariana Marques Nogueira; de Sá-Nakanishi, Anacharis Babeto; de Castro Ghizoni, Cristiane Vizioli; Bersani Amado, Ciomar Aparecida; Peralta, Rosane Marina; Bracht, Adelar; Comar, Jurandir Fernando

    2015-06-01

    The purpose of the present study was to evaluate the oxidative status of the brain of arthritic rats, based mainly on the observation that arthritis induces a pronounced oxidative stress in the liver of arthritis rats and that morphological alterations have been reported to occur in patients with rheumatoid arthritis. Rats with adjuvant-induced arthritis were used. These animals presented higher levels of reactive oxygen species (ROS) in the total brain homogenate (25% higher) and in the mitochondria (+55%) when compared to healthy rats. The nitrite plus nitrate contents, nitric oxide (NO) markers, were also increased in both mitochondria (+27%) and cytosol (+14%). Arthritic rats also presented higher levels of protein carbonyl groups in the total homogenate (+43%), mitochondria (+69%) and cytosol (+145%). Arthritis caused a diminution of oxygen consumption in isolated brain mitochondria only when ascorbate was the electron donor. The disease diminished the mitochondrial cytochrome c oxidase activity by 55%, but increased the transmembrane potential by 16%. The pro-oxidant enzyme xanthine oxidase was 150%, 110% and 283% higher, respectively, in the brain homogenate, mitochondria and cytosol of arthritic animals. The same occurred with the calcium-independent NO-synthase activity that was higher in the brain homogenate (90%) and cytosol (122%) of arthritic rats. The catalase activity, on the other hand, was diminished by arthritis in all cellular fractions (between 30 and 40%). It is apparent that the brain of rats with adjuvant-induced arthritis presents a pronounced oxidative stress and a significant injury to lipids and proteins, a situation that possibly contributes to the brain symptoms of the arthritis disease.

  10. Brain death induces the alteration of liver protein expression profiles in rabbits.

    Science.gov (United States)

    Du, Bing; Li, Ling; Zhong, Zhibiao; Fan, Xiaoli; Qiao, Bingbing; He, Chongxiang; Fu, Zhen; Wang, Yanfeng; Ye, Qifa

    2014-08-01

    At present, there is no accurate method for evaluating the quality of liver transplant from a brain-dead donor. Proteomics are used to investigate the mechanisms involved in brain death‑induced liver injury and to identify sensitive biomarkers. In the present study, age‑ and gender‑matched rabbits were randomly divided into the brain death and sham groups. The sham served as the control. A brain‑death model was established using an intracranial progressive pressurized method. The differentially expressed proteins extracted from the liver tissues of rabbits that were brain‑dead for 6 h in the two groups were determined by two‑dimensional gel electrophoresis and matrix‑assisted laser desorption ionization time of flight mass spectrometry. Although there was no obvious functional and morphological difference in 2, 4 and 6 h after brain death, results of the proteomics analysis revealed 973±34 and 987±38 protein spots in the control and brain death groups, respectively. Ten proteins exhibited a ≥2‑fold alteration. The downregulated proteins were: aldehyde dehydrogenase, runt‑related transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate‑cysteine ligase regulatory subunit and microsomal cytochrome B5. By contrast, the expression of dihydropyrimidinase-related protein 4, peroxiredoxin‑6, 3‑phosphoinositide‑dependent protein kinase‑1, 3-mercaptopyruvate and alcohol dehydrogenase were clearly upregulated. Immunohistochemistry and western blot analysis results revealed that the expression of RUNX1 was gradually increased in a time‑dependent manner in 2, 4, and 6 h after brain death. In conclusion, alteration of the liver protein expression profile induced by brain death indicated the occurrence of complex pathological changes even if no functional or morphological difference was identified. Thus, RUNX1 may be a sensitive predict factor for evaluating the quality of brain death donated liver.

  11. Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue.

    Science.gov (United States)

    Okonogi, Noriyuki; Nakamura, Kazuhiro; Suzuki, Yoshiyuki; Suto, Nana; Suzue, Kazutomo; Kaminuma, Takuya; Nakano, Takashi; Hirai, Hirokazu

    2014-07-01

    Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. However, previous studies using whole-body irradiation and bone marrow (BM) transplantation models have shown that adult BM cells migrate into the brain tissue and differentiate into microglia (BM-derived microglia; BMDM). Here, we investigated whether cranial irradiation alone was sufficient to induce the generation of BMDM in the adult mouse brain. Transgenic mice that express green fluorescent protein (GFP) under the control of a murine stem cell virus (MSCV) promoter (MSCV-GFP mice) were used. MSCV-GFP mice express GFP in BM cells but not in the resident microglia in the brain. Therefore, these mice allowed us to detect BM-derived cells in the brain without BM reconstitution. MSCV-GFP mice, aged 8-12 weeks, received 13.0 Gy irradiation only to the cranium, and BM-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. No BM-derived cells were detected in control non-irradiated MSCV-GFP mouse brains, but numerous GFP-labeled BM-derived cells were present in the brain stem, basal ganglia and cerebral cortex of the irradiated MSCV-GFP mice. These BM-derived cells were positive for Iba1, a marker for microglia, indicating that GFP-positive BM-derived cells were microglial in nature. The population of BMDM was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. Our results clearly show that cranial irradiation alone is sufficient to induce the generation of BMDM in the adult mouse.

  12. Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    El-Akabawy, Gehan; El-Kholy, Wael

    2014-05-01

    Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain.

  13. Using non-invasive brain stimulation to augment motor training-induced plasticity

    Directory of Open Access Journals (Sweden)

    Pascual-Leone Alvaro

    2009-03-01

    Full Text Available Abstract Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS and transcranial direct current stimulation (tDCS. These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date.

  14. Comparative proteomics of rat brain in the BCNU-induced model of cortical dysplasia

    Institute of Scientific and Technical Information of China (English)

    郭谊

    2014-01-01

    Objective To screen the differential proteins in the brain(neocortex and hippocampus)between the rats with cortical dysplasia(CD)and control ones,and investigate the role of their alteration in the development of epilepsy in CD.Methods Cortical dysplasia was induced in rat pups via in utero delivery of BCNU.A two-dimensional electrophoresis

  15. Ligustilide prevents cognitive impairment and attenuates neurotoxicity in D-galactose induced aging mice brain.

    Science.gov (United States)

    Li, Jie-Jia; Zhu, Qing; Lu, Ya-Peng; Zhao, Peng; Feng, Zhan-Bo; Qian, Zhong-Ming; Zhu, Li

    2015-01-21

    Ligustilide (LIG) is a principal active ingredient of traditional Chinese medicine, Radix Angelica sinensis, which has versatile pharmacological activities including neuroprotection. Previous studies have demonstrated that LIG has beneficial effects on cognition deficits associated with cerebral damage or neurodegenerative disorders. In present study, we investigated the neuroprotective effect of LIG on cognitive impairment and neurotoxicity in the brain of aging mouse induced by d-galactose (d-gal). The aging model mice were induced by subcutaneous (S.C.) injection of d-gal once daily for 8 weeks and LIG (80 mg/kg) was simultaneously administered orally. The Morris water maze (MWM) test was used to assess the spatial learning and memory abilities. The activity of Na(+)-K(+)-ATPase and the content of lipid peroxidation product malondialdehyde (MDA) in brain were examined. The levels of glial fibrillary acidic protein (GFAP), growth-associated protein GAP-43, and cleaved caspase-3 in brain were also determined by immunohistochemistry. The MWM test showed that LIG administration markedly improved behavioral performance of d-gal treated mice. This action could be partly explained by the results that LIG reduced the level of MDA as well as increased the activity of Na(+)-K(+)-ATPase in the brain of d-gal induced aging mice. Moreover, LIG significantly raised the expression of GAP-43 and reduced cleaved caspase-3 and GFAP levels in the brain of d-gal treated mice. These results demonstrated that LIG improves d-gal-induced cognitive dysfunction and brain toxicity, which suggests that LIG may be developed as a new medicine for the treatment of aged-related conditions.

  16. Neuroprotection of GST, an extract of traditional Chinese herb, against ischemic brain injury induced by transient brain ischemia and reperfusion in rat hippocampus.

    Science.gov (United States)

    Sun, Ya-Feng; Pei, Dong-Sheng; Zhang, Qing-Xiu; Zhang, Guang-Yi

    2008-06-01

    In this study, we investigated the effect of GST, an extract of Chinese traditional herb, on transient brain ischemia/reperfusion-induced neuronal cell death. Immunoblotting was used to detect the phosphorylation of MLK, JNK and c-jun. Transient (15 minutes) brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats. GST was administrated to the SD rats 20 minutes before ischemia or 1 hour after ischemia. Our data showed that the pretreatment of GST could inhibit phosphorylation of MLK, JNK and c-jun. Moreover, GST showed potent neuroprotective effects on ischemic brain damage in vivo and administration of it 1 hour after ischemia also achieved the protective effects. These results indicate that GST has a prominent neuroprotection action against brain ischemic damage and provides a promising therapeutic approach for ischemic brain injury.

  17. Bitter taste stimuli induce differential neural codes in mouse brain.

    Directory of Open Access Journals (Sweden)

    David M Wilson

    Full Text Available A growing literature suggests taste stimuli commonly classified as "bitter" induce heterogeneous neural and perceptual responses. Here, the central processing of bitter stimuli was studied in mice with genetically controlled bitter taste profiles. Using these mice removed genetic heterogeneity as a factor influencing gustatory neural codes for bitter stimuli. Electrophysiological activity (spikes was recorded from single neurons in the nucleus tractus solitarius during oral delivery of taste solutions (26 total, including concentration series of the bitter tastants quinine, denatonium benzoate, cycloheximide, and sucrose octaacetate (SOA, presented to the whole mouth for 5 s. Seventy-nine neurons were sampled; in many cases multiple cells (2 to 5 were recorded from a mouse. Results showed bitter stimuli induced variable gustatory activity. For example, although some neurons responded robustly to quinine and cycloheximide, others displayed concentration-dependent activity (p<0.05 to quinine but not cycloheximide. Differential activity to bitter stimuli was observed across multiple neurons recorded from one animal in several mice. Across all cells, quinine and denatonium induced correlated spatial responses that differed (p<0.05 from those to cycloheximide and SOA. Modeling spatiotemporal neural ensemble activity revealed responses to quinine/denatonium and cycloheximide/SOA diverged during only an early, at least 1 s wide period of the taste response. Our findings highlight how temporal features of sensory processing contribute differences among bitter taste codes and build on data suggesting heterogeneity among "bitter" stimuli, data that challenge a strict monoguesia model for the bitter quality.

  18. Mild brain ischemia induces unique physiological properties in striatal astrocytes.

    Science.gov (United States)

    Wang, Li-Ping; Cheung, Giselle; Kronenberg, Golo; Gertz, Karen; Ji, Shengbo; Kempermann, Gerd; Endres, Matthias; Kettenmann, Helmut

    2008-07-01

    We studied the properties of GFAP-expressing cells in adult mouse striatum using acute brain slices from transgenic animals expressing EGFP under GFAP promoter. Under physiological conditions, two distinct populations of GFAP-EGFP cells could be identified: (1) brightly fluorescent cells had bushy processes, passive membrane properties, glutamate transporter activity, and high gap junction coupling rate typical for classical astrocytes; (2) weakly fluorescent cells were characterized by thin, clearly distinguishable processes, voltage-gated currents, complex responses to kainate, and low coupling rate reminiscent of an astrocyte subtype recently described in the hippocampus. Mild focal cerebral ischemia confers delayed neuronal cell death and astrogliosis in the striatum. Following middle cerebral artery occlusion and reperfusion, brightly fluorescent cells were the dominant GFAP-EGFP population observed within the ischemic lesion. Interestingly, the majority of these cells expressed voltage-gated channels, showed complex responses to kainate, and a high coupling rate exceeding that of brightly fluorescent control cells. A minority of cells had passive membrane properties and was coupled less compared with passive control cells. We conclude that, in the adult striatum, astrocytes undergo distinct pathophysiological changes after ischemic insults. The dominant population in the ischemic lesion constitutes a novel physiological phenotype unlike any normal astrocyte and generates a large syncytium which might be a neuroprotective response of reactive astrocytes.

  19. Comparison of the four proposed Apgar scoring systems in the assessment of birth asphyxia and adverse early neurologic outcomes.

    Directory of Open Access Journals (Sweden)

    Hosein Dalili

    Full Text Available To compare the Conventional, Specified, Expanded and Combined Apgar scoring systems in predicting birth asphyxia and the adverse early neurologic outcomes.This prospective cohort study was conducted on 464 admitted neonates. In the delivery room, after delivery the umbilical cord was double clamped and a blood samples was obtained from the umbilical artery for blood gas analysis, meanwhile on the 1- , 5- and 10- minutes Conventional, Specified, Expanded, and Combined Apgar scores were recorded. Then the neonates were followed and intracranial ultrasound imaging was performed, and the following information were recorded: the occurrence of birth asphyxia, hypoxic Ischemic Encephalopathy (HIE, intraventricular hemorrhage (IVH, and neonatal seizure.The Combined-Apgar score had the highest sensitivity (97% and specificity (99% in predicting birth asphyxia, followed by the Specified-Apgar score that was also highly sensitive (95% and specific (97%. The Expanded-Apgar score was highly specific (95% but not sensitive (67% and the Conventional-Apgar score had the lowest sensitivity (81% and low specificity (81% in predicting birth asphyxia. When adjusted for gestational age, only the low 5-minute Combined-Apgar score was independently associated with the occurrence of HIE (B = 1.61, P = 0.02 and IVH (B = 2.8, P = 0.01.The newly proposed Combined-Apgar score is highly sensitive and specific in predicting birth asphyxia and also is a good predictor of the occurrence of HIE and IVH in asphyxiated neonates.

  20. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    Science.gov (United States)

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  1. Evaluation of region selective bilirubin-induced brain damage as a basis for a pharmacological treatment

    Science.gov (United States)

    Dal Ben, Matteo; Bottin, Cristina; Zanconati, Fabrizio; Tiribelli, Claudio; Gazzin, Silvia

    2017-01-01

    The neurologic manifestations of neonatal hyperbilirubinemia in the central nervous system (CNS) exhibit high variations in the severity and appearance of motor, auditory and cognitive symptoms, which is suggestive of a still unexplained selective topography of bilirubin-induced damage. By applying the organotypic brain culture (OBC: preserving in vitro the cellular complexity, connection and architecture of the in vivo brain) technique to study hyperbilirubinemia, we mapped the regional target of bilirubin-induced damage, demonstrated a multifactorial toxic action of bilirubin, and used this information to evaluate the efficacy of drugs applicable to newborns to protect the brain. OBCs from 8-day-old rat pups showed a 2–13 fold higher sensitivity to bilirubin damage than 2-day-old preparations. The hippocampus, inferior colliculus and cerebral cortex were the only brain regions affected, presenting a mixed inflammatory-oxidative mechanism. Glutamate excitotoxicity was appreciable in only the hippocampus and inferior colliculus. Single drug treatment (indomethacin, curcumin, MgCl2) significantly improved cell viability in all regions, while the combined (cocktail) administration of the three drugs almost completely prevented damage in the most affected area (hippocampus). Our data may supports an innovative (complementary to phototherapy) approach for directly protecting the newborn brain from bilirubin neurotoxicity. PMID:28102362

  2. Transcriptional Profile of HIV-induced Nuclear Translocation of Amyloid β in Brain Endothelial Cells

    Science.gov (United States)

    András, Ibolya E.; Rampersaud, Evadnie; Eum, Sung Yong; Toborek, Michal

    2015-01-01

    Background and Aims Increased amyloid deposition in HIV-infected brains may contribute to the pathogenesis of neurocognitive dysfunction in infected patients. We have previously shown that exposure to HIV results in enhanced amyloid β (Aβ) levels in human brain microvascular endothelial cells, suggesting that brain endothelial cells contribute to accumulation of Aβ in HIV-infected brains. Importantly, Aβ not only accumulates in the cytoplasm of HIV-exposed cells but also enters the nuclei of brain endothelial cells. Methods cDNA microarray analysis was performed in order to examine changes in the transcriptional profile associated with Aβ nuclear entry in the presence of HIV-1. Results Gene network analysis indicated that inhibition of nuclear entry of Aβ resulted in enrichment in gene sets involved in apoptosis and survival, endoplasmic reticulum stress response, immune response, cell cycle, DNA damage, oxidative stress, cytoskeleton remodeling and transforming growth factor b (TGFβ) receptor signaling. Conclusions The obtained data indicate that HIV-induced Aβ nuclear uptake affects several cellular stress-related pathways relevant for HIV-induced Aβ pathology. PMID:25446617

  3. Brain histamine mediates the bombesin-induced central activation of sympatho-adrenomedullary outflow.

    Science.gov (United States)

    Okuma, Y; Yokotani, K; Murakami, Y; Osumi, Y

    1997-01-01

    Intracerebroventricular (i.c.v.) administration of bombesin (0.3 nmol) increased plasma levels of both adrenaline and noradrenaline in urethane anesthetized rats. These bombesin-induced increases were inhibited by i.c.v. pretreatment with pyrilamine, an H1-receptor antagonist. Ranitidine, an H2-receptor antagonist also inhibited the increase of adrenaline, however, its effective dose was much larger than that of pyrilamine. Furthermore, the bombesin-induced increase of noradrenaline was not effectively inhibited by ranitidine. In the next series, turnover of histamine was assessed by measuring accumulation of tele-methylhistamine (t-MH), a major metabolite of brain histamine. I.c.v. administration of bombesin (0.3-3 nmol) increased turnover of hypothalamic histamine, while its intravenous administration was without effect. The present results suggest that the bombesin-induced central activation of sympatho-adrenomedullary outflow is probably, at least in part, mediated through brain histaminergic neurons.

  4. CT cold areas in both putamens in cases with history of perinatal asphyxia

    Energy Technology Data Exchange (ETDEWEB)

    Ishizaki, Asayo; Maruyama, Hiroshi (Tokyo Women' s Medical Coll. (Japan))

    1982-12-01

    CT bilaterally showed a cold area in the putamen of 5 infants with cerebral palsy who had had asphyxia at birth. The etiology was discussed, and 4 of the cases were clinically studied. All four patients had convulsive tetraplegia, or convulsive bilateral paralysis with the element of athetosis. Three of them had a history of infantile epilepsy, accompanied by abnormal ocular movement. Two patients with tetraplegia showed marked hypotonia of the trunk in ventral support (Landau). Impairment of the bilateral putamens in the abnormal muscle tone was inferred.

  5. Urinary Uric Acid/Creatinine Ratio - A Marker For Perinatal Asphyxia

    Science.gov (United States)

    Patel, Kinjal Prahaladbhai; Makadia, Mayur Goradhanbhai; Patel, Vishwal Indravardan; Nilayangode, Haridas Neelakandan

    2017-01-01

    Background Perinatal hypoxia is one of the leading causes of perinatal mortality in developing countries. Both apgar score and arterial blood pH predict the neonatal mortality in asphyxia. Apgar score alone does not predict neurologic outcome and as it is influenced by various factors. This study was conducted to evaluate the utility and sensitivity of urinary uric acid to creatinine ratio (UA/Cr ratio) in asphyxia diagnosis, compared to invasive Arterial Blood Gas (ABG) analysis. Aim To assess the urinary uric acid/creatinine ratio as an additional marker for perinatal asphyxia compared with ABG analysis in apgar score monitoring. Materials and Methods The present case control study was conducted at a teaching hospital in Central Gujarat. Data of 40 healthy newborns and 40 asphyxiated newborns were collected. In absence of regional estimates, a sample of size 39 was required to attain a power of 80% at 5% alpha (type I error) considering a moderate effect size of 0.65. (UA/Cr) ratio was measured from the spot urine sample collected during 24-72 hours of birth. Statistical analysis was performed by Independent t-test, Pearson’s correlation coefficient (r) and Receiver Operating Characteristic (ROC) plots. Results The mean (UA/Cr ratio) (2.75±0.18 vs 1.78±0.23) is significantly higher in asphyxiated group than in the control group (p0.05). Urinary UA/Cr ratio with criterion of >2.3 had 100% sensitivity, 100% specificity with AUC of 1 (p<0.0001) had a better predictive value. Conclusions Apgar score is usually reduced in neonates with congenital anomalies and premature neonates. Hence, it is preferable that the clinical diagnosis of asphyxia by apgar scores be supported by other investigations so that early decision can be taken about the level of care the baby needs. pH, lactates and base deficits change with establishment of respiration following resuscitation. However, pH, lactate, base deficit estimations are invasive and need rapid estimations. Non

  6. Pentosan polysulfate protects brain endothelial cells against bacterial lipopolysaccharide-induced damages.

    Science.gov (United States)

    Veszelka, Szilvia; Pásztói, Mária; Farkas, Attila E; Krizbai, István; Ngo, Thi Khue Dung; Niwa, Masami; Abrahám, Csongor S; Deli, Mária A

    2007-01-01

    Peripheral inflammation can aggravate local brain inflammation and neuronal death. The blood-brain barrier (BBB) is a key player in the event. On a relevant in vitro model of primary rat brain endothelial cells co-cultured with primary rat astroglia cells lipopolysaccharide (LPS)-induced changes in several BBB functions have been investigated. LPS-treatment resulted in a dose- and time-dependent decrease in the integrity of endothelial monolayers: transendothelial electrical resistance dropped, while flux of permeability markers fluorescein and albumin significantly increased. Immunostaining for junctional proteins ZO-1, claudin-5 and beta-catenin was significantly weaker in LPS-treated endothelial cells than in control monolayers. LPS also reduced the intensity and changed the pattern of ZO-1 immunostaining in freshly isolated rat brain microvessels. The activity of P-glycoprotein, an important efflux pump at the BBB, was also inhibited by LPS. At the same time production of reactive oxygen species and nitric oxide was increased in brain endothelial cells treated with LPS. Pentosan polysulfate, a polyanionic polysaccharide could reduce the deleterious effects of LPS on BBB permeability, and P-glycoprotein activity. LPS-stimulated increase in the production of reactive oxygen species and nitric oxide was also decreased by pentosan treatment. The protective effect of pentosan for brain endothelium can be of therapeutical significance in bacterial infections affecting the BBB.

  7. A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats.

    Science.gov (United States)

    Kharatishvili, I; Nissinen, J P; McIntosh, T K; Pitkänen, A

    2006-06-30

    Although traumatic brain injury is a major cause of symptomatic epilepsy, the mechanism by which it leads to recurrent seizures is unknown. An animal model of posttraumatic epilepsy that reliably reproduces the clinical sequelae of human traumatic brain injury is essential to identify the molecular and cellular substrates of posttraumatic epileptogenesis, and perform preclinical screening of new antiepileptogenic compounds. We studied the electrophysiologic, behavioral, and structural features of posttraumatic epilepsy induced by severe, non-penetrating lateral fluid-percussion brain injury in rats. Data from two independent experiments indicated that 43% to 50% of injured animals developed epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency was 0.3+/-0.2 seizures per day and mean seizure duration was 113+/-46 s. Behavioral seizure severity increased over time in the majority of animals. Secondarily-generalized seizures comprised an average of 66+/-37% of all seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of animals with posttraumatic epilepsy compared with those subjected to traumatic brain injury without epilepsy. Stereologic cell counts indicated a loss of dentate hilar neurons ipsilaterally following traumatic brain injury. Our data suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after severe non-penetrating fluid-percussion brain injury in rats, and that the lateral fluid percussion model can serve as a clinically-relevant tool for pathophysiologic and preclinical studies.

  8. Videogame training strategy-induced change in brain function during a complex visuomotor task.

    Science.gov (United States)

    Lee, Hyunkyu; Voss, Michelle W; Prakash, Ruchika Shaurya; Boot, Walter R; Vo, Loan T K; Basak, Chandramallika; Vanpatter, Matt; Gratton, Gabriele; Fabiani, Monica; Kramer, Arthur F

    2012-07-01

    Although changes in brain function induced by cognitive training have been examined, functional plasticity associated with specific training strategies is still relatively unexplored. In this study, we examined changes in brain function during a complex visuomotor task following training using the Space Fortress video game. To assess brain function, participants completed functional magnetic resonance imaging (fMRI) before and after 30 h of training with one of two training regimens: Hybrid Variable-Priority Training (HVT), with a focus on improving specific skills and managing task priority, or Full Emphasis Training (FET), in which participants simply practiced the game to obtain the highest overall score. Control participants received only 6 h of FET. Compared to FET, HVT learners reached higher performance on the game and showed less brain activation in areas related to visuo-spatial attention and goal-directed movement after training. Compared to the control group, HVT exhibited less brain activation in right dorsolateral prefrontal cortex (DLPFC), coupled with greater performance improvement. Region-of-interest analysis revealed that the reduction in brain activation was correlated with improved performance on the task. This study sheds light on the neurobiological mechanisms of improved learning from directed training (HVT) over non-directed training (FET), which is related to visuo-spatial attention and goal-directed motor planning, while separating the practice-based benefit, which is related to executive control and rule management.

  9. Chronic exposure to Tributyltin induces brain functional damage in juvenile common carp (Cyprinus carpio.

    Directory of Open Access Journals (Sweden)

    Zhi-Hua Li

    Full Text Available The aim of the present study was to investigate the effect of Tributyltin (TBT on brain function and neurotoxicity of freshwater teleost. The effects of long-term exposure to TBT on antioxidant related indices (MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase, Na+-K+-ATPase and neurological parameters (AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide in the brain of common carp were evaluated. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L for 15, 30, and 60 days. Based on the results, a low level and short-term TBT-induced stress could not induce the notable responses of the fish brain, but long-term exposure (more than 15 days to TBT could lead to obvious physiological-biochemical responses (based on the measured parameters. The results also strongly indicated that neurotoxicity of TBT to fish. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity.

  10. Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

    Science.gov (United States)

    C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

    2014-12-01

    3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

  11. Delayed radiation-induced necrosis of the brain stem; A case report

    Energy Technology Data Exchange (ETDEWEB)

    Yukawa, Osamu; Kodama, Yasunori; Kyoda, Jun; Yuki, Kiyoshi; Taniguchi, Eiji; Katayama, Shoichi; Hiroi, Tadashi (National Kure Hospital, Hiroshima (Japan)); Uozumi, Toru

    1993-03-01

    A 46-year-old man had surgery for a mixed glioma of the frontotemporal lobe. Postoperatively he received 50 Gy of irradiation. Sixteen months later he developed left hemiparesis and left facial palsy. MRI revealed lesion brain stem and basal ganglia. Despite chemotherapy and an additional 50 Gy dose, the patient deteriorated. Autopsy revealed a wide spread radiation-induced necrosis in the right cerebral hemisphere, midbrain and pons. In radiation therapy, great care must be taken to protect the normal brain tissue. (author).

  12. Detection of cysteine protease in Taenia solium-induced brain granulomas in naturally infected pigs

    DEFF Research Database (Denmark)

    Mkupasi, Ernatus Martin; Sikasunge, Chummy Sikalizyo; Ngowi, Helena Aminiel

    2013-01-01

    In order to further characterize the immune response around the viable or degenerating Taenia solium cysts in the pig brain, the involvement of cysteine protease in the immune evasion was assessed. Brain tissues from 30 adult pigs naturally infected with T. solium cysticercosis were subjected...... of a disintegrating parasite surrounded with high inflammatory cells. The results of immunohistochemistry indicated caspase-3 positive cells interspaced between inflammatory infiltrate mainly in stage I lesions, indicating the presence of cysteine protease. This result confirms the earlier hypothesis that cysteine...... protease may play a role in inducing immune evasion through apoptosis around viable T. solium cysts....

  13. Risk Factors for Birth Asphyxia in an Urban Health Facility in Cameroon

    Directory of Open Access Journals (Sweden)

    Andreas CHIABI

    2013-08-01

    Full Text Available How to Cite This Article: Chiabi A, Nguefack S, Mah E, Nodem S, Mbuagbaw L, Mbonda E, Tchokoteu PF, Doh A. Risk Factors for Birth Asphyxia in an Urban Health Facility in Cameroon. Iran J Child Neurol. 2013 Summer; 7(3:46-54.ObjectiveThe World Health Organization (WHO estimates that 4 million children are born with asphyxia every year, of which 1 million die and an equal number survive with severe neurologic sequelae. The purpose of this study was to identify the risk factors of birth asphyxia and the hospital outcome of affected neonates.Materials & MethodsThis study was a prospective case-control study on term neonates in a tertiary hospital in Yaounde, with an Apgar score of < 7 at the 5th minute as the case group, that were matched with neonates with an Apgar score of ≥ 7 at the 5th minute as control group. Statistical analysis of relevant variables of the mother and neonates was carried out to determine the significant risk factors.ResultsThe prevalence of neonatal asphyxia was 80.5 per 1000 live births. Statistically significant risk factors were the single matrimonial status, place of antenatal visits, malaria, pre-eclampsia/eclampsia, prolonged labor, arrest of labour,prolonged rupture of membranes, and non-cephalic presentation. Hospital mortality was 6.7%, that 12.2% of them had neurologic deficits and/or abnormal transfontanellar ultrasound/electroencephalogram on discharge, and 81.1% hada satisfactory outcome.ConclusionThe incidence of birth asphyxia in this study was 80.5% per1000 live birth with a mortality of 6.7%. Antepartum risk factors were: place of antenatal visit, malaria during pregnancy, and preeclampsia/eclampsia. Whereas prolonged labor, stationary labor, and term prolonged rupture of membranes were intrapartum risk faktors. Preventive measures during prenatal  visits through informing and communicating with pregnant women should be reinforced. References1. World Health Organisation. Perinatal mortality: a listingof

  14. Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities.

    Science.gov (United States)

    Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

    2015-09-30

    Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal-occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention.

  15. Administration of sesamol improved blood-brain barrier function in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    VanGilder, R L; Kelly, K A; Chua, M D; Ptachcinski, R L; Huber, Jason D

    2009-07-01

    Uncontrolled or poorly controlled blood glucose during diabetes is an important factor in worsened vascular function. While evidence suggests that hyperglycemia-induced oxidative stress plays a prominent role in development of microangiopathy of the retina, kidney, and nerves, the role oxidative stress plays on blood-brain barrier (BBB) function and structure has lagged behind. In this study, a natural antioxidant, sesamol, was administered to streptozotocin (STZ)-induced diabetic rats to examine the role that oxidative stress plays on BBB structure and function. Experiments were conducted at 56 days after STZ injection. Male Sprague-Dawley rats randomly were divided into four treatment groups CON--control; STZ--STZ-induced diabetes; CON + S--control + sesamol; STZ + S--STZ-induced diabetes + sesamol. Functional and structural changes to the BBB were measured by in situ brain perfusion and western blot analysis of changes in tight junction protein expression. Oxidative stress markers were visualized by fluorescent confocal microscopy and assayed by spectrophotometric analysis. Results demonstrated that the increased BBB permeability observed in STZ-induced diabetic rats was attenuated in STZ + S rats to levels observed in CON. Sesamol treatment reduced the negative impact of STZ-induced diabetes on tight junction protein expression in isolated cerebral microvessels. Oxidative stress markers were elevated in STZ as compared to CON. STZ + S displayed an improved antioxidant capacity which led to a reduced expression of superoxide and peroxynitrite and reduced lipid peroxidation. In conclusion, this study showed that sesamol treatment enhanced antioxidant capacity of the diabetic brain and led to decreased perturbation of hyperglycemia-induced changes in BBB structure and function.

  16. The Behaviour of Protein Carbonyls in Newborns with Birth Respiratory Distress and Asphyxia

    Directory of Open Access Journals (Sweden)

    Gabriela ZAHARIE

    2009-12-01

    Full Text Available Objective: A prospective study was carried out in premature newborns with respiratory distress syndrome (RDS and asphyxia at birth in order to identify and analyze the effects of RDS on proteins. Material and Methods: Protein peroxidation was studied using the Reznick spectrophotometric method. The study group included 14 premature newborns with respiratory distress and asphyxia at birth. The control group included 13 newborns that were born on term, eutrophic and healthy. The determinations were carried out using venous blood. Statistical data analyses were performed using Statistica software. The comparisons between groups (study and controls were performed by applying parametric and non-parametric tests according with the type of distribution. Results: Statistically significant correlations were found between the value of protein carbonyls (PC and the weight of premature newborns in the case group (p < 0.05, as well as between the PC value and the presence of respiratory distress due to surfactant deficiency in the study group. The average PC value in the study group was higher in the third day as compared with the first day. The PC value was significantly higher in the control group as compared with study group. Conclusion: The results of our study revealed that the respiratory distress in the premature newborn and oxygen therapy stimulate the peroxidation of proteins.

  17. Mangiferin regulates interleukin-6 and cystathionine-b-synthase in lipopolysaccharide-induced brain injury.

    Science.gov (United States)

    Fu, Yan-Yan; Zhang, Fang; Zhang, Lei; Liu, Hong-Zhi; Zhao, Zi-Ming; Wen, Xiang-Ru; Wu, Jian; Qi, Da-Shi; Sun, Ying; Du, Yang; Dong, Hong-Yan; Liu, Yong-Hai; Song, Yuan-Jian

    2014-07-01

    Mangiferin has been extensively applied in different fields due to its anti-inflammatory properties. However, the precise mechanism used by mangiferin on lipopolysaccharide (LPS)-induced inflammation has not been elucidated. Here, we discuss the potential mechanism of mangiferin during a LPS-induced brain injury. Brain injury was induced in ICR mice via intraperitoneal LPS injection (5 mg/kg). Open- and closed-field tests were used to detect the behaviors of mice, while immunoblotting was performed to measure the expression of interleukin-6 (IL-6) and cystathionine-b-synthase (CBS) in the hippocampus after mangiferin was orally administered (p.o.). Mangiferin relieved LPS-induced sickness 6 and 24 h after LPS injection; in addition, this compound suppressed LPS-induced IL-6 production after 24 h of LPS induction as well as the downregulation of LPS-induced CBS expression after 6 and 24 h of LPS treatment in the hippocampus. Therefore, mangiferin attenuated sickness behavior by regulating the expression of IL-6 and CBS.

  18. Alleviation of ischemia-induced brain edema by activation of the central histaminergic system in rats.

    Science.gov (United States)

    Irisawa, Yumi; Adachi, Naoto; Liu, Keyue; Arai, Tatsuru; Nagaro, Takumi

    2008-09-01

    We have reported that facilitation of central histaminergic activity prevents the development of ischemia-induced brain injury. Since cerebral edema is a major cause of brain damage, we studied effects on brain edema of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H(3)-receptor antagonist, both of which enhance central histaminergic activity. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery in rats, and the water content and infarct size were determined 24 h after reperfusion. Changes in the extracellular concentration of histamine were examined in the striatum by a microdialysis procedure, and effects of these compounds were evaluated. Repeated administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the increase in the water contents in ischemic regions. Simultaneous administration of thioperamide (5 mg/kg, s.c.) with L-histidine (1000 mg/kg, i.p.) completely prevented edema formation and alleviated brain infarction, although a single dose of L-histidine, immediately after reperfusion, showed no benefits. The striatal histamine level was gradually increased after reperfusion as well as during ischemia. Simultaneous administration of thioperamide with L-histidine markedly increased the brain histamine concentration, and the value increased up to 230% of that in the saline group 5 - 6 h after reperfusion. L-Histidine alone did not affect the increase in the histamine output after ischemia. These findings suggest that further activation of the central histaminergic system after initiation of cerebral ischemia prevents development of ischemia-induced brain edema.

  19. Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

    Science.gov (United States)

    Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari

    2013-10-01

    Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.

  20. Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Cianfoni, A., E-mail: acianfoni@hotmail.com [Neuroradiology, Neurocenter of Italian Switzerland–Ospedale regionale Lugano, Via Tesserete 46, Lugano, 6900, CH (Switzerland); Caulo, M., E-mail: caulo@unich.it [Department of Neuroscience and Imaging, University of Chieti, Via dei Vestini 33, 6610 Chieti. Italy (Italy); Cerase, A., E-mail: alfonsocerase@gmail.com [Unit of Neuroimaging and Neurointervention NINT, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, V.le Bracci 16, Siena (Italy); Della Marca, G., E-mail: dellamarca@rm.unicatt.it [Neurology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Falcone, C., E-mail: carlo_falc@libero.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Di Lella, G.M., E-mail: gdilella@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Gaudino, S., E-mail: sgaudino@sirm.org [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Edwards, J., E-mail: edwardjc@musc.edu [Neuroscience Dept., Medical University of South Carolina, 96J Lucas st, 29425, Charleston, SC (United States); Colosimo, C., E-mail: colosimo@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy)

    2013-11-01

    Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

  1. Glioblastoma cell-secreted interleukin-8 induces brain endothelial cell permeability via CXCR2.

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    Julie Dwyer

    Full Text Available Glioblastoma constitutes the most aggressive and deadly of brain tumors. As yet, both conventional and molecular-based therapies have met with limited success in treatment of this cancer. Among other explanations, the heterogeneity of glioblastoma and the associated microenvironment contribute to its development, as well as resistance and recurrence in response to treatments. Increased vascularity suggests that tumor angiogenesis plays an important role in glioblastoma progression. However, the molecular crosstalk between endothelial and glioblastoma cells requires further investigation. To examine the effects of glioblastoma-derived signals on endothelial homeostasis, glioblastoma cell secretions were collected and used to treat brain endothelial cells. Here, we present evidence that the glioblastoma secretome provides pro-angiogenic signals sufficient to disrupt VE-cadherin-mediated cell-cell junctions and promote endothelial permeability in brain microvascular endothelial cells. An unbiased angiogenesis-specific antibody array screen identified the chemokine, interleukin-8, which was further demonstrated to function as a key factor involved in glioblastoma-induced permeability, mediated through its receptor CXCR2 on brain endothelia. This underappreciated interface between glioblastoma cells and associated endothelium may inspire the development of novel therapeutic strategies to induce tumor regression by preventing vascular permeability and inhibiting angiogenesis.

  2. Brain IL-1β was involved in reserpine-induced behavioral depression in rats

    Institute of Scientific and Technical Information of China (English)

    Qing-jun HUANG; Hong JIANG; Xin-ling HAO; Thomas R MINOR

    2004-01-01

    AIM: To investigate the mechanism of brain interleukin-1 β (IL-1 β) in reserpine-induced behavioral depression in rats. METHODS: Porsult swim test was used in the measurement of depressive behavior and ELISA was used in measurement of brain IL-1 β. RESULTS: Intraperitoneal injection of reserpine (0, 4, 6, and 8 mg/kg, ip) increased floating time in the Porsult swim test in a dose-and time-dependent manner in rats. Intracerebroventricular injection (icv) of IL-1 β receptor antagonist (IL-lra, 6 mg/kg) blocked the increment of floating time in Porsult swim test at 48 and 72 h after reserpine injection, but not at 1 and 24 h after injection. Brain IL-lβ increased after reserpine treatment in posterior cortex, hippocampus, and hypothalamus. The increase of IL-1 β concentration starts at 24 hours after injection of reserpine and reached the peak at 48 h. CONCLUSION: Reserpine induced behavioral depression partially via brain interleukin-1 β generation.

  3. Endomorphins, endogenous opioid peptides, provide antioxidant defense in the brain against free radical-induced damage.

    Science.gov (United States)

    Lin, Xin; Yang, Ding-Jian; Cai, Wen-Qing; Zhao, Qian-Yu; Gao, Yan-Feng; Chen, Qiang; Wang, Rui

    2003-11-20

    Oxidative stress has been considered to be a major cause of cellular injuries in a variety of chronic health problems, such as carcinogenesis and neurodegenerative disorders. The brain appears to be more susceptible to oxidative damage than other organs. Therefore, the existence of antioxidants may be essential in brain protective systems. The antioxidative and free radical scavenging effects of endomorphin 1 (EM1) and endomorphin 2 (EM2), endogenous opioid peptides in the brain, have been investigated in vitro. The oxidative damage was initiated by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrocholoride) (AAPH) and hydrogen peroxide (H2O2). The linoleic acid peroxidation, DNA and protein damage were monitored by formation of hydroperoxides, by plasmid pBR 322 DNA nicking assay and single-cell alkaline electrophoresis, and by SDS-polyacrylamide gel electrophoresis. Endomorphins can inhibit lipid peroxidation, DNA strand breakage, and protein fragmentation induced by free radical. Endomorphins also reacted with galvinoxyl radicals in homogeneous solution, and the pseudo-first-order rate constants were determined spectrophotometrically by following the disappearance of galvinoxyl radicals. In all assay systems, EM1 was more potent than EM2 and GSH, a major intracellular water-soluble antioxidant. We propose that endomorphins are one of the protective systems against free radical-induced damage in the brain.

  4. Possible effects of rosuvastatin on noise-induced oxidative stress in rat brain.

    Science.gov (United States)

    Ersoy, Alevtina; Koc, Emine Rabia; Sahin, Semsettin; Duzgun, Ulkuhan; Acar, Burcu; Ilhan, Atilla

    2014-01-01

    The problem of noise has recently gained more attention as it has become an integral part of our daily lives. However, its influence has yet to be fully elucidated. Other than being an unpleasant stimulus, noise may cause health disorders through annoyance and stress, including oxidative stress. Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, may possess antioxidant properties. Based on rat models, our project investigates the effect of rosuvastatin on noise-induced oxidative stress in the brain tissue. Thirty-two male Wistar albino rats were used. The rats were divided into four groups: Noise exposure plus rosuvastatin usage, only noise exposure, only rosuvastatin usage, and control. After the data had been collected, oxidant and antioxidant parameters were analyzed in the cerebral cortex, brain stem, and cerebellum. Results indicated that superoxide dismutase values were significantly decreased in the cerebral cortex, while malondialdehyde values in the brainstem and cerebellum were significantly increased in the group with only noise exposure. Superoxide dismutase values in the brainstem were significantly increased, but nitric oxide values in the cerebellum and brainstem and malondialdehyde values in the cerebellum and cerebral cortex were significantly decreased in the group where only rosuvastatin was used. During noise exposure, the use of rosuvastatin caused significantly increased superoxide dismutase values in the cerebral cortex and brainstem, but significantly reduced malondialdehyde values in the brain stem. Consequently, our data show that brain tissue was affected by oxidative stress due to continued exposure to noise. This noise-induced stress decreases with rosuvastatin therapy.

  5. Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity

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    Karsten eMueller

    2015-07-01

    Full Text Available Previous cross-sectional studies on body-weight-related alterations in brain structure revealed profound changes in the gray matter (GM and white matter (WM that resemble findings obtained from individuals with advancing age. This suggests that obesity may lead to structural brain changes that are comparable with brain aging. Here, we asked whether weight-loss-dependent improved metabolic and neurotrophic functioning parallels the reversal of obesity-related alterations in brain structure. To this end we applied magnetic resonance imaging together with voxel-based morphometry and diffusion-tensor imaging in overweight to obese individuals who participated in a fitness course with intensive physical training three days per week over a period of three months. After the fitness course, participants presented, with inter-individual heterogeneity, a reduced body mass index (BMI, reduced serum leptin concentrations, elevated high-density lipoprotein-cholesterol (HDL-C, and alterations of serum brain-derived neurotrophic factor (BDNF concentrations suggesting changes of metabolic and neurotrophic function. Exercise-dependent changes in BMI and serum concentration of BDNF, leptin, and HDL-C were related to an increase in GM density in the left hippocampus, the insular cortex, and the left cerebellar lobule. We also observed exercise-dependent changes of diffusivity parameters in surrounding WM structures as well as in the corpus callosum. These findings suggest that weight-loss due to physical exercise in overweight to obese participants induces profound structural brain plasticity, not primarily of sensorimotor brain regions involved in physical exercise, but of regions previously reported to be structurally affected by an increased body weight and functionally implemented in gustation and cognitive processing.

  6. Chemotherapy-induced amenorrhea: a prospective study of brain activation changes and neurocognitive correlates.

    Science.gov (United States)

    Conroy, Susan K; McDonald, Brenna C; Ahles, Tim A; West, John D; Saykin, Andrew J

    2013-12-01

    Chemotherapy-induced amenorrhea (CIA) often occurs in pre- and peri-menopausal BC patients, and while cancer/chemotherapy and abrupt estrogen loss have separately been shown to affect cognition and brain function, studies of the cognitive effects of CIA are equivocal, and its effects on brain function are unknown. Functional MRI (fMRI) during a working memory task was used to prospectively assess the pattern of brain activation and deactivation prior to and 1 month after chemotherapy in BC patients who experienced CIA (n = 9), post-menopausal BC patients undergoing chemotherapy (n = 9), and pre- and post-menopausal healthy controls (n = 6 each). Neurocognitive testing was also performed at both time points. Repeated measures general linear models were used to assess statistical significance, and age was a covariate in all analyses. We observed a group-by-time interaction in the combined magnitudes of brain activation and deactivation (p = 0.006): the CIA group increased in magnitude from baseline to post-treatment while other groups maintained similar levels over time. Further, the change in brain activity magnitude in CIA was strongly correlated with change in processing speed neurocognitive testing score (r = 0.837 p = 0.005), suggesting this increase in brain activity reflects effective cognitive compensation. Our results demonstrate prospectively that the pattern of change in brain activity from pre- to post-chemotherapy varies according to pre-treatment menopausal status. Cognitive correlates add to the potential clinical significance of these findings. These findings have implications for risk appraisal and development of prevention or treatment strategies for cognitive changes in CIA.

  7. Combined cognitive-psychological-physical intervention induces reorganization of intrinsic functional brain architecture in older adults.

    Science.gov (United States)

    Zheng, Zhiwei; Zhu, Xinyi; Yin, Shufei; Wang, Baoxi; Niu, Yanan; Huang, Xin; Li, Rui; Li, Juan

    2015-01-01

    Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age.

  8. Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

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    Carl-Johan Boraxbekk

    2015-07-01

    Full Text Available Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results: Episodic memory performance improved significantly (p = 0.010 after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA. Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions: Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.

  9. Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A.

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    Fayçal Guedj

    Full Text Available Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG - a member of a natural polyphenols family, found in great amount in green tea leaves - is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice.

  10. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

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    Zhiwei Zheng

    2015-01-01

    Full Text Available Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age.

  11. Demethoxycurcumin Retards Cell Growth and Induces Apoptosis in Human Brain Malignant Glioma GBM 8401 Cells

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    Tzuu-Yuan Huang

    2012-01-01

    Full Text Available Demethoxycurcumin (DMC; a curcumin-related demethoxy compound has been recently shown to display antioxidant and antitumor activities. It has also produced a potent chemopreventive action against cancer. In the present study, the antiproliferation (using the MTT assay, DMC was found to have cytotoxic activities against GBM 8401 cell with IC50 values at 22.71 μM and induced apoptosis effects of DMC have been investigated in human brain malignant glioma GBM 8401 cells. We have studied the mitochondrial membrane potential (MMP, DNA fragmentation, caspase activation, and NF-κB transcriptional factor activity. By these approaches, our results indicated that DMC has produced an inhibition of cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects were observed to increase in proportion with the dosage of DMC treatment, and the apoptosis was induced by DMC in human brain malignant glioma GBM 8401 cells via mitochondria- and caspase-dependent pathways.

  12. BRAIN DYSFUNCTION OF PATIENTS WITH QIGONG INDUCED MENTAL DISORDER REVEALED BY EVOKED POTENTIALS RECORDING

    Institute of Scientific and Technical Information of China (English)

    LU Yingzhi; ZONG Wenbin; CHEN Xingshi

    2003-01-01

    Objective: In order to investigate the brain function of patients with Qigong induced mental disorder (QIMD), this study was carried out. Methods: Four kinds of evoked potentials, including contingent negative variation (CNV), auditory evoked potentials (AEP), visual evoked potentials (VEP), and somatosensory evoked potentials (SEP), were recorded from 12 patients with Qigong induced mental disorder.Comparison of their evoked potentials with the data from some normal controls was made. Results: The results revealed that there were 3 kinds of abnormal changes in evoked potentials of patients with QIMD that is latency prolongation, amplitude increase and amplitude decrease, as compared with normal controls. Conclusion: Brain dysfunction of patients with QIMD was confirmed. Its biological mechanism needs further studying.

  13. Sequential process in brain-derived neurotrophic factor-induced functional periodontal tissue regeneration.

    Science.gov (United States)

    Konishi, Akihiro; Takeda, Katsuhiro; Fujita, Tsuyoshi; Kajiya, Mikihito; Matsuda, Shinji; Kittaka, Mizuho; Shiba, Hideki; Kurihara, Hidemi

    2016-04-01

    We recently demonstrated that brain-derived neurotrophic factor (BDNF) promotes periodontal tissue regeneration. The purpose of this study was to establish an essential component of a rational approach for the clinical application of BDNF in periodontal regenerative therapy. Here, we assessed the sequence of early events in BDNF-induced periodontal tissue regeneration, especially from the aspect of cementum regeneration. Brain-derived neurotrophic factor was applied into experimental periodontal defects in Beagle dogs. The localization of cells positive for neurotrophic tyrosine kinase, receptor, type 2, proliferating cell nuclear antigen, osteopontin, integrin αVβ3, and integrin α2β1 was evaluated by immunohistochemistry. The effects of BDNF on adhesion of cultured human periodontal ligament cells was examined by an in vitro study. The results suggest that BDNF could induce rapid cementum regeneration by stimulating adhesion, proliferation, and differentiation of periodontal ligament cells in the early regenerative phase, resulting in enhancement of periodontal tissue regeneration.

  14. Melatonin reduces traumatic brain injur y-induced oxidative stress in the cerebral cortex and blood of rats

    Institute of Scientific and Technical Information of China (English)

    Nilgnenol; Mustafa Nazrolu

    2014-01-01

    Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We in-vestigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vita-min E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain inju-ry-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.

  15. Myeloperoxidase-derived oxidants induce blood-brain barrier dysfunction in vitro and in vivo.

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    Andreas Üllen

    Full Text Available Peripheral leukocytes can exacerbate brain damage by release of cytotoxic mediators that disrupt blood-brain barrier (BBB function. One of the oxidants released by activated leukocytes is hypochlorous acid (HOCl formed via the myeloperoxidase (MPO-H2O2-Cl(- system. In the present study we examined the role of leukocyte activation, leukocyte-derived MPO and MPO-generated oxidants on BBB function in vitro and in vivo. In a mouse model of lipopolysaccharide (LPS-induced systemic inflammation, neutrophils that had become adherent released MPO into the cerebrovasculature. In vivo, LPS-induced BBB dysfunction was significantly lower in MPO-deficient mice as compared to wild-type littermates. Both, fMLP-activated leukocytes and the MPO-H2O2-Cl(- system inflicted barrier dysfunction of primary brain microvascular endothelial cells (BMVEC that was partially rescued with the MPO inhibitor 4-aminobenzoic acid hydrazide. BMVEC treatment with the MPO-H2O2-Cl(- system or activated neutrophils resulted in the formation of plasmalogen-derived chlorinated fatty aldehydes. 2-chlorohexadecanal (2-ClHDA severely compromised BMVEC barrier function and induced morphological alterations in tight and adherens junctions. In situ perfusion of rat brain with 2-ClHDA increased BBB permeability in vivo. 2-ClHDA potently activated the MAPK cascade at physiological concentrations. An ERK1/2 and JNK antagonist (PD098059 and SP600125, respectively protected against 2-ClHDA-induced barrier dysfunction in vitro. The current data provide evidence that interference with the MPO pathway could protect against BBB dysfunction under (neuroinflammatory conditions.

  16. Effect of Brain-Derived Neurotrophic Factor Haploinsufficiency on Stress-Induced Remodeling of Hippocampal Neurons

    OpenAIRE

    Magariños, A.M.; Li, C. J.; Toth, J. Gal; Bath, K.G.; Jing, D; Lee, F S; MCEWEN, B. S.

    2011-01-01

    Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the ...

  17. Protective role of Cynodon dactylon in ameliorating the aluminium-induced neurotoxicity in rat brain regions.

    Science.gov (United States)

    Sumathi, Thangarajan; Shobana, Chandrasekar; Kumari, Balasubramanian Rathina; Nandhini, Devarajulu Nisha

    2011-12-01

    Cynodon dactylon (Poaceae) is a creeping grass used as a traditional ayurvedic medicine in India. Aluminium-induced neurotoxicity is well known and different salts of aluminium have been reported to accelerate damage to biomolecules like lipids, proteins and nucleic acids. The objective of the present study was to investigate whether the aqueous extract of C. dactylon (AECD) could potentially prevent aluminium-induced neurotoxicity in the cerebral cortex, hippocampus and cerebellum of the rat brain. Male albino rats were administered with AlCl(3) at a dose of 4.2 mg/kg/day i.p. for 4 weeks. Experimental rats were given C. dactylon extract in two different doses of 300 mg and 750 mg/keg/day orally 1 h prior to the AlCl(3) administration for 4 weeks. At the end of the experiments, antioxidant status and activities of ATPases in cerebral cortex, hippocampus and cerebellum of rat brain were measured. Aluminium administration significantly decreased the level of GSH and the activities of SOD, GPx, GST, Na(+)/K(+) ATPase, and Mg(2+) ATPase and increased the level of lipid peroxidation (LPO) in all the brain regions when compared with control rats. Pre-treatment with AECD at a dose of 750 mg/kg b.w increased the antioxidant status and activities of membrane-bound enzymes (Na(+)/K(+) ATPase and Mg(2+) ATPase) and also decreased the level of LPO significantly, when compared with aluminium-induced rats. The results of this study indicated that AECD has potential to protect the various brain regions from aluminium-induced neurotoxicity.

  18. A Fluid Helmet Liner for Protection Against Blast Induced Traumatic Brain Injury

    Science.gov (United States)

    2010-05-01

    Induced Traumatic Brain Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER N00014-08-1-0261 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Young, Laurence , R... Laurence R. Young Steven F. Son George A. Christou Matthew D. Alley Rahul Goel Andrew P. Vechart Benjamin R. Schimizze Table of Contents...Beach, South Carolina, Battelle Press, Columbus, pp. 29-38,1997. 10. Grover ,R., Ree , F. A., and Holmes, N., "Equation of state from Si02 Aerogel

  19. The Ayurvedic drug, Ksheerabala, ameliorates quinolinic acid-induced oxidative stress in rat brain

    OpenAIRE

    Swathy, S. S.; Indira, M.

    2010-01-01

    One of the mechanisms of neurotoxicity is the induction of oxidative stress. There is hardly any cure for neurotoxicity in modern medicine, whereas many drugs in Ayurveda possess neuroprotective effects; however, there is no scientific validation for these drugs. Ksheerabala is an ayurvedic drug which is used to treat central nervous system disorders, arthritis, and insomnia. The aim of our study was to evaluate the effect of Ksheerabala on quinolinic acid-induced toxicity in rat brain. The o...

  20. Non-verbal emotion communication training induces specific changes in brain function and structure.

    Science.gov (United States)

    Kreifelts, Benjamin; Jacob, Heike; Brück, Carolin; Erb, Michael; Ethofer, Thomas; Wildgruber, Dirk

    2013-01-01

    The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure.

  1. Curcumin Mediated Attenuation of Carbofuran Induced Oxidative Stress in Rat Brain

    Science.gov (United States)

    Jaiswal, Sunil Kumar; Sharma, Ashish; Gupta, Vivek Kumar; Singh, Rakesh Kumar; Sharma, Bechan

    2016-01-01

    The indiscriminate use of carbofuran to improve crop productivity causes adverse effects in nontargets including mammalian systems. The objective of this study was to evaluate carbofuran induced oxidative stress in rat brain stem and its attenuation by curcumin, a herbal product. Out of 6 groups of rats, 2 groups received two different doses of carbofuran, that is, 15 and 30% of LD50, respectively, for 30 days. Out of these, 2 groups receiving same doses of carbofuran were pretreated with curcumin (100 mg/kg body weight). The levels of antioxidants, TBARS, GSH, SOD, catalase, and GST were determined in rat brain stem. The 2 remaining groups served as placebo and curcumin treated, respectively. The data suggested that carbofuran at different doses caused significant alterations in the levels of TBARS and GSH in dose dependent manner. The TBARS and GSH contents were elevated. The activities of SOD, catalase, and GST were significantly inhibited at both doses of carbofuran. The ratio of P/A was also found to be sharply increased. The pretreatment of curcumin exhibited significant protection from carbofuran induced toxicity. The results suggested that carbofuran at sublethal doses was able to induce oxidative stress in rat brain which could be attenuated by curcumin. PMID:27213055

  2. Curcumin Mediated Attenuation of Carbofuran Induced Oxidative Stress in Rat Brain

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Jaiswal

    2016-01-01

    Full Text Available The indiscriminate use of carbofuran to improve crop productivity causes adverse effects in nontargets including mammalian systems. The objective of this study was to evaluate carbofuran induced oxidative stress in rat brain stem and its attenuation by curcumin, a herbal product. Out of 6 groups of rats, 2 groups received two different doses of carbofuran, that is, 15 and 30% of LD50, respectively, for 30 days. Out of these, 2 groups receiving same doses of carbofuran were pretreated with curcumin (100 mg/kg body weight. The levels of antioxidants, TBARS, GSH, SOD, catalase, and GST were determined in rat brain stem. The 2 remaining groups served as placebo and curcumin treated, respectively. The data suggested that carbofuran at different doses caused significant alterations in the levels of TBARS and GSH in dose dependent manner. The TBARS and GSH contents were elevated. The activities of SOD, catalase, and GST were significantly inhibited at both doses of carbofuran. The ratio of P/A was also found to be sharply increased. The pretreatment of curcumin exhibited significant protection from carbofuran induced toxicity. The results suggested that carbofuran at sublethal doses was able to induce oxidative stress in rat brain which could be attenuated by curcumin.

  3. Sodium butyrate reverses the inhibition of Krebs cycle enzymes induced by amphetamine in the rat brain.

    Science.gov (United States)

    Valvassori, Samira S; Calixto, Karen V; Budni, Josiane; Resende, Wilson R; Varela, Roger B; de Freitas, Karolina V; Gonçalves, Cinara L; Streck, Emilio L; Quevedo, João

    2013-12-01

    There is increasing interest in the possibility that mitochondrial impairment may play an important role in bipolar disorder (BD). The Krebs cycle is the central point of oxidative metabolism, providing carbon for biosynthesis and reducing agents for generation of ATP. Recently, studies have suggested that histone deacetylase (HDAC) inhibitors may have antimanic effects. The present study aims to investigate the effects of sodium butyrate (SB), a HDAC inhibitor, on Krebs cycle enzymes activity in the brain of rats subjected to an animal model of mania induced by D-amphetamine (D-AMPH). Wistar rats were first given D-AMPH or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with SB or Sal. The citrate synthase (CS), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were evaluated in the prefrontal cortex, hippocampus, and striatum of rats. The D-AMPH administration inhibited Krebs cycle enzymes activity in all analyzed brain structures and SB reversed D-AMPH-induced dysfunction analyzed in all brain regions. These findings suggest that Krebs cycle enzymes' inhibition can be an important link for the mitochondrial dysfunction seen in BD and SB exerts protective effects against the D-AMPH-induced Krebs cycle enzymes' dysfunction.

  4. Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase.

    Science.gov (United States)

    Kronenberg, Golo; Harms, Christoph; Sobol, Robert W; Cardozo-Pelaez, Fernando; Linhart, Heinz; Winter, Benjamin; Balkaya, Mustafa; Gertz, Karen; Gay, Shanna B; Cox, David; Eckart, Sarah; Ahmadi, Michael; Juckel, Georg; Kempermann, Gerd; Hellweg, Rainer; Sohr, Reinhard; Hörtnagl, Heide; Wilson, Samuel H; Jaenisch, Rudolf; Endres, Matthias

    2008-07-09

    Folate deficiency and resultant increased homocysteine levels have been linked experimentally and epidemiologically with neurodegenerative conditions like stroke and dementia. Moreover, folate deficiency has been implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that the pathogenic mechanisms include uracil misincorporation and, therefore, analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase (Ung-/-) versus wild-type controls. Folate depletion increased nuclear mutation rates in Ung-/- embryonic fibroblasts, and conferred death of cultured Ung-/- hippocampal neurons. Feeding animals a folate-deficient diet (FD) for 3 months induced degeneration of CA3 pyramidal neurons in Ung-/- but not Ung+/+ mice along with decreased hippocampal expression of brain-derived neurotrophic factor protein and decreased brain levels of antioxidant glutathione. Furthermore, FD induced cognitive deficits and mood alterations such as anxious and despair-like behaviors that were aggravated in Ung-/- mice. Independent of Ung genotype, FD increased plasma homocysteine levels, altered brain monoamine metabolism, and inhibited adult hippocampal neurogenesis. These results indicate that impaired uracil repair is involved in neurodegeneration and neuropsychiatric dysfunction induced by experimental folate deficiency.

  5. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, John, E-mail: jmweaver@salud.unm.edu [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Yang, Yirong [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Purvis, Rebecca [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Weatherwax, Theodore [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Rosen, Gerald M. [Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD 21201 (United States); Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, MD 21201 (United States); Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Liu, Ke Jian [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    2014-03-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissue pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in

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

    Science.gov (United States)

    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

  7. HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling.

    Science.gov (United States)

    Hill, James M; Zhao, Yuhai; Clement, Christian; Neumann, Donna M; Lukiw, Walter J

    2009-10-28

    Herpes simplex virus type-1 (HSV-1) infection of human brain cells induces changes in gene expression favorable to the propagation of the infecting agent and detrimental to the function of the host cells. We report that infection of human primary neural cells with a high phenotypic reactivator HSV-1 (17syn+) induces upregulation of a brain-enriched microRNA (miRNA)-146a that is associated with proinflammatory signaling in stressed brain cells and Alzheimer's disease. Expression of cytoplasmic phospholipase A2, the inducible prostaglandin synthase cyclooxygenase-2, and the neuroinflammatory cytokine interleukin-1beta were each upregulated. A known miRNA-146a target in the brain, complement factor H, was downregulated. These data suggest a role for HSV-1-induced miRNA-146a in the evasion of HSV-1 from the complement system, and the activation of key elements of the arachidonic acid cascade known to contribute to Alzheimer-type neuropathological change.

  8. xperimental Study of Protective Effect of Qingkailing(清开灵) on Brain Damage Induced by Glutamate

    Institute of Scientific and Technical Information of China (English)

    岳少杰; 虞佩兰; 罗自强; 曾庆善; 陶永光; 伍赶球

    2001-01-01

    Objective: To observe the effect of Qingkailing (QKL) on brain damage induced by glutamate, in order to seek for effective drugs for antagonizing neurotoxicity of glutamate. Methods:The number and morphological metrology of neurocytes in cerebral cortex and hippocampus were detected by MIAS-300 image analyser, electron microscope and immunohistochemical methods. Results:QKL could alleviate the glutamate induced accumulation of water and sodium in brain tissue,relieve the metrological and structural damage of cerebral cells in cortex and hippocampus, reduce the percentage of c-fos positive cell in brain. Conclusion: QKL could protect brain damage induced by glutamate, which might be related to the inhibition of QKL on the enhancement of c-fos gene expression induced by glutamate.

  9. Expression of manganese superoxide dismutase in rat blood, heart and brain during induced systemic hypoxia

    Directory of Open Access Journals (Sweden)

    Septelia I. Wanandi

    2011-02-01

    Full Text Available Background: Hypoxia results in an increased generation of ROS. Until now, little is known about the role of MnSOD - a major endogenous antioxidant enzyme - on the cell adaptation response against hypoxia. The aim of this study was to  determine the MnSOD mRNA expression and levels of specific activity in blood, heart and brain of rats during induced systemic hypoxia.Methods: Twenty-five male Sprague Dawley rats were subjected to systemic hypoxia in an hypoxic chamber (at 8-10% O2 for 0, 1, 7, 14 and 21 days, respectively. The mRNA relative expression of MnSOD was analyzed using Real Time RT-PCR. MnSOD specific activity was determined using xanthine oxidase inhibition assay.Results: The MnSOD mRNA relative expression in rat blood and heart was decreased during early induced systemic hypoxia (day 1 and increased as hypoxia continued, whereas the mRNA expression in brain was increased since day 1 and reached its maximum level at day 7. The result of MnSOD specific activity during early systemic hypoxia was similar to the mRNA expression. Under very late hypoxic condition (day 21, MnSOD specific activity in blood, heart and brain was significantly decreased. We demonstrate a positive correlation between MnSOD mRNA expression and specific activity in these 3 tissues during day 0-14 of induced systemic hypoxia. Furthermore, mRNA expression and specific activity levels in heart strongly correlate with those in blood.Conclusion: The MnSOD expression at early and late phases of induced systemic hypoxia is distinctly regulated. The MnSOD expression in brain differs from that in blood and heart revealing that brain tissue can  possibly survive better from induced systemic hypoxia than heart and blood. The determination of MnSOD expression in blood can be used to describe its expression in heart under systemic hypoxic condition. (Med J Indones 2011; 20:27-33Keywords: MnSOD, mRNA expression, ROS, specific activity, systemic hypoxia

  10. Development of optical neuroimaging to detect drug-induced brain functional changes in vivo

    Science.gov (United States)

    Du, Congwu; Pan, Yingtian

    2014-03-01

    Deficits in prefrontal function play a crucial role in compulsive cocaine use, which is a hallmark of addiction. Dysfunction of the prefrontal cortex might result from effects of cocaine on neurons as well as from disruption of cerebral blood vessels. However, the mechanisms underlying cocaine's neurotoxic effects are not fully understood, partially due to technical limitations of current imaging techniques (e.g., PET, fMRI) to differentiate vascular from neuronal effects at sufficiently high temporal and spatial resolutions. We have recently developed a multimodal imaging platform which can simultaneously characterize the changes in cerebrovascular hemodynamics, hemoglobin oxygenation and intracellular calcium fluorescence for monitoring the effects of cocaine on the brain. Such a multimodality imaging technique (OFI) provides several uniquely important merits, including: 1) a large field-of-view, 2) high spatiotemporal resolutions, 3) quantitative 3D imaging of the cerebral blood flow (CBF) networks, 4) label-free imaging of hemodynamic changes, 5) separation of vascular compartments (e.g., arterial and venous vessels) and monitoring of cortical brain metabolic changes, 6) discrimination of cellular (neuronal) from vascular responses. These imaging features have been further advanced in combination with microprobes to form micro-OFI that allows quantification of drug effects on subcortical brain. In addition, our ultrahigh-resolution ODT (μODT) enables 3D microangiography and quantitative imaging of capillary CBF networks. These optical strategies have been used to investigate the effects of cocaine on brain physiology to facilitate the studies of brain functional changes induced by addictive substance to provide new insights into neurobiological effects of the drug on the brain.

  11. Effect of α-Ketoglutarate on Cyanide-induced Biochemical Alterations in Rat Brain and Liver

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the biochemical changes in rat brain and liver following acute exposure to a lethal dose of cyanide, and its response to treatment of α-ketoglutarate (α-KG) in the absence or presence of sodium thiosulfate (STS). Methods Female rats were administered 2.0 LD50 potassium cyanide (KCN; oral) in the absence or presence of pre-treatment (-10 min), simultaneous treatment (0 min) or post-treatment (+2-3 min) of α-KG (2.0 g/kg, oral) and/or STS (1.0 g/kg,intraperitoneal, -15 min, 0 min or + 2-3 min). At the time of onset of signs and symptoms of KCN toxicity (2-4 min) and at the time of death (5-15 min), various parameters particularly akin to oxidative stress viz. Cytochrome oxidase (CYTOX),superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH) and oxidized glutathione (GSSG) in brain, and CYTOX, sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP), GSH and GSSG in liver homogenate were measured. Results At both time intervals brain CYTOX, SOD, GPx, and GSH significantly reduced (percent inhibition compared to control) to 24%, 56%, 77%, and 65%, and 44%, 46%, 78%, and 57%, respectively. At the corresponding time points liver CYTOX and GSH reduced to 74% and 63%, and 44% and 68%, respectively. The levels of GSSG in the brain and liver, and hepatic ALP and SDH were unchanged. Pre-treatment and simultaneous treatment of α-KG alone or with STS conferred significant protection on above variables. Post-treatment was effective in restoring the changes in liver but failed to normalize the changes in the brain. Conclusions Oral treatment with α-KG alone or in combination with STS has protective effects on cyanide-induced biochemical alterations in rat brain and liver.

  12. EFFECT OF HYDROALCOHOLIC EXTRACT OF TERMINALIA CATAPPA L. (COMBRETACEAE ON FREE RADICALS INDUCED IN RAT BRAIN

    Directory of Open Access Journals (Sweden)

    Calderón, Abhel

    2013-07-01

    Full Text Available The hydroalcoholic extract of Terminalia catappa leaves was tested in vivo to determine its antioxidant activity. The objective was to determine the antioxidant effect of the extract of T. catappa against free radicals induced in rat brain. We worked with two groups, the control consisting of positive control and negative control subsets which were administered carbon tetrachloride (CTC 1 ml·Kg-1 body weight and 2 mL of physiological saline solution (PSS, respectively. The experimental group consisted of two subgroups treated with the hydroalcoholic extract of T. catappa + CTC: one with 0.8 mg of extract T. catappa/kg bodyweight and the other with 1.5 mg T. catappa/kg body weight, for seven days. In all groups was determined the amount of free radicals in the brain by the technique of thiobarbituric acid reactive substances. From the positive control was obtained an average concentration of 26.68 μg malondialdehyde/g brain tissue, and in the negative control an average concentration of 9.76 μg malondialdehyde/g brain tissue; in the experimental group treated with T. catappa to 0.8 mg·kg-1 body weight and 1.5 mg·kg-1 body weight was obtained an average concentration of 13.64 μg malondialdehyde/g brain tissue and 15.80 μg malondialdehyde/g brain tissue, respectively. It was determined that the group treated with the hydroalcoholic extract of T. catappa concentration to 0.8 mg·Kg-1 body weight showed significant inhibition of free radicals compared to the positive control subgroup.

  13. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-05

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity.

  14. Changes of neuronal calcium channel following brain damage induced by injection of pertussis bacilli in rats

    Institute of Scientific and Technical Information of China (English)

    陈立华; 于嘉; 刘丽旭; 曹美鸿

    2002-01-01

    To explore changes of neuronal calcium channel following brain damage induced by injection of pertussis bacilli in rats, and to investigate the relationship between cytosolic free calcium concentration ( [ Ca2 + ] i ) in the synaptosome and Ca2 + -ATPase activities of mitochondria. Methods: The level of [ Ca2+ ]i in the synaptosome and Ca2+ -ATPase activities of mitochondria in the acute brain damage induced by injection of pertussis bacilli (PB)in rat was determined and nimodipine was administrated to show its effects on [ Ca2+ ]i in the synaptosome and on alteration of Ca2+ -ATPase activity in the mitochondria.Seventy-three rats were randomly divided into four groups,ie, normal control group (Group A ), sham-operation control group (Group B), PB group (Group C) and nimodipine treatment group (Group D). Results: The level of [ Ca2+ ]i was significantly increased in the PB-injected cerebral hemisphere in the Group C as compared with that in the Group A and the Group B at 30 minutes after injection of PB. The level of [ Ca2+ ]i was kept higher in the 4 hours and 24 hours subgroups after the injection in the Group C ( P < 0.05).In contrast, the Ca2+ -ATPase activities were decreased remarkably among all of the subgroups in the Group C.Nimodipine, which was administered after injection of PB,could significantly decrease the [ Ca2+ ]i and increase the activity of Ca2 + -ATPase ( P < 0.05 ). Conclusions: The neuronal calcium channel is opened after injection of PB. There is a negative correlation between activities of Ca2 +-ATPase and [ Ca2 + ]i.Nimodipine can reduce brain damage through stimulating the activities of Ca2+ -ATPase in the mitochondria, and decrease the level of [ Ca2+ ]i in the synaptosome.Treatment with nimodipine dramatically reduces the effects of brain damage induced by injection of PB.

  15. Hypoxia inducible factor-1alpha mediates protection of DL-3-n-butylphthalide in brain microvascular endothelial cells against oxygen glucose deprivation-induced injury

    Institute of Scientific and Technical Information of China (English)

    Weihong Yang; Ling Li; Ruxun Huang; Zhong Pei; Songjie Liao; Jinsheng Zeng

    2012-01-01

    Studies have demonstrated that DL-3-n-butylphthalide can significantly alleviate oxygen glucose deprivation-induced injury of human umbilical vein endothelial cells at least partly associated with its enhancement on oxygen glucose deprivation -induced hypoxia inducible factor-1α expression. In this study, we hypothesized that DL-3-n-butylphthalide can protect against oxygen glucose deprivation-induced injury of newborn rat brain microvascular endothelial cells by means of upregulating hypoxia inducible factor-1α expression. MTT assay and Hoechst staining results showed that DL-3-n-butylphthalide protected brain microvascular endothelial cells against oxygen glucose deprivation-induced injury in a dose-dependent manner. Western blot and immunofluorescent staining results further confirmed that the protective effect was related to upregulation of hypoxia inducible factor-1α. Real-time RT-PCR reaction results showed that DL-3-n-butylphthalide reduced apoptosis by inhibiting downregulation of pro-apoptotic gene caspase-3 mRNA expression and upregulation of apoptosis-executive protease bcl-2 mRNA expression; however, DL-3-n-butylphthalide had no protective effects on brain microvascular endothelial cells after knockdown of hypoxia inducible factor-1α by small interfering RNA. These findings suggest that DL-3-n-butylphthalide can protect brain microvascular endothelial cells against oxygen glucose deprivation-induced injury by upregulating bcl-2 expression and downregulating caspase-3 expression though hypoxia inducible factor-1α pathway.

  16. Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions

    Directory of Open Access Journals (Sweden)

    Benedito M.A.C.

    2001-01-01

    Full Text Available Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei are involved in the generation of rapid eye movement (REM sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase, the enzyme which inactivates acetylcholine (Ach in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min-1 mg protein-1 were assayed photometrically. The results (mean ± SD obtained showed a statistically significant (Student t-test increase in total Achase activity in the pons (control: 147.8 ± 12.8, REM sleep-deprived: 169.3 ± 17.4, N = 6 for both groups, P<0.025 and thalamus (control: 167.4 ± 29.0, REM sleep-deprived: 191.9 ± 15.4, N = 6 for both groups, P<0.05. Increases in membrane-bound Achase activity in the pons (control: 171.0 ± 14.7, REM sleep-deprived: 189.5 ± 19.5, N = 6 for both groups, P<0.05 and soluble enzyme activity in the medulla oblongata (control: 147.6 ± 16.3, REM sleep-deprived: 163.8 ± 8.3, N = 6 for both groups, P<0.05 were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity

  17. Genetic effects on source level evoked and induced oscillatory brain responses in a visual oddball task.

    Science.gov (United States)

    Antonakakis, Marios; Zervakis, Michalis; van Beijsterveldt, Catharina E M; Boomsma, Dorret I; De Geus, Eco J C; Micheloyannis, Sifis; Smit, Dirk J A

    2016-02-01

    Stimuli in simple oddball target detection paradigms cause evoked responses in brain potential. These responses are heritable traits, and potential endophenotypes for clinical phenotypes. These stimuli also cause responses in oscillatory activity, both evoked responses phase-locked to stimulus presentation and phase-independent induced responses. Here, we investigate whether phase-locked and phase-independent oscillatory responses are heritable traits. Oscillatory responses were examined in EEG recordings from 213 twin pairs (91 monozygotic and 122 dizygotic twins) performing a visual oddball task. After group Independent Component Analysis (group-ICA) and time-frequency decomposition, individual differences in evoked and induced oscillatory responses were compared between MZ and DZ twin pairs. Induced (phase-independent) oscillatory responses consistently showed the highest heritability (24-55%) compared to evoked (phase-locked) oscillatory responses and spectral energy, which revealed lower heritability at 1-35.6% and 4.5-32.3%, respectively. Since the phase-independent induced response encodes functional aspects of the brain response to target stimuli different from evoked responses, we conclude that the modulation of ongoing oscillatory activity may serve as an additional endophenotype for behavioral phenotypes and psychiatric genetics.

  18. Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction.

    Science.gov (United States)

    Zhao, Wei; Wang, Jun; Bi, Weina; Ferruzzi, Mario; Yemul, Shrishailam; Freire, Daniel; Mazzola, Paolo; Ho, Lap; Dubner, Lauren; Pasinetti, Giulio Maria

    2015-10-01

    Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction.

  19. Human induced rotation and reorganization of the brain of domestic dogs.

    Directory of Open Access Journals (Sweden)

    Taryn Roberts

    Full Text Available Domestic dogs exhibit an extraordinary degree of morphological diversity. Such breed-to-breed variability applies equally to the canine skull, however little is known about whether this translates to systematic differences in cerebral organization. By looking at the paramedian sagittal magnetic resonance image slice of canine brains across a range of animals with different skull shapes (N = 13, we found that the relative reduction in skull length compared to width (measured by Cephalic Index was significantly correlated to a progressive ventral pitching of the primary longitudinal brain axis (r = 0.83, as well as with a ventral shift in the position of the olfactory lobe (r = 0.81. Furthermore, these findings were independent of estimated brain size or body weight. Since brachycephaly has arisen from generations of highly selective breeding, this study suggests that the remarkable diversity in domesticated dogs' body shape and size appears to also have led to human-induced adaptations in the organization of the canine brain.

  20. Development of a new biomechanical indicator for primary blast-induced brain injury

    Institute of Scientific and Technical Information of China (English)

    Feng Zhu; Cliff C.Chou; King H.Yang; Albert I.King

    2015-01-01

    Primary blast-induced traumatic brain injury (bTBI) has been observed at the boundary of brain tissue and cerebrospinal fluid (CSF).Such injury can hardly be explained by using the theory of compressive wave propagation,since both the solid and fluid materials have similar compressibility and thus the intracranial pressure (ICP) has a continuous distribution across the boundary.Since they have completely different shear properties,it is hypothesized the injury at the interface is caused by shear wave.In the present study,a preliminary combined numerical and theoretical analysis was conducted based on the theory of shear wave propagation]reflection.Simulation results show that higher lateral acceleration of brain tissue particles is concentrated in the boundary region.Based on this finding,a new biomechanical vector,termed as strain gradient,was suggested for primary bTBI.The subsequent simple theoretical analysis reveals that this parameter is proportional to the value of lateral acceleration.At the boundary of lateral ventricles,high spatial strain gradient implies that the brain tissue in this area (where neuron cells may be contained) undergo significantly different strains and large velocity discontinuity,which may result in mechanical damage of the neuron cells.

  1. Brain dynamics for perception of tactile allodynia (touch-induced pain) in postherpetic neuralgia

    Science.gov (United States)

    Geha, P. Y.; Baliki, M. N.; Wang, X.; Harden, R. N.; Paice, J. A.; Apkarian, A. V.

    2008-01-01

    Postherpetic neuralgia (PHN) is a debilitating chronic pain condition often accompanied by a sensation of pain when the affected region is touched (tactile allodynia). Here we identify brain regions involved in stimulus-induced touch-evoked pain (dynamical mechanical allodynia, DMA), compare brain activity between DMA and spontaneous pain (described earlier for the same patients in [28], delineate regions that specifically code the magnitude of perceived allodynia, and show the transformation of allodynia-related information in the brain as a time-evolving network. Eleven PHN patients were studied for DMA and its modulation with Lidoderm therapy (patches of 5% lidocaine applied to the PHN affected body part). Continuous ratings of pain while the affected body part was brushed during fMRI were contrasted with non-painful touch when brushing was applied to an equivalent opposite body site, and with fluctuations of a bar observed during scanning, at three sessions relative to Lidoderm treatment. Lidoderm treatment did not decrease DMA ratings but did decrease spontaneous pain. Multiple brain areas showed preferential activity for allodynia. However, mainly responses in the bilateral putamen and left medial temporal gyrus were related to the magnitude of allodynia. Both DMA and spontaneous pain perceptions were best represented within the same sub-cortical structures but with minimal overlap, implying that PHN pain modulates behavioral learning and hedonics. These results have important clinical implications regarding adequate therapy. PMID:18384958

  2. Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation

    Directory of Open Access Journals (Sweden)

    Leo Pruimboom

    2015-01-01

    Full Text Available In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health.

  3. Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation.

    Science.gov (United States)

    Pruimboom, Leo; Raison, Charles L; Muskiet, Frits A J

    2015-01-01

    In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health.

  4. Mescaline-induced changes of brain-cortex ribosomes. Role of sperimidine in counteracting the destabilizing effect of mescaline of brain-cortex ribosomes.

    Science.gov (United States)

    Datta, R K; Antopol, W; Ghosh, J J

    1971-11-01

    1. The effect of spermidine on the mescaline-induced changes of brain-cortex ribosomes was studied by adding spermidine during the treatment of goat brain-cortex slices with mescaline. 2. Mescaline treatment of brain-cortex slices removed a portion of the endogenous spermidine from ribosomes and this removal was significantly prevented when spermidine was present during mescaline treatment. 3. Spermidine present during mescaline treatment of brain-cortex slices counteracted, to some extent, the destabilizing effect of mescaline on ribosomes with respect to heat denaturation. 4. Mescaline treatment of brain-cortex slices made ribosomes more susceptible to breakdown, releasing protein and RNA, and resulting in loss of ribosomal enzymic activities. However, spermidine present during mescaline treatment counteracted moderately the mescaline-induced ribosomal susceptibility to breakdown and ribosomal loss of enzymic activities. 5. Ribosomes of mescaline-treated cortex slices were rapidly degraded by ribonuclease and trypsin. However, if spermidine was present during mescaline treatment of brain-cortex slices the rates of degradation diminished.

  5. Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain

    Science.gov (United States)

    Cho, HongSeok; Lee, Hwa-Youn; Han, Mun; Choi, Jong-ryul; Ahn, Sanghyun; Lee, Taekwan; Chang, Yongmin; Park, Juyoung

    2016-01-01

    Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs. PMID:27510760

  6. Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain

    Science.gov (United States)

    Cho, Hongseok; Lee, Hwa-Youn; Han, Mun; Choi, Jong-Ryul; Ahn, Sanghyun; Lee, Taekwan; Chang, Yongmin; Park, Juyoung

    2016-08-01

    Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs.

  7. Mesenteric hypoperfusion and inflammation induced by brain death are not affected by inhibition of the autonomic storm in rats

    Directory of Open Access Journals (Sweden)

    Rafael Simas

    2015-06-01

    Full Text Available OBJECTIVES: Brain death is typically followed by autonomic changes that lead to hemodynamic instability, which is likely associated with microcirculatory dysfunction and inflammation. We evaluated the role of the microcirculation in the hemodynamic and inflammatory events that occur after brain death and the effects of autonomic storm inhibition via thoracic epidural blockade on mesenteric microcirculatory changes and inflammatory responses. METHODS: Male Wistar rats were anesthetized and mechanically ventilated. Brain death was induced via intracranial balloon inflation. Bupivacaine (brain death-thoracic epidural blockade group or saline (brain death group infusion via an epidural catheter was initiated immediately before brain death induction. Sham-operated animals were used as controls (SH group. The mesenteric microcirculation was analyzed via intravital microscopy, and the expression of adhesion molecules was evaluated via immunohistochemistry 180 min after brain death induction. RESULTS: A significant difference in mean arterial pressure behavior was observed between the brain death-thoracic epidural blockade group and the other groups, indicating that the former group experienced autonomic storm inhibition. However, the proportion of perfused small vessels in the brain death-thoracic epidural blockade group was similar to or lower than that in the brain death and SH groups, respectively. The expression of intercellular adhesion molecule 1 was similar between the brain death-thoracic epidural blockade and brain death groups but was significantly lower in the SH group than in the other two groups. The number of migrating leukocytes in the perivascular tissue followed the same trend for all groups. CONCLUSIONS: Although thoracic epidural blockade effectively inhibited the autonomic storm, it did not affect mesenteric hypoperfusion or inflammation induced by brain death.

  8. Autopsy reenactment--a useful technique in the evaluation of adhesive tape asphyxia.

    Science.gov (United States)

    Herbst, Jonathon; Stanley, Wayne; Byard, Roger W

    2014-05-01

    A 19-year-old woman was found dead with her face and head wrapped in plastic adhesive tape in a cupboard beside an opened helium cylinder. Despite the alleged presence of a suicide message on a social networking website, the unusual circumstances raised the possibility at the time of autopsy of either accidental death from sexual asphyxia or homicide. A carefully monitored reenactment demonstrated, however, that the type of commercial adhesive tape that had been used did not cause complete airway obstruction and that it was possible to wrap a considerable length of tape around the head and neck with the breath held. All of the features at autopsy were, therefore, compatible with self-infliction. Asphyxial death was attributed to the combined effects of smothering from tape and anoxia from helium, an extremely rare combination in young females.

  9. Metabolic Changes Following Perinatal Asphyxia: Role of Astrocytes and Their Interaction with Neurons.

    Science.gov (United States)

    Logica, Tamara; Riviere, Stephanie; Holubiec, Mariana I; Castilla, Rocío; Barreto, George E; Capani, Francisco

    2016-01-01

    Perinatal Asphyxia (PA) represents an important cause of severe neurological deficits including delayed mental and motor development, epilepsy, major cognitive deficits and blindness. The interaction between neurons, astrocytes and endothelial cells plays a central role coupling energy supply with changes in neuronal activity. Traditionally, experimental research focused on neurons, whereas astrocytes have been more related to the damage mechanisms of PA. Astrocytes carry out a number of functions that are critical to normal nervous system function, including uptake of neurotransmitters, regulation of pH and ion concentrations, and metabolic support for neurons. In this work, we aim to review metabolic neuron-astrocyte interactions with the purpose of encourage further research in this area in the context of PA, which is highly complex and its mechanisms and pathways have not been fully elucidated to this day.

  10. Nonoliguric hyperkalemia in a late preterm infant with severe birth asphyxia.

    Science.gov (United States)

    Xiong, Xiaoyu; Chen, Dan; Zhang, Jing; Mao, Jian; Li, Juan

    2013-01-01

    Nonoliguric hyperkalemia (NOHK) is common during the first days after birth in premature infants with gestational age term or late preterm infants. We present a case of a 3 hours baby at 34 weeks and 3 days' gestational age who was delivered of severe birth asphyxia by cesarean section for failing to vaginal delivery. Serum potassium reached to 8.3 mmol/L at 12 hours age, with normal urinary output and serum urea and creatinine. Abnormal ECG of tall peaked T waves was developed. Marked fall in serum Ca(2+) of 0.6 mmol/L and total calcium of 1.13 mmol/L was also noted. Cerebral lesions in the head MRI demonstrated extensive periventricular white matter injury.

  11. Cannabinoids: Well-Suited Candidates for the Treatment of Perinatal Brain Injury

    Directory of Open Access Journals (Sweden)

    José Martínez-Orgado

    2013-07-01

    Full Text Available Perinatal brain injury can be induced by a number of different damaging events occurring during or shortly after birth, including neonatal asphyxia, neonatal hypoxia-ischemia and stroke-induced focal ischemia. Typical manifestations of these conditions are the presence of glutamate excitoxicity, neuroinflammation and oxidative stress, the combination of which can potentially result in apoptotic-necrotic cell death, generation of brain lesions and long-lasting functional impairment. In spite of the high incidence of perinatal brain injury, the number of clinical interventions available for the treatment of the affected newborn babies is extremely limited. Hence, there is a dramatic need to develop new effective therapies aimed to prevent acute brain damage and enhance the endogenous mechanisms of long-term brain repair. The endocannabinoid system is an endogenous neuromodulatory system involved in the control of multiple central and peripheral functions. An early responder to neuronal injury, the endocannabinoid system has been described as an endogenous neuroprotective system that once activated can prevent glutamate excitotoxicity, intracellular calcium accumulation, activation of cell death pathways, microglia activation, neurovascular reactivity and infiltration of circulating leukocytes across the blood-brain barrier. The modulation of the endocannabinoid system has proven to be an effective neuroprotective strategy to prevent and reduce neonatal brain injury in different animal models and species. Also, the beneficial role of the endocannabinoid system on the control of the endogenous repairing responses (neurogenesis and white matter restoration to neonatal brain injury has been described in independent studies. This review addresses the particular effects of several drugs that modulate the activity of the endocannabinoid system on the progression of different manifestations of perinatal brain injury during both the acute and chronic

  12. Ovariectomy-induced chronic abdominal hypernociception in rats: Relation with brain oxidative stress

    Directory of Open Access Journals (Sweden)

    Bárbara B. Garrido-Suárez

    2015-12-01

    Full Text Available Context: Ovarian hormone deficiency observed in menopausal women increases the production of reactive oxygen species, which could be implicated in central sensitization subjacent in chronic functional pain syndromes. Aims: To examine the hyperalgesic state induced by ovariectomy in adult rats and its relation to some oxidative stress outcomes. Methods: The female Wistar rats were divided into normal, sham ovariectomized (OVX and OVX groups, which were tested for mechanical and thermal hypernociception during 6 weeks and a single acetic acid-induced test 6 weeks after surgery. Redox biomarkers determinations of superoxide dismutase (SOD enzyme activity, glutathione (GSH and nitrates/nitrites as an indicator of nitric oxide (NO concentrations were determined in the brain and cerebellum of 6 animals of each group. Results: Exclusivity OVX rats developed a robust state of mechanical hypernociception and allodynia in the abdomen, hindlimbs and proximal tail. Besides, thermal pain thresholds (hot plate decreased. That was established 3-4 weeks after OVX and lasted for the 6 weeks of the experiment. Increases in visceral sensitivity were also observed in OVX rats. SOD enzyme activity decreased in OVX rats, which showed major deficit for this enzymatic defense under visceral inflammatory injury. However GSH concentrations were increased in brain of OVX animals that allow the balance during acute inflammation. NO concentrations were raised only in OVX rats exposure to chemical inflammatory injury. Conclusions: OVX in rats provide a useful model, which mimics the functional pain in females that could be related with brain oxidative stress.

  13. Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain.

    Science.gov (United States)

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy; Wankhar, Dapkupar

    2015-09-01

    The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress.

  14. Effect of miroestrol on ovariectomy-induced cognitive impairment and lipid peroxidation in mouse brain.

    Science.gov (United States)

    Monthakantirat, Orawan; Sukano, Wichitsak; Umehara, Kaoru; Noguchi, Hiroshi; Chulikhit, Yaowared; Matsumoto, Kinzo

    2014-09-25

    Miroestrol (MR) is a phytoestrogen isolated from Pueraria candollei var. mirifica (KwaoKrueaKhao), a Thai medicinal plant used for rejuvenation. We examined the effects of MR on cognitive function, oxidative brain damage, and the expression of genes encoding brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element-binding protein (CREB), factors implicated in neurogenesis and synaptic plasticity, in ovariectomized (OVX) mice. OVX decreased serum 17β-estradiol level and uterine weight. OVX also impaired object recognition performance in the novel object recognition test and spatial cognitive performance in the Y-maze test and the water maze test. Daily treatment of MR dose-dependently attenuated OVX-induced cognitive dysfunction. Moreover, OVX mice had a significantly increased level of thiobarbituric acid-reactive substances, and down-regulated expression levels of BDNF and CREB mRNAs in the hippocampus and frontal cortex. MR treatment as well as hormone replacement therapy with 17β-estradiol significantly reversed these neurochemical alterations caused by OVX. These results suggest that MR ameliorates cognitive deficits in OVX animals via attenuation of OVX-induced oxidative stress and down-regulation of BDNF and CREB mRNA transcription in the brain. Our findings raise the possibility that MR and Pueraria candollei var. mirifica, the plant of origin of MR, may have a beneficial effect on cognitive deficits like AD in which menopause/ovariectomy are implicated as risk factors.

  15. Changes induced by sodium cromoglycate on brain serotonin turnover in morphine dependent and abstinent mice.

    Science.gov (United States)

    San-Martin-Clark, O; Leza, J C; Lizasoain, I; Lorenzo, P

    1993-01-01

    This study was designed to explain the action of sodium cromoglycate (CRO) on the brain serotonergic system in control, morphine tolerant (by SC implantation of a 75 mg morphine pellet), and also in morphine dependent mice just before naloxone-precipitated withdrawal. After SC injections of CRO in control mice, morphine tolerant mice (day 4 of addiction), and 1 h before abstinence (withdrawal was induced by SC injection of 1 mg/kg naloxone on day 4 of addiction), animals were decapitated and various brain areas were rapidly removed. 5HT (Serotonin) and 5HIAA (5-hydroxyindole-3-acetic acid) were measured by high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD). The ratio 5HIAA/5HT provided one index by which the turnover of the indoleamine was measured. CRO increased the turnover of 5HT in most of the brain areas studied in both control and morphine dependent mice. Furthermore, previous administration of CRO prior to naloxone challenge induced a significant increase in the 5HIAA/5HT ratio in the hypothalamus and striatum. These results are discussed as the reason for the preventive effect of CRO on jumping behaviour in morphine abstinent mice.

  16. A brain-machine interface for control of medically-induced coma.

    Science.gov (United States)

    Shanechi, Maryam M; Chemali, Jessica J; Liberman, Max; Solt, Ken; Brown, Emery N

    2013-10-01

    Medically-induced coma is a drug-induced state of profound brain inactivation and unconsciousness used to treat refractory intracranial hypertension and to manage treatment-resistant epilepsy. The state of coma is achieved by continually monitoring the patient's brain activity with an electroencephalogram (EEG) and manually titrating the anesthetic infusion rate to maintain a specified level of burst suppression, an EEG marker of profound brain inactivation in which bursts of electrical activity alternate with periods of quiescence or suppression. The medical coma is often required for several days. A more rational approach would be to implement a brain-machine interface (BMI) that monitors the EEG and adjusts the anesthetic infusion rate in real time to maintain the specified target level of burst suppression. We used a stochastic control framework to develop a BMI to control medically-induced coma in a rodent model. The BMI controlled an EEG-guided closed-loop infusion of the anesthetic propofol to maintain precisely specified dynamic target levels of burst suppression. We used as the control signal the burst suppression probability (BSP), the brain's instantaneous probability of being in the suppressed state. We characterized the EEG response to propofol using a two-dimensional linear compartment model and estimated the model parameters specific to each animal prior to initiating control. We derived a recursive Bayesian binary filter algorithm to compute the BSP from the EEG and controllers using a linear-quadratic-regulator and a model-predictive control strategy. Both controllers used the estimated BSP as feedback. The BMI accurately controlled burst suppression in individual rodents across dynamic target trajectories, and enabled prompt transitions between target levels while avoiding both undershoot and overshoot. The median performance error for the BMI was 3.6%, the median bias was -1.4% and the overall posterior probability of reliable control was 1 (95

  17. Oxidative stress induces the decline of brain EPO expression in aging rats.

    Science.gov (United States)

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (pEPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (pEPO (r=-0.701, pEPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability.

  18. Does kainic acid induce partial brain lesion in an invertebrate model: sepia officinalis? Comparison with electrolytic lesion.

    Science.gov (United States)

    Graindorge, Nicolas; Jozet-Alves, Christelle; Chichery, Raymond; Dickel, Ludovic; Bellanger, Cécile

    2008-10-31

    The present study investigates the feasibility of excitotoxic lesions in the cuttlefish in the mapping of brain functions in Cephalopods. Adult animals were injected locally with a neurotoxin, kainic acid. The brain region receiving the neurotoxin was the vertical lobe, a key brain structure for learning and memory processes. Brain damage induced by these injections was evaluated using different histological stainings: hematoxilin-eosin, Fink-Heimer and DAPI. The results were compared with histological changes after electrolytic lesion of the vertical lobe. Neurodegeneration was revealed in and around the injection site: an intense area of proliferative cells, degenerating terminal axon ramifications and cell death. In comparison with electrolytic lesion, excitotoxic lesion displays important advantages, since fibres of passage are not destroyed by kainic acid injection, which induces only a restricted lesion and so is an appropriate method of investigating the role of the vertical lobe or other brain regions in a Cephalopod model, Sepia officinalis.

  19. Change in brain network connectivity during PACAP38-induced migraine attacks

    DEFF Research Database (Denmark)

    Amin, Faisal Mohammad; Hougaard, Anders; Magon, Stefano

    2016-01-01

    OBJECTIVE: To investigate resting-state functional connectivity in the salience network (SN), the sensorimotor network (SMN), and the default mode network (DMN) during migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38 (PACAP38). METHODS: In a double-blind, randomized......, and visual cortices) and decreased (right cerebellum and left frontal lobe) connectivity with DMN. We found no resting-state network changes after VIP (n = 15). CONCLUSIONS: PACAP38-induced migraine attack is associated with altered connectivity of several large-scale functional networks of the brain....... study, 24 female migraine patients without aura received IV PACAP38 or vasoactive intestinal polypeptide (VIP) over 20 minutes. Both peptides are closely related and cause vasodilation, but only PACAP38 induces migraine attacks. VIP was therefore used as active placebo. Resting-state functional MRI...

  20. Detection of cysteine protease in Taenia solium-induced brain granulomas in naturally infected pigs.

    Science.gov (United States)

    Mkupasi, Ernatus Martin; Sikasunge, Chummy Sikalizyo; Ngowi, Helena Aminiel; Leifsson, Pall S; Johansen, Maria Vang

    2013-10-18

    In order to further characterize the immune response around the viable or degenerating Taenia solium cysts in the pig brain, the involvement of cysteine protease in the immune evasion was assessed. Brain tissues from 30 adult pigs naturally infected with T. solium cysticercosis were subjected to histopathology using hematoxylin and eosin stain, and immunohistochemistry using caspase-3 antibodies. Histopathological evaluation revealed lesions of stage I which was characterized by presence of viable parasite surrounded with minimal to moderate inflammatory cells and stage III characterized by the presence of a disintegrating parasite surrounded with high inflammatory cells. The results of immunohistochemistry indicated caspase-3 positive cells interspaced between inflammatory infiltrate mainly in stage I lesions, indicating the presence of cysteine protease. This result confirms the earlier hypothesis that cysteine protease may play a role in inducing immune evasion through apoptosis around viable T. solium cysts.

  1. Placement of field probes for stabilization of breathing-induced B0-fluctuations in the brain

    DEFF Research Database (Denmark)

    Andersen, Mads; Madsen, Kristoffer H.; Hanson, Lars G.;

    ). It is a fundamental challenge, however, that the B0 measurements are spatially sparse (e.g. 16 probes), and performed outside the brain. Typically, the field is modelled by a linear combination of the spatial shim fields that the scanner can produce (such as spherical harmonics up to 3rd order), and the coefficients......Introduction: B0-fluctuations induced by breathing and body motion lead to artifacts for certain brain imaging sequences at ultra-high field (7T). A promising solution is to monitor the B0-fluctuations during the scan using external field probes, and update the shim currents in real-time (1...... for these spatial terms are determined by least square fitting to the field probe measurements. The probes must be placed carefully to ensure that the spherical harmonics can be distinguished using these few samples, and they must be placed close to the head so that the spatial field model is valid and to have good...

  2. A Hypothesis: Hydrogen Sulfide Might Be Neuroprotective against Subarachnoid Hemorrhage Induced Brain Injury

    Directory of Open Access Journals (Sweden)

    Yong-Peng Yu

    2014-01-01

    Full Text Available Gases such as nitric oxide (NO and carbon monoxide (CO play important roles both in normal physiology and in disease. Recent studies have shown that hydrogen sulfide (H2S protects neurons against oxidative stress and ischemia-reperfusion injury and attenuates lipopolysaccharides (LPS induced neuroinflammation in microglia, exhibiting anti-inflammatory and antiapoptotic activities. The gas H2S is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow, and leukocyte adhesion. It has been known that multiple factors, including oxidative stress, free radicals, and neuronal nitric oxide synthesis as well as abnormal inflammatory responses, are involved in the mechanism underlying the brain injury after subarachnoid hemorrhage (SAH. Based on the multiple physiologic functions of H2S, we speculate that it might be a promising, effective, and specific therapy for brain injury after SAH.

  3. Changes in brain gangliosides of the neotene and metamorphic (thyroxine-induced) newt axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Hilbig, R; Schmitt, M; Rahmann, H

    1987-01-01

    Qualitative and quantitative changes in the concentration of proteins, sialoglycoproteins and gangliosides and in the composition of gangliosides in the brains of the neotene and the thyroxine-induced metamorphic newt axolotl (Ambystoma mexicanum) were investigated. During metamorphosis two polar gangliosides (GT1b and GQ1b) decreased by about 5% each. On the contrary GD1a increased to 10%. Another developmental trend was a slight increase of two other disialogangliosides (GD1b, GD2). Additionally, incorporation profiles (2-8 days) of 14C-N-Ac-mannosamine, the specific precursor for gangliosides, in the brain of neotene and metamorphic axolotls were followed giving evidence of significant changes in the sialoglycoconjugate metabolism of the central nervous system during metamorphosis of this newt.

  4. Working toward exposure thresholds for blast-induced traumatic brain injury: thoracic and acceleration mechanisms

    CERN Document Server

    Courtney, Michael; 10.1016/j.neuroimage.2010.05.025

    2011-01-01

    Research in blast-induced lung injury resulted in exposure thresholds that are useful in understanding and protecting humans from such injury. Because traumatic brain injury (TBI) due to blast exposure has become a prominent medical and military problem, similar thresholds should be identified that can put available research results in context and guide future research toward protecting warfighters as well as diagnosis and treatment. At least three mechanical mechanisms by which the blast wave may result in brain injury have been proposed - a thoracic mechanism, head acceleration and direct cranial transmission. These mechanisms need not be mutually exclusive. In this study, likely regions of interest for the first two mechanisms based on blast characteristics (positive pulse duration and peak effective overpressure) are developed using available data from blast experiments and related studies, including behind-armor blunt trauma and ballistic pressure wave studies. These related studies are appropriate to in...

  5. Neuroprotective effects of bloodletting atJing points combined with mild induced hypothermia in acute severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Yue Tu; Xiao-mei Miao; Tai-long Yi; Xu-yi Chen; Hong-tao Sun; Shi-xiang Cheng; Sai Zhang

    2016-01-01

    Bloodletting atJing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting atJing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe trau-matic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inlfammatory response were lessened. These ifndings suggest that the combined effects of bloodletting atJing points (20 µL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.

  6. Possible effects of rosuvastatin on noise-induced oxidative stress in rat brain

    Directory of Open Access Journals (Sweden)

    Alevtina Ersoy

    2014-01-01

    Full Text Available The problem of noise has recently gained more attention as it has become an integral part of our daily lives. However, its influence has yet to be fully elucidated. Other than being an unpleasant stimulus, noise may cause health disorders through annoyance and stress, including oxidative stress. Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, may possess antioxidant properties. Based on rat models, our project investigates the effect of rosuvastatin on noise-induced oxidative stress in the brain tissue. Thirty-two male Wistar albino rats were used. The rats were divided into four groups: Noise exposure plus rosuvastatin usage, only noise exposure, only rosuvastatin usage, and control. After the data had been collected, oxidant and antioxidant parameters were analyzed in the cerebral cortex, brain stem, and cerebellum. Results indicated that superoxide dismutase values were significantly decreased in the cerebral cortex, while malondialdehyde values in the brainstem and cerebellum were significantly increased in the group with only noise exposure. Superoxide dismutase values in the brainstem were significantly increased, but nitric oxide values in the cerebellum and brainstem and malondialdehyde values in the cerebellum and cerebral cortex were significantly decreased in the group where only rosuvastatin was used. During noise exposure, the use of rosuvastatin caused significantly increased superoxide dismutase values in the cerebral cortex and brainstem, but significantly reduced malondialdehyde values in the brain stem. Consequently, our data show that brain tissue was affected by oxidative stress due to continued exposure to noise. This noise-induced stress decreases with rosuvastatin therapy.

  7. Protective effect of bacoside A on cigarette smoking-induced brain mitochondrial dysfunction in rats.

    Science.gov (United States)

    Anbarasi, Kothandapani; Vani, Ganapathy; Devi, Chennam Srinivasulu Shyamala

    2005-01-01

    Chronic exposure to cigarette smoke affects the structure and function of mitochondria, which may account for the pathogenesis of smoking-related diseases. Bacopa monniera Linn., used in traditional Indian medicine for various neurological disorders, was shown to possess mitrochondrial membrane-stabilizing properties in the rat brain during exposure to morphine. We investigated the protective effect of bacoside A, the active principle of Bacopa monniera, against mitochondrial dysfunction in rat brain induced by cigarette smoke. Male Wistar albino rats were exposed to cigarette smoke and administered bacoside A for a period of 12 weeks. The mitochondrial damage in the brain was assessed by examining the levels of lipid peroxides, cholesterol, phospholipid, cholesterol/phospholipid (C/P) ratio, and the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, and cytochrome C oxidase. The oxidative phosphorylation (rate of succinate oxidation, respiratory control ratio and ADP/O ratio, and the levels of ATP) was evaluated for the assessment of mitochondrial functional capacity. We found significantly elevated levels of lipid peroxides, cholesterol, and C/P ratio, and decreased levels of phospholipids and mitochondrial enzymes in the rats exposed to cigarette smoke. Measurement of oxidative phosphorylation revealed a marked depletion in all the variables studied. Administration of bacoside A prevented the structural and functional impairment of mitochondria upon exposure to cigarette smoke. From the results, we suggest that chronic cigarette smoke exposure induces damage to the mitochondria and that bacoside A protects the brain from this damage by maintaining the structural and functional integrity of the mitochondrial membrane.

  8. Exposures to conditioned flavours with different hedonic values induce contrasted behavioural and brain responses in pigs.

    Directory of Open Access Journals (Sweden)

    Caroline Clouard

    Full Text Available This study investigated the behavioural and brain responses towards conditioned flavours with different hedonic values in juvenile pigs. Twelve 30-kg pigs were given four three-day conditioning sessions: they received three different flavoured meals paired with intraduodenal (i.d. infusions of 15% glucose (F(Glu, lithium chloride (F(LiCl, or saline (control treatment, F(NaCl. One and five weeks later, the animals were subjected to three two-choice feeding tests without reinforcement to check the acquisition of a conditioned flavour preference or aversion. In between, the anaesthetised pigs were subjected to three (18FDG PET brain imaging coupled with an olfactogustatory stimulation with the conditioned flavours. During conditioning, the pigs spent more time lying inactive, and investigated their environment less after the F(LiCl than the F(NaCl or F(Glu meals. During the two-choice tests performed one and five weeks later, the F(NaCl and F(Glu foods were significantly preferred over the F(LICl food even in the absence of i.d. infusions. Surprisingly, the F(NaCl food was also preferred over the F(Glu food during the first test only, suggesting that, while LiCl i.d. infusions led to a strong flavour aversion, glucose infusions failed to induce flavour preference. As for brain imaging results, exposure to aversive or less preferred flavours triggered global deactivation of the prefrontal cortex, specific activation of the posterior cingulate cortex, as well as asymmetric brain responses in the basal nuclei and the temporal gyrus. In conclusion, postingestive visceral stimuli can modulate the flavour/food hedonism and further feeding choices. Exposure to flavours with different hedonic values induced metabolism differences in neural circuits known to be involved in humans in the characterization of food palatability, feeding motivation, reward expectation, and more generally in the regulation of food intake.

  9. Blood-brain barrier permeability during dopamine-induced hypertension in fetal sheep.

    Science.gov (United States)

    Harris, A P; Robinson, R; Koehler, R C; Traystman, R J; Gleason, C A

    2001-07-01

    Dopamine is often used as a pressor agent in sick newborn infants, but an increase in arterial blood pressure could disrupt the blood-brain barrier (BBB), especially in the preterm newborn. Using time-dated pregnant sheep, we tested the hypothesis that dopamine-induced hypertension increases fetal BBB permeability and cerebral water content. Barrier permeability was assessed in nine brain regions, including cerebral cortex, caudate, thalamus, brain stem, cerebellum, and spinal cord, by intravenous injection of the small tracer molecule [(14)C]aminoisobutyric acid at 10 min after the start of dopamine or saline infusion. We studied 23 chronically catheterized fetal sheep at 0.6 (93 days, n = 10) and 0.9 (132 days, n = 13) gestation. Intravenous infusion of dopamine increased mean arterial pressure from 38 +/- 3 to 53 +/- 5 mmHg in 93-day fetuses and from 55 +/- 5 to 77 +/- 8 mmHg in 132-day fetuses without a decrease in arterial O(2) content. These 40% increases in arterial pressure are close to the maximum hypertension reported for physiological stresses at these ages in fetal sheep. No significant increases in the brain transfer coefficient of aminoisobutyric acid were detected in any brain region in dopamine-treated fetuses compared with saline controls at 0.6 or 0.9 gestation. There was also no significant increase in cortical water content with dopamine infusion at either age. We conclude that a 40% increase in mean arterial pressure during dopamine infusion in normoxic fetal sheep does not produce substantial BBB disruption or cerebral edema even as early as 0.6 gestation.

  10. Tilapia (Oreochromis mossambicus) brain cells respond to hyperosmotic challenge by inducing myo-inositol biosynthesis.

    Science.gov (United States)

    Gardell, Alison M; Yang, Jun; Sacchi, Romina; Fangue, Nann A; Hammock, Bruce D; Kültz, Dietmar

    2013-12-15

    This study aimed to determine the regulation of the de novo myo-inositol biosynthetic (MIB) pathway in Mozambique tilapia (Oreochromis mossambicus) brain following acute (25 ppt) and chronic (30, 60 and 90 ppt) salinity acclimations. The MIB pathway plays an important role in accumulating the compatible osmolyte, myo-inositol, in cells in response to hyperosmotic challenge and consists of two enzymes, myo-inositol phosphate synthase and inositol monophosphatase. In tilapia brain, MIB enzyme transcriptional regulation was found to robustly increase in a time (acute acclimation) or dose (chronic acclimation) dependent manner. Blood plasma osmolality and Na(+) and Cl(-) concentrations were also measured and significantly increased in response to both acute and chronic salinity challenges. Interestingly, highly significant positive correlations were found between MIB enzyme mRNA and blood plasma osmolality in both acute and chronic salinity acclimations. Additionally, a mass spectrometry assay was established and used to quantify total myo-inositol concentration in tilapia brain, which closely mirrored the hyperosmotic MIB pathway induction. Thus, myo-inositol is a major compatible osmolyte that is accumulated in brain cells when exposed to acute and chronic hyperosmotic challenge. These data show that the MIB pathway is highly induced in response to environmental salinity challenge in tilapia brain and that this induction is likely prompted by increases in blood plasma osmolality. Because the MIB pathway uses glucose-6-phosphate as a substrate and large amounts of myo-inositol are being synthesized, our data also illustrate that the MIB pathway likely contributes to the high energetic demand posed by salinity challenge.

  11. Music-induced emotions can be predicted from a combination of brain activity and acoustic features.

    Science.gov (United States)

    Daly, Ian; Williams, Duncan; Hallowell, James; Hwang, Faustina; Kirke, Alexis; Malik, Asad; Weaver, James; Miranda, Eduardo; Nasuto, Slawomir J

    2015-12-01

    It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music-induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music-induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,pemotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01).

  12. Imipramine induces brain-derived neurotrophic factor mRNA expression in cultured astrocytes.

    Science.gov (United States)

    Takano, Katsura; Yamasaki, Hiroshi; Kawabe, Kenji; Moriyama, Mitsuaki; Nakamura, Yoichi

    2012-01-01

    Depression is one of the most prevalent and livelihood-threatening forms of mental illnesses and the neural circuitry underlying depression remains incompletely understood. Recent studies suggest that the neuronal plasticity involved with brain-derived neurotrophic factor (BDNF) plays an important role in the recovery from depression. Some antidepressants are reported to induce BDNF expression in vivo; however, the mechanisms have been considered solely in neurons and not fully elucidated. In the present study, we evaluated the effects of imipramine, a classic tricyclic antidepressant drug, on BDNF expression in cultured rat brain astrocytes. Imipramine dose-dependently increased BDNF mRNA expression in astrocytes. The imipramine-induced BDNF increase was suppressed with inhibitors for protein kinase A (PKA) or MEK/ERK. Moreover, imipramine exposure activated transcription factor cAMP response element binding protein (CREB) in a dose-dependent manner. These results suggested that imipramine induced BDNF expression through CREB activation via PKA and/or ERK pathways. Imipramine treatment in depression might exert antidepressant action through BDNF production from astrocytes, and glial BDNF expression might be a target of developing novel antidepressants.

  13. Modafinil treatment prevents REM sleep deprivation-induced brain function impairment by increasing MMP-9 expression.

    Science.gov (United States)

    He, Bin; Peng, Hua; Zhao, Ying; Zhou, Hui; Zhao, Zhongxin

    2011-12-01

    Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats.

  14. Blast-induced electromagnetic fields in the brain from bone piezoelectricity.

    Science.gov (United States)

    Lee, Ka Yan Karen; Nyein, Michelle K; Moore, David F; Joannopoulos, J D; Socrate, Simona; Imholt, Timothy; Radovitzky, Raul; Johnson, Steven G

    2011-01-01

    In this paper, we show that bone piezoelectricity-a phenomenon in which bone polarizes electrically in response to an applied mechanical stress and produces a short-range electric field-may be a source of intense blast-induced electric fields in the brain, with magnitudes and timescales comparable to fields with known neurological effects. We compute the induced charge density in the skull from stress data on the skull from a finite-element full-head model simulation of a typical IED-scale blast wave incident on an unhelmeted human head as well as a human head protected by a kevlar helmet, and estimate the resulting electric fields in the brain in both cases to be on the order of 10 V/m in millisecond pulses. These fields are more than 10 times stronger than the IEEE safety guidelines for controlled environments (IEEE Standards Coordinating Committee 28, 2002) and comparable in strength and timescale to fields from repetitive Transcranial Magnetic Stimulation (rTMS) that are designed to induce neurological effects (Wagner et al., 2006a). They can be easily measured by RF antennas, and may provide the means to design a diagnostic tool that records a quantitative measure of the head's exposure to blast insult.

  15. Dichlorvos and lindane induced oxidative stress in rat brain: Protective effects of ginger

    Directory of Open Access Journals (Sweden)

    Poonam Sharma

    2012-01-01

    Full Text Available Background: Dichlorvos and lindane pesticide causes toxicity in animals including humans. Ginger (Zingiber officinale is widely used as a culinary medicine in the Ayurvedic system of medicine, possessing a number of pharmacological properties. Objective: This study was designed to assess ameliorating effects of ginger juice in dichlorvos and lindane induced neurotoxicity in wistar rats. Materials and Methods: Dichlorvos (8.8 mg/kg bw and lindane (8.8 mg/kg bw were orally administered alone as well as in combination to adult male and female wistar rats for 14 days followed by the post-treatment of ginger juice (100 mg/kg bw for 14 days. Lipid peroxidation (LPO, reduced glutathione (GSH, and activities of antioxidant enzymes such as superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione S-transferase (GST, glutathione reductase (GR, quinine reductase (QR, and protein level were measured to evaluate the toxicity of these pesticides in brain. Results: Dichlorvos and lindane administration alone and in combination increased LPO and decreased the GSH level, SOD, CAT, GPx, GST, GR, QR activity, and protein. Oxidative stress due to abnormal production of reactive oxygen species (ROS is believed to be involved in the toxicities induced by these pesticides. Post-treatment of ginger juice decreased LPO and increased the level of GSH, SOD, CAT, GPx, GST, GR, QR activity and protein in the brain of rats. Conclusions: The results indicated that dichlorovos and lindane induced tissue damage was ameliorated by ginger juice.

  16. Aldosterone-induced brain MAPK signaling and sympathetic excitation are angiotensin II type-1 receptor dependent.

    Science.gov (United States)

    Zhang, Zhi-Hua; Yu, Yang; Wei, Shun-Guang; Felder, Robert B

    2012-02-01

    Angiotensin II (ANG II)-induced mitogen-activated protein kinase (MAPK) signaling upregulates angiotensin II type-1 receptors (AT(1)R) in hypothalamic paraventricular nucleus (PVN) and contributes to AT(1)R-mediated sympathetic excitation in heart failure. Aldosterone has similar effects to increase AT(1)R expression in the PVN and sympathetic drive. The present study was undertaken to determine whether aldosterone also activates the sympathetic nervous system via MAPK signaling and, if so, whether its effect is independent of ANG II and AT(1)R. In anesthetized rats, a 4-h intravenous infusion of aldosterone induced increases (P < 0.05) in phosphorylated (p-) p44/42 MAPK in PVN, PVN neuronal excitation, renal sympathetic nerve activity (RSNA), mean blood pressure (MBP), and heart rate (HR). Intracerebroventricular or bilateral PVN microinjection of the p44/42 MAPK inhibitor PD-98059 reduced the aldosterone-induced RSNA, HR, and MBP responses. Intracerebroventricular pretreatment (5 days earlier) with pooled small interfering RNAs targeting p44/42 MAPK reduced total and p-p44/42 MAPK, aldosterone-induced c-Fos expression in the PVN, and the aldosterone-induced increases in RSNA, HR, and MBP. Intracerebroventricular infusion of either the mineralocorticoid receptor antagonist RU-28318 or the AT(1)R antagonist losartan blocked aldosterone-induced phosphorylation of p44/42 MAPK and prevented the increases in RSNA, HR, and MBP. These data suggest that aldosterone-induced sympathetic excitation depends upon that AT(1)R-induced MAPK signaling in the brain. The short time course of this interaction suggests a nongenomic mechanism, perhaps via an aldosterone-induced transactivation of the AT(1)R as described in peripheral tissues.

  17. Feasibility of Implementing an Early Intervention Program in an Urban Low-Income Setting to Improve Neurodevelopmental Outcome in Survivors Following Birth Asphyxia

    OpenAIRE

    2011-01-01

    Birth asphyxia is a leading cause of neonatal mortality, accounting for 23% of neonatal deaths. An early intervention program (EIP) could improve neuro-developmental outcomes in survivors of birth asphyxia, but its feasibility in low-income countries has not been tested.  In this pilot study in Zambia, eighty live-born infants > 1500 g of weight who had birth asphyxia and received resuscitation with bag and mask were enrolled for a study of standard care or EIP. Mothers/babies pairs were rand...

  18. Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment.

    Science.gov (United States)

    De Foubert, G; Carney, S L; Robinson, C S; Destexhe, E J; Tomlinson, R; Hicks, C A; Murray, T K; Gaillard, J P; Deville, C; Xhenseval, V; Thomas, C E; O'Neill, M J; Zetterström, T S C

    2004-01-01

    Recent studies indicate that brain-derived neurotrophic factor (BDNF) may be implicated in the clinical action of antidepressant drugs. Repeated (2-3 weeks) administration of antidepressant drugs increases BDNF gene expression. The onset of this response as well as concomitant effects on the corresponding BDNF protein is however, unclear. The present study investigated the effects of acute and chronic administration of the selective serotonin reuptake inhibitor, fluoxetine (10mg/kg p.o.), upon regional rat brain levels of BDNF mRNA and protein expression. To improve the clinical significance of the study, fluoxetine was administered orally and mRNA and protein levels were determined ex vivo using the techniques of in situ hybridisation histochemistry and immunocytochemistry respectively. Direct measurement of BDNF protein was also carried out using enzyme-linked immunosorbent assay (ELISA). Four days of once daily oral administration of fluoxetine induced decreases in BDNF mRNA (hippocampus, medial habenular and paraventricular thalamic nuclei). Whilst 7 days of treatment showed a non-significant increase in BDNF mRNA, there were marked and region-specific increases following 14 days of treatment. BDNF protein levels remained unaltered until 21 days of fluoxetine treatment, when the numbers of BDNF immunoreactive cells were increased, reaching significance in the pyramidal cell layer of CA1 and CA3 regions of Ammon's horn (CA1 and CA3) but not in the other sub-regions of the hippocampus. Indicative of the highly regional change within the hippocampus, the ELISA method failed to demonstrate significant up-regulation at 21 days, measuring levels of BDNF protein in the whole hippocampus. In contrast to the detected time dependent and biphasic response of the BDNF gene, activity-regulated, cytoskeletal-associated protein (Arc) mRNA showed a gradual increase during the 14-day course of treatment. The results presented here show that BDNF is expressed differentially

  19. Compound 48/80-induced serotonin release from brain mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Lambracht-Hall, M.; Marathias, K.P.; Theoharides, T.C.

    1986-03-01

    Mast cells secrete a variety of potent mediators and are mostly known to participate in allergic reactions. Here the authors report that perfused brain mast cells can take up and release serotonin (5-HT) in response to compound 48/80. Thalamic or hypothalamic slices were loaded with /sup 3/H-5-HT (5 x 10/sup -7/M, for 12 min at 37/sup 0/C), washed and placed in individual 2 ml-perfusion wells. A Krebs-Ringer bicarbonate buffer with 1 x 10/sup -6/M imipramine (KRB + IMI) saturated with 5% CO/sub 2//95% O/sub 2/ at 37/sup 0/C and pH 7.4, was used throughout at a perfusion rate of 1 ml/min. After a 60 min wash in KRB + IMI, with or without Ca/sup +2/ + 0.1 M EDTA, the slices were perfused for 45 min with 100 ..mu..g/ml compound 48/80 with or without Ca/sup +2/. The tissue was washed for 30 min as before and then perfused with high K/sup +/ KRB (40mM KCl) for 45 min to induce neuronal depolarization. Finally, calcium was restored to Ca/sup +2/-depleted tissues and all samples were again perfused for 45 min with high K/sup +/ KRB. The first 5-HT peak due to 48/80-induced mast cell release was independent of extracellular Ca/sup +2/, while the second 5-HT peak due to high K/sup +/ was not. These studies indicate that the 48/80-induced 5-HT release was not of neuronal origin and that brain mast cells can utilize intracellular Ca/sup +2/, much like their peritoneal counterparts. The authors are now studying brain mast cells secretion in response to neuropeptides.

  20. Blast-induced traumatic brain injury: a new trend of blast injury research

    Institute of Scientific and Technical Information of China (English)

    Yan Zhao; Zheng-Guo Wang

    2015-01-01

    Blast injury has become the major life-and function-threatening injuries in recent warfares.There is increased research interest in the mental disorders caused by blast-induced traumatic brain injury (bTBI),which has been proved as one of the "signature wounds" in modern battlefield.We reviewed the recent progresses in bTBl-related researches and concluded that the new era of blast injury research has shifted from the traditional physical impairments to cognitive dysfunctional/mental disorders that are proved to be more related to the outcome of combat casualty care.

  1. 2-Methylcitric acid impairs glutamate metabolism and induces permeability transition in brain mitochondria.

    Science.gov (United States)

    Amaral, Alexandre Umpierrez; Cecatto, Cristiane; Castilho, Roger Frigério; Wajner, Moacir

    2016-04-01

    Accumulation of 2-methylcitric acid (2MCA) is observed in methylmalonic and propionic acidemias, which are clinically characterized by severe neurological symptoms. The exact pathogenetic mechanisms of brain abnormalities in these diseases are poorly established and very little has been reported on the role of 2MCA. In the present work we found that 2MCA markedly inhibited ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate, with a less significant inhibition in pyruvate plus malate respiring mitochondria. However, no alterations occurred when α-ketoglutarate or succinate was used as respiratory substrates, suggesting a defect on glutamate oxidative metabolism. It was also observed that 2MCA decreased ATP formation in glutamate plus malate or pyruvate plus malate-supported mitochondria. Furthermore, 2MCA inhibited glutamate dehydrogenase activity at concentrations as low as 0.5 mM. Kinetic studies revealed that this inhibitory effect was competitive in relation to glutamate. In contrast, assays of osmotic swelling in non-respiring mitochondria suggested that 2MCA did not significantly impair mitochondrial glutamate transport. Finally, 2MCA provoked a significant decrease in mitochondrial membrane potential and induced swelling in Ca(2+)-loaded mitochondria supported by different substrates. These effects were totally prevented by cyclosporine A plus ADP or ruthenium red, indicating induction of mitochondrial permeability transition. Taken together, our data strongly indicate that 2MCA behaves as a potent inhibitor of glutamate oxidation by inhibiting glutamate dehydrogenase activity and as a permeability transition inducer, disturbing mitochondrial energy homeostasis. We presume that 2MCA-induced mitochondrial deleterious effects may contribute to the pathogenesis of brain damage in patients affected by methylmalonic and propionic acidemias. We propose that brain glutamate oxidation is disturbed by 2-methylcitric acid (2MCA), which

  2. Restoring GM1 ganglioside expression ameliorates axonal outgrowth inhibition and cognitive impairments induced by blast traumatic brain injury

    Science.gov (United States)

    Rubovitch, Vardit; Zilberstein, Yael; Chapman, Joab; Schreiber, Shaul; Pick, Chaim G.

    2017-01-01

    Blast induced traumatic brain injury (B-TBI) may cause various degrees of cognitive and behavioral disturbances but the exact brain pathophysiology involved is poorly understood. It was previously suggested that ganglioside alteration on the axon surface as well as axonal regenerating inhibitors (ARIs) such as myelin associated glycoprotein (MAG) were involved in axonal outgrowth inhibition (AOI), leading to brain damage. GM1 ganglioside content in the brain was significantly reduced while GD1 ganglioside was not affected. The axonal regeneration was also reduced as seen by the phosphorylated NF-H expression. Moreover, B-TBI induced a significant elevation in MAG expression in the brains of the injured mice. The blast injured mice exhibited a significant decline in spatial memory as seen by the Y-maze test. In addition, the injured mice showed pronounced damage to the visual memory (as evaluated by the Novel object recognition test). A single low dose of GM1 (2 mg/kg; IP), shortly after the injury, prevented both the cognitive and the cellular changes in the brains of the injured mice. These results enlighten part of the complicated mechanism that underlies the damage induced by B-TBI and may also suggest a potential new treatment strategy for brain injuries. PMID:28112258

  3. Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia

    Science.gov (United States)

    Adibzadeh, F.; Verhaart, R. F.; Verduijn, G. M.; Fortunati, V.; Rijnen, Z.; Franckena, M.; van Rhoon, G. C.; Paulides, M. M.

    2015-02-01

    To provide an adequate level of protection for humans from exposure to radio-frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health effects are avoided. The basic restrictions in terms of the specific energy absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a therapeutic application of non-ionizing EMF is hyperthermia (HT), in which intense RF energy is focused at a target region. Deep HT in the head and neck (H&N) region involves inducing energy at 434 MHz for 60 min on target. Still, stray exposure of the brain is considerable, but to date only very limited side-effects were observed. The objective of this study is to investigate the stringency of the current basic restrictions by relating the induced EM dose in the brain of patients treated with deep head and neck (H&N) HT to the scored acute health effects. We performed a simulation study to calculate the induced peak 10 g spatial-averaged SAR (psSAR10g) in the brains of 16 selected H&N patients who received the highest SAR exposure in the brain, i.e. who had the minimum brain-target distance and received high forwarded power during treatment. The results show that the maximum induced SAR in the brain of the patients can exceed the current basic restrictions (IEEE and ICNIRP) on psSAR10g for occupational environments by 14 times. Even considering the high local SAR in the brain, evaluation of acute effects by the common toxicity criteria (CTC) scores revealed no indication of a serious acute neurological effect. In addition, this study provides pioneering quantitative human data on the association between maximum brain SAR level and acute adverse effects when brains are exposed to prolonged RF EMF.

  4. 新生儿窒息多器官损害发生率、高危因素和转归的多中心研究%Incidence, risk factors and outcomes of multiple organ damage after neonatal asphyxia

    Institute of Scientific and Technical Information of China (English)

    新生儿窒息多器官损害临床诊断多中心研究协作组

    2016-01-01

    was lower [92.2% (214/232) vs 98.0% (250/255),P<0.01], and the mortality rate was higher [4.3% (10/232) vs 0(0/255),P<0.01]. The recovery rate in groupⅠ was lower than that of groupⅡ [79.1%(34/43) vs 86.5% (32/37),P<0.01], and the mortality rate was higher [20.9% (9/43) vs 2.7% (1/37),P<0.01]. ConclusionNeonatal asphyxia might lead to MOD including brain, heart, lungs, liver and gastrointestinal system, especially when babies were severe asphyxiated and complicated with serious metabolic acidosis.

  5. Characteristics of brain injury induced by shock wave propagation in solids after underwater explosion in rats

    Directory of Open Access Journals (Sweden)

    Xin-ling LI

    2016-09-01

    Full Text Available Objective  To observe the characteristics of rat brain injury induced by shock wave propagation in solids resulting from underwater explosion and explore the related mechanism. Methods  Explosion source outside the simulated ship cabin underwater was detonated for establishing a model of brain injury in rats by shock wave propagation in solid; 72 male SD rats were randomly divided into normal control group (n=8, injury group 1 (600mg RDX paper particle explosion source, n=32, injury group 2 (800mg RDX paper particle explosion source, n=32. The each injury group was randomly divided into 4 subgroups (n=8, 3, 6, 24 and 72h groups. The division plate as a whole and the head of 8 rats in each injury group were measured for the peak value of the solid shock wave, its rising time and the duration time of shock wave propagation in solid. To observe the physiological changes of animals after injury, plasma samples were collected for determination of brain damage markers, NSE and S-100β. All the animals were sacrificed, the right hemisphere of the brain was taken in each group of animals, weighting after baking, and the brain water content was calculated. Pathological examination was performed for left cerebral hemisphere in 24-h group. The normal pyramidal cells in the hippocampal CA1 region were counted. Results  The peak value, rising time and duration time of shock wave propagation on the division plate and head were 1369.74±91.70g, 0.317±0.037ms and 24.85±2.53ms, 26.83±3.09g, 0.901±0.077ms and 104.21±6.26ms respectively in injury group 1, 1850.11±83.86g, 0.184±0.031ms and 35.61±2.66ms, 39.75±3.14g, 0.607±0.069ms and 132.44±7.17ms in injury group 2 (P<0.01. After the injury, there was no abnormality in the anatomy, and brain damage markers NSE, S-100β increased, reached the peak at 24 h, and they were highest in injury group 2 and lowest in control group with a statistically significant difference (P<0.05. The brain water content

  6. S100B modulates IL-6 release and cytotoxicity from hypothermic brain cells and inhibits hypothermia-induced axonal outgrowth.

    Science.gov (United States)

    Schmitt, Katharina R L; Kern, Claudia; Lange, Peter E; Berger, Felix; Abdul-Khaliq, Hashim; Hendrix, Sven

    2007-09-01

    Brain protection is essential during neonatal and pediatric cardiac surgery. Deep hypothermia is still the most important method for achieving neuroprotection during cardiopulmonary bypass. Previously, we could demonstrate that deep hypothermia induces substantial cytotoxicity in brain cells as well as increased release of the pro-inflammatory cytokine interleukin-6 (IL-6), which plays an important role in neuroprotection and neuroregeneration. Deep hypothermia is also associated with increased levels of the astrocytic protein S100B in the serum and cerebrospinal fluid of patients. Since S100B may modulate pro-inflammatory cytokines and may stimulate neurite outgrowth, we have tested the hypothesis that nanomolar concentrations of S100B may increase IL-6 release from brain cells and support axonal outgrowth from organotypic brain slices under hypothermic conditions. S100B administration substantially reduced neuronal and glial cytotoxicity under hypothermic conditions. In the presence of S100B hypothermia-induced IL-6 release in primary astrocytes was significantly increased but reduced in BV-2 microglial cells and primary neurons. Surprisingly, deep hypothermia increased axonal outgrowth from brain slices and--in contrast to our hypothesis--this hypothermia-induced neurite outgrowth was inhibited by S100B. These data suggest that S100B differentially influences cytokine release and cytotoxicity from distinct brain cells and may inhibit neuroregeneration by suppressing hypothermia-induced axonal outgrowth.

  7. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    Science.gov (United States)

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.

  8. Moderately delayed post-insult treatment with normobaric hyperoxia reduces excitotoxin-induced neuronal degeneration but increases ischemia-induced brain damage

    Directory of Open Access Journals (Sweden)

    Haelewyn Benoit

    2011-04-01

    Full Text Available Abstract Background The use and benefits of normobaric oxygen (NBO in patients suffering acute ischemic stroke is still controversial. Results Here we show for the first time to the best of our knowledge that NBO reduces both NMDA-induced calcium influxes in vitro and NMDA-induced neuronal degeneration in vivo, but increases oxygen and glucose deprivation-induced cell injury in vitro and ischemia-induced brain damage produced by middle cerebral artery occlusion in vivo. Conclusions Taken together, these results indicate that NBO reduces excitotoxin-induced calcium influx and subsequent neuronal degeneration but favors ischemia-induced brain damage and neuronal death. These findings highlight the complexity of the mechanisms involved by the use of NBO in patients suffering acute ischemic stroke.

  9. Psychobiology of drug-induced religious experience: from the brain "locus of religion" to cognitive unbinding.

    Science.gov (United States)

    Nencini, Paolo; Grant, Kathleen A

    2010-11-01

    The recent interest in the psychopharmacological underpinnings of religious experiences has led to both the laboratory characterizations of drug-induced mystical events and psychobiological models of religious experiences rooted in evolution and fitness. Our examination of this literature suggests that these theories may be congruent only within more modern religious and cultural settings and are not generalizable to all historical beliefs, as would be expected from an evolutionarily conserved biological mechanism. The strong influence of culture on the subjective effects of drugs as well as religious thoughts argues against the concept of a common pathway in the brain uniquely responsible for these experiences. Rather, the role of personal beliefs, expectations and experiences may interject bias into the interpretation of psychoactive drug action as a reflection of biologically based religious thought. Thus, psychobiological research proposing specific brain mechanisms should consider anthropological and historical data to address alternative explanations to the "fitness" of religious thought. A psychobiological model of the religious experience based on the concept of cognitive unbinding seems to accommodate these data better than that of a specific brain locus of religion.

  10. Why and how physical activity promotes experience-induced brain plasticity

    Directory of Open Access Journals (Sweden)

    Gerd eKempermann

    2010-12-01

    Full Text Available Adult hippocampal neurogenesis is an unusual case of brain plasticity, since new neurons (and not just neurites and synapses are added to the network in an activity-dependent way. At the behavioral level the plasticity-inducing stimuli include both physical and cognitive activity. In reductionistic animal studies these types of activity can be studied separately in paradigms like voluntary wheel running and environmental enrichment. In both of these, adult neurogenesis is increased but the net effect is primarily due to different mechanisms at the cellular level. Locomotion appears to stimulate the precursor cells, from which adult neurogenesis originates, to increased proliferation and maintenance over time, whereas environmental enrichment, as well as learning, predominantly promotes survival of immature neurons, that is the progeny of the proliferating precursor cells. Surprisingly, these effects are additive: boosting the potential for adult neurogenesis by physical activity increases the recruitment of cells following cognitive stimulation in an enriched environment. Why is that? We argue that locomotion actually serves as an intrinsic feedback mechanism, signaling to the brain, including its neural precursor cells, that the likelihood of cognitive challenges increases. In the wild (other than in front of a TV, no separation of physical and cognitive activity occurs. Physical activity might thus be much more than a generally healthy garnish to leading an active life but an evolutionarily fundamental aspect of activity, which is needed to provide the brain and its systems of plastic adaptation with the appropriate regulatory input and feedback.

  11. Brain Fos expression and intestinal motor alterations during nematode-induced inflammation in the rat.

    Science.gov (United States)

    Castex, N; Fioramonti, J; Ducos de Lahitte, J; Luffau, G; More, J; Bueno, L

    1998-01-01

    Brain-gut interactions and intestinal motility were studied during pulmonary and jejunal inflammation induced by Nippostrongylus brasiliensis. Jejunal electromyographic activity was continuously recorded from day 1 before to day 28 after infection. Expression of c-fos was assessed in the brain by immunohistochemistry, and myeloperoxidase (MPO) activity was determined in lung and intestine on days 1,7,14, 21, and 28 postinfection. The cyclic intestinal motor pattern was replaced by an irregular activity from day 4, corresponding to larvae migration to the intestine, to day 14. c-fos was expressed in the caudal nucleus of the solitary tract (NTS) and lateral parabrachial nucleus (LPB) on day 1 (lung stage of N. brasiliensis) and in the medial part of the NTS, the LPB, and locus ceruleus on day 7. Pulmonary and intestinal MPO activity was increased from days 1 to 21 postinfection. During N. brasiliensis infection, c-fos expression indicates that specific and different brain nuclei are activated at the onset of pulmonary and intestinal inflammation, which is associated with motor disorders.

  12. Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism.

    Science.gov (United States)

    Shin, Andrew C; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A; Zielinski, Elizabeth; Zhou, Jian-Ying; Scherer, Thomas; Lindtner, Claudia; White, Phillip J; Lapworth, Amanda L; Ilkayeva, Olga; Knippschild, Uwe; Wolf, Anna M; Scheja, Ludger; Grove, Kevin L; Smith, Richard D; Qian, Wei-Jun; Lynch, Christopher J; Newgard, Christopher B; Buettner, Christoph

    2014-11-04

    Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α-keto acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in nonhuman primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes.

  13. Radiation-induced blood-brain barrier changes: pathophysiological mechanisms and clinical implications.

    Science.gov (United States)

    d'Avella, D; Cicciarello, R; Angileri, F F; Lucerna, S; La Torre, D; Tomasello, F

    1998-01-01

    The pathophysiology of whole-brain radiation (WBR) toxicity remains incompletely understood. The possibility of a primary change in blood-brain barrier (BBB) associated with microvascular damage was investigated. Rats were exposed to conventional fractionation in radiation (200 +/- cGy/d, 5d/wk; total dose, 4,000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid (AIB) technique coupled with standard electron microscopy (EM) and morphometric techniques as well as studies of the transcapillary passage of horseradish peroxidase (HRP). At 15 days after WBR, AIB transport across BBB increased significantly in cerebral cortex. EM disclosed vesicular transport of HRP across the intact endothelium without opening of the tight junctions. Ninety days after WBR, well-defined alterations of the microvasculature were observed. The main feature of cortical microvessels was their collapsed aspect, associated with perivascular edema containing cell debris. Data suggest a possible association between damage of the microvascular/glial unit of tissue injury and development of radiation-induced brain cerebral dysfunction. We hypothesize the following sequence of pathophysiological events: WBR causes an early increase in BBB permeability, which produces perivascular edema and microvascular collapse. The interference with microcirculation affects blood flow and energy supply to the tissue, resulting in structural damage on an ischemic/dysmetabolic basis.

  14. Light and electron microscopic evaluation of hydrogen ion-induced brain necrosis.

    Science.gov (United States)

    Petito, C K; Kraig, R P; Pulsinelli, W A

    1987-10-01

    Excessive accumulation of hydrogen ions in the brain may play a pivotal role in initiating the necrosis seen in infarction and following hyperglycemic augmentation of ischemic brain damage. To examine possible mechanisms involved in hydrogen ion-induced necrosis, sequential structural changes in rat brain were examined following intracortical injection of sodium lactate solution (pH 4.5), as compared with injections at pH 7.3. Following pH 7.3 injection, neuronal swelling developed between 1 and 6 h, but only a needle track wound surrounded by a thin rim of necrotic neurons and vacuolated neuropil was present 24 h after injection. In contrast, pH 4.5 injection produced neuronal necrosis as soon as 1 h after injection, followed by necrosis of astrocytes and intravascular thrombi at 3 and 6 h. Alterations common to both groups included vascular permeability to horseradish peroxidase, dilation of extracellular spaces, astrocyte swelling, capillary compression, and vascular stasis. These data suggest that neurons, astrocytes, and endothelia can be directly damaged by increased acid in the interstitial space. Lethal injury initially appeared to affect neurons, while subsequent astrocyte necrosis and vascular occlusion may damage tissue by secondary ischemia.

  15. Measuring Brain Stimulation Induced Changes in Cortical Properties Using TMS-EEG.

    Science.gov (United States)

    Chung, Sung Wook; Rogasch, Nigel C; Hoy, Kate E; Fitzgerald, Paul B

    2015-01-01

    Neuromodulatory brain stimulation can induce plastic reorganization of cortical circuits that persist beyond the period of stimulation. Most of our current knowledge about the physiological properties has been derived from the motor cortex. The integration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a valuable method for directly probing excitability, connectivity and oscillatory dynamics of regions throughout the brain. Offering in depth measurement of cortical reactivity, TMS-EEG allows the evaluation of TMS-evoked components that may act as a marker for cortical excitation and inhibition. A growing body of research is using concurrent TMS and EEG (TMS-EEG) to explore the effects of different neuromodulatory techniques such as repetitive TMS and transcranial direct current stimulation on cortical function, particularly in non-motor regions. In this review, we outline studies examining TMS-evoked potentials and oscillations before and after, or during a single session of brain stimulation. Investigating these studies will aid in our understanding of mechanisms involved in the modulation of excitability and inhibition by neuroplasticity following different stimulation paradigms.

  16. Role of brain dopaminergic system in the adrenomedullin-induced diuresis and natriuresis.

    Science.gov (United States)

    Díaz, Emilia; Silva, María; Israel, Anita

    2003-11-01

    Intracerebroventricular (IVT) administration of adrenomedullin (AM) to conscious male hydrated rats increases urinary volume and sodium excretion. The possible involvement of brain dopamine (DA) system on the renal action of IVT-AM was investigated. AM-induced diuretic and natriuretic action was prevented following selective central dopaminergic denervation with 6-hydroxydopamine (6OHDA) in combination with desmethylimipramine (DMI). Selective D(2) DA receptor antagonism with haloperidol, sulpiride, and remoxipride; or with the D(1) DA receptor antagonist, SCH 23390, blunted the increase in urinary volume and sodium excretion induced by IVT-AM. The present results suggest that AM acts centrally, at least in part, via an interaction with endogenous DA through the activation of both DA D(1)/D(2) receptor subtype.

  17. Spatial Memory Deficit and Tau Hyperphosphorylation Induced by Inhibiting PP2A in Rat Brain

    Institute of Scientific and Technical Information of China (English)

    TIAN Qing; ZHENG Hong-yun; CHEN Juan; LI Hong-lian; GONG Cheng-xin; WANG Jian-zhi

    2005-01-01

    Hyperphosphorylation of Tau in Alzheimer's disease (AD) brain appears to be caused by a down-regulation of protein phosphatase 2A (PP2A). In this study, we selectively inhibited PP2A by injection of okadaic acid (OA) into the Meynert nucleus basalis of rats and found that 0.4 pmol of OA injection induced approximately 60% inhibition of PP2A 24 h after injection, 13% inhibition 48 h after injection and no obvious inhibition 72 h after injection. Hyperphosphorylation of Tau at Ser-198/Ser-199/Ser-202 and Ser-396/Ser-404 and spatial memory deficit of rats were induced 24 h after 0.4 pmol of OA injection. This study suggests that a down-regulation of PP2A may underlie abnormal hyperphosphorylation of cytoskeletal proteins leading to neurofibrillary degeneration in AD.

  18. Ethyl-eicosapentaenoate modulates changes in neurochemistry and brain lipids induced by parkinsonian neurotoxin 1-methyl-4-phenylpyridinium in mouse brain slices.

    Science.gov (United States)

    Meng, QingJia; Luchtman, Dirk W; El Bahh, Bouchaib; Zidichouski, Jeffrey A; Yang, Jun; Song, Cai

    2010-12-15

    Evidence suggests a link between Parkinson's disease and the dietary intake of omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs). Presently, we investigated whether an acute dose of parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) affects brain n-3 and n-6 PUFA content and expression of fatty acid metabolic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) in brain slices from C57Bl/6 mice. Furthermore, we investigated whether feeding a diet of n-3 PUFA ethyl-eicosapentaenoate (E-EPA) to these mice can attenuate the MPP(+) induced changes in brain PUFA content and expression of cPLA2 and COX-2, and attenuate MPP(+) induced changes in neurotransmitters and metabolites and apoptotic markers, bax, bcl-2 and caspase-3. MPP(+) increased brain content of n-6 PUFAs linoleic acid and arachidonic acid, and increased the mRNA expression of cPLA2. MPP(+) also depleted striatal dopamine levels and increased dopamine turnover, and depleted noradrenaline levels in the frontal cortex. The neurotoxin induced increases in bax, bcl-2 and caspase-3 mRNA expression that approached significance. E-EPA by itself increased brain n-3 content, including EPA and docosapentaenoic acid (C22:5, n-3), and increased cortical dopamine. More importantly, E-EPA attenuated the MPP(+) induced increase in n-6 fatty acids content, partially attenuated the striatal dopaminergic turnover, and prevented the increases of pro-apoptotic bax and caspase-3 mRNAs. In conclusion, increases in n-6 PUFAs in the acute stage of exposure to parkinsonian neurotoxins may promote pro-inflammatory conditions. EPA may provide modest beneficial effects in Parkinson's disease, but further investigation is warranted.

  19. Experimental study of blast-induced traumatic brain injury using a physical head model.

    Science.gov (United States)

    Zhang, Jiangyue; Pintar, Frank A; Yoganandan, Narayan; Gennarelli, Thomas A; Son, Steven F

    2009-11-01

    This study was conducted to quantify intracranial biomechanical responses and external blast overpressures using physical head model to understand the biomechanics of blast traumatic brain injury and to provide experimental data for computer simulation of blast-induced brain trauma. Ellipsoidal-shaped physical head models, made from 3-mm polycarbonate shell filled with Sylgard 527 silicon gel, were used. Six blast tests were conducted in frontal, side, and 45 degrees oblique orientations. External blast overpressures and internal pressures were quantified with ballistic pressure sensors. Blast overpressures, ranging from 129.5 kPa to 769.3 kPa, were generated using a rigid cannon and 1.3 to 3.0 grams of pentaerythritol tetranitrate (PETN) plastic sheet explosive (explosive yield of 13.24 kJ and TNT equivalent mass of 2.87 grams for 3 grams of material). The PETN plastic sheet explosive consisted of 63% PETN powder, 29% plasticizer, and 8% nitrocellulose with a density of 1.48 g/cm3 and detonation velocity of 6.8 km/s. Propagation and reflection of the shockwave was captured using a shadowgraph technique. Shockwave speeds ranging from 423.3 m/s to 680.3 m/s were recorded. The model demonstrated a two-stage response: a pressure dominant (overpressure) stage followed by kinematic dominant (blast wind) stage. Positive pressures in the brain simulant ranged from 75.1 kPa to 1095 kPa, and negative pressures ranged from -43.6 kPa to -646.0 kPa. High- and normal-speed videos did not reveal observable deformations in the brain simulant from the neutral density markers embedded in the midsagittal plane of the head model. Amplitudes of the internal positive and negative pressures were found to linearly correlate with external overpressure. Results from the current study suggested a pressure-dominant brain injury mechanism instead of strain injury mechanism under the blast severity of the current study. These quantitative results also served as the validation and calibration

  20. Neuroprotective effects of nitric oxide donor NOC-18 against brain ischemia-induced mitochondrial damages: role of PKG and PKC.

    Science.gov (United States)

    Arandarcikaite, Odeta; Jokubka, Ramunas; Borutaite, Vilmante

    2015-01-23

    In this study we sought to determine whether NO donor NOC-18 can protect brain mitochondria against ischemia-induced dysfunction, particularly opening of mitochondrial permeability transition pore (MPTP), and cell death. We found that inhibition of respiration with NAD-dependent substrates, but not with succinate, was observed after 30 min ischemia indicating that complex I of the mitochondrial respiratory chain is the primary site affected by ischemia. There was no loss of mitochondrial cytochrome c during 30-120 min of brain ischemia. Prolonged, 90 min ischemia substantially decreased calcium retention capacity of brain mitochondria suggesting sensitization of mitochondria to Ca(2+)-induced MPTP opening, and this was prevented by NOC-18 infusion prior to ischemia. NOC-18 did not prevent ischemia-induced inhibition of mitochondrial respiration, however, it partially protected against ischemia-induced necrosis. Protective effects of NOC-18 were abolished in the presence of selective inhibitors of protein kinase G (PKG) and protein kinase C (PKC). These results indicate that pre-treatment with NOC-18 protected brain mitochondria against ischemia-induced MPTP opening by decreasing mitochondrial sensitivity to calcium and partly protected brain cells against necrotic death in PKG- and PKC-depending manner.

  1. Molecular mechanisms of increased cerebral vulnerability after repeated mild blast-induced traumatic brain injury

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    Alaa Kamnaksh

    2014-06-01

    Full Text Available The consequences of a mild traumatic brain injury can be especially severe if it is repeated within the period of increased cerebral vulnerability (ICV that follows the initial insult. To better understand the molecular mechanisms that contribute to ICV, we exposed rats to different levels of mild blast overpressure (5 exposures; total pressure range: 15.54–19.41 psi or 107.14–133.83 kPa at a rate of 1 per 30 min, monitored select physiological parameters, and assessed behavior. Two days post-injury or sham, we determined changes in protein biomarkers related to various pathologies in behaviorally relevant brain regions and in plasma. We found that oxygen saturation and heart rate were transiently depressed following mild blast exposure and that injured rats exhibited significantly increased anxiety- and depression-related behaviors. Proteomic analyses of the selected brain regions showed evidence of substantial oxidative stress and vascular changes, altered cell adhesion, and inflammation predominantly in the prefrontal cortex. Importantly, these pathological changes as well as indications of neuronal and glial cell loss/damage were also detected in the plasma of injured rats. Our findings illustrate some of the complex molecular changes that contribute to the period of ICV in repeated mild blast-induced traumatic brain injury. Further studies are needed to determine the functional and temporal relationship between the various pathomechanisms. The validation of these and other markers can help to diagnose individuals with ICV using a minimally invasive procedure and to develop evidence-based treatments for chronic neuropsychiatric conditions.

  2. Establishment of a blunt impact-induced brain injury model in rabbits

    Directory of Open Access Journals (Sweden)

    LI Kui

    2012-04-01

    Full Text Available 【Abstract】 Objective: To establish an animal model to replicate the blunt impact brain injury in forensic medicine. Methods: Twenty-four New Zealand white rabbits were randomly divided into control group (n=4, minor injury group (n=10 and severe injury group (n=10. Based on the BIM-Ⅱ Horizontal Bio-impact Machine, self-designed iron bar was used to produce blunt brain injury. Two rabbits from each injury group were randomly selected to monitor the change of intracranial pressure (ICP during the impact-ing process by pressure microsensors. Six hours after injury, all the rabbits were dissected to observe the injury mor-phology and underwent routine pathological examination. Results: Varying degrees of nervous system positive signs were observed in all the injured rabbits. Within 6 hours, the mortality rate was 1/10 in the minor injury group and 6/10 in the severe injury group. Morphological changes con-sisted of different levels of scalp hematoma, skull fracture, epidural hematoma, subdural hematoma, subarachnoid hemo-rrhage and brain injury. At the moment of hitting, the ICP was greater in severe injury group than in mild injury group; and within the same group, the impact side showed positive pressure while the opposite side showed negative pressure. Conclusions: Under the rigidly-controlled experimen-tal condition, this animal model has a good reproducibility and stable results. Meanwhile, it is able to simulate the mor-phology of iron strike-induced injury, thus can be used to study the mechanism of blunt head injury in forensic medicine. Key words: Brain injuries; Forensic medicine; Wounds, nonpenetrating; Models, animal; Rabbits

  3. Overexpression of Extracellular Superoxide Dismutase Protects against Brain Injury Induced by Chronic Hypoxia

    Science.gov (United States)

    Zaghloul, Nahla; Patel, Hardik; Codipilly, Champa; Marambaud, Philippe; Dewey, Stephen; Frattini, Stephen; Huerta, Patricio T.; Nasim, Mansoor; Miller, Edmund J.; Ahmed, Mohamed

    2014-01-01

    Extracellular superoxide dismutase (EC-SOD) is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1%) for 10 days (H-KI) and compared to transgenic animals housed in room air (RA-KI), wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT). Overall brain metabolism evaluated by positron emission tomography (PET) showed that H-WT mice had significantly higher uptake of 18FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation. PMID:25268361

  4. Overexpression of extracellular superoxide dismutase protects against brain injury induced by chronic hypoxia.

    Directory of Open Access Journals (Sweden)

    Nahla Zaghloul

    Full Text Available Extracellular superoxide dismutase (EC-SOD is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1% for 10 days (H-KI and compared to transgenic animals housed in room air (RA-KI, wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT. Overall brain metabolism evaluated by positron emission tomography (PET showed that H-WT mice had significantly higher uptake of 18FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation.

  5. Programmed Cell Death in the Honey Bee (Apis mellifera) (Hymenoptera: Apidae) Worker Brain Induced by Imidacloprid.

    Science.gov (United States)

    Wu, Yan-Yan; Zhou, Ting; Wang, Qiang; Dai, Ping-Li; Xu, Shu-Fa; Jia, Hui-Ru; Wang, Xing

    2015-08-01

    Honey bees are at an unavoidable risk of exposure to neonicotinoid pesticides, which are used worldwide. Compared with the well-studied roles of these pesticides in nontarget site (including midgut, ovary, or salivary glands), little has been reported in the target sites, the brain. In the current study, laboratory-reared adult worker honey bees (Apis mellifera L.) were treated with sublethal doses of imidacloprid. Neuronal apoptosis was detected using the TUNEL technique for DNA labeling. We observed significantly increased apoptotic markers in dose- and time-dependent manners in brains of bees exposed to imidacloprid. Neuronal activated caspase-3 and mRNA levels of caspase-1, as detected by immunofluorescence and real-time quantitative PCR, respectively, were significantly increased, suggesting that sublethal doses of imidacloprid may induce the caspase-dependent apoptotic pathway. Additionally, the overlap of apoptosis and autophagy in neurons was confirmed by transmission electron microscopy. It further suggests that a relationship exists between neurotoxicity and behavioral changes induced by sublethal doses of imidacloprid, and that there is a need to determine reasonable limits for imidacloprid application in the field to protect pollinators.

  6. Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria.

    Science.gov (United States)

    Singh, Namrata; Hroudová, Jana; Fišar, Zdeněk

    2015-08-01

    The aim of this study was to investigate changes in the activity of individual mitochondrial respiratory chain complexes (I, II/III, IV) and citrate synthase induced by pharmacologically different cannabinoids. In vitro effects of selected cannabinoids on mitochondrial enzymes were measured in crude mitochondrial fraction isolated from pig brain. Both cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol, anandamide, and R-(+)-WIN55,212-2, and antagonist/inverse agonists of cannabinoid receptors, AM251, and cannabidiol were examined in pig brain mitochondria. Different effects of these cannabinoids on mitochondrial respiratory chain complexes and citrate synthase were found. Citrate synthase activity was decreased only by Δ(9)-tetrahydrocannabinol and AM251. Significant increase in the complex I activity was induced by anandamide. At micromolar concentration, all the tested cannabinoids inhibited the activity of electron transport chain complexes II/III and IV. Stimulatory effect of anandamide on activity of complex I may participate on distinct physiological effects of endocannabinoids compared to phytocannabinoids or synthetic cannabinoids. Common inhibitory effect of cannabinoids on activity of complex II/III and IV confirmed a non-receptor-mediated mechanism of cannabinoid action on individual components of system of oxidative phosphorylation.

  7. Changes induced by sodium cromoglycate in brain catecholamine turnover in morphine dependent and abstinent mice.

    Science.gov (United States)

    San-Martín-Clark, O; Cuéllar, B; De Alba, J; Leza, J C; Lorenzo, P

    1995-04-01

    The effects of sodium cromoglycate (CRO) were studied in relation to the metabolism of brain catecholamines: dopamine (DA) and noradrenaline (NA), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG). CRO was injected SC in control mice, morphine-tolerant mice (tolerance was induced by SC implantation of a 75 mg morphine pellet; CRO was administered on day 4 of addiction) and 30 min before abstinence (withdrawal was induced by SC injection of naloxone (1 mg/kg) on day 4 of addiction). Brain catecholamines and their metabolites were measured using high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD), for DA, NA, DOPAC and HVA, and coupled with fluorescence detection for MHPG. The ratios of DOPAC + HVA/DA and MHPG/NA were kept as an index of DA and NA turnovers, respectively. CRO administered 30 min before naloxone-precipitated withdrawal diminished significantly NA levels in frontal cortex. CRO increased DA turnover in striatum and frontal cortex in naive animals and significantly diminished DA levels in frontal cortex and DOPAC levels in frontal cortex and midbrain in morphine-dependent mice. These findings are discussed in relation to the protective effects of CRO on opiate withdrawal and the effects of CRO on locomotor activity.

  8. Imaging artifacts induced by electrical stimulation during conventional fMRI of the brain.

    Science.gov (United States)

    Antal, Andrea; Bikson, Marom; Datta, Abhishek; Lafon, Belen; Dechent, Peter; Parra, Lucas C; Paulus, Walter

    2014-01-15

    Functional magnetic resonance imaging (fMRI) of brain activation during transcranial electrical stimulation is used to provide insight into the mechanisms of neuromodulation and targeting of particular brain structures. However, the passage of current through the body may interfere with the concurrent detection of blood oxygen level-dependent (BOLD) signal, which is sensitive to local magnetic fields. To test whether these currents can affect concurrent fMRI recordings we performed conventional gradient echo-planar imaging (EPI) during transcranial direct current (tDCS) and alternating current stimulation (tACS) on two post-mortem subjects. tDCS induced signals in both superficial and deep structures. The signal was specific to the electrode montage, with the strongest signal near cerebrospinal fluid (CSF) and scalp. The direction of change relative to non-stimulation reversed with tDCS stimulation polarity. For tACS there was no net effect of the MRI signal. High-resolution individualized modeling of current flow and induced static magnetic fields suggested a strong coincidence of the change EPI signal with regions of large current density and magnetic fields. These initial results indicate that (1) fMRI studies of tDCS must consider this potentially confounding interference from current flow and (2) conventional MRI imaging protocols can be potentially used to measure current flow during transcranial electrical stimulation. The optimization of current measurement and artifact correction techniques, including consideration of the underlying physics, remains to be addressed.

  9. Protective effect of arjunolic acid against arsenic-induced oxidative stress in mouse brain.

    Science.gov (United States)

    Sinha, Mahua; Manna, Prasenjit; Sil, Parames C

    2008-02-01

    Arsenic, a notoriously poisonous metalloid, is ubiquitous in the environment, and it affects nearly all organ systems of animals including humans. The present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid against arsenic-induced oxidative damage in murine brain. Sodium arsenite was selected as a source of arsenic for this study. The free-radical-scavenging activity and the in vivo antioxidant power of arjunolic acid were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of sodium arsenite at a dose of 10 mg/kg body weight for 2 days significantly decreased the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase, the level of cellular metabolites, reduced glutathione, total thiols and increased the level of oxidized glutathione. In addition, it enhanced the levels of lipid peroxidation end products and protein carbonyl content. Treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days prior to arsenic administration almost normalized above indices. Histological findings due to arsenic intoxication and arjunolic acid treatment supported the other biochemical changes in murine brains. Results of 2,2-diphenyl-1-picryl hydrazyl radical scavenging and ferric reducing/antioxidant power assays clearly showed the in vitro radical scavenging as well as the in vivo antioxidant power of arjunolic acid, respectively. The effect of a well-established antioxidant, vitamin C, has been included in the study as a positive control. Combining all, results suggest that arjunolic acid possessed the ability to ameliorate arsenic-induced oxidative insult in murine brain and is probably due to its antioxidant activity.

  10. Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking.

    Science.gov (United States)

    Maggioli, E; McArthur, S; Mauro, C; Kieswich, J; Kusters, D H M; Reutelingsperger, C P M; Yaqoob, M; Solito, E

    2016-01-01

    Sex differences have been widely reported in neuroinflammatory disorders, focusing on the contributory role of estrogen. The microvascular endothelium of the brain is a critical component of the blood-brain barrier (BBB) and it is recognized as a major interface for communication between the periphery and the brain. As such, the cerebral capillary endothelium represents an important target for the peripheral estrogen neuroprotective functions, leading us to hypothesize that estrogen can limit BBB breakdown following the onset of peripheral inflammation. Comparison of male and female murine responses to peripheral LPS challenge revealed a short-term inflammation-induced deficit in BBB integrity in males that was not apparent in young females, but was notable in older, reproductively senescent females. Importantly, ovariectomy and hence estrogen loss recapitulated an aged phenotype in young females, which was reversible upon estradiol replacement. Using a well-established model of human cerebrovascular endothelial cells we investigated the effects of estradiol upon key barrier features, namely paracellular permeability, transendothelial electrical resistance, tight junction integrity and lymphocyte transmigration under basal and inflammatory conditions, modeled by treatment with TNFα and IFNγ. In all cases estradiol prevented inflammation-induced defects in barrier function, action mediated in large part through up-regulation of the central coordinator of tight junction integrity, annexin A1. The key role of this protein was then further confirmed in studies of human or murine annexin A1 genetic ablation models. Together, our data provide novel mechanisms for the protective effects of estrogen, and enhance our understanding of the beneficial role it plays in neurovascular/neuroimmune disease.

  11. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    Science.gov (United States)

    Ho, Yuen-Shan; Yang, Xifei; Yeung, Sze-Chun; Chiu, Kin; Lau, Chi-Fai; Tsang, Andrea Wing-Ting; Mak, Judith Choi-Wo; Chang, Raymond Chuen-Chung

    2012-01-01

    Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  12. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    Directory of Open Access Journals (Sweden)

    Yuen-Shan Ho

    Full Text Available Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD. To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  13. Asfixia perinatal e problemas cardíacos Perinatal asphyxia and heart problems

    Directory of Open Access Journals (Sweden)

    Gesmar Volga H. Herdy

    1998-08-01

    Full Text Available OBJETIVO: Avaliar a gravidade das complicações cardíacas na asfixia neonatal, sua evolução e correlacioná-las com o grau e duração do processo hipóxico. MÉTODOS: Foram estudados 90 bebês nos últimos 7 anos com grau de Apgar PURPOSE: To evaluate the severity of cardiac complications of neonatal asphyxia in relation to the length and degree of hipoxia. METHODS: Ninety babies with an Apgar score <6 were examined in the intensive care unit at our institution during seven years. Arterial blood for measuring pH, glucose, LDH and MB fraction of CK, together with serial electrocardiogram (ECG, echocardiogram and chest X rays was obtained. The fatal cases were studied with macro and microscopic examination. RESULTS: From a total of 90 cases, 73 were premature: 30 (41% appropriate for gestation age (AGA and 43 (59% small for gestation age (SGA. Twenty one (23% cases had arterial pH <7.2. The most common clinical conditions were: pneumonia 28 (31%, anemia 24 (26% and jaundice 12 (13%. The main cardiological findings were: systolic murmur in 46 (50%, signs of heart hypertrophy in 18 (20% and heart failure in 8 (9%. On ECG the main findings were ST and T abnormalities. The echocardiogram showed a patent ductus arteriosus (PDA in 20 (22%, tricuspid regurgitation in 6 (7%, pulmonary hypertension in 6 (7%, dyskinesia and ventricular dilatation in 4 (5%. Necropsy was performed in 23 cases and macro and microscopy obtained in 14; the most frequent findings were: myocite necrosis in 8 (54%, congestion, vacuolization and loss of striae in 4 (29%. CONCLUSION: In the majority of cases, patients had a benign course, even those presenting with severe acidemia. Many abnormal EKGs and echocardiograms became normal after a few weeks. Among those who had a fatal outcome, the severity of histological lesions was observed in babies who had suffered asphyxia for more prolonged periods.

  14. Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine CCL2 in the central nervous system

    DEFF Research Database (Denmark)

    Toft-Hansen, Henrik; Buist, Richard; Sun, Xue-Jun

    2006-01-01

    Inflammatory leukocytes infiltrate the CNS parenchyma in neuroinflammation. This involves cellular migration across various structures associated with the blood-brain barrier: the vascular endothelium, the glia limitans, and the perivascular space between them. Leukocytes accumulate spontaneously...... symptoms. Metalloproteinase (MPs) enzymes are implicated in leukocyte infiltration in neuroinflammation. Unmanipulated Tg mice had elevated expression of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-10, and -12 mRNA in the brain. PTx further induced expression of tissue inhibitor...

  15. Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain.

    Science.gov (United States)

    Guo, Chuang; Wang, Pu; Zhong, Man-Li; Wang, Tao; Huang, Xue-Shi; Li, Jia-Yi; Wang, Zhan-You

    2013-01-01

    Prior work has shown that iron interacts with hyperphosphorylated tau, which contributes to the formation of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD), whereas iron chelator desferrioxamine (DFO) slows down the clinical progression of the cognitive decline associated with this disease. However, the effects of DFO on tau phosphorylation in the presence or absence of iron have yet to be determined. Using amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mouse brain as a model system, we investigated the effects and potential mechanisms of intranasal administration of DFO on iron induced abnormal tau phosphorylation. High-dose iron treatment markedly increased the levels of tau phosphorylation at the sites of Thr205, Thr231 and Ser396, whereas highly induced tau phosphorylation was abolished by intranasal administration of DFO in APP/PS1 transgenic mice. Moreover, DFO intranasal administration also decreases Fe-induced the activities of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β), which in turn suppressing tau phosphorylation. Cumulatively, our data show that intranasal DFO treatment exerts its suppressive effects on iron induced tau phosphorylation via CDK5 and GSK3β pathways. More importantly, elucidation of DFO mechanism in suppressing tau phosphorylation may provide insights for developing therapeutic strategies to combat AD.

  16. Subcutaneous fat necrosis in neonates with hypoxic ischaemic encephalopathy registered in the Swiss National Asphyxia and Cooling Register

    OpenAIRE

    Grass, Beate; Weibel, Lisa; Hagmann, Cornelia; Brotschi, Barbara

    2015-01-01

    Background Neonates with hypoxic ischaemic encephalopathy (HIE) are routinely treated with therapeutic hypothermia (TH) for 72 h in order to improve neurological outcome. Subcutaneous fat necrosis (SCFN) is an adverse event occurring in neonates with HIE. Methods We analyzed risk factors for SCFN regarding demographic factors, cooling methods and deviation from target temperature range during hypothermia therapy. Data of all neonates registered in the National Asphyxia and Cooling Register in...

  17. Clinical significance of blood gas and electrolyte analysis, CK, CK-MB and HBDH changes in neonatal asphyxia

    Institute of Scientific and Technical Information of China (English)

    Bao-Hua Xu; Xin Lin; Mi-Jia Huang

    2016-01-01

    Objective:To investigate the clinical significance of blood gas and electrolyte analysis, CK, CK-MB and HBDH changes in neonatal asphyxia.Methods:A total of 100 newborns with asphyxia who visited in our hospital were collected, and divided into severe group (n=20) and mild group (n=80) according to the asphyxia degree, and 50 healthy newborns regarded as control group. The 3 groups received blood gas analysis (pH, BE and PaCO2), electrolyte (K+, Na+ and Ca2+) and 3 kinds of enzymes (CK, CK-MB and HBDH) were tested and compared.Results: Compared with control group, pH and BE of blood gas indexes decreased significantly and PaCO2 increased significantly in severe group (P0.05). Compared with mild group, pH and BE of blood gas indexes decreased significantly and PaCO2 increased significantly in severe group (P0.05). Compared with mild group, the level of Ca2+ decreased significantly in severe group (P<0.05); Compared with control group, the levels of CK, CK-MB and HBDH increased significantly in severe and mild group (P<0.05). Compared with mild group, the levels of CK, CK-MB and HBDH increased significantly in severe group (P<0.05).Conclusions:The detection of blood gas and electrolyte analysis, CK, CK-MB and HBDH can provide an objective evidence for the diagnosis of neonatal asphyxia and estimation of severity degree which was helpful in clinical treatment.

  18. Biliverdin Reductase-A correlates with inducible nitric oxide synthasein in atorvastatin treated aged canine brain

    Institute of Scientific and Technical Information of China (English)

    Fabio Di Domenico; Marzia Perluigi; Eugenio Barone

    2013-01-01

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are stil unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cel ular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/tyrosine kinase activity is able to modulate cel signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebel um and liver of the same animals. We demonstrated that atorvastatin treatment (80 mg/day for 14.5 months) to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebel um. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as wel as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not

  19. Induced Currents in a Rat's Brain due a Radio Frequency Fields: Numerical Simulation with a Pixel Model

    Science.gov (United States)

    Rojas, R.; Garcia, R. D.; Rodríguez, A. O.

    2008-08-01

    The increasing use of high fields in Magnetic Resonance Systems poses new challenges for their operation within safety limits. At high frequencies, electromagnetic fields induce current densities that may damage the organs to be imaged. These eddy currents are transformed in heat via the Joule's effect causing possible severe damage in tissues and organs. The electric field effects in a rat's brain were studied from numerically computed induced currents using a pixel-based model. Numerical simulations were calculated solving the Maxwell's equations with a Finite Element Method for a circular-shaped coil and the pixel model of a rat's brain. Simulations of the electric field were computed and graphically displayed as bi-dimensional transversal images. Profiles of current density as a function of position for four different frequencies were computed from the simulations. An increment of the induced currents can be appreciates at the surface of the brain, and it vanished towards the centre.

  20. RESVERATROL PRECONDITIONING INDUCES A NOVEL EXTENDED WINDOW OF ISCHEMIC TOLERANCE IN THE MOUSE BRAIN

    Science.gov (United States)

    Koronowski, Kevin B.; Dave, Kunjan R.; Saul, Isabel; Camarena, Vladimir; Thompson, John W.; Neumann, Jake T.; Young, Juan I.; Perez-Pinzon, Miguel A.

    2015-01-01

    Background and Purpose Prophylactic treatments that afford neuroprotection against stroke may emerge from the field of preconditioning. Resveratrol mimics ischemic preconditioning, reducing ischemic brain injury when administered two days prior to global ischemia in rats. This protection is linked to Sirt1 and enhanced mitochondrial function possibly through its repression of UCP2. BDNF is another neuroprotective protein associated with Sirt1. In this study we sought to identify the conditions of resveratrol preconditioning (RPC) that most robustly induce neuroprotection against focal ischemia in mice. Methods We tested four different RPC paradigms against a middle cerebral artery occlusion (MCAo) model of stroke. Infarct volume and neurological score were calculated 24 hours following MCAo. Sirt1-chromatin binding was evaluated by ChIP-qPCR. Percoll gradients were used to isolate synaptic fractions and changes in protein expression were determined via Western blot analysis. BDNF concentration was measured using a BDNF-specific ELISA assay. Results While repetitive RPC induced neuroprotection from MCAo, strikingly one application of RPC 14 days prior to MCAo showed the most robust protection, reducing infarct volume by 33% and improving neurological score by 28%. Fourteen days following RPC, Sirt1 protein was increased 1.5 fold and differentially bound to the UCP2 and BDNF promoter regions. Accordingly, synaptic UCP2 protein decreased by 23% and cortical BDNF concentration increased 26%. Conclusions RPC induces a novel extended window of ischemic tolerance in the brain that lasts for at least 14 days. Our data suggest that this tolerance may be mediated by Sirt1, through upregulation of BDNF and downregulation of UCP2. PMID:26159789

  1. A Novel Preclinical Model of Moderate Primary Blast-Induced Traumatic Brain Injury.

    Science.gov (United States)

    Divani, Afshin A; Murphy, Amanda J; Meints, Joyce; Sadeghi-Bazargani, Homayoun; Nordberg, Jessica; Monga, Manoj; Low, Walter C; Bhatia, Prerana M; Beilman, Greg J; SantaCruz, Karen S

    2015-07-15

    Blast-induced traumatic brain injury (bTBI) is the "signature" injury of the recent Iraq and Afghanistan wars. Here, we present a novel method to induce bTBI using shock wave (SW) lithotripsy. Using a lithotripsy machine, Wistar rats (N = 70; 408.3 ± 93 g) received five SW pulses to the right side of the frontal cortex at 24 kV and a frequency of 60 Hz. Animals were then randomly divided into three study endpoints: 24 h (n = 25), 72 h (n = 19) and 168 h (n = 26). Neurological and behavioral assessments (Garcia's test, beam walking, Rotarod, and elevated plus maze) were performed at the baseline, and further assessments followed at 3, 6, 24, 72, and 168 h post-injury, if applicable. We performed digital subtraction angiography (DSA) to assess presence of cerebral vasospasm due to induced bTBI. Damage to brain tissue was assessed by an overall histological severity (OHS) score based on depth of injury, area of hemorrhage, and extent of axonal injury. Except for beam walking, OHS was significantly correlated with the other three outcome measures with at least one of their assessments during the first 6 h after the experiment. OHS manifested the highest absolute correlation coefficients with anxiety at the baseline and 6 h post-injury (r(baseline) = -0.75, r(6hrs) = 0.85; p<0.05). Median hemispheric differences for contrast peak values (obtained from DSA studies) for 24, 72, and 168 h endpoints were 3.45%, 3.05% and 0.2%, respectively, with statistically significant differences at 1 versus 7 d (p<0.05) and 3 versus 7 d (p<0.01). In this study, we successfully established a preclinical rat model of bTBI with characteristics similar to those observed in clinical cases. This new method may be useful for future investigations aimed at understanding bTBI pathophysiology.

  2. Blocking brain-derived neurotrophic factor inhibits injury-induced hyperexcitability of hippocampal CA3 neurons.

    Science.gov (United States)

    Gill, Raminder; Chang, Philip K-Y; Prenosil, George A; Deane, Emily C; McKinney, Rebecca A

    2013-12-01

    Brain trauma can disrupt synaptic connections, and this in turn can prompt axons to sprout and form new connections. If these new axonal connections are aberrant, hyperexcitability can result. It has been shown that ablating tropomyosin-related kinase B (TrkB), a receptor for brain-derived neurotrophic factor (BDNF), can reduce axonal sprouting after hippocampal injury. However, it is unknown whether inhibiting BDNF-mediated axonal sprouting will reduce hyperexcitability. Given this, our purpose here was to determine whether pharmacologically blocking BDNF inhibits hyperexcitability after injury-induced axonal sprouting in the hippocampus. To induce injury, we made Schaffer collateral lesions in organotypic hippocampal slice cultures. As reported by others, we observed a 50% reduction in axonal sprouting in cultures treated with a BDNF blocker (TrkB-Fc) 14 days after injury. Furthermore, lesioned cultures treated with TrkB-Fc were less hyperexcitable than lesioned untreated cultures. Using electrophysiology, we observed a two-fold decrease in the number of CA3 neurons that showed bursting responses after lesion with TrkB-Fc treatment, whereas we found no change in intrinsic neuronal firing properties. Finally, evoked field excitatory postsynaptic potential recordings indicated an increase in network activity within area CA3 after lesion, which was prevented with chronic TrkB-Fc treatment. Taken together, our results demonstrate that blocking BDNF attenuates injury-induced hyperexcitability of hippocampal CA3 neurons. Axonal sprouting has been found in patients with post-traumatic epilepsy. Therefore, our data suggest that blocking the BDNF-TrkB signaling cascade shortly after injury may be a potential therapeutic target for the treatment of post-traumatic epilepsy.

  3. 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.

  4. Cigarette smoking induces heat shock protein 70 kDa expression and apoptosis in rat brain: Modulation by bacoside A.

    Science.gov (United States)

    Anbarasi, K; Kathirvel, G; Vani, G; Jayaraman, G; Shyamala Devi, C S

    2006-01-01

    Cigarette smoking is associated with the development of several diseases and antioxidants play a major role in the prevention of smoking-related diseases. Apoptosis is suggested as a possible contributing factor in the pathogenesis of smoking-induced toxicity. Therefore the present study was designed to investigate the influence of chronic cigarette smoke exposure on apoptosis and the modulatory effect of bacoside A (triterpenoid saponin isolated from the plant Bacopa monniera) on smoking-induced apoptosis in rat brain. Adult male albino rats of Wistar strain were exposed to cigarette smoke and simultaneously administered with bacoside A (10 mg/kg b.w./day, orally) for a period of 12 weeks. Expression of brain hsp70 was analyzed by Western blotting. Apoptosis was identified by DNA fragmentation, terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick end labeling (TUNEL) staining and transmission electron microscopy. The results showed that exposure to cigarette smoke induced hsp70 expression and apoptosis as characterized by DNA laddering, increased TUNEL-positive cells and ultrastructural apoptotic features in the brain. Administration of bacoside A prevented expression of hsp70 and neuronal apoptosis during cigarette smoking. We speculate that apoptosis may be responsible for the smoking-induced brain damage and bacoside A can protect the brain from the toxic effects of cigarette smoking.

  5. A STUDY OF EFFECT OF PERINATAL ASPHYXIA ON THYROID HORMONE IN NEONATES

    Directory of Open Access Journals (Sweden)

    Rajesh

    2015-08-01

    Full Text Available AIMS AND OBJECTIVE: To study the effect of perinatal asphyxia on thyroid hormones of term neonates . MATERIAL AND METHOD S : It was a prospective case control study and it was conducted in department of pediatrics, Kamala Nehru Hospital Gandhi Medical College, Bhopal. Total 60 full term neonates who have completed 37 wks of gestation at birth included in study, 30 asphyxiated newborn taken as cases and 30 healthy neonates as control. For inclusion of cases criteria was, 1 and 5 minute APGAR score 7 and no sepsis setting. Classification of HIE done on the bases of Sarnat and Sarnat staging. Blood samples were collected for determination of thyroid profile (T 4, T 3 and TSH, first within 6 hours of birth and seconds 18 to 24hour of age. RESULT: Out of 30 cases, 13.13% were HIE - I, 50% were HIE - II and 36.67% were HIE - III. Mean value of TSH was low at 6 hours as well as at 18 - 24 hours between case and control group while mean value of T 3 andT 4 were low at only 18 - 24hrs of a ge. CONCLUSION : The mean T 3, T 4 and TSH levels at birth of asphyxiated newborn was significantly lower than the control group at 18 - 24 hours . Due to low TSH surge, asphyxiated babies could not increase their T 3 and T 4 level significantly

  6. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

    Directory of Open Access Journals (Sweden)

    Shotaro Michinaga

    Full Text Available Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice. Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV administration of BQ788 (ETB antagonist, IRL-2500 (ETB antagonist, or FR139317 (ETA antagonist prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

  7. Origin and timing of brain lesions in term infants with neonatal encephalopathy

    NARCIS (Netherlands)

    Cowan, F; Rutherford, M; Groenendaal, F; Eken, P; Mercuri, E; Bydder, GM; Meiners, LC; Dubowitz, LMS; de Vries, LS

    2003-01-01

    Background The role of intrapartum asphyxia in neonatal encephalopathy and seizures in term infants is not clear, and antenatal factors are being implicated in the causal pathway for these disorders. However, there is no evidence that brain damage occurs before birth. We aimed to test the hypothesis

  8. Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats.

    Science.gov (United States)

    Shiha, Ahmed Anis; de Cristóbal, Javier; Delgado, Mercedes; Fernández de la Rosa, Rubén; Bascuñana, Pablo; Pozo, Miguel A; García-García, Luis

    2015-02-01

    The role of serotonin (5-hydroxytryptamine; 5-HT) in epileptogenesis still remains controversial. In this regard, it has been reported that serotonergic drugs can alter epileptogenesis in opposite ways. The main objective of this work was to investigate the effect of the selective 5-HT selective reuptake inhibitor (SSRI) fluoxetine administered subacutely (10mg/kg/day×7 days) on the eventual metabolic impairment induced by the lithium-pilocarpine model of epilepsy in rats. In vivo 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F] FDG) positron emission tomography (PET) was performed to assess the brain glucose metabolic activity on days 3 and 30 after the insult. In addition, at the end of the experiment (day 33), several histochemical and neurochemical assessments were performed for checking the neuronal functioning and integrity. Three days after the insult, a marked reduction of [(18)F] FDG uptake (about 30% according to the brain region) was found in all brain areas studied. When evaluated on day 30, although a hypometabolism tendency was observed, no statistically significant reduction was present in any region analyzed. In addition, lithium-pilocarpine administration was associated with medium-term hippocampal and cortical damage, since it induced neurodegeneration, glial activation and augmented caspase-9 expression. Regarding the effect of fluoxetine, subacute treatment with this SSRI did not significantly reduce the mortality rate observed after pilocarpine-induced seizures. However, fluoxetine did prevent not only the short-term metabolic impairment, but also the aforementioned signs of neuronal damage in surviving animals to lithium-pilocarpine protocol. Finally, fluoxetine increased the density of GABAA receptor both at the level of the dentate gyrus and CA1-CA2 regions in pilocarpine-treated animals. Overall, our data suggest a protective role for fluoxetine against pilocarpine-induced brain damage. Moreover, this action may be associated with an increase of

  9. Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced and splicing changes that classify brain region transcriptomes

    Directory of Open Access Journals (Sweden)

    Lilach eSoreq

    2013-05-01

    Full Text Available MicroRNAs (miRNAs are key post transcriptional regulators of their multiple target genes. However, the detailed profile of miRNA expression in Parkinson's disease, the second most common neurodegenerative disease worldwide and the first motor disorder has not been charted yet. Here, we report comprehensive miRNA profiling by next-generation small-RNA sequencing, combined with targets inspection by splice-junction and exon arrays interrogating leukocyte RNA in Parkinson’s disease patients before and after deep brain stimulation (DBS treatment and of matched healthy control volunteers (HC. RNA-Seq analysis identified 254 miRNAs and 79 passenger strand forms as expressed in blood leukocytes, 16 of which were modified in patients pre treatment as compared to HC. 11 miRNAs were modified following brain stimulation, 5 of which were changed inversely to the disease induced changes. Stimulation cessation further induced changes in 11 miRNAs. Transcript isoform abundance analysis yielded 332 changed isoforms in patients compared to HC, which classified brain transcriptomes of 47 PD and control independent microarrays. Functional enrichment analysis highlighted mitochondrion organization. DBS induced 155 splice changes, enriched in ubiquitin homeostasis. Cellular composition analysis revealed immune cell activity pre and post treatment. Overall, 217 disease and 74 treatment alternative isoforms were predictably targeted by modified miRNAs within both 3’ and 5’ untranslated ends and coding sequence sites. The stimulation-induced network sustained 4 miRNAs and 7 transcripts of the disease network. We believe that the presented dynamic networks provide a novel avenue for identifying disease and treatment-related therapeutic targets. Furthermore, the identification of these networks is a major step forward in the road for understanding the molecular basis for neurological and neurodegenerative diseases and assessment of the impact of brain stimulation

  10. Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

    DEFF Research Database (Denmark)

    Penkowa, M; Molinero, A; Carrasco, J

    2001-01-01

    , and caused a significant mortality (62%) only in the latter mice, indicating that interleukin-6 deficiency increased the susceptibility to kainic acid-induced brain damage. To compare the histopathological damage caused to the brain, control and interleukin-6 null mice were administered 8.75mg/kg kainic acid...... morphological hippocampal damage, oxidative stress and apoptotic neuronal death were increased. Since metallothionein-I+II levels were lower, and those of inducible nitric oxide synthase higher, these concomitant changes are likely to contribute to the observed increased oxidative stress and neuronal death...

  11. Brain Research to Ameliorate Impaired Neurodevelopment - Home-based Intervention Trial (BRAIN-HIT

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    Mahantshetti Niranjana S

    2010-04-01

    Full Text Available Abstract Background This randomized controlled trial aims to evaluate the effects of an early developmental intervention program on the development of young children in low- and low-middle-income countries who are at risk for neurodevelopmental disability because of birth asphyxia. A group of children without perinatal complications are evaluated in the same protocol to compare the effects of early developmental intervention in healthy infants in the same communities. Birth asphyxia is the leading specific cause of neonatal mortality in low- and low-middle-income countries and is also the main cause of neonatal and long-term morbidity including mental retardation, cerebral palsy, and other neurodevelopmental disorders. Mortality and morbidity from birth asphyxia disproportionately affect more infants in low- and low-middle-income countries, particularly those from the lowest socioeconomic groups. There is evidence that relatively inexpensive programs of early developmental intervention, delivered during home visit by parent trainers, are capable of improving neurodevelopment in infants following brain insult due to birth asphyxia. Methods/Design This trial is a block-randomized controlled trial that has enrolled 174 children with birth asphyxia and 257 without perinatal complications, comparing early developmental intervention plus health and safety counseling to the control intervention receiving health and safety counseling only, in sites in India, Pakistan, and Zambia. The interventions are delivered in home visits every two weeks by parent trainers from 2 weeks after birth until age 36 months. The primary outcome of the trial is cognitive development, and secondary outcomes include social-emotional and motor development. Child, parent, and family characteristics and number of home visits completed are evaluated as moderating factors. Discussion The trial is supervised by a trial steering committee, and an independent data monitoring

  12. Over-expression of Slit2 induces vessel formation and changes blood vessel permeability in mouse brain

    Institute of Scientific and Technical Information of China (English)

    Hai-xiong HAN; Jian-guo GENG

    2011-01-01

    Aim:To investigate the effect of the axon guidance cue Slit2 on the density of blood vessels and permeability of the blood-brain barrier in mouse brain.Methods:hSlit2 transgenic mouse line was constructed,and the phenotypes of the mice were compared with wild-type mice in respect to the lateral ventricle (LV),ventricle pressure,and the choroids plexus.An in vivo Miles permeability assay and an amyloid-β permeability assay were used to assess the permeability of brain blood vessels.Brain vessel casting and intracerebral hemorrhage models were built to investigate vessel density in the transgenic mice.An in vitro permeability assay was used to test whether Slit2 could change the permeability and tight junctions of blood vessel endothelial cells.Results:Hydrocephalus occurred in some transgenic mice,and a significantly larger lateral ventricle area and significantly higher ventricle pressure were observed in the transgenic mice.The transgenic mice displayed changed construction of the choroids plexus,which had more micro vessels,dilated vessels,gaps between epithelial cells and endothelial cells than wild-type mice.Slit2 significantly increased brain vessel density and the permeability of brain vessels to large molecules.These blood vessels were more sensitive to cues that induce brain hemorrhage.At the cellular level,Slit2 disturbed the integrity of tight junctions in blood vessel endothelial cells and improved the permeability of the endothelial cell layer.Thus,it promoted the entry of amyloid-β peptides from the serum into the central nervous system,where they bound to neurons.Conclusion:Slit2 increases vessel density and permeability in the brains of transgenic mice.Thus,Slit2 induces numerous changes in brain vessels and the barrier system.

  13. Monocrotophos induces the expression and activity of xenobiotic metabolizing enzymes in pre-sensitized cultured human brain cells.

    Science.gov (United States)

    Tripathi, Vinay K; Kumar, Vivek; Singh, Abhishek K; Kashyap, Mahendra P; Jahan, Sadaf; Pandey, Ankita; Alam, Sarfaraz; Khan, Feroz; Khanna, Vinay K; Yadav, Sanjay; Lohani, Mohtshim; Pant, Aditya B

    2014-01-01

    The expression and metabolic profile of cytochrome P450s (CYPs) is largely missing in human brain due to non-availability of brain tissue. We attempted to address the issue by using human brain neuronal (SH-SY5Y) and glial (U373-MG) cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC), cyclophosphamide (CPA), ethanol and known neurotoxicant- monocrotophos (MCP), a widely used organophosphorous pesticide. Both the cells show significant induction in the expression and CYP-specific activity against classical inducers and MCP. The induction level of CYPs was comparatively lower in MCP exposed cells than cells exposed to classical inducers. Pre-exposure (12 h) of cells to classical inducers significantly added the MCP induced CYPs expression and activity. The findings were concurrent with protein ligand docking studies, which show a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown significantly high docking scores with all the three studied CYP regulators. The expression of CYPs in neuronal and glial cells has suggested their possible association with the endogenous physiology of the brain. The findings also suggest the xenobiotic metabolizing capabilities of these cells against MCP, if received a pre-sensitization to trigger the xenobiotic metabolizing machinery. MCP induced CYP-specific activity in neuronal cells could help in explaining its effect on neurotransmission, as these CYPs are known to involve in the synthesis/transport of the neurotransmitters. The induction of CYPs in glial cells is also of significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The data provide better understanding of the metabolizing capability of the human brain cells against xenobiotics.

  14. Monocrotophos induces the expression and activity of xenobiotic metabolizing enzymes in pre-sensitized cultured human brain cells.

    Directory of Open Access Journals (Sweden)

    Vinay K Tripathi

    Full Text Available The expression and metabolic profile of cytochrome P450s (CYPs is largely missing in human brain due to non-availability of brain tissue. We attempted to address the issue by using human brain neuronal (SH-SY5Y and glial (U373-MG cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC, cyclophosphamide (CPA, ethanol and known neurotoxicant- monocrotophos (MCP, a widely used organophosphorous pesticide. Both the cells show significant induction in the expression and CYP-specific activity against classical inducers and MCP. The induction level of CYPs was comparatively lower in MCP exposed cells than cells exposed to classical inducers. Pre-exposure (12 h of cells to classical inducers significantly added the MCP induced CYPs expression and activity. The findings were concurrent with protein ligand docking studies, which show a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown significantly high docking scores with all the three studied CYP regulators. The expression of CYPs in neuronal and glial cells has suggested their possible association with the endogenous physiology of the brain. The findings also suggest the xenobiotic metabolizing capabilities of these cells against MCP, if received a pre-sensitization to trigger the xenobiotic metabolizing machinery. MCP induced CYP-specific activity in neuronal cells could help in explaining its effect on neurotransmission, as these CYPs are known to involve in the synthesis/transport of the neurotransmitters. The induction of CYPs in glial cells is also of significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The data provide better understanding of the metabolizing capability of the human brain cells against

  15. Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine.

    Science.gov (United States)

    Abdel-Salam, Omar M E; El-Sayed El-Shamarka, Marwa; Salem, Neveen A; El-Mosallamy, Aliaa E M K; Sleem, Amany A

    2012-01-01

    Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms and impaired memory, owing to blockade of striatal dopamine D2 receptors. Cinnarizine is a calcium channel blocker with D2 receptor blocking properties which is widely used in treatment of vertiginous disorders. The present study aimed to see whether cinnarizine would worsen the effect of haloperidol on memory function and on oxidative stress in mice brain. Cinnarizine (5, 10 or 20 mg/kg), haloperidol, or haloperidol combined with cinnarizine was administered daily via the subcutaneous route and mice were examined on weekly basis for their ability to locate a submerged plate in the water maze test. Mice were euthanized 30 days after starting drug injection. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) were determined in brain. Haloperidol substantially impaired water maze performance. The mean time taken to find the escape platform (latency) was significantly delayed by haloperidol (2 mg/kg, i.p.) on weeks 1-8 of the test, compared with saline control group. In contrast, those treated with haloperidol and cinnarizine showed significantly shorter latencies, which indicated that learning had occurred immediately. Haloperidol resulted in increased MDA in cortex, striatum, cerebellum and midbrain. GSH decreased in cortex, striatum and cerebellum and nitric oxide increased in cortex. Meanwhile, treatment with cinnarizine (20 mg/kg) and haloperidol resulted in significant decrease in MDA cortex, striatum, cerebellum and midbrain and an increase in GSH in cortex and striatum, compared with haloperidol group. These data suggest that cinnarizine improves the haloperidol induced brain oxidative stress and impairment of learning and memory in the water maze test in mice.

  16. CB1 cannabinoid receptors are involved in neuroleptic-induced enhancement of brain neurotensin

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    Parichehr Hassanzadeh

    2014-03-01

    Full Text Available Objective(s: Targeting the neuropeptide systems has been shown to be useful for the development of more effective antipsychotic drugs. Neurotensin, an endogenous neuropeptide, appears to be involved in the mechanism of action of antipsychotics. However, the available data provide conflicting results and the mechanism(s by which antipsychotics affect brain neurotensin neurotransmission have not been identified. Therefore, we aimed to investigate the effects of fluphenazine and amisulpride on brain regional contents of neurotensin considering the role of cannabinoid CB1 receptors which interact with neurotensin neurotransmission. Materials and Methods:Fluphenazine (0.5, 1, and 3 mg/kg or amisulpride (3, 5, and 10 mg/kg were administered intraperitoneally to male Wistar rats either for one day or 28 consecutive days.Twenty four hours after the last injection of drug or vehicle, neurotensin contents were determined in the mesocorticolimbic and nigrostriatal dopamine regions by radioimmunoassay. In the case of any significant change, the effect of pre-treatment with CB1 receptor antagonist, AM251 was investigated. Results:Chronic, but not acute, treatment with the highest dose of fluphenazine or amisulpride resulted in significant enhancement of neurotensin contents in the prefronatal cortex and nucleus accumbens. Fluphenazine also elevated neurotensin levels in the anterior and posterior caudate nuclei and substantia nigra. Neither amisulpride nor fluphenazine affected neurotensin contents in the amygdala or hippocampus. Pre-treatment with AM251 (3 mg/kg prevented the neuroleptic-induced elevation of neurotensin. AM251 showed no effect by itself. Conclusion:The brain neurotensin under the regulatory action of CB1 receptors is involved in[T1]  the effects of amisulpride and fluphenazine.

  17. Establishment of a blunt impact-induced brain injury model in rabbits

    Institute of Scientific and Technical Information of China (English)

    LI Kui; CAO Yun-xing; YANG Yong-qiang; YIN Zhi-yong; ZHAO Hui; WANG Li-jun

    2012-01-01

    Objective: To establish an animal model to replicate the blunt impact brain injury in forensic medicine.Methods:Twenty-four New Zealand white rabbits were randomly divided into control group (n=4),minor injury group (n=10) and severe injury group (n=10).Based on the BIM- Ⅱ Horizontal Bio-impact Machine,self-designed iron bar was used to produce blunt brain injury.Two rabbits from each injury group were randomly selected to monitor the change ofintracranial pressure (ICP) during the impacting process by pressure microsensors.Six hours after injury,all the rabbits were dissected to observe the injury morphology and underwent routine pathological examination.Results: Varying degrees of nervous system positive signs were observed in all the injured rabbits.Within 6 hours,the mortality rate was 1/10 in the minor injury group and 6/10 in the severe injury group.Morphological changes consisted of different levels of scalp hematoma,skull fracture,epiduraI hematoma,subdural hematoma,subarachnoid hemorrhage and brain injury.At the moment of hitting,the ICP was greater in severe injury group than in mild injury group; and within the same group,the impact side showed positive pressure while the opposite side showed negative pressure.Conclusions:Under the rigidly-controlled experimental condition,this animal model has a good reproducibility and stable results.Meanwhile,it is able to simulate the morphology of iron strike-induced injury,thus can be used to study the mechanism of blunt head injury in forensic medicine.

  18. Rice From Mercury Contaminated Areas in Guizhou Province Induces c-jun Expression in Rat Brain

    Institute of Scientific and Technical Information of China (English)

    JIN-PING CHENG; WEN-HUA WANG; LI-YA QU; JIN-PING JIA; MIN ZHENG; XIU-LING JI; TAO YUAN

    2005-01-01

    Objective Mercury (Hg), as one of the priority pollutants and also a hot topic of frontier environmental research in many countries, has been paid higher attention in the world since the middle of the last century. Guizhou Province (at N24°30′-29°13′, E103°1′-109°30′, 1 100 m above the sea level, with subtropical humid climate) in southwest China is an important mercury production center. It has been found that the mercury content in most media of aquatics, soil, atmosphere and in biomass of corns, plants and animals, is higher than the national standard.The present study aims to explore the influence of mercury pollution on the health of local citizens. Methods The effect of rice from two mercury polluted experimental plots of Guizhou Province on the expression of c-jun mRNA in rat brain and c-jun protein in cortex, hippocampus and ependyma was observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. Results The results showed that the mercury polluted rice induced expression of c-jun mRNA and its protein significantly. Selenium can reduce Hg uptake, an antagonism between selenium and mercury on the expression of c-jun mRNA and c-jun protein. Conclusion c-jun participates in the toxicity process of brain injury by mercury polluted rice, the expression of c- jun mRNA in brain, and c-jun protein in rat cortex and hippocampus can predict neurotoxicity of mercury polluted rice. People should be advised to be cautious in eating any kind of Hg-polluted foods. To reveal the relationship between c-jun induction and apoptosis, further examinations are required.

  19. Hyperthermia-induced disruption of functional connectivity in the human brain network.

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    Gang Sun

    Full Text Available BACKGROUND: Passive hyperthermia is a potential risk factor to human cognitive performance and work behavior in many extreme work environments. Previous studies have demonstrated significant effects of passive hyperthermia on human cognitive performance and work behavior. However, there is a lack of a clear understanding of the exact affected brain regions and inter-regional connectivities. METHODOLOGY AND PRINCIPAL FINDINGS: We simulated 1 hour environmental heat exposure to thirty-six participants under two environmental temperature conditions (25 °C and 50 °C, and collected resting-state functional brain activity. The functional connectivities with a preselected region of interest (ROI in the posterior cingulate cortex and precuneus (PCC/PCu, furthermore, inter-regional connectivities throughout the entire brain using a prior Anatomical Automatic Labeling (AAL atlas were calculated. We identified decreased correlations of a set of regions with the PCC/PCu, including the medial orbitofrontal cortex (mOFC and bilateral medial temporal cortex, as well as increased correlations with the partial orbitofrontal cortex particularly in the bilateral orbital superior frontal gyrus. Compared with the normal control (NC group, the hyperthermia (HT group showed 65 disturbed functional connectivities with 50 of them being decreased and 15 of them being increased. While the decreased correlations mainly involved with the mOFC, temporal lobe and occipital lobe, increased correlations were mainly located within the limbic system. In consideration of physiological system changes, we explored the correlations of the number of significantly altered inter-regional connectivities with differential rectal temperatures and weight loss, but failed to obtain significant correlations. More importantly, during the attention network test (ANT we found that the number of significantly altered functional connectivities was positively correlated with an increase in

  20. Herpes Virus Entry Mediator Signaling in the Brain Is Imperative in Acute Inflammation-Induced Anorexia and Body Weight Loss

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    Kwang Kon Kim

    2013-09-01

    Full Text Available BackgroundReduced appetite and body weight loss are typical symptoms of inflammatory diseases. A number of inflammatory stimuli are responsible for the imbalance in energy homeostasis, leading to metabolic disorders. The herpes virus entry mediator (HVEM protein plays an important role in the development of various inflammatory diseases, such as intestinal inflammation and diet-induced obesity. However, the role of HVEM in the brain is largely unknown. This study aims to investigate whether HVEM signaling in the brain is involved in inflammation-induced anorexia and body weight loss.MethodsFood intake and body weight were measured at 24 hours after intraperitoneal injection of lipopolysaccharide (LPS or intracerebroventricular injection of recombinant mouse LIGHT (also called tumor necrosis factor receptor superfamily 14, TNFSF14, an HVEM ligand, into 8- to 10-week-old male C57BL/6 mice and mice lacking HVEM expression (HVEM-/-. We also assessed LPS-induced change in hypothalamic expression of HVEM using immunohistochemistry.ResultsAdministration of LPS significantly reduced food intake and body weight, and moreover, increased expression of HVEM in the hypothalamic arcuate nucleus. However, LPS induced only minor decreases in food intake and body weight in HVEM-/- mice. Administration of LIGHT into the brain was very effective at decreasing food intake and body weight in wild-type mice, but was less effective in HVEM-/- mice.ConclusionActivation of brain HVEM signaling is responsible for inflammation-induced anorexia and body weight loss.

  1. Continuous infusion of proinflammatory cytokines into the brain to study brain cytokine induced local and systemic immune effects.

    Science.gov (United States)

    Schöning, B; Elepfandt, P; Lanksch, W R; Volk, H D; Woiciechowsky, C

    1999-07-01

    Proinflammatory cytokines are produced in the brain after various kinds of insult (ischemia, trauma, infection). In this process interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha are most important. These cytokines are key mediators of inflammation. Furthermore, these cytokines can act as neurotransmitters and develop direct effects on the central nervous system (CNS) including fever, sleep and stimulation of the neuroendocrine as well as sympathetic nervous system. Moreover, IL-1beta and TNF-alpha may also be involved in brain repair and regenerating processes. However, most of the data about the role of cytokines in the brain have been obtained from either in vitro studies or bolus injections into the brain parenchyma or cerebroventricular system. On the other hand, it is known that cytokines are released continuously into the brain after a cerebral insult over a period of 24 to 48 h. In order to further complete the knowledge about the interactions between neural and immune cells to overcome the primary insult and initiate repair and regeneration in the CNS, a new animal model of local inflammation reaction was established using chronic intracerebral infusion of rat recombinant cytokines.

  2. Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders.

    Science.gov (United States)

    Meng, Qingying; Zhuang, Yumei; Ying, Zhe; Agrawal, Rahul; Yang, Xia; Gomez-Pinilla, Fernando

    2017-02-01

    The complexity of the traumatic brain injury (TBI) pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing), and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.

  3. Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Qingying Meng

    2017-02-01

    Full Text Available The complexity of the traumatic brain injury (TBI pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing, and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.

  4. Human Umbilical Cord Blood Cells Restore Brain Damage Induced Changes in Rat Somatosensory Cortex

    Science.gov (United States)

    Geißler, Maren; Dinse, Hubert R.; Neuhoff, Sandra; Kreikemeier, Klaus; Meier, Carola

    2011-01-01

    Intraperitoneal transplantation of human umbilical cord blood (hUCB) cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury. PMID:21673795

  5. Different protocols of treadmill exercise induce distinct neuroplastic effects in rat brain motor areas.

    Science.gov (United States)

    Real, Caroline C; Garcia, Priscila C; Britto, Luiz R G; Pires, Raquel S

    2015-10-22

    A variety of exercise protocols have been used to promote experimental neuroplasticity. However, the plastic brain responses generated by several aspects of training (types, frequency, regimens, duration) remain undetermined. The aim of this study was to compare the plastic changes in the glutamatergic system and synaptic proteins in motor cortex, striatum and cerebellum promoted by two different treadmill exercise regimens. The present study analyzed by immunohistochemistry and Western blotting the expression of the subunits of AMPA receptors (GluA1 and GluA2/3) and synaptic proteins (synapsin I and synaptophysin) in adult male Wistar rat brains. The animals were divided into animals subjected to two different frequencies of aerobic exercise groups and sedentary animals. The exercise groups were: intermittent treadmill exercise (ITE) - animals that exercised 3 times a week (every other day) during four weeks, and continuous treadmill exercise (CTE) - animals that exercised every day during four weeks. Our results reveal that different protocols of treadmill exercise were able to promote distinct synaptic reorganization processes among the exercised groups. In general, the intermittent exercise regimen induced a higher expression of presynaptic proteins, whereas the continuous exercise regimen increased postsynaptic GluA1 and GluA2/3 receptors.

  6. Soybean andtempeh total isolfavones improved antioxidant activities in normal and scopolamine-induced rat brain

    Institute of Scientific and Technical Information of China (English)

    Aliya Ahmad; Vasudevan Mani; Kalavathy Ramasamy; Atish Prakash; Abu Bakar Abdul Majeed

    2015-01-01

    Objective:To highlight the comparative studies between total isoflavone extracts from soybean and tempeh on the neuronal oxidative stress and antioxidant activities. Methods: The total isoflavones were administered orally for 15 days with 3 selected doses (10, 20 and 40 mg/kg). Piracetam (400 mg/kg,p.o.) was used as a standard drug while scopolamine (1 mg/kg,i.p.) was used as a drug that promoted amnesia in selected groups. The oxidative markers (thiobarbituric acid reactive substances and nitric oxide) were measured in brain homogenate. The antioxidant activities evaluated were catalase, superoxide dismutase, glutathione reductase and glutathione. Results: Our results showed that soybean and tempeh isoflavones significantly improved the levels of catalase, superoxide dismutase, glutathione reductase and glutathione while decreased levels of thiobarbituric acid reactive substances and nitric oxide in both the brain of normal as well as scopolamine-induced animals. Conclusions: Our findings suggested that soybean and tempeh isoflavones could be useful in the management and prevention of age-related neurodegenerative changes including Alzheimer’s disease through its antioxidant activities.

  7. Changes in brain protein expression are linked to magnesium restriction-induced depression-like behavior.

    Science.gov (United States)

    Whittle, Nigel; Li, Lin; Chen, Wei-Qiang; Yang, Jae-Won; Sartori, Simone B; Lubec, Gert; Singewald, Nicolas

    2011-04-01

    There is evidence to suggest that low levels of magnesium (Mg) are associated with affective disorders, however, causality and central neurobiological mechanisms of this link are largely unproven. We have recently shown that mice fed a low Mg-containing diet (10% of daily requirement) display enhanced depression-like behavior sensitive to chronic antidepressant treatment. The aim of the present study was to utilize this model to gain insight into underlying mechanisms by quantifying amygdala/hypothalamus protein expression using gel-based proteomics and correlating changes in protein expression with changes in depression-like behavior. Mice fed Mg-restricted diet displayed reduced brain Mg tissue levels and altered expression of four proteins, N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1), manganese-superoxide dismutase (MnSOD), glutamate dehydrogenase 1 (GDH1) and voltage-dependent anion channel 1. The observed alterations in protein expression may indicate increased nitric oxide production, increased anti-oxidant response to increased oxidative stress and potential alteration in energy metabolism. Aberrant expressions of DDAH1, MnSOD and GDH1 were normalized by chronic paroxetine treatment which also normalized the enhanced depression-like behavior, strengthening the link between the changes in these proteins and depression-like behavior. Collectively, these findings provide first evidence of low magnesium-induced alteration in brain protein levels and biochemical pathways, contributing to central dysregulation in affective disorders.

  8. Metabolic and electric brain patterns during pleasant and unpleasant emotions induced by music masterpieces.

    Science.gov (United States)

    Flores-Gutiérrez, Enrique O; Díaz, José-Luís; Barrios, Fernando A; Favila-Humara, Rafael; Guevara, Miguel Angel; del Río-Portilla, Yolanda; Corsi-Cabrera, María

    2007-07-01

    Brain correlates comparing pleasant and unpleasant states induced by three dissimilar masterpiece excerpts were obtained. Related emotional reactions to the music were studied using Principal Component Analysis of validated reports, fMRI, and EEG coherent activity. A piano selection by Bach and a symphonic passage from Mahler widely differing in musical features were used as pleasing pieces. A segment by Prodromidès was used as an unpleasing stimulus. Ten consecutive 30 s segments of each piece alternating with random static noise were played to 19 non-musician volunteers for a total of 30 min of auditory stimulation. Both brain approaches identified a left cortical network involved with pleasant feelings (Bach and Mahler vs. Prodromidès) including the left primary auditory area, posterior temporal, inferior parietal and prefrontal regions. While the primary auditory zone may provide an early affective quality, left cognitive areas may contribute to pleasant feelings when melodic sequences follow expected rules. In contrast, unpleasant emotions (Prodromidès vs. Bach and Mahler) involved the activation of the right frontopolar and paralimbic areas. Left activation with pleasant and right with unpleasant musical feelings is consistent with right supremacy in novel situations and left in predictable processes. When all musical excerpts were jointly compared to noise, in addition to bilateral auditory activation, the left temporal pole, inferior frontal gyrus, and frontopolar area were activated suggesting that cognitive and language processes were recruited in general responses to music. Sensory and cognitive integration seems required for musical emotion.

  9. Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex.

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    Maren Geissler

    Full Text Available Intraperitoneal transplantation of human umbilical cord blood (hUCB cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury.

  10. Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis.

    Science.gov (United States)

    Hescham, Sarah; Temel, Yasin; Schipper, Sandra; Lagiere, Mélanie; Schönfeld, Lisa-Maria; Blokland, Arjan; Jahanshahi, Ali

    2017-03-01

    Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

  11. Oscillatory brain activity related to control mechanisms during laboratory-induced reactive aggression

    Directory of Open Access Journals (Sweden)

    Ulrike M Krämer

    2009-11-01

    Full Text Available Aggressive behavior is a common reaction in humans after an interpersonal provocation, but little is known about the underlying brain mechanisms. The present study analyzed oscillatory brain activity while participants were involved in an aggressive interaction to examine the neural processes subserving the associated decision and evaluation processes. Participants were selected from a larger sample because of their high scores in trait aggressiveness. We used a competitive reaction time task that induces aggressive behavior through provocation. Each trial is separated in a decision phase, during which the punishment for the opponent is set, and an outcome phase, during which the actual punishment is applied or received. We observed provocation-related differences during the decision phase in the theta band which differed depending on participants’ aggressive behavior: High provocation was associated with an increased frontal theta response in participants refraining from retaliation, but with reduced theta power in those who got back to the opponent. Moreover, more aggressive decisions after being punished were associated with a decrease of frontal theta power. Non-aggressive and aggressive participants differed also in their outcome-related response: Being punished led to an increased frontal theta power compared to win trials in the latter only, pointing to differences in evaluation processes associated with their different behavioral reactions. The data thus support previous evidence for a role of prefrontal areas in the control of reactive aggression and extend behavioral studies on associations between aggression or violence and impaired prefrontal functions.

  12. Soybean and tempeh total isoflvones improved antioxidant activities in normal and scopolamine-induced rat brain

    Directory of Open Access Journals (Sweden)

    Aliya Ahmad

    2015-11-01

    Full Text Available Objective: To highlight the comparative studies between total isoflavone extracts from soybean and tempeh on the neuronal oxidative stress and antioxidant activities. Methods: The total isoflavones were administered orally for 15 days with 3 selected doses (10, 20 and 40 mg/kg. Piracetam (400 mg/kg, p.o. was used as a standard drug while scopolamine (1 mg/kg, i.p. was used as a drug that promoted amnesia in selected groups. The oxidative markers (thiobarbituric acid reactive substances and nitric oxide were measured in brain homogenate. The antioxidant activities evaluated were catalase, superoxide dismutase, glutathione reductase and glutathione. Results: Our results showed that soybean and tempeh isoflavones significantly improved the levels of catalase, superoxide dismutase, glutathione reductase and glutathione while decreased levels of thiobarbituric acid reactive substances and nitric oxide in both the brain of normal as well as scopolamine-induced animals. Conclusions: Our findings suggested that soybean and tempeh isoflavones could be useful in the management and prevention of age-related neurodegenerative changes including Alzheimer’s disease through its antioxidant activities.

  13. Temperature elevation profile inside the rat brain induced by a laser beam

    Science.gov (United States)

    Ersen, Ali; Abdo, Ammar; Sahin, Mesut

    2014-01-01

    The thermal effect may be a desired outcome or a concerning side effect in laser-tissue interactions. Research in this area is particularly motivated by recent advances in laser applications in diagnosis and treatment of neurological disorders. Temperature as a side effect also limits the maximum power of optical transfer and harvesting of energy in implantable neural prostheses. The main objective was to investigate the thermal effect of a near-infrared laser beam directly aimed at the brain cortex. A small, custom-made thermal probe was inserted into the rat brain to make direct measurements of temperature elevations induced by a free-air circular laser beam. The time dependence and the spatial distribution of the temperature increases were studied and the maximum allowable optical power was determined to be 2.27 W/cm2 for a corresponding temperature increase of 0.5°C near the cortical surface. The results can be extrapolated for other temperature elevations, where the margin to reach potentially damaging temperatures is more relaxed, by taking advantage of linearity. It is concluded that the thermal effect depends on several factors such as the thermal properties of the neural tissue and of its surrounding structures, the optical properties of the particular neural tissue, and the laser beam size and shape. Because so many parameters play a role, the thermal effect should be investigated for each specific application separately using realistic in vivo models.

  14. Relationship between trauma-induced coagulopathy and progressive hemorrhagic injury in patients with traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Jia Liu; Heng-Li Tian

    2016-01-01

    Progressive hemorrhagic injury (PHI) can be divided into coagulopathy-related PHI and normal coagulation PHI.Coagulation disorders after traumatic brain injuries can be included in trauma-induced coagulopathy (TIC).Some studies showed that TIC is associated with PHI and increases the rates of disability and mortality.In this review,we discussed some mechanisms in TIC,which is of great importance in the development of PHI,including tissue factor (TF) hypothesis,protein C pathway and thrombocytopenia.The main mechanism in the relation of TIC to PHI is hypocoagulability.We also reviewed some coagulopathy parameters and proposed some possible risk factors,predictors and therapies.

  15. Study on the violet LED-induced fluorescence spectra of thioredoxin reductase from human brain

    Institute of Scientific and Technical Information of China (English)

    Xiufeng Lan(兰秀风); Tao Yang(杨涛); Shumei Gao(高淑梅); Xiaosen Luo(骆晓森); Zhonghua Shen(沈中华); Jian Lu(陆建); Xiaowu Ni(倪晓武); Lin Xu(许琳)

    2003-01-01

    The technique of fluorescence spectroscopy is applied to study thioredoxin reductase (TrxR) in the ce;lsof human brain. Experimental results show that, by the violet light emitting diode (LED, λmax=407 nm)light irradiation, TrxR is able to emit three striking spectral bands (528 - 582 nm; 588 - 660 nm; 683 - 700nm). The fluorescence intensity is linear to the concentration of TrxR. The spectrum of denatured TrxR israther different from that of organized TrxR, which reflects the structure change between denatured TrxRand organized TrxR. Furthermore, physical and biochemical mechanisms of fluorescence production forLED light-induced TrxR spectra and its characteristics are analyzed. This paper may be useful to betterunderstand the structure of TrxR, and to provide new spectroscopic information to improve the resolutionfor this kind of biology structure.

  16. Newcastle disease virus (NDV) induces protein oxidation and nitration in brain and liver of chicken: Ameliorative effect of vitamin E.

    Science.gov (United States)

    Venkata Subbaiah, Kadiam C; Valluru, Lokanatha; Rajendra, Wudayagiri; Ramamurthy, Chiteti; Thirunavukkarusu, Chinnasamy; Subramanyam, Rajagopal

    2015-07-01

    The present study was aimed at investigating the therapeutic efficacy of vitamin E on oxidative injury in brain and liver of Newcastle disease virus (NDV) challenged chickens. We have analyzed the xanthine oxidase (XOD) activity; uric acid (UA) levels and superoxide radical generation by using electron spin resonance spectroscopy. Further, protein oxidation, nitration and apoptosis were evaluated in the brain and liver of the control, NDV-infected and NDV+Vit. E treated groups. A significant elevation was observed in XOD activity and UA levels in brain (p<0.001) and liver (p<0.05) of NDV infected birds when compared to controls. Further, significant increase in the production of superoxides, enhanced intracellular protein carbonyls and nitrates were observed in the brain and liver of NDV-infected birds over healthy subjects. Apoptosis studies also suggested that a larger number of TUNEL positive cells were observed in brain and a moderately in liver of NDV-infected chickens. However, all these perturbations were significantly ameliorated in NDV+Vit. E treated chickens as compared to NDV-infected birds. Taken together, our results suggested that NDV-induced neuronal and hepatic damage at least in part mediates oxidative stress and on the other hand, supplementation of vitamin E mitigates NDV-induced oxidative damage thereby protects brain and liver of chickens. These findings could provide new insights into the understanding of NDV pathogenesis and therapeutic effects of dietary antioxidants.

  17. Neck Flexion Induces Larger Deformation of the Brain Than Extension at a Rotational Acceleration, Closed Head Trauma

    Directory of Open Access Journals (Sweden)

    Hans-Arne Hansson

    2014-01-01

    Full Text Available A closed head trauma induces incompletely characterized temporary movement and deformation of the brain, contributing to the primary traumatic brain injury. We used the pressure patterns recorded with light-operated miniature sensors in anaesthetized adult rabbits exposed to a sagittal plane rotational acceleration of the head, lasting 1 ms, as a measure of brain deformation. Two exposure levels were used and scaled to correspond to force levels reported to cause mild and moderate diffuse injury in an adult man, respectively. Flexion induced transient, strong, extended, and predominantly negative pressures while extension generated a short positive pressure peak followed by a minor negative peak. Low level flexion caused as strong, extended negative pressures as did high level extension. Time differences were demonstrated between the deformation of the cerebrum, brainstem, and cerebellum. Available X-ray and MRI techniques do not have as high time resolution as pressure recordings in demonstrating complex, sequential compression and stretching of the brain during a trauma. The exposure to flexion caused more protracted and extensive deformation of the brain than extension, in agreement with a published histopathological report. The severity and extent of the brain deformation generated at a head trauma thus related to the direction at equal force.

  18. Injury of Mouse Brain Mitochondria Induced by Cigarette Smoke Extract and Effect of Vitamin C on It in vitro

    Institute of Scientific and Technical Information of China (English)

    YU-MEI YANG; GENG-TAO LIU

    2003-01-01

    To investigate the toxicity of cigarette smoke extract (CSE) and nicotine on mouse brain mitochondria as well as the protective effect of vitamin C in vitro. Method Mouse brain mitochondria in vitro was incubated with CSE or nicotine in the absence or presence of vitamin C for 60 minutes, and the changes of mitochondrial function and structure were measured. Results CSE inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner.However, no significant changes in the peroxidation indices were observed when mitochondrial respiratory enzymes activity was inhibited, and protection of mitochondria from CSE-induced injury by vitamin C was not displayed in vitro. The effect of CSE on mouse brain mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. CSE inhibited swelling of mitochondria at 6.5 μmol/L Ca2+, but promoted swelling response at 250 μmol/L Ca2+. Nicotine, the major component of cigarette smoke, showed no significant damage in mouse brain mitochondria in vitro. The CSE treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane appeared to be preserved. Conclusion The toxic effect of CSE on brain mitochondria may be due to its direct action on enzymatic activity rather than through oxygen free radical injury. Nicotine is not the responsible component for the toxicity of CSE to brain mitochondria.

  19. Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

    Science.gov (United States)

    Megha, Kanu; Deshmukh, Pravin Suryakantrao; Banerjee, Basu Dev; Tripathi, Ashok Kumar; Ahmed, Rafat; Abegaonkar, Mahesh Pandurang

    2015-12-01

    Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (pmicrowave exposed groups (pmicrowave exposed animal (pmicrowave exposed groups as compared to their corresponding values in sham exposed group (pmicrowave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect. The study also indicates that increased oxidative stress and inflammatory response might be the factors involved in DNA damage following low intensity microwave exposure.

  20. Human brain dopamine metabolism in levodopa-induced dyskinesia and wearing-off.

    Science.gov (United States)

    Rajput, Ali H; Fenton, Mark E; Di Paolo, Thérèse; Sitte, Harold; Pifl, Christian; Hornykiewicz, Oleh

    2004-06-01

    The objective of this study was to identify dopamine (DA) metabolism pattern in Lewy body Parkinson's disease (PD) patients with dyskinesia (Dysk) only, with wearing-off (WO) only, or no motor complications (NMC) induced by levodopa (LD). DA, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methoxytyramine (3-MT) were measured individual basal ganglia nuclei of nine PD patients who received LD for 6-18 years. Three patients had only Dysk, three only WO, and three had neither Dysk nor WO. Biochemical measurements in PD brains were compared with four non-neurological control brains from individuals matched for age and post-mortem retrieval time. DA levels in the PD were reduced in the caudate by 87% and putamen by 99%. In the caudates, the HVA/DA molar ratio as an index of DA metabolism was similar in the WO and the Dysk patients. However, in the putamen, the ratio of HVA/DA was significantly higher in the WO compared with the Dysk (p = 0.03)and the NMC (p = 0.04) groups of patients. In the putamen, the DOPAC levels were higher in the WO cases while in the Dysk cases, 3-MT levels were higher. The results suggest that in the WO only cases, the putaminal DA was in large measure metabolized intraneuronally while the DA metabolism in our Dysk only patients was mainly extraneuronal. We conclude that the magnitude and the site (intra vs. extraneuronal) of the synaptic DA metabolism in the putamen plays a significant role in LD-induced Dysk and WO.

  1. Stereotactic laser induced thermotherapy (LITT): a novel treatment for brain lesions regrowing after radiosurgery.

    Science.gov (United States)

    Torres-Reveron, Juan; Tomasiewicz, Hilarie C; Shetty, Anil; Amankulor, Nduka M; Chiang, Veronica L

    2013-07-01

    Since the inception of radiosurgery, the management of brain metastases has become a common problem for neurosurgeons. Although the use of stereotactic radiosurgery and/or whole brain radiation therapy serves to control the majority of disease burden, patients who survive longer than 6-8 months sometimes face the problem of symptomatic radiographically regrowing lesions with few treatment options. Here we investigate the feasibility of use of MRI-guided stereotactic laser induced thermotherapy (LITT) as a novel treatment option for these lesions. Six patients who had previously undergone gamma knife stereotactic radiosurgery for brain metastases were selected. All patients had an initial favorable response to radiosurgery but subsequently developed regrowth of at least one lesion associated with recurrent edema and progressive neurological symptoms requiring ongoing steroids for symptom control. All lesions were evaluated for craniotomy, but were deemed unresectable due to deep location or patient's comorbidities. Stereotactic biopsies were performed prior to the thermotherapy procedure in all cases. LITT was performed using the Visualase system and follow-up MRI imaging was used to determine treatment response. In all six patients biopsy results were negative for tumor and consistent with adverse radiation effects also known as radiation necrosis. Patients tolerated the procedure well and were discharged from the hospital within 48 h of the procedure. In 4/6 cases there was durable improvement of neurological symptoms until death. In all cases steroids were weaned off within 2 months. One patient died from systemic causes related to his cancer a month after the procedure. One patient had regrowth of the lesion 3 months after the procedure and required re-initiation of steroids and standard craniotomy for surgical resection. There were no complications directly related to the thermocoagulation procedure. Stereotactic laser induced thermotherapy is a feasible

  2. Noise Trauma Induced Plastic Changes in Brain Regions outside the Classical Auditory Pathway

    Science.gov (United States)

    Chen, Guang-Di; Sheppard, Adam; Salvi, Richard

    2017-01-01

    The effects of intense noise exposure on the classical auditory pathway have been extensively investigated; however, little is known about the effects of noise-induced hearing loss on non-classical auditory areas in the brain such as the lateral amygdala (LA) and striatum (Str). To address this issue, we compared the noise-induced changes in spontaneous and tone-evoked responses from multiunit clusters (MUC) in the LA and Str with those seen in auditory cortex (AC). High-frequency octave band noise (10–20 kHz) and narrow band noise (16–20 kHz) induced permanent thresho ld shifts (PTS) at high-frequencies within and above the noise band but not at low frequencies. While the noise trauma significantly elevated spontaneous discharge rate (SR) in the AC, SRs in the LA and Str were only slightly increased across all frequencies. The high-frequency noise trauma affected tone-evoked firing rates in frequency and time dependent manner and the changes appeared to be related to severity of noise trauma. In the LA, tone-evoked firing rates were reduced at the high-frequencies (trauma area) whereas firing rates were enhanced at the low-frequencies or at the edge-frequency dependent on severity of hearing loss at the high frequencies. The firing rate temporal profile changed from a broad plateau to one sharp, delayed peak. In the AC, tone-evoked firing rates were depressed at high frequencies and enhanced at the low frequencies while the firing rate temporal profiles became substantially broader. In contrast, firing rates in the Str were generally decreased and firing rate temporal profiles become more phasic and less prolonged. The altered firing rate and pattern at low frequencies induced by high frequency hearing loss could have perceptual consequences. The tone-evoked hyperactivity in low-frequency MUC could manifest as hyperacusis whereas the discharge pattern changes could affect temporal resolution and integration. PMID:26701290

  3. Involvement of extracellular signal regulated kinases in traumatic brain injury-induced depression in rodents.

    Science.gov (United States)

    Kuo, Jinn-Rung; Cheng, Yi-Hsuan; Chen, Yi-Shion; Chio, Chung-Ching; Gean, Po-Wu

    2013-07-15

    Traumatic brain injury (TBI) is the most common cause of death and acquired disability among children and young adults in the developed countries. In clinical studies, the incidence of depression is high after TBI, and the mechanisms behind TBI-induced depression remain unclear. In the present study, we subjected rats to a moderate fluid percussion into the closed cranial cavity to induce TBI. After 3 days of recovery, injured rats were given a forced swim test (FST) and novelty-suppressed feeding tests. We found that TBI rats exhibited increased duration of immobility and longer latency to begin chewing food in a new environment compared with sham-operated rats. Western blot analysis showed that TBI led to a decrease in the phosphorylated levels of extracellular signal regulated kinases (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK). Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), significantly reduced the duration of immobility when administered once per day for 14 days. Consistent with behavioral tests, fluoxetine treatment reversed TBI-induced decrease in p-ERK1/2 and p-p38 MAPK levels. Pre-treatment with a selective tryptophan hydroxylase inhibitor para-chlorophenylalanine (PCPA) blocked the antidepressant effect of fluoxetine. PCPA also prevented the effect of fluoxetine on ERK1/2 phosphorylation without affecting p38 MAPK phosphorylation. Pre-treatment with ERK inhibitor SL327 but not p38 MAPK inhibitor SB203580 prevented the antidepressant effect of fluoxetine. These results suggest that ERK1/2 plays a critical role in TBI-induced depression.

  4. Influence of Punica granatum L. on region specific responses in rat brain during Alloxan-Induced diabetes

    Institute of Scientific and Technical Information of China (English)

    Sushil Kumar Middha; Talambedu Usha; Tekupalli RaviKiran

    2012-01-01

    Objective: The present study was carried out to investigate the effects of Punica granatum peel methanolic extract (PGPE) on cerebral cortex (CC) and Hippocampus (HC) brain antioxidant defense system and markers of lipid and protein oxidation in alloxan induced diabetic rats.Methods:Oral administration of PGPE (75 and 150 mg of kg body weight) for 45 days resulted in significant reduction in blood glucose levels. Results: Supplementation of diabetic rats with PGPE showed increased activities of SOD and GPx with concomitant decrease in MDA and PC content. Region-specific changes were more evident in the HC when compared to CC. Conclusions: The present study indicated that PGPE can ameliorate brain oxidative stress in alloxan induced diabetic rats by up regulating antioxidant defense mechanism by attenuating lipid and protein oxidation. PGPE thus may be used as a potential therapeutic agent in preventing diabetic complications in the brain.

  5. Interindividual Variability and Intraindividual Reliability of Intermittent Theta Burst Stimulation-induced Neuroplasticity Mechanisms in the Healthy Brain

    NARCIS (Netherlands)

    Schilberg, Lukas; Schuhmann, Teresa; Sack, Alexander T

    2017-01-01

    We combined patterned TMS with EMG in several sessions of a within-subject design to assess and characterize intraindividual reliability and interindividual variability of TMS-induced neuroplasticity mechanisms in the healthy brain. Intermittent theta burst stimulation (iTBS) was applied over M1 to

  6. Mechanism of noradrenaline-induced stimulation of Na-K ATPase activity in the rat brain: implications on REM sleep deprivation-induced increase in brain excitability.

    Science.gov (United States)

    Mallick, Birendra Nath; Singh, Sudhuman; Singh, Abhishek

    2010-03-01

    Rapid eye movement (REM) sleep is a unique phenomenon expressed in all higher forms of animals. Its quantity varies in different species and with ageing; it is also affected in several psycho-somatic disorders. Several lines of studies showed that after REM sleep loss, the levels of noradrenaline (NA) increase in the brain. The NA in the brain modulates neuronal Na-K ATPase activity, which helps maintaining the brain excitability status. The detailed mechanism of increase in NA level after REM sleep loss and the effect of NA on stimulation of Na-K ATPase in the neurons have been discussed. The findings have been reviewed and discussed with an aim to understand the role of REM sleep in maintaining brain excitability status.

  7. Radiation-induced inflammatory markers of brain injury are modulated by PPARdelta activation in vitro and in vivo

    Science.gov (United States)

    Schnegg, Caroline Isabel

    As a result of improvements in cancer therapy and health care, the population of long-term cancer survivors is growing. For these approximately 12 million long-term cancer survivors, brain metastases are a significant risk. Fractionated partial or whole-brain irradiation (fWBI) is often required to treat both primary and metastatic brain cancer. Radiation-induced normal tissue injury, including progressive cognitive impairment, however, can significantly affect the well-being of the approximately 200,000 patients who receive these treatments each year. Recent reports indicate that radiation-induced brain injury is associated with chronic inflammatory and oxidative stress responses, as well as increased microglial activation in the brain. Anti-inflammatory drugs may, therefore, be a beneficial therapy to mitigate radiation-induced brain injury. We hypothesized that activation of peroxisomal proliferator activated receptor delta (PPARō) would prevent or ameliorate radiation-induced brain injury, including cognitive impairment, in part, by alleviating inflammatory responses in microglia. For our in vitro studies, we hypothesized that PPARō activation would prevent the radiation-induced inflammatory response in microglia following irradiation. Incubating BV-2 murine microglial cells with the (PPAR)ō agonist, L-165041, prevented the radiation-induced increase in: i) intracellular ROS generation, ii) Cox-2 and MCP-1 expression, and iii) IL-1β and TNF-α message levels. This occured, in part, through PPARō-mediated modulation of stress activated kinases and proinflammatory transcription factors. PPARō inhibited NF-κB via transrepression by physically interacting with the p65 subunit, and prevented activation of the PKCα/MEK1/2/ERK1/2/AP-1 pathway by inhibiting the radiation-induced increase in intracellular ROS generation. These data support the hypothesis that PPARō activation can modulate the radiation-induced oxidative stress and inflammatory responses in

  8. Single pulse TMS-induced modulations of resting brain neurodynamics encoded in EEG phase.

    Science.gov (United States)

    Stamoulis, Catherine; Oberman, Lindsay M; Praeg, Elke; Bashir, Shahid; Pascual-Leone, Alvaro

    2011-06-01

    Integration of electroencephalographic (EEG) recordings and transcranial magnetic stimulation (TMS) provides a useful framework for quantifying stimulation-induced modulations of neural dynamics. Amplitude and frequency modulations by different TMS protocols have been previously investigated, but the study of stimulation-induced effects on EEG phase has been more limited. We examined changes in resting brain dynamics following single TMS pulses, focusing on measures in the phase domain, to assess their sensitivity to stimulation effects. We observed a significant, approximately global increase in EEG relative phase following prolonged (>20 min) single-pulse TMS. In addition, we estimated higher rates of phase fluctuation from the slope of estimated phase curves, and higher numbers of phase resetting intervals following TMS over motor cortex, particularly in frontal and centro-parietal/parietal channels. Phase changes were only significantly different from their pre-TMS values at the end of the stimulation session, which suggests that prolonged single-pulse TMS may result in cumulative changes in neural activity reflected in the phase of the EEG. This is a novel result, as prior studies have reported only transient stimulation-related effects in the amplitude and frequency domains following single-pulse TMS.

  9. Enhanced inositide turnover in brain during bicuculline-induced status epilepticus

    Energy Technology Data Exchange (ETDEWEB)

    Van Rooijen, L.A.; Vadnal, R.; Dobard, P.; Bazan, N.G.

    1986-04-29

    Because brain inositides are enriched in the 1-stearoyl-2-arachidonoyl species, they form a likely source for the tetraenoic free fatty acids (FFA) and diacylglycerols (DG) that are accumulated during seizures. To study inositide turnover during bicuculline-induced seizures, rats were injected intraventricularly and bilaterally with 10-20 microCi /sup 32/P, mechanically ventilated and sacrificed by 6.5 KW head-focused microwave irradiation. Seizure activity was recorded by electroencephalography. Bicuculline-induced seizure activity resulted in: a) almost 50% increase in /sup 32/P labeling of phosphatidic acid (PA); phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2) also increased (24% and 36%, respectively); b) no change in other lipids; and c) water-soluble phosphodiesteratic degradation products, analyzed by high voltage paper electrophoresis, increased 24% in the amount of radiotracer recovered as inositol 1,4-bisphosphate (IP2) and by 44% in the amount recovered as inositol 1,4,5-trisphosphate (IP3). These data indicate that during experimental status epilepticus the cerebral inositide cycle is accelerated: PIP2----(IP3----IP2----IP----I) + DG----PA----PI----PIP----PIP2.

  10. Anaesthetics-Induced Neurotoxicity in Developing Brain: An Update on Preclinical Evidence

    Directory of Open Access Journals (Sweden)

    Zhaowei Zhou

    2014-03-01

    Full Text Available Every year millions of young people are treated with anaesthetic agents for surgery and sedation in a seemingly safe manner. However, growing and convincing preclinical evidence in rodents and nonhuman primates, together with recent epidemiological observations, suggest that exposure to anaesthetics in common clinical use can be neurotoxic to the developing brain and lead to long-term neurological sequelae. These findings have seriously questioned the safe use of general anaesthetics in obstetric and paediatric patients. The mechanisms and human applicability of anaesthetic neurotoxicity and neuroprotection have remained under intense investigation over the past decade. Ongoing pre-clinical investigation may have significant impact on clinical practice in the near future. This review represents recent developments in this rapidly emerging field. The aim is to summarise recently available laboratory data, especially those being published after 2010, in the field of anaesthetics-induced neurotoxicity and its impact on cognitive function. In addition, we will discuss recent findings in mechanisms of early-life anaesthetics-induced neurotoxicity, the role of human stem cell-derived models in detecting such toxicity, and new potential alleviating strategies.

  11. P. falciparum isolate-specific distinct patterns of induced apoptosis in pulmonary and brain endothelial cells.

    Directory of Open Access Journals (Sweden)

    Nadine N'Dilimabaka

    Full Text Available The factors implicated in the transition from uncomplicated to severe clinical malaria such as pulmonary oedema and cerebral malaria remain unclear. It is known that alterations in vascular integrity due to endothelial cell (EC activation and death occur during severe malaria. In this study, we assessed the ability of different P. falciparum clinical isolates to induce apoptosis in ECs derived from human lung and brain. We observed that induction of EC apoptosis was sensitive to the environmental pH and required direct contact between the parasite and the cell, though it was not correlated to the ability of the parasite to cytoadhere. Moreover, the extent of induced apoptosis in the two EC types varied with the isolate. Analysis of parasite genes transcript led us to propose that the activation of different pathways, such as Plasmodium apoptosis-linked pathogenicity factors (PALPF, PALPF-2, PALPF-5 and PF11_0521, could be implied in EC death. These observations provide an experimental framework to decipher the molecular mechanism implicated in the genesis of severe malaria.

  12. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons.

    Science.gov (United States)

    Murphy, D D; Cole, N B; Segal, M

    1998-09-15

    Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons.

  13. The early signal substances induced by heat stress in brains of mice

    Institute of Scientific and Technical Information of China (English)

    Chunxu WANG; Hanxing WANG

    2008-01-01

    To study the effects of early signal substances induced by heat stress in brains of Kunming mice, six-month-old mice (n=72) were pretreated with heat stress and subsequent ischemia/reperfusion by clipping of their bilateral cervical common arteries for 7 min. According to different treatments, animals were randomly divided into four groups: (1) normal control group; (2) heat stress pre-treatment followed by ischemia and reperfusion group (HS/IR); (3) ischemia and reperfusion group (IR); (4) heat stress group (HS). Animals in the later three groups were subdivided into 3 subgroups (1 day, 4 days, 14 days), respectively. The changes in the expression of cAMP res-ponse element binding protein (CREB) and calcitonin gene-related peptide (CGRP) were detected by immuno-histochemistry and computer image analysis methods. The results showed that compared with the normal group, the expressions of CREB in the hippocampal CA1 region increased significantly in the HS, HS/IR and IR groups (P<0.05). Compared to the normal group, heat stress could result in CGRP excretion and redistribution in the cerebrum, with the highest level in the 4 d HS/IR group. Following heat stress, CGRP immunoreactivity was observed in varicose fibers and neuronal perikarya within the CA1 region. The results indicate that heat stress can induce CREB expression, which in turn stimulates CGRP secretion.

  14. Biochemical brain markers and purinergic parameters in rat CSF after seizure induced by pentylenetetrazol.

    Science.gov (United States)

    Oses, Jean Pierre; Leke, Renata; Portela, Luis Valmor; Lara, Diogo R; Schmidt, André P; Casali, Emerson André; Wofchuk, Susana; Souza, Diogo O; Sarkis, João José Freitas

    2004-09-30

    Cellular and molecular mechanisms involved in the generation of seizures and the magnitude of neural cells injury are not fully understood. We evaluated astrocyte and/or neuronal injury in rats in the pentylenetetrazol model of acute seizures by measuring S100B and NSE levels in cerebrospinal fluid. Additionally, we determined ADP and GDP hydrolysis by soluble nucleoside triphosphate diphosphohydrolase in the cerebrospinal fluid, and the concentration of nucleosides adenosine, inosine and guanosine as putative markers of brain injury. After pentylenetetrazol-induced seizures: (i) S100B values increased from 10 to 30 min, returning to control levels at 24 h; NSE levels presented a biphasic increase: an increase at 10 to 30 min returning to control levels, and again at 240 min followed by a decline at 24 h; (ii) nucleotidase activities increased from 10 min, returning to control levels at 240 min; (iii) guanosine and inosine levels increased exclusively after 30 min. In summary, this study showed biochemical changes in the cerebrospinal fluid occurring after seizures induced by pentylenetetrazol. Such events may have a modulating effect upon seizure expression, particularly nucleoside triphosphate diphosphohydrolase activities and nucleoside concentrations, but are nevertheless followed by neural death as evidenced by the increase in NSE and S100B levels.

  15. Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: dose/volume-response relations

    Energy Technology Data Exchange (ETDEWEB)

    Levegruen, S.; Schlegel, W. [Dept. of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg (Germany); Hof, H.; Debus, J. [Dept. of Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Essig, M. [Dept. of Radiology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2004-12-01

    Purpose: to evaluate late radiation effects in the brain after radiosurgery of patients with cerebral arteriovenous malformations (AVMs) and to quantify dose/volume-response relations for radiation-induced changes of brain tissue identified on follow-up neuroimaging. Patients and methods: data from 73 AVM patients who had stereotactic linac radiosurgery at DKFZ (German Cancer Research Center), Heidelberg, Germany, were retrospectively analyzed. The endpoint of radiation-induced changes of brain tissue on follow-up magnetic resonance (MR) neuroimaging (i.e., edema and blood-brain-barrier breakdown [BBBB]) was evaluated. Each endpoint was further differentiated into three levels with respect to the extent of the image change (small, intermediate, and large). A previous analysis of the data found correlation of the endpoints with several dose/volume variables (DV) derived from each patient's dose distribution in the brain, including the mean dose in a volume of 20 cm{sup 3} (Dmean20) and the absolute brain volume (including the AVM target) receiving a dose of at least 12 Gy (V12). To quantify dose/volume-response relations, patients were ranked according to DV (i.e., Dmean20 and V12) and classified into four groups of equal size. For each group, the actuarial rates of developing the considered endpoints within 2.5 years after radiosurgery were determined from Kaplan-Meier estimates. The dose/volume-response curves were fitted with a sigmoid-shape logistic function and characterized by DV{sub 50}, the dose for a 50% incidence, and the slope parameter k. Results: dose/volume-response relations, based on two alternative, but correlated, dose distribution variables that are a function of both dose and volume, were observed for radiation-induced changes of brain tissue. DV{sub 50} values of fitted dose/volume-response curves for tissue changes of large extent (e.g., V12{sub 50} = 22.0 {+-} 2.6 cm{sup 3} and Dmean20{sub 50} = 17.8 {+-} 2.0 Gy for the combined endpoint

  16. 3-nitropropionic acid-induced mitochondrial permeability transition: comparative study of mitochondria from different tissues and brain regions.

    Science.gov (United States)

    Mirandola, Sandra R; Melo, Daniela R; Saito, Angela; Castilho, Roger F

    2010-02-15

    The adult rat striatum is particularly vulnerable to systemic administration of the succinate dehydrogenase inhibitor 3-nitropropionic acid (3NP), which is known to induce degeneration of the caudate-putamen, as occurs in Huntington's disease. The aim of the present study was to compare the susceptibility of isolated mitochondria from different rat brain regions (striatum, cortex, and cerebellum) as well as from the liver, kidney, and heart to mitochondrial permeability transition (MPT) induced by 3NP and Ca(2+). In the presence of micromolar Ca(2+) concentrations, 3NP induces MPT in a dose-dependent manner, as estimated by mitochondrial swelling and a decrease in the transmembrane electrical potential. A 3NP concentration capable of promoting a 10% inhibition of ADP-stimulated, succinate-supported respiration was sufficient to stimulate Ca(2+)-induced MPT. Brain and heart mitochondria were generally more sensitive to 3NP and Ca(2+)-induced MPT than mitochondria from liver and kidney. In addition, a partial inhibition of mitochondrial respiration by 3NP resulted in more pronounced MPT in striatal mitochondria than in cortical or cerebellar organelles. A similar inhibition of succinate dehydrogenase activity was observed in rat tissue homogenates obtained from various brain regions as well as from liver, kidney, and heart 24 hr after a single i.p. 3NP dose. Mitochondria isolated from forebrains of 3NP-treated rats were also more susceptible to Ca(2+)-induced MPT than those of control rats. We propose that the increased susceptibility of the striatum to 3NP-induced neurodegeneration may be partially explained by its susceptibility to MPT, together with the greater vulnerability of this brain region to glutamate receptor-mediated Ca(2+) influx.

  17. Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the stability of brain-cortex ribosomes.

    Science.gov (United States)

    Datta, R K; Ghosh, J J

    1970-05-01

    1. During the action of mescaline sulphate on goat brain-cortex slices the ribosomal particles become susceptible to breakdown, releasing protein, RNA, acidsoluble nucleotides and ninhydrin-positive materials, resulting in loss of ribosomal enzyme activities. 2. Ribosomes of the mescaline-treated cortex slices undergo rapid degradation in the presence of trypsin and ribonuclease. 3. Mescaline does not alter the chemical and nucleotide compositions or the u.v.-absorption characteristics of ribosomal particles, however.

  18. MR imaging findings of generalized tonic clonic seizure induced brain changes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Ah; Chung, Jin Il; Yonn, Pyeong Ho; Kim, Dong Ik; Chung, Tae Sub; Kim, Joo Hee [College of Medicine, Yonsei Unversity, Seoul (Korea, Republic of)

    2000-03-01

    To evaluate MRI signal changes in the brain induced by generalized tonic clonic seizure. Six patients who underwent MRI within three days of generalized tonic clonic seizure were retrospectively reviewed. Diffusion -weighted images were added in three patients during initial examination, and in six, the follow-up MRI was performed nine days to five months after the onset of seizure. We evaluated the patterns of signal change, location of the lesion and degree of contrast enhancement, and the signal change seen on diffusion weighted images. We also compared the signal changes seen on initial and follow-up MRI. In all six patients, MR images showed focally increased T2 signal intensity, and swelling and increased volume of the involved cortical gyrus. In five, the lesion was mainly located in the cortical gray matter and subcortical white matter; namely, in the bilateral cingulate gyri, and the bilateral parieto-occipital, left parietal, left frontoparietal, and left temporal lobe. In the remaining patient, the lesion was located in the right hippocampus. Two patients showed bilateral lesions and one showed multiple lesions. In four patients, T1-weighted images revealed decreased signal intensity of the same location, and in one, gyral contrast enhancement was noted. On diffusion-weighted images, three patients showed increased signal intensity. Follow-up MRI demonstrated complete resolution of the abnormal signal change (n=3D5), or a decrease (n=3D1). A transient increase in MR signal intensity with increased volume was noted in cortical and subcortical white matter after generalized tonic clonic seizure. This finding reflects the vasogenic and cytotoxic edema induced by seizure and can help exclude etiologic lesions such as tumors, inflammation and demyelinating disease that induce epilepsy. (author)

  19. Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons.

    Science.gov (United States)

    Magariños, A M; Li, C J; Gal Toth, J; Bath, K G; Jing, D; Lee, F S; McEwen, B S

    2011-03-01

    Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the hippocampus and released from neurons in an activity-dependent manner, as a mediator of the stress-induced dendritic remodeling. The analysis of Golgi-impregnated hippocampal sections revealed that wild type (WT) C57BL/6 male mice showed a similar CA3 apical dendritic remodeling in response to three weeks of CRS to that previously described for rats. Haploinsufficient BDNF mice (BDNF(±) ) did not show such remodeling, but, even without CRS, they presented shorter and simplified CA3 apical dendritic arbors, like those observed in stressed WT mice. Furthermore, unstressed BDNF(±) mice showed a significant decrease in total hippocampal volume. The dendritic arborization of CA1 pyramidal neurons was not affected by CRS or genotype. However, only in WT mice, CRS induced changes in the density of dendritic spine shape subtypes in both CA1 and CA3 apical dendrites. These results suggest a complex role of BDNF in maintaining the dendritic and spine morphology of hippocampal neurons and the associated volume of the hippocampal formation. The inability of CRS to modify the dendritic structure of CA3 pyramidal neurons in BDNF(±) mice suggests an indirect, perhaps permissive, role of BDNF in mediating hippocampal dendritic remodeling.

  20. Zingiber Officinale Alters 3,4-methylenedioxymethamphetamine-Induced Neurotoxicity in Rat Brain

    Directory of Open Access Journals (Sweden)

    Mehdi Mehdizadeh

    2012-01-01

    Full Text Available Objective: The spice Zingiber officinale or ginger possesses antioxidant activity and neuroprotective effects. The effects of this traditional herbal medicine on 3,4-methylenedioxymethamphetamine (MDMA induced neurotoxicity have not yet been studied. The present study considers the effects of Zingiber officinale on MDMA-induced spatial memory impairment and apoptosis in the hippocampus of male rats.Materials and Methods: In this experimental study, 21 adult male Sprague Dawley rats (200-250 g were classified into three groups (control, MDMA, and MDMA plus ginger. The groups were intraperitoneally administered 10 mg/kg MDMA, 10 mg/kg MDMA plus 100 mg/kg ginger extract, or 1 cc/kg normal saline as the control solution for one week (n=7 per group. Learning memory was assessed by Morris water maze (MWM after the last administration. Finally, the brains were removed to study the cell number in the cornu ammonis (CA1 hippocampus by light microscope, Bcl-2 by immunoblotting, and Bax expression by reverse transcription polymerase chain reaction (RT-PCR. Data was analyzed using SPSS 16 software and a one-way ANOVA test.Results: Escape latency and traveled distances decreased significantly in the MDMA plus ginger group relative to the MDMA group (p<0.001. Cell number increased in the MDMA plus ginger group in comparison to the MDMA group. Down-regulation of Bcl-2 and up-regulation of Bax were observed in the MDMA plus ginger group in comparison to the MDMA group (p<0.05.Conclusion: Our findings suggest that ginger consumption may lead to an improvement of MDMA-induced neurotoxicity.

  1. Chemoprotective role of quercetin in manganese-induced toxicity along the brain-pituitary-testicular axis in rats.

    Science.gov (United States)

    Adedara, Isaac A; Subair, Temitayo I; Ego, Valerie C; Oyediran, Oluwasetemi; Farombi, Ebenezer O

    2017-02-01

    Reproductive dysfunction in response to manganese exposure has been reported in humans and animals. Quercetin, a bioflavonoid widely distributed in fruits, vegetables and beverages has been shown to possess antioxidant, anti-inflammatory and anti-apoptotic activities in different experimental model systems. However, there is dearth of scientific information on the influence of quercetin on manganese-induced reproductive toxicity. This study was designed to evaluate the influence of quercetin on manganese-induced functional alterations along the brain-pituitary- testicular axis in rats. Manganese was administered alone at 15 mg/kg body weight or orally co-treated with quercetin at 10 and 20 mg/kg body weight for 45 consecutive days. Results indicated that quercetin co-treatment significantly (p quercetin mediated suppression of inflammatory indices and caspase-3 activity was accompanied by preservation of histo-architectures of the brain, testes and epididymis in manganese-treated rats. The significant reversal of manganese-induced decreases in reproductive hormones (i.e. luteinizing hormone, follicle-stimulating hormone and testosterone) and testicular activities of acid phosphatase, alkaline phosphatase and lactate dehydrogenase by quercetin was complemented by an increase in sperm quality and quantity in the treated rats. Collectively, quercetin modulated manganese-induced toxicity along the brain-pituitary-testicular axis in rats via its intrinsic antioxidant, anti-inflammatory and anti-apoptotic activities, and may thus represent a potential pharmacological agent against manganese-induced male reproductive deficits in humans.

  2. Low dose X-irradiation mitigates diazepam induced depression in rat brain.

    Science.gov (United States)

    Kaur, Amandeep; Singla, Neha; Dhawan, D K

    2016-10-01

    Depression is considered as one of the most prevalent health ailments. Various anti-depressant drugs have been used to provide succour to this ailment, but with little success and rather have resulted in many side effects. On the other hand, low dose of ionizing radiations are reported to exhibit many beneficial effects on human body by stimulating various biological processes. The present study was conducted to investigate the beneficial effects of low doses of X-rays, if any, during diazepam induced depression in rats. Female Sprague Dawley rats were segregated into four different groups viz: Normal control, Diazepam treated, X-irradiated and Diazepam + X-irradiated. Depression model was created in rats by subjecting them to diazepam treatment at a dosage of 2 mg/kg b.wt./day for 3 weeks. The skulls of animals belonging to X-irradiated and Diazepam + X-irradiated rats were X-irradiated with a single fraction of 0.5 Gy, given twice a day for 3 days, thereby delivered dose of 3 Gy. Diazepam treated animals showed significant alterations in the neurobehavior and neuro-histoarchitecture, which were improved after X-irradiation. Further, diazepam exposure significantly decreased the levels of neurotransmitters and acetylcholinesterase activity, but increased the monoamine oxidase activity in brain. Interestingly, X-rays exposure to diazepam treated rats increased the levels of neurotransmitters, acetylcholinesterase activity and decreased the monoamine oxidase activity. Further, depressed rats also showed increased oxidative stress with altered antioxidant parameters, which were normalized on X-rays exposure. The present study, suggests that low dose of ionizing radiations, shall prove to be an effective intervention and a novel therapy in controlling depression and possibly other brain related disorders.

  3. A multi-mode shock tube for investigation of blast-induced traumatic brain injury.

    Science.gov (United States)

    Reneer, Dexter V; Hisel, Richard D; Hoffman, Joshua M; Kryscio, Richard J; Lusk, Braden T; Geddes, James W

    2011-01-01

    Blast-induced mild traumatic brain injury (bTBI) has become increasingly common in recent military conflicts. The mechanisms by which non-impact blast exposure results in bTBI are incompletely understood. Current small animal bTBI models predominantly utilize compressed air-driven membrane rupture as their blast wave source, while large animal models use chemical explosives. The pressure-time signature of each blast mode is unique, making it difficult to evaluate the contributions of the different components of the blast wave to bTBI when using a single blast source. We utilized a multi-mode shock tube, the McMillan blast device, capable of utilizing compressed air- and compressed helium-driven membrane rupture, and the explosives oxyhydrogen and cyclotrimethylenetrinitramine (RDX, the primary component of C-4 plastic explosives) as the driving source. At similar maximal blast overpressures, the positive pressure phase of compressed air-driven blasts was longer, and the positive impulse was greater, than those observed for shockwaves produced by other driving sources. Helium-driven shockwaves more closely resembled RDX blasts, but by displacing air created a hypoxic environment within the shock tube. Pressure-time traces from oxyhydrogen-driven shockwaves were very similar those produced by RDX, although they resulted in elevated carbon monoxide levels due to combustion of the polyethylene bag used to contain the gases within the shock tube prior to detonation. Rats exposed to compressed air-driven blasts had more pronounced vascular damage than those exposed to oxyhydrogen-driven blasts of the same peak overpressure, indicating that differences in blast wave characteristics other than peak overpressure may influence the extent of bTBI. Use of this multi-mode shock tube in small animal models will enable comparison of the extent of brain injury with the pressure-time signature produced using each blast mode, facilitating evaluation of the blast wave components

  4. Acute renal failure potentiates methylmalonate-induced oxidative stress in brain and kidney of rats.

    Science.gov (United States)

    Schuck, P F; Alves, L; Pettenuzzo, L F; Felisberto, F; Rodrigues, L B; Freitas, B W; Petronilho, F; Dal-Pizzol, F; Streck, E L; Ferreira, G C

    2013-03-01

    Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. The disease is clinically characterized by progressive neurological deterioration and kidney failure, whose pathophysiology is still unclear. In the present work we investigated the effects of acute MMA administration on various parameters of oxidative stress in cerebral cortex and kidney of young rats, as well as the influence of acute renal failure on MMA-elicited effects on these parameters. Acute renal failure was induced by gentamicin, an aminoglycoside antibiotic whose utilization over prolonged periods causes nephrotoxicity. The administration of gentamicin alone increased carbonyl content and inhibited superoxide dismutase (SOD) activity in cerebral cortex, as well as increased thiobarbituric acid-reactive substances (TBA-RS) and sulfhydryl levels and diminished glutathione peroxidase activity in kidney. On the other hand, MMA administration increased TBA-RS levels in cerebral cortex and decreased SOD activity in kidney. Furthermore, the simultaneous administration of MMA and gentamicin to the rats provoked an augment in TBA-RS levels and superoxide generation in cerebral cortex and in TBA-RS, carbonyl and sulfhydryl levels in kidney, while diminished SOD activity in both studied tissues. Finally, nitrate/nitrite content, reduced glutathione levels, 2',7'-dihydrodichlorofluorescein oxidation and catalase activity were not affected by this animal treatment in either tissue. In conclusion, our present data are in line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on oxidative stress parameters in brain and peripheral tissues.

  5. Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.

    Science.gov (United States)

    Duffy, B A; Chun, K P; Ma, D; Lythgoe, M F; Scott, R C

    2014-03-01

    Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus.

  6. The impact of early aerobic exercise on brain microvascular alterations induced by cerebral hypoperfusion.

    Science.gov (United States)

    Leardini-Tristão, Marina; Borges, Juliana Pereira; Freitas, Felipe; Rangel, Raquel; Daliry, Anissa; Tibiriçá, Eduardo; Estato, Vanessa

    2017-02-15

    The therapeutic potential of early exercise training following cerebral hypoperfusion was investigated on brain perfusion and inflammation in rats with permanent bilateral occlusion of the common carotid arteries (2VO). Wistar rats were subjected to 2VO or sham surgery and each group was then subdivided randomly into sedentary or exercise groups. Early exercise training was initiated after three days of 2VO or sham surgery and consisted of seven days of treadmill training (30min/day at ∼60% of maximal exercise test), composing four groups: 1) Sham sedentary (Sham-Sed), 2) Sham exercised (Sham-Ex), 3) 2VO sedentary (2VO-Sed) and 4) 2VO exercised (2VO-Ex). Microvascular cerebral blood flow (MCBF) and NADPH oxidase and eNOS gene expression were evaluated by laser speckle contrast imaging and RT-PCR, respectively, and brain functional capillary density and endothelial-leukocyte interactions were evaluated by fluorescence intravital video-microscopy. The 2VO-Sed group presented a decrease in MCBF (Sham-Sed: 230.9±12.2 vs. 2VO-Sed: 183.6±10.6 arbitrary perfusion units, Pexercise was able to prevent the cerebral microvascular inflammation by decreasing endothelial-leukocyte interactions (2VO-Ex: 0.9±0.3 vs. 2VO-Sed: 5±0.6cells/min/100μm, Pbrain NADPH oxidase gene expression (2VO-Ex: 1.7±0.1 arbitrary units, Pexercise may represent a means of preventing the microvascular alterations induced by chronic cerebral hypoperfusion.

  7. Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.

    Directory of Open Access Journals (Sweden)

    Dashdemberel Narantuya

    Full Text Available BACKGROUND AND PURPOSE: Microglia are resident immunocompetent and phagocytic cells of central nervous system (CNS, which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal cerebral ischemia model in rat. METHODS: Transient middle cerebral artery occlusion (MCAO in rats was induced by the intraluminal filament technique. HMO6 cells, human microglial cell line, were transplanted intravenously at 48 hours after MCAO. Functional tests were performed and the infarct volume was measured at 7 and 14 days after MCAO. Migration and cell survival of transplanted microglial cells and host glial reaction in the brain were studied by immunohistochemistry. Gene expression of neurotrophic factors, cytokines and chemokines in transplanted cells and host rat glial cells was determined by laser capture microdissection (LCM and quantitative real time-PCR. RESULTS: HMO6 human microglial cells transplantation group demonstrated significant functional recovery compared with control group. At 7 and 14 days after MCAO, infarct volume was significantly reduced in the HMO group. In the HMO6 group, number of apoptotic cells was time-dependently reduced in the infarct core and penumbra. In addition, number of host rat microglia/macrophages and reactive astrocytes was significantly decreased at 7 and 14 days after MCAO in the penumbra. Gene expression of various neurotrophic factors (GDNF, BDNF, VEGF and BMP7 and anti-inflammatory cytokines (IL4 and IL5 was up-regulated in transplanted HMO6 cells of brain tissue compared with those in culture. The expression of GDNF and VEGF in astrocytes in penumbra was significantly up-regulated in the HMO6 group. CONCLUSIONS: Our results indicate that transplantation of HMO6 human microglial cells reduces ischemic deficits and apoptotic events in stroke animals. The results were mediated

  8. Nanoscale Particulate Matter from Urban Traffic Rapidly Induces Oxidative Stress and Inflammation in Olfactory Epithelium with Concomitant Effects on Brain

    Science.gov (United States)

    Cheng, Hank; Saffari, Arian; Sioutas, Constantinos; Forman, Henry J.; Morgan, Todd E.; Finch, Caleb E.

    2016-01-01

    Background: Rodent models for urban air pollution show consistent induction of inflammatory responses in major brain regions. However, the initial impact of air pollution particulate material on olfactory gateways has not been reported. Objective: We evaluated the olfactory neuroepithelium (OE) and brain regional responses to a nanosized subfraction of urban traffic ultrafine particulate matter (nPM, < 200 nm) in vivo, ex vivo, and in vitro. Methods: Adult mice were exposed to reaerosolized nPM for 5, 20, and 45 cumulative hours over 3 weeks. The OE, the olfactory bulb (OB), the cerebral cortex, and the cerebellum were analyzed for oxidative stress and inflammatory responses. Acute responses of the OE to liquid nPM suspensions were studied with ex vivo and primary OE cultures. Results: After exposure to nPM, the OE and OB had rapid increases of 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosine (3-NT) protein adducts, whereas the cerebral cortex and cerebellum did not respond at any time. All brain regions showed increased levels of tumor necrosis factor-α (TNFα) protein by 45 hr, with earlier induction of TNFα mRNA in OE and OB. These responses corresponded to in vitro OE and mixed glial responses, with rapid induction of nitrite and inducible nitric oxide synthase (iNOS), followed by induction of TNFα. Conclusions: These findings show the differential time course of oxidative stress and inflammatory responses to nPM between the OE and the brain. Slow cumulative transport of inhaled nPM into the brain may contribute to delayed responses of proximal and distal brain regions, with potential input from systemic factors. Citation: Cheng H, Saffari A, Sioutas C, Forman HJ, Morgan TE, Finch CE. 2016. Nanoscale particulate matter from urban traffic rapidly induces oxidative stress and inflammation in olfactory epithelium with concomitant effects on brain. Environ Health Perspect 124:1537–1546; http://dx.doi.org/10.1289/EHP134 PMID:27187980

  9. Modulation of Postnatal Neurogenesis by Perinatal Asphyxia: Effect of D1 and D2 Dopamine Receptor Agonists.

    Science.gov (United States)

    Tapia-Bustos, A; Perez-Lobos, R; Vío, V; Lespay-Rebolledo, C; Palacios, E; Chiti-Morales, A; Bustamante, D; Herrera-Marschitz, M; Morales, P

    2017-01-01

    Perinatal asphyxia (PA) is associated to delayed cell death, affecting neurocircuitries of basal ganglia and hippocampus, and long-term neuropsychiatric disabilities. Several compensatory mechanisms have been suggested to take place, including cell proliferation and neurogenesis. There is evidence that PA can increase postnatal neurogenesis in hippocampus and subventricular zone (SVZ), modulated by dopamine, by still unclear mechanisms. We have studied here the effect of selective dopamine receptor agonists on cell death, cell proliferation and neurogenesis in organotypic cultures from control and asphyxia-exposed rats. Hippocampus and SVZ sampled at 1-3 postnatal days were cultured for 20-21 days. At day in vitro (DIV) 19, cultures were treated either with SKF38393 (10 and 100 µM, a D1 agonist), quinpirole (10 µM, a D2 agonist) or sulpiride (10 μM, a D2 antagonist) + quinpirole (10 μM) and BrdU (10 μM, a mitosis marker) for 24 h. At DIV 20-21, cultures were processed for immunocytochemistry for microtubule-associated protein-2 (MAP-2, a neuronal marker), and BrdU, evaluated by confocal microscopy. Some cultures were analysed for cell viability at DIV 20-21 (LIVE/DEAD kit). PA increased cell death, cell proliferation and neurogenesis in hippocampus and SVZ cultures. The increase in cell death, but not in cell proliferation, was inhibited by both SKF38393 and quinpirole treatment. Neurogenesis was increased by quinpirole, but only in hippocampus, in cultures from both asphyxia-exposed and control-animals, effect that was antagonised by sulpiride, leading to the conclusion that dopamine modulates neurogenesis in hippocampus, mainly via D2 receptors.

  10. The Appetite-Inducing Peptide, Ghrelin, Induces Intracellular Store-Mediated Rises in Calcium in Addiction and Arousal-Related Laterodorsal Tegmental Neurons in Mouse Brain Slices

    DEFF Research Database (Denmark)

    Hauberg, Katrine; Kohlmeier, Kristi Anne

    2015-01-01

    Ghrelin, a gut and brain peptide, has recently been shown to be involved in motivated behavior and regulation of the sleep and wakefulness cycle. The laterodorsal tegmental nucleus (LDT) is involved in appetitive behavior and control of the arousal state of an organism, and accordingly, behavioral...... this peptide has been shown in other cell types to lead to rises in calcium via release of calcium from intracellular stores. To determine whether ghrelin induced intracellular calcium rises in mouse LDT neurons, we conducted calcium imaging studies in LDT brain slices loaded with the calcium binding dye, Fura...

  11. Glucocorticoids regulation of FosB/ΔFosB expression induced by chronic opiate exposure in the brain stress system.

    Directory of Open Access Journals (Sweden)

    Daniel García-Pérez

    Full Text Available Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects of ΔFosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/ΔFosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/ΔFosB was measured in control (sham-operated and adrenalectomized (ADX rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/ΔFosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell (NAc, bed nucleus of the stria terminalis (BNST, central amygdala (CeA, hypothalamic paraventricular nucleus (PVN and nucleus of the solitary tract noradrenergic cell group (NTS-A(2. Adrenalectomy attenuated the increased production of FosB/ΔFosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/ΔFosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A(2 TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/ΔFosB to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.

  12. Critical role of peripheral vasoconstriction in fatal brain hyperthermia induced by MDMA (Ecstasy) under conditions that mimic human drug use.

    Science.gov (United States)

    Kiyatkin, Eugene A; Kim, Albert H; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2014-06-04

    MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed "rave" parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22-23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ~1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues.

  13. Alcohol-induced One-carbon Metabolism Impairment Promotes Dysfunction of DNA Base Excision Repair in Adult Brain*

    Science.gov (United States)

    Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G.; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J.; Bergeson, Susan E.; Henderson, George I.; Kruman, Inna I.

    2012-01-01

    The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr+/− mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain. PMID:23118224

  14. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

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    Junhwan Kim

    2016-01-01

    Full Text Available Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  15. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

    Science.gov (United States)

    Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  16. Neuroprotective effect of Cucumis melo Var. flexuosus leaf extract on the brains of rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Ibrahim, Doaa S

    2017-02-01

    The central nervous system is one of the most vulnerable organs affected by the oxidative stress associated with diabetes mellitus. Healthy food provides an important source for antioxidants. Therefore, the protective effect of Cucumis melo var. flexuosus (C. melo var. flexuosus) leaf extract on the brains of diabetic rats was investigated. Adult male albino rats divided into 5 groups of 6 rats each were assigned into a normal control group and four diabetic groups. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg bw). One of the four diabetic groups was left untreated and was considered as a diabetic control group while the three other groups were treated with C. melo var. flexuosus leaf extract at the doses of 30, 60 and 120 mg/kg bw for a period of 30 days. After completion of experimental duration plasma and brains were used for evaluating biochemical changes. The obtained data showed that C. melo var. flexuosus leaf extract treatment lowered blood glucose, glycated hemoglobin, brain tumor necrosis factor-alpha, interleukin levels, brain malondialdehyde content and caspase-3 activity. Furthermore, the treatment resulted in a marked increase in plasma dopamine, melatonin, brain vascular endothelial growth factor-A levels, brain catalase and superoxide dismutase activities. From the present study, it can be concluded that the C. melo var. flexuosus leaf extract exerts a neuroprotective effect against oxidative damage associated with diabetes.

  17. Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study.

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    Kuo-Chen Wei

    Full Text Available The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI-monitored focused ultrasound (FUS-induced blood-brain barrier (BBB disruption to enhance Temozolomide (TMZ delivery for improving Glioblastoma Multiforme (GBM treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF and plasma by LC-MS\\MS. The effects of treatment on tumor progression (by MRI, animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment.

  18. Resuscitation therapy for traumatic brain injury-induced coma in rats:mechanisms of median nerve electrical stimulation

    Institute of Scientific and Technical Information of China (English)

    Zhen Feng; Ying-jun Zhong; Liang Wang; Tian-qi Wei

    2015-01-01

    In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually in-creased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our ifndings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the pre-frontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

  19. Resuscitation therapy for traumatic brain injury-induced coma in rats: mechanisms of median nerve electrical stimulation

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    Zhen Feng

    2015-01-01

    Full Text Available In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

  20. Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney.

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh; Samini, Fariborz

    2017-03-01

    Restraint stress has been indicated to induce oxidative damage in tissues. Several investigations have reported that curcumin (CUR) may have a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CUR on restraint stress induced oxidative stress damage in the brain, liver and kidneys. For chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days. The animals received systemic administrations of CUR daily for 21days. In order to evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), as well as antioxidant enzyme activities superoxide dismutase (SOD) glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were measured in the brain, liver and kidney of rats after the end of restraint stress. The restraint stress significantly increased MDA level, but decreased the level of GSH and activists of SOD, GPx, GR, and CAT the brain, liver and kidney of rats in comparison to the normal rats (Poxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in the tissues versus the control group (Pstress-induced oxidative damage in the brain, liver and kidney of rats and propose that CUR may be useful agents against oxidative stress in the tissues.

  1. Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model

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    Zhang, Xu; Zhou, Jianying; Chin, Mark H; Schepmoes, Athena A; Petyuk, Vladislav A; Weitz, Karl K; Petritis, Brianne O; Monroe, Matthew E; Camp, David G; Wood, Stephen A; Melega, William P; Bigelow, Diana J; Smith, Desmond J; Qian, Weijun; Smith, Richard D

    2010-02-15

    Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in each analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-β pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of

  2. Reducing one million child deaths from birth asphyxia – a survey of health systems gaps and priorities

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    Manandhar Ananta

    2007-05-01

    Full Text Available Abstract Background Millions of child deaths and stillbirths are attributable to birth asphyxia, yet limited information is available to guide policy and practice, particularly at the community level. We surveyed selected policymakers, programme implementers and researchers to compile insights on policies, programmes, and research to reduce asphyxia-related deaths. Method A questionnaire was developed and pretested based on an extensive literature review, then sent by email (or airmail or fax, when necessary to 453 policymakers, programme implementers, and researchers active in child health, particularly at the community level. The survey was available in French and English and employed 5-point scales for respondents to rate effectiveness and feasibility of interventions and indicators. Open-ended questions permitted respondents to furnish additional details based on their experience. Significance testing was carried out using chi-square, F-test and Fisher's exact probability tests as appropriate. Results 173 individuals from 32 countries responded (44%. National newborn survival policies were reported to exist in 20 of 27 (74% developing countries represented, but respondents' answers were occasionally contradictory and revealed uncertainty about policy content, which may hinder policy implementation. Respondents emphasized confusing terminology and a lack of valid measurement indicators at community level as barriers to obtaining accurate data for decision making. Regarding interventions, birth preparedness and essential newborn care were considered both effective and feasible, while resuscitation at community level was considered less feasible. Respondents emphasized health systems strengthening for both supply and demand factors as programme priorities, particularly ensuring wide availability of skilled birth attendants, promotion of birth preparedness, and promotion of essential newborn care. Research priorities included operationalising

  3. Inulin supplementation during gestation mitigates acrylamide-induced maternal and fetal brain oxidative dysfunctions and neurotoxicity in rats.

    Science.gov (United States)

    Krishna, Gokul; Muralidhara

    2015-01-01

    Accumulating evidence suggests that the developing brain is more susceptible to a variety of chemicals. Recent studies have shown a link between the enteric microbiota and brain function. While supplementation of non-digestible oligosaccharides during pregnancy has been demonstrated to positively influence human health mediated through stimulation of beneficial microbiota, our understanding on their neuromodulatory propensity is limited. In the present study, our primary focus was to examine whether supplementation of inulin (a well known fructan) during gestation can abrogate acrylamide (ACR)-induced oxidative impairments and neurotoxicity in maternal and fetal brain of rats. Initially, in a dose-determinative study, we recapitulated the impact of ACR exposure during gestation days (GD 6-19) on gestational parameters, extent of oxidative impairments in brain (maternal/fetal), cholinergic function and neurotoxicity. Subsequently, pregnant rats orally (gavage) administered with inulin (IN, 2 g/kg/day in two equal installments) supplements during gestation days (GD 0-19) were exposed to ACR (200 ppm) in drinking water. IN supplements significantly attenuated ACR-induced changes in exploratory activity (reduced open field exploration) measured on GD 14. Further, IN restored the placental weights among ACR exposed dams. Analysis of biochemical markers revealed that IN supplements effectively offset ACR associated oxidative stress not only in the maternal brain, but in the fetal brain as well. Elevated levels of protein carbonyls in maternal brain regions were completely normalized with IN supplements. More importantly, IN supplements significantly augmented the number of Bifidobacteria in the cecum of ACR rats which correlated well with the neurorestorative effect as evidenced by restored dopamine levels in the maternal cortex and fetal brain acetylcholinesterase activity among ACR-exposed dams. Further, IN supplements also conferred significant protection against

  4. Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression.

    Science.gov (United States)

    Adlard, P A; Cotman, C W

    2004-01-01

    Exercise is increasingly recognized as an intervention that can reduce CNS dysfunctions such as cognitive decline, depression and stress. Previously we have demonstrated that brain-derived neurotrophic factor (BDNF) is increased in the hippocampus following exercise. In this study we tested the hypothesis that exercise can counteract a reduction in hippocampal BDNF protein caused by acute immobilization stress. Since BDNF expression is suppressed by corticosterone (CORT), circulating CORT levels were also monitored. In animals subjected to 2 h immobilization stress, CORT was elevated immediately following, and at 1 h after the cessation of stress, but remained unchanged from baseline up to 24 h post-stress. The stress protocol resulted in a reduction in BDNF protein at 5 and 10 h post-stress that returned to baseline at 24 h. To determine if exercise could prevent this stress-induced reduction in BDNF protein, animals were given voluntary access to running wheels for 3 weeks prior to the stress. Stressed animals, in the absence of exercise, again demonstrated an initial elevation in CORT (at 0 h) and a subsequent decrease in hippocampal BDNF at the 10 h time point. Exercising animals, both non-stressed and stressed, demonstrated circulating CORT and hippocampal BDNF protein levels that were significantly elevated above control values at both time points examined (0 and 10 h post-stress). Thus, the persistently high CORT levels in exercised animals did not affect the induction of BDNF with exercise, and the effect of immobilization stress on BDNF protein was overcome. To examine the role of CORT in the stress-related regulation of BDNF protein, experiments were carried out in adrenalectomized (ADX) animals. BDNF protein was not downregulated as a result of immobilization stress in ADX animals, while there continued to be an exercise-induced upregulation of BDNF. This study demonstrates that CORT modulates stress-related alterations in BDNF protein. Further, exercise

  5. Oxidative Stress Induced by Cigarette Smoke Extracts in Human Brain Cells (T98G) and Human Brain Microvascular Endothelial Cells (HBMEC) in Mono- and Co-Culture.

    Science.gov (United States)

    Kim, Ju-Hyeong; Cho, Myung-Haing; Choi, Kyung-Chul; Lee, Kyuhong; Kim, Kwang-Sik; Shim, Soon-Mi

    2015-01-01

    The objective of the current study was to examine oxidative stress induced by cigarette smoke extract (CSE) or cigarette smoke condensate (CSC) in human brain cells (T98G) and human brain microvascular endothelial cells (HBMEC) in mono- and co-culture systems. Cell viability of T98G cells exposed to CSC (0.05-4 mg/ml) was significantly decreased compared to CSE (0.025-20%). There were no marked differences between quantities of reactive oxygen species (ROS) generation by either CSE (2, 4, and 10%) or CSC (0.2, 0.4, and 0.8 mg/ml) treatment compared to control. However, a significant effect was noted in ROS generation following CSC incubation at 4mg/ml. Cellular integrity of HBMEC decreased to 74 and 64% within 120 h of exposure at the IC50 value of CSE and CSC, respectively. This study suggests that chronic exposure to cigarette smoking might initiate damage to the blood-brain barrier.

  6. Brain-computer interfacing using modulations of alpha activity induced by covert shifts of attention

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    Schmidt Nico M

    2011-05-01

    Full Text Available Abstract Background Visual brain-computer interfaces (BCIs often yield high performance only when targets are fixated with the eyes. Furthermore, many paradigms use intense visual stimulation, which can be irritating especially in long BCI sessions. However, BCIs can more directly directly tap the neural processes underlying visual attention. Covert shifts of visual attention induce changes in oscillatory alpha activity in posterior cortex, even in the absence of visual stimulation. The aim was to investigate whether different pairs of directions of attention shifts can be reliably differentiated based on the electroencephalogram. To this end, healthy participants (N = 8 had to strictly fixate a central dot and covertly shift visual attention to one out of six cued directions. Results Covert attention shifts induced a prolonged alpha synchronization over posterior electrode sites (PO and O electrodes. Spectral changes had specific topographies so that different pairs of directions could be differentiated. There was substantial variation across participants with respect to the direction pairs that could be reliably classified. Mean accuracy for the best-classifiable pair amounted to 74.6%. Furthermore, an alpha power index obtained during a relaxation measurement showed to be predictive of peak BCI performance (r = .66. Conclusions Results confirm posterior alpha power modulations as a viable input modality for gaze-independent EEG-based BCIs. The pair of directions yielding optimal performance varies across participants. Consequently, participants with low control for standard directions such as left-right might resort to other pairs of directions including top and bottom. Additionally, a simple alpha index was shown to predict prospective BCI performance.

  7. Contribution of brain serotonin subtype 1B receptors in levodopa-induced motor complications.

    Science.gov (United States)

    Morin, Nicolas; Morissette, Marc; Grégoire, Laurent; Rajput, Alex; Rajput, Ali H; Di Paolo, Thérèse

    2015-12-01

    L-DOPA-induced dyskinesias (LID) are abnormal involuntary movements limiting the chronic use of L-DOPA, the main pharmacological treatment of Parkinson's disease. Serotonin receptors are implicated in the development of LID and modulation of basal ganglia 5-HT1B receptors is a potential therapeutic alternative in Parkinson's disease. In the present study, we used receptor-binding autoradiography of the 5-HT1B-selective radioligand [3H]GR125743 to investigate possible contributions of changes in ligand binding of this receptor in LID in post-mortem brain specimens from Parkinson's disease patients (n=14) and control subjects (n=11), and from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys treated with saline (n=5), L-DOPA (n=4) or L-DOPA+2-methyl-6-(phenylethynyl)pyridine (MPEP) (n=5), and control monkeys (n=4). MPEP is the prototypal metabotropic glutamate 5 (mGlu5) receptor antagonist and has been shown to reduce the development of LID in these monkeys in a chronic treatment of one month. [3H]GR125743 specific binding to striatal and pallidal 5-HT1B receptors respectively were only increased in L-DOPA-treated MPTP monkeys (dyskinetic monkeys) as compared to controls, saline and L-DOPA+MPEP MPTP monkeys; dyskinesias scores correlated positively with this binding. Parkinson's disease patients with motor complications (L-DOPA-induced dyskinesias and wearing-off) had higher [3H]GR125743 specific binding compared to those without motor complications and controls in the basal ganglia. Reduction of motor complications was associated with normal striatal 5-HT1B receptors, suggesting the potential of this receptor for the management of motor complications in Parkinson's disease.

  8. The Ayurvedic drug, Ksheerabala, ameliorates quinolinic acid-induced oxidative stress in rat brain.

    Science.gov (United States)

    Swathy, S S; Indira, M

    2010-01-01

    One of the mechanisms of neurotoxicity is the induction of oxidative stress. There is hardly any cure for neurotoxicity in modern medicine, whereas many drugs in Ayurveda possess neuroprotective effects; however, there is no scientific validation for these drugs. Ksheerabala is an ayurvedic drug which is used to treat central nervous system disorders, arthritis, and insomnia. The aim of our study was to evaluate the effect of Ksheerabala on quinolinic acid-induced toxicity in rat brain. The optimal dose of Ksheerabala was found from a dose escalation study, wherein it was found that Ksheerabala showed maximum protection against quinolinic acid-induced neurotoxicity at a dose of 15 microL/100 g body weight/day, which was selected for further experiments. Four groups of female albino rats were maintained for 21 days as follows: 1. Control group, 2. Quinolinic acid (55 microg/100 g body weight), 3. Ksheerabala (15 microL/100 g body weight), 4. Ksheerabala (15 microL/100 g body weight) + Quinolinic acid (55 microg/100 g body weight). At the end of the experimental period, levels of lipid peroxidation products, protein carbonyls, and activities of scavenging enzymes were analyzed. The results revealed that quinolinic acid intake caused enhanced lipid and protein peroxidation as evidenced by increased levels of peroxidation products such as malondialdehyde, hydroperoxide, conjugated dienes, and protein carbonyls. On the other hand, the activities of scavenging enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase, and glutathione reductase as well as the concentration of glutathione were reduced. On coadminstration of Ksheerabala along with quinolinic acid, the levels of all the biochemical parameters were restored to near-normal levels, indicating the protective effect of the drug. These results were reinforced by histopathological studies.

  9. Neuroprotective effects of cold-inducible RNA-binding protein during mild hypothermia on traumatic brain injur y

    Institute of Scientific and Technical Information of China (English)

    Guan Wang; Jian-ning Zhang; Jia-kui Guo; Ying Cai; Hong-sheng Sun; Kun Dong; Cheng-gang Wu

    2016-01-01

    Cold-inducible RNA-binding protein (CIRP), a key regulatory protein, could be facilitated by mild hypothermia in the brain, heart and liver. This study observed the effects of mild hypothermia at 31 ± 0.5°C on traumatic brain injury in rats. Results demonstrated that mild hypothermia suppressed apoptosis in the cortex, hippocampus and hypothalamus, facilitated CIRP mRNA and protein expression in these regions, especially in the hypothalamus. The anti-apoptotic effect of mild hypothermia disappeared after CIRP silencing. There was no correlation between mitogen-activated extracellular signal-regulated kinase activation and CIRP silencing. CIRP silencing inhibited extracellular signal-regulated kinase-1/2 activation. These indicate that CIRP inhibits apoptosis by affecting extracellular signal-regulated kinase-1/2 activation, and exerts a neuroprotective effect during mild hypothermia for traumatic brain injury.

  10. Radiation damage to the normal monkey brain: experimental study induced by interstitial irradiation.

    Directory of Open Access Journals (Sweden)

    Mishima N

    2003-06-01

    Full Text Available Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT, magnetic resonance imaging (MRI, and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis.

  11. Neuroprotective effects of dexmedetomidine against hyperoxia-induced injury in the developing rat brain

    Science.gov (United States)

    Endesfelder, Stefanie; Makki, Hanan; von Haefen, Clarissa; Spies, Claudia D.; Bührer, Christoph; Sifringer, Marco

    2017-01-01

    Dexmedetomidine (DEX) is a highly selective agonist of α2-receptors with sedative, anxiolytic, and analgesic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on hippocampal neurogenesis, specifically the proliferation capacity and maturation of neurons and neuronal plasticity following the induction of hyperoxia in neonatal rats. Six-day old sex-matched Wistar rats were exposed to 80% oxygen or room air for 24 h and treated with 1, 5 or 10 μg/kg of dexmedetomidine or normal saline. A single pretreatment with DEX attenuated the hyperoxia-induced injury in terms of neurogenesis and plasticity. In detail, both the proliferation capacity (PCNA+ cells) as well as the expression of neuronal markers (Nestin+, PSA-NCAM+, NeuN+ cells) and transcription factors (SOX2, Tbr1/2, Prox1) were significantly reduced under hyperoxia compared to control. Furthermore, regulators of neuronal plasticity (Nrp1, Nrg1, Syp, and Sema3a/f) were also drastically decreased. A single administration of dexmedetomid