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Sample records for brain damage induced

  1. Methadone-Induced Toxic Brain Damage

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    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.

  2. BHT blocks NF-kappaB activation and ethanol-induced brain damage.

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    Crews, Fulton; Nixon, Kimberly; Kim, Daniel; Joseph, James; Shukitt-Hale, Barbara; Qin, Liya; Zou, Jian

    2006-11-01

    Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol-induced degeneration is unknown, but is not simple glutamate-N-methyl-D-aspartate (NMDA) excitotoxicity. To test the hypothesis that oxidative stress and inflammation are mechanisms of binge ethanol-induced brain damage, we administered 4 antioxidants, e.g., butylated hydroxytoluene (BHT), ebselen (Eb), vitamin E (VE), and blueberry (BB) extract, during binge ethanol treatment and assessed various measures of neurodegeneration. Adult Sprague-Dawley rats were treated with intragastric ethanol 3 times per day (8-12 g/kg/d) alone or in combination with antioxidants or isocaloric diet for 4 days. Animals were killed, and brains were perfused and extracted for histochemical silver stain determination of brain damage, markers of neurogenesis, or other immunohistochemistry. Some animals were used for determination of nuclear factor kappa B (NF-kappaB)-DNA binding by electrophoretic mobility shift assay (EMSA) or for reverse transcription-polymerase chain reaction (RT-PCR) of cyclooxygenase 2 (COX2). Binge ethanol induced corticolimbic brain damage and reduced neurogenesis. Treatment with BHT reversed binge induced brain damage and blocked ethanol inhibition of neurogenesis in all regions studied. Interestingly, the other antioxidants studied, e.g., Eb, VE, and BB, did not protect against binge-induced brain damage. Binge ethanol treatment also caused microglia activation, increased NF-kappaB-DNA binding and COX2 expression. Butylated hydroxytoluene reduced binge-induced NF-kappaB-DNA binding and COX2 expression. Binge-induced brain damage and activation of NF-kappaB-DNA binding are blocked by BHT. These studies support a neuroinflammatory mechanism of binge ethanol-induced brain damage.

  3. 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.

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

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    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.

  5. Protective effects of melatonin on the ionizing radiation induced DNA damage in the rat brain.

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    Undeger, Ulko; Giray, Belma; Zorlu, A Faruk; Oge, Kamil; Baçaran, Nurçen

    2004-03-01

    Melatonin is an endogenously produced antioxidant with radioprotective actions while ionizing radiation is a well-known cytotoxic and mutagenic agent of which the biological results are attributable to its free radical producing effects. The effect of melatonin on the DNA strand breakage and lipid peroxidation induced by ionizing radiation in the rat brain were investigated in order to clarify its radioprotective ability. The DNA strand breakage in rat brain exposed to 1000 cGy ionizing radiation was assessed by alkaline single cell gel electrophoresis and the lipid peroxidation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) concentrations. A significant increase in DNA damage (p radiation treated rat brain. Pre-treatment of rats with intraperitoneal doses of 100 mg/kg melatonin provided a significant decrease in the DNA strand breakage and lipid peroxidation. Our results indicate that melatonin can protect brain cells from oxidative damage induced by ionizing radiation.

  6. 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

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

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    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

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

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    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.

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

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    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.

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

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    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.

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

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    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

  12. 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.

  13. 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.

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    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.

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

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    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.

  15. Endoplasmic Reticulum Stress Mediates Methamphetamine-Induced Blood-Brain Barrier Damage.

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    Qie, Xiaojuan; Wen, Di; Guo, Hongyan; Xu, Guanjie; Liu, Shuai; Shen, Qianchao; Liu, Yi; Zhang, Wenfang; Cong, Bin; Ma, Chunling

    2017-01-01

    Methamphetamine (METH) abuse causes serious health problems worldwide, and long-term use of METH disrupts the blood-brain barrier (BBB). Herein, we explored the potential mechanism of endoplasmic reticulum (ER) stress in METH-induced BBB endothelial cell damage in vitro and the therapeutic potential of endoplasmic reticulum stress inhibitors for METH-induced BBB disruption in C57BL/6J mice. Exposure of immortalized BMVEC (bEnd.3) cells to METH significantly decreased cell viability, induced apoptosis, and diminished the tightness of cell monolayers. METH activated ER stress sensor proteins, including PERK, ATF6, and IRE1, and upregulated the pro-apoptotic protein CHOP. The ER stress inhibitors significantly blocked the upregulation of CHOP. Knockdown of CHOP protected bEnd.3 cells from METH-induced cytotoxicity. Furthermore, METH elevated the production of reactive oxygen species (ROS) and induced the dysfunction of mitochondrial characterized by a Bcl2/Bax ratio decrease, mitochondrial membrane potential collapse, and cytochrome c. ER stress release was partially reversed by ROS inhibition, and cytochrome c release was partially blocked by knockdown of CHOP. Finally, PBA significantly attenuated METH-induced sodium fluorescein (NaFluo) and Evans Blue leakage, as well as tight junction protein loss, in C57BL/6J mice. These data suggest that BBB endothelial cell damage was caused by METH-induced endoplasmic reticulum stress, which further induced mitochondrial dysfunction, and that PBA was an effective treatment for METH-induced BBB disruption.

  16. 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.

  17. Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

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    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.

  18. Contextualizing aquired brain damage

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2014-01-01

    Contextualizing aquired brain damage Traditional approaches study ’communicational problems’ often in a discourse of disabledness or deficitness. With an ontology of communcation as something unique and a presupposed uniqueness of each one of us, how could an integrational approach (Integrational...... for people with aquired brain injuries will be presented and comparatively discussed in a traditional versus an integrational perspective. Preliminary results and considerations on ”methods” and ”participation” from this study will be presented along with an overview of the project's empirical data....

  19. Radiation damage to the normal monkey brain: experimental study induced by interstitial irradiation.

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    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.

  20. Prenatal Brain Damage in Preeclamptic Animal Model Induced by Gestational Nitric Oxide Synthase Inhibition

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    Begoña Pellicer

    2011-01-01

    Full Text Available Cerebral palsy is a major neonatal handicap with unknown aetiology. There is evidence that prenatal brain injury is the leading cause of CP. Severe placental pathology accounts for a high percentage of cases. Several factors predispose to prenatal brain damage but when and how they act is unclear. The aim of this paper was to determine if hypoxia during pregnancy leads to damage in fetal brain and to evaluate the localization of this injury. An animal model of chronic hypoxia produced by chronic administration of a nitric oxide synthase inhibitor (L-NAME was used to evaluate apoptotic activity in fetal brains and to localize the most sensitive areas. L-NAME reproduces a preeclamptic-like condition with increased blood pressure, proteinuria, growth restriction and intrauterine mortality. Apoptotic activity was increased in L-NAME brains and the most sensitive areas were the subventricular and pallidum zone. These results may explain the clinical features of CP. Further studies are needed.

  1. Contextualizing aquired brain damage

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    Contextualizing aquired brain damage Traditional approaches study ’communicational problems’ often in a discourse of disabledness or deficitness. With an ontology of communcation as something unique and a presupposed uniqueness of each one of us, how could an integrational approach (Integrational...... Linguistics) help facilitate a new methodological perspective on the study of problems in interpersonal communication and could such a research contribute to develop a methodology that studied ”howabledness” (a term borrowed from Pirkko Raudaskoski) rather than disabledness? A study on ”inclusion” at a centre...... for people with aquired brain injuries will be presented and comparatively discussed in a traditional versus an integrational perspective. Preliminary results and considerations on ”methods” and ”participation” from this study will be presented along with an overview of the project's empirical data....

  2. Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats.

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    Huang, Jingyang; Liu, Baoyi; Yang, Chenghui; Chen, Haili; Eunice, Dzivor; Yuan, Zhongrui

    2013-10-16

    Hyperglycemia adversely affects the outcome of ischemic stroke. Extracellular HMGB1 plays a role in aggravating brain damage in the postischemic brain. The aim of this study was to determine whether the extracellular HMGB1 is involved in the worsened ischemic damage during hyperglycemic stroke. Male Wistar rats underwent middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Acute hyperglycemia was induced by an injection of 50% dextrose. Rats received glycyrrhizin, a specific HMGB1 inhibitor, or vehicle. HMGB-1 in cerebrospinal fluid and in brain parenchyma was detected at 2 or 4 h post-reperfusion. Neurological deficits, infarct volume and cerebral edema were assessed 24 h post-MCAO the disruption of blood-brain barrier (BBB) and the expression of tight junction protein Occludin were measured at 4 h post-reperfusion. Hyperglycemia enhanced the early release of HMGB1 from ischemic brain tissue, which was accompanied by increased infarct volume, neurological deficit, cerebral edema and BBB disruption. Glycyrrhizin alleviated the aggravation of infarct volume, neurological deficit, cerebral edema and BBB disruption by decreasing the degradation of tight junction protein Occludin in the ischemic hemisphere of hyperglycemic rats. In conclusion, enhanced early extracellular release of HMGB1 might represent an important mechanism for worsened ischemic damage, particularly early BBB disruption, during hyperglycemic stroke. An HMGB1 inhibitor glycyrrhizin is a potential therapeutic option for hyperglycemic stroke.

  3. Contextualizing aquired brain damage

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2014-01-01

    Linguistics) help facilitate a new methodological perspective on the study of problems in interpersonal communication and could such a research contribute to develop a methodology that studied ”howabledness” (a term borrowed from Pirkko Raudaskoski) rather than disabledness? A study on ”inclusion” at a centre......Contextualizing aquired brain damage Traditional approaches study ’communicational problems’ often in a discourse of disabledness or deficitness. With an ontology of communcation as something unique and a presupposed uniqueness of each one of us, how could an integrational approach (Integrational...

  4. L-tyrosine induces DNA damage in brain and blood of rats.

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    De Prá, Samira D T; Ferreira, Gabriela K; Carvalho-Silva, Milena; Vieira, Júlia S; Scaini, Giselli; Leffa, Daniela D; Fagundes, Gabriela E; Bristot, Bruno N; Borges, Gabriela D; Ferreira, Gustavo C; Schuck, Patrícia F; Andrade, Vanessa M; Streck, Emilio L

    2014-01-01

    Mutations in the tyrosine aminotransferase gene have been identified to cause tyrosinemia type II which is inherited in an autosomal recessive manner. Studies have demonstrated that an excessive production of ROS can lead to reactions with macromolecules, such as DNA, lipids, and proteins. Considering that the L-tyrosine may promote oxidative stress, the main objective of this study was to investigate the in vivo effects of L-tyrosine on DNA damage determined by the alkaline comet assay, in brain and blood of rats. In our acute protocol, Wistar rats (30 days old) were killed 1 h after a single intraperitoneal L-tyrosine injection (500 mg/kg) or saline. For chronic administration, the animals received two subcutaneous injections of L-tyrosine (500 mg/kg, 12-h intervals) or saline administered for 24 days starting at postnatal day (PD) 7 (last injection at PD 31), 12 h after the last injection, the animals were killed by decapitation. We observed that acute administration of L-tyrosine increased DNA damage frequency and damage index in cerebral cortex and blood when compared to control group. Moreover, we observed that chronic administration of L-tyrosine increased DNA damage frequency and damage index in hippocampus, striatum, cerebral cortex and blood when compared to control group. In conclusion, the present work demonstrated that DNA damage can be encountered in brain from animal models of hypertyrosinemia, DNA alterations may represent a further means to explain neurological dysfunction in this inherited metabolic disorder and to reinforce the role of oxidative stress in the pathophysiology of tyrosinemia type II.

  5. 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.

  6. Detection of Low Level Microwave Radiation Induced Deoxyribonucleic Acid Damage Vis-à-vis Genotoxicity in Brain of Fischer Rats

    Science.gov (United States)

    Deshmukh, Pravin Suryakantrao; Megha, Kanu; Banerjee, Basu Dev; Ahmed, Rafat Sultana; Chandna, Sudhir; Abegaonkar, Mahesh Pandurang; Tripathi, Ashok Kumar

    2013-01-01

    Background: Non-ionizing radiofrequency radiation has been increasingly used in industry, commerce, medicine and especially in mobile phone technology and has become a matter of serious concern in present time. Objective: The present study was designed to investigate the possible deoxyribonucleic acid (DNA) damaging effects of low-level microwave radiation in brain of Fischer rats. Materials and Methods: Experiments were performed on male Fischer rats exposed to microwave radiation for 30 days at three different frequencies: 900, 1800 and 2450 MHz. Animals were divided into 4 groups: Group I (Sham exposed): Animals not exposed to microwave radiation but kept under same conditions as that of other groups, Group II: Animals exposed to microwave radiation at frequency 900 MHz at specific absorption rate (SAR) 5.953 × 10−4 W/kg, Group III: Animals exposed to 1800 MHz at SAR 5.835 × 10−4 W/kg and Group IV: Animals exposed to 2450 MHz at SAR 6.672 × 10−4 W/kg. At the end of the exposure period animals were sacrificed immediately and DNA damage in brain tissue was assessed using alkaline comet assay. Results: In the present study, we demonstrated DNA damaging effects of low level microwave radiation in brain. Conclusion: We concluded that low SAR microwave radiation exposure at these frequencies may induce DNA strand breaks in brain tissue. PMID:23833433

  7. 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.

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

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    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.

  9. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: an FTIR microspectroscopic imaging study.

    Science.gov (United States)

    Cakmak, Gulgun; Miller, Lisa M; Zorlu, Faruk; Severcan, Feride

    2012-04-15

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH(2) groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH(3) groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  11. Emotionalism Following Brain Damage

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    Peter Allman

    1991-01-01

    Full Text Available Emotionalism is an heightened tendency to cry, or more rarely, laugh. It is commonly associated with brain damage and is often distressing to both patients and carers. Emotionalism is easily confused with depression, and when severe it can interfere with treatment. The aetiology is poorly understood but its response to drugs with different modes of action suggests that there is more than one underlying mechanism. When the components of emotionalism are studied separately a wide range is observed and they combine in a more complex and varied way than commonly held stereotyped views suggest. Most patients with emotionalism are helped by simple education and reassurance. Some severe cases respond dramatically to tricyclic antidepressants, levodopa or fluoxetine.

  12. 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.

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

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    Eridan eRocha-Ferreira

    2015-02-01

    subsequent brain damage.

  14. Beneficial Effects of Teucrium polium and Metformin on Diabetes-Induced Memory Impairments and Brain Tissue Oxidative Damage in Rats

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    S. Mojtaba Mousavi

    2015-01-01

    Full Text Available Objective. The effects of hydroalcoholic extract of Teucrium polium and metformin on diabetes-induced memory impairment and brain tissues oxidative damage were investigated. Methods. The rats were divided into: (1 Control, (2 Diabetic, (3 Diabetic-Extract 100 (Dia-Ext 100, (4 Diabetic-Extract 200 (Dia-Ext 200, (5 Diabetic-Extract 400 (Dia-Ext 400, and (6 Diabetic-Metformin (Dia-Met. Groups 3–6 were treated by 100, 200, and 400 mg/kg of the extract or metformin, respectively, for 6 weeks (orally. Results. In passive avoidance test, the latency to enter the dark compartment in Diabetic group was lower than that of Control group (P<0.01. In Dia-Ext 100, Dia-Ext 200, and Dia-Ext 400 and Metformin groups, the latencies were higher than those of Diabetic group (P<0.01. Lipid peroxides levels (reported as malondialdehyde, MDA, concentration in the brain of Diabetic group were higher than Control (P<0.001. Treatment by all doses of the extract and metformin decreased the MDA concentration (P<0.01. Conclusions. The results of present study showed that metformin and the hydroalcoholic extract of Teucrium polium prevent diabetes-induced memory deficits in rats. Protection against brain tissues oxidative damage might have a role in the beneficial effects of the extract and metformin.

  15. 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

  16. Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by Soman. (Reannouncement with new availability information)

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    Sparenborg, S.; Brennecke, L.H.; Jaax, N.K.; Braitman, D.J.

    1992-12-31

    The involvement of the NMDA receptor in the neurotoxicity induced by soman, an organophosphorus compound which irreversibly inhibits cholinesterase, was studied in guinea pigs. The drug MK-801 (0.5, 1 or 5 mg/kg, i.p.) was given as a pretreatment before a convulsant dose of soman or as a post treatment (30, 100 or 300 micron g/kg, i.m.) 5 min after the development of soman-induced status epilepticus. Pyridostigmine, atropine and pralidoxime chloride were also given to each subject to counteract the lethality of soman. All subjects that were challenged with soman and given the vehicle for MK-801 (saline) exhibited severe convulsions and electrographic seizure activity. Neuronal necrosis was found in the hippocampus, amygdala, thalamus and the pyriform and cerebral cortices of those subjects surviving for 48 hr. Pretreatment with 0.5 or 1 mg/kg doses of MK-801 did not prevent nor delay the onset of seizure activity but did diminish its intensity and led to its early arrest. At the largest dose (5 mg/kg), MK-801 completely prevented the development of seizure activity and brain damage. Post treatment with MK-801 prevented, arrested or reduced seizure activity, convulsions and neuronal necrosis in a dose-dependent manner. The NMDA receptor may play a more critical role in the spread and maintenance, rather than the initiation of cholinergically-induced seizure activity....Seizure-related brain damage, Organophosphorus compound, Nerve agent, Cholinesterase inhibition, Excitotoxicity, Guinea pig.

  17. Air pollution and brain damage.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Azzarelli, Biagio; Acuna, Hilda; Garcia, Raquel; Gambling, Todd M; Osnaya, Norma; Monroy, Sylvia; DEL Tizapantzi, Maria Rosario; Carson, Johnny L; Villarreal-Calderon, Anna; Rewcastle, Barry

    2002-01-01

    Exposure to complex mixtures of air pollutants produces inflammation in the upper and lower respiratory tract. Because the nasal cavity is a common portal of entry, respiratory and olfactory epithelia are vulnerable targets for toxicological damage. This study has evaluated, by light and electron microscopy and immunohistochemical expression of nuclear factor-kappa beta (NF-kappaB) and inducible nitric oxide synthase (iNOS), the olfactory and respiratory nasal mucosae, olfactory bulb, and cortical and subcortical structures from 32 healthy mongrel canine residents in Southwest Metropolitan Mexico City (SWMMC), a highly polluted urban region. Findings were compared to those in 8 dogs from Tlaxcala, a less polluted, control city. In SWMMC dogs, expression of nuclear neuronal NF-kappaB and iNOS in cortical endothelial cells occurred at ages 2 and 4 weeks; subsequent damage included alterations of the blood-brain barrier (BBB), degenerating cortical neurons, apoptotic glial white matter cells, deposition of apolipoprotein E (apoE)-positive lipid droplets in smooth muscle cells and pericytes, nonneuritic plaques, and neurofibrillary tangles. Persistent pulmonary inflammation and deteriorating olfactory and respiratory barriers may play a role in the neuropathology observed in the brains of these highly exposed canines. Neurodegenerative disorders such as Alzheimer's may begin early in life with air pollutants playing a crucial role.

  18. Investigation of cavitation as a possible damage mechanism in blast-induced traumatic brain injury.

    Science.gov (United States)

    Goeller, Jacques; Wardlaw, Andrew; Treichler, Derrick; O'Bruba, Joseph; Weiss, Greg

    2012-07-01

    Cavitation was investigated as a possible damage mechanism for war-related traumatic brain injury (TBI) due to an improvised explosive device (IED) blast. When a frontal blast wave encounters the head, a shock wave is transmitted through the skull, cerebrospinal fluid (CSF), and tissue, causing negative pressure at the contrecoup that may result in cavitation. Numerical simulations and shock tube experiments were conducted to determine the possibility of cranial cavitation from realistic IED non-impact blast loading. Simplified surrogate models of the head consisted of a transparent polycarbonate ellipsoid. The first series of tests in the 18-inch-diameter shock tube were conducted on an ellipsoid filled with degassed water to simulate CSF and tissue. In the second series, Sylgard gel, surrounded by a layer of degassed water, was used to represent the tissue and CSF, respectively. Simulated blast overpressure in the shock tube tests ranged from a nominal 10-25 pounds per square inch gauge (psig; 69-170 kPa). Pressure in the simulated CSF was determined by Kulite thin line pressure sensors at the coup, center, and contrecoup positions. Using video taken at 10,000 frames/sec, we verified the presence of cavitation bubbles at the contrecoup in both ellipsoid models. In all tests, cavitation at the contrecoup was observed to coincide temporally with periods of negative pressure. Collapse of the cavitation bubbles caused by the surrounding pressure and elastic rebound of the skull resulted in significant pressure spikes in the simulated CSF. Numerical simulations using the DYSMAS hydrocode to predict onset of cavitation and pressure spikes during cavity collapse were in good agreement with the tests. The numerical simulations and experiments indicate that skull deformation is a significant factor causing cavitation. These results suggest that cavitation may be a damage mechanism contributing to TBI that requires future study.

  19. Radiation induces progenitor cell death, microglia activation, and blood-brain barrier damage in the juvenile rat cerebellum

    Science.gov (United States)

    Zhou, Kai; Boström, Martina; Ek, C. Joakim; Li, Tao; Xie, Cuicui; Xu, Yiran; Sun, Yanyan; Blomgren, Klas; Zhu, Changlian

    2017-01-01

    Posterior fossa tumors are the most common childhood intracranial tumors, and radiotherapy is one of the most effective treatments. However, irradiation induces long-term adverse effects that can have significant negative impacts on the patient’s quality of life. The purpose of this study was to characterize irradiation-induced cellular and molecular changes in the cerebellum. We found that irradiation-induced cell death occurred mainly in the external germinal layer (EGL) of the juvenile rat cerebellum. The number of proliferating cells in the EGL decreased, and 82.9% of them died within 24 h after irradiation. Furthermore, irradiation induced oxidative stress, microglia accumulation, and inflammation in the cerebellum. Interestingly, blood-brain barrier damage and blood flow reduction was considerably more pronounced in the cerebellum compared to other brain regions. The cerebellar volume decreased by 39% and the migration of proliferating cells to the internal granule layer decreased by 87.5% at 16 weeks after irradiation. In the light of recent studies demonstrating that the cerebellum is important not only for motor functions, but also for cognition, and since treatment of posterior fossa tumors in children typically results in debilitating cognitive deficits, this differential susceptibility of the cerebellum to irradiation should be taken into consideration for future protective strategies. PMID:28382975

  20. 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.

  1. Sarin-induced brain damage in rats is attenuated by delayed administration of midazolam.

    Science.gov (United States)

    Chapman, Shira; Yaakov, Guy; Egoz, Inbal; Rabinovitz, Ishai; Raveh, Lily; Kadar, Tamar; Gilat, Eran; Grauer, Ettie

    2015-07-01

    Sarin poisoned rats display a hyper-cholinergic activity including hypersalivation, tremors, seizures and death. Here we studied the time and dose effects of midazolam treatment following nerve agent exposure. Rats were exposed to sarin (1.2 LD50, 108 μg/kg, im), and treated 1 min later with TMB4 and atropine (TA 7.5 and 5 mg/kg, im, respectively). Midazolam was injected either at 1 min (1 mg/kg, im), or 1 h later (1 or 5 mg/kg i.m.). Cortical seizures were monitored by electrocorticogram (ECoG). At 5 weeks, rats were assessed in a water maze task, and then their brains were extracted for biochemical analysis and histological evaluation. Results revealed a time and dose dependent effects of midazolam treatment. Rats treated with TA only displayed acute signs of sarin intoxication, 29% died within 24h and the ECoG showed seizures for several hours. Animals that received midazolam within 1 min survived with only minor clinical signs but with no biochemical, behavioral, or histological sequel. Animals that lived to receive midazolam at 1h (87%) survived and the effects of the delayed administration were dose dependent. Midazolam 5 mg/kg significantly counteracted the acute signs of intoxication and the impaired behavioral performance, attenuated some of the inflammatory response with no effect on morphological damage. Midazolam 1mg/kg showed only a slight tendency to modulate the cognitive function. In addition, the delayed administration of both midazolam doses significantly attenuated ECoG compared to TA treatment only. These results suggest that following prolonged seizure, high dose midazolam is beneficial in counteracting adverse effects of sarin poisoning.

  2. Isoflurane Damages the Developing Brain of Mice and Induces Subsequent Learning and Memory Deficits through FASL-FAS Signaling

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    Xiuwen Yi

    2015-01-01

    Full Text Available Background. Isoflurane disrupts brain development of neonatal mice, but its mechanism is unclear. We explored whether isoflurane damaged developing hippocampi through FASL-FAS signaling pathway, which is a well-known pathway of apoptosis. Method. Wild type and FAS- or FASL-gene-knockout mice aged 7 days were exposed to either isoflurane or pure oxygen. We used western blotting to study expressions of caspase-3, FAS (CD95, and FAS ligand (FASL or CD95L proteins, TUNEL staining to count apoptotic cells in hippocampus, and Morris water maze (MWM to evaluate learning and memory. Result. Isoflurane increased expression of FAS and FASL proteins in wild type mice. Compared to isoflurane-treated FAS- and FASL-knockout mice, isoflurane-treated wild type mice had higher expression of caspase-3 and more TUNEL-positive hippocampal cells. Expression of caspase-3 in wild isoflurane group, wild control group, FAS/FASL-gene-knockout control group, and FAS/FASL-gene-knockout isoflurane group showed FAS or FASL gene knockout might attenuate increase of caspase-3 caused by isoflurane. MWM showed isoflurane treatment of wild type mice significantly prolonged escape latency and reduced platform crossing times compared with gene-knockout isoflurane-treated groups. Conclusion. Isoflurane induces apoptosis in developing hippocampi of wild type mice but not in FAS- and FASL-knockout mice and damages brain development through FASL-FAS signaling.

  3. Right Hemisphere Brain Damage

    Science.gov (United States)

    ... or hemispheres. Each hemisphere is responsible for different body functions and skills. In most people, the left side of the brain contains the person's language functions. The right side contributes to a number ...

  4. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage.

    Science.gov (United States)

    Bae, Ok-Nam; Majid, Arshad

    2013-08-21

    Urgent need exists for new therapeutic options in ischemic stroke. We recently demonstrated that carnosine, an endogenous dipeptide consisting of alanine and histidine, is robustly neuroprotective in ischemic brain injury and has a wide clinically relevant therapeutic time window. The precise mechanistic pathways that mediate this neuroprotective effect are not known. Following in vivo administration, carnosine is hydrolyzed into histidine, a precursor of histamine. It has been hypothesized that carnosine may exert its neuroprotective activities through the histidine/histamine pathway. Herein, we investigated whether the neuroprotective effect of carnosine is mediated by the histidine/histamine pathway using in vitro primary astrocytes and cortical neurons, and an in vivo rat model of ischemic stroke. In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death. In primary neuronal cultures, carnosine was found to be neuroprotective but histamine receptor antagonists had no effect on the extent of neuroprotection. The in vivo effect of histidine and carnosine was compared using a rat model of ischemic stroke; only carnosine exhibited neuroprotection. Taken together, our data demonstrate that although the protective effects of carnosine may be partially mediated by activity at the histamine type 1 receptor on astrocytes, the histidine/histamine pathway does not appear to play a critical role in carnosine induced neuroprotection.

  5. Human-induced pluripotent stem cells form functional neurons and improve recovery after grafting in stroke-damaged brain.

    Science.gov (United States)

    Oki, Koichi; Tatarishvili, Jemal; Wood, James; Koch, Philipp; Wattananit, Somsak; Mine, Yutaka; Monni, Emanuela; Tornero, Daniel; Ahlenius, Henrik; Ladewig, Julia; Brüstle, Oliver; Lindvall, Olle; Kokaia, Zaal

    2012-06-01

    Reprogramming of adult human somatic cells to induced pluripotent stem cells (iPSCs) is a novel approach to produce patient-specific cells for autologous transplantation. Whether such cells survive long-term, differentiate to functional neurons, and induce recovery in the stroke-injured brain are unclear. We have transplanted long-term self-renewing neuroepithelial-like stem cells, generated from adult human fibroblast-derived iPSCs, into the stroke-damaged mouse and rat striatum or cortex. Recovery of forepaw movements was observed already at 1 week after transplantation. Improvement was most likely not due to neuronal replacement but was associated with increased vascular endothelial growth factor levels, probably enhancing endogenous plasticity. Transplanted cells stopped proliferating, could survive without forming tumors for at least 4 months, and differentiated to morphologically mature neurons of different subtypes. Neurons in intrastriatal grafts sent axonal projections to the globus pallidus. Grafted cells exhibited electrophysiological properties of mature neurons and received synaptic input from host neurons. Our study provides the first evidence that transplantation of human iPSC-derived cells is a safe and efficient approach to promote recovery after stroke and can be used to supply the injured brain with new neurons for replacement. Copyright © 2012 AlphaMed Press.

  6. The effects of different fractions of Coriandrum sativum on pentylenetetrazole-induced seizures and brain tissues oxidative damage in rats

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    Akbar Anaeigoudari

    2016-03-01

    Full Text Available Objective: In the present work, the effects of different fractions of Coriandrum sativum (C. sativum, on pentylenetetrazole (PTZ-induced seizures and brain tissues oxidative damage were investigated in rats. Materials and Methods: The rats were divided into the following groups: (1 vehicle, (2 PTZ (90 mg/kg, (3 water fraction (WF of C. sativum (25 and 100 mg/kg, (4 n-butanol fraction (NBF of C. sativum (25 and 100 mg/kg, and (5 ethyl acetate fraction (EAF of C. sativum (25 and 100 mg/kg. Results: The first generalized tonic-clonic seizures (GTCS latency in groups treated with 100 mg /kg of WF or EAF was significantly higher than that of PTZ group (p< 0.01. In contrast to WF, the EAF and NBF were not effective in increasing the first minimal clonic seizure (MCS latency. Malondialdehyde (MDA levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of control animals (p< 0.001. Pretreatment with WF, NBF, or EAF resulted in a significant reduction in the MDA levels of hippocampi (pConclusion: The present study showed that different fractions of C. sativum possess antioxidant activity in the brain and WF and EAF of this plant have anticonvulsant effects.

  7. Triethyllead-induced peroxidative damage in various regions of the rat brain

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    Ali, S.F. (Univ. of Arkansas for Medical Sciences, Little Rock (USA)); Bondy, S.C. (Univ. of California, Irvine (USA))

    1989-01-01

    Adult male Fisher 344 rats (8-10 wk old) were dosed ip with 1.75 mg/kg body weight of triethyllead chloride (TEL) for 5 consecutive days. Rats were sacrificed 1, 7, or 21 d after the last injection. The rate of lipid peroxidation was significantly elevated in frontal cortex at all three time points assayed (1, 7, or 21 d). However, hippocampal and cerebellar membranes showed no changes in peroxidative capacity at these time points. In order to determine whether cortical membrane damage was reflected in alteration of a restricted protein population, a series of high-affinity receptor binding sites was determined in cortical membranes derived from treated rats 7 d after the last injection of triethyllead. The rate of lipid peroxidation was significantly increased in the frontal cortex of triethyllead treated rats; however, no changes in the binding of ({sup 3}H)spiroperidol, ({sup 3}H)quinuclidinyl benzilate, and ({sup 3}H)benzodiazepine were seen in animals exposed to triethyllead. The cortical wet weight, protein content, and cell number were also unchanged by TEL treatment, reflecting an absence of gross damage.

  8. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-22

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

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

    Directory of Open Access Journals (Sweden)

    Ming-Yan Hei

    2012-10-01

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

  11. A Brain-Damage Advantage for Lefties?

    Science.gov (United States)

    Bower, B.

    1985-01-01

    Reports that people who are predominantly left-handed apparently are able to withstand moderate brain damage with relatively few of the motor problems observed in right-handed victims of brain damage. Other brain-related differences between left- and right-handed individuals are also noted. (JN)

  12. Arsenic-induced mitochondrial oxidative damage is mediated by decreased PGC-1α expression and its downstream targets in rat brain.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-08-25

    The present study was carried out to investigate the molecular mechanism of arsenic-induced mitochondrial oxidative damage and its relation to biogenesis in rat brain. Chronic sodium arsenite (25 ppm, orally) administration for 12 weeks decreased mitochondrial complexes activities and mRNA expression of selective complexes subunits. The expression of mitochondrial biogenesis regulator PGC-1α, and its downstream targets NRF-1, NRF-2 and Tfam were decreased significantly both at mRNA and protein levels suggesting impaired biogenesis following chronic arsenic-exposure. In addition to this, protein expression analysis also revealed activation of Bax and caspase-3, leading to translocation of cytochrome c from mitochondria to cytosol suggesting induction of apoptotic pathway under oxidative stress. This was further confirmed by electron microscopy study which depicted morphological changes in mitochondria in terms of altered nuclear and mitochondrial shape and chromatin condensation in arsenic-treated rats. The immunohistochemical studies showed both nuclear and cytosolic localization of NRF-1 and NRF-2 in arsenic-exposed rat brain further suggesting regulatory role of these transcription factors under arsenic neurotoxicity. The results of present study indicate that arsenic-induced mitochondrial oxidative damage is associated with decreased mitochondrial biogenesis in rat brain that may present as important target to reveal the mechanism for arsenic-induced neurotoxicity.

  13. Brain Damage in Deaf Vocational Rehabilitation Clients.

    Science.gov (United States)

    Getz, Marc; Vernon, McCay

    1986-01-01

    Screening of 54 deaf vocational clients by the Bender-Gestalt and other tests indicated the likely presence of significantly more brain damage than among the hearing population with a particularly high correlation between low IQ and brain damage in the deaf population. (DB)

  14. Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

    DEFF Research Database (Denmark)

    Hansen, H.H.; Ramos, J.A.; Fernández-Ruiz, J.

    2002-01-01

    The ability of cannabinoid CB, receptors to influence glutamatergic excitatory neurotransmission has fueled interest in how these receptors and their endogenous ligands may interact in conditions of excitotoxic insults. The present study characterized the impact of stimulated and inhibited CB...... receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA......-induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest...

  15. Endoplasmic reticulum stress-induced apoptosis in the penumbra aggravates secondary damage in rats with traumatic brain injur y

    Institute of Scientific and Technical Information of China (English)

    Guo-zhu Sun; Fen-fei Gao; Zong-mao Zhao; Hai Sun; Wei Xu; Li-wei Wu; Yong-chang He

    2016-01-01

    Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated, mitochondrial, and endo-plasmic reticulum stress pathways. Few studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury, and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic penumbra. Here, we established rat models of lfuid percussion-induced traumatic brain injury and found that protein expression of caspase-12, caspase-3 and the endoplasmic reticulum stress marker 78 kDa glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 hours. Furthermore, numbers of terminal deoxynucleotidyl transferase-mediat-ed dUTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after injury. These ifndings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra, and may play an important role in the pathophysiology of secondary brain injury.

  16. The effects of captopril on lipopolysaccharide induced learning and memory impairments and the brain cytokine levels and oxidative damage in rats.

    Science.gov (United States)

    Abareshi, Azam; Hosseini, Mahmoud; Beheshti, Farimah; Norouzi, Fatemeh; Khazaei, Majid; Sadeghnia, Hamid Reza; Boskabady, Mohammad Hossein; Shafei, Mohammad Naser; Anaeigoudari, Akbar

    2016-12-15

    Renin-angiotensin system has a role in inflammation and also involves in learning and memory. In the present study, the effects of captopril on lipopolysaccharide (LPS) induced learning and memory impairments, hippocampal cytokine levels and brain tissues oxidative damage was investigated. The rats were divided and treated : [1] saline (Control), [2] LPS (1mg/kg), [3-5] 10, 50 or 100mg/kg captopril 30min before LPS. The treatment was started since six days before the behavioral experiments and continued during the behavioral tests (LPS injection two h before each behavioral experiment). Administration of LPS prolonged the escape latency and traveled path to find the platform in Morris water maze (MWM) test (Pcaptopril improved performances of the rats in MWM (Pcaptopril (Pcaptopril (Pcaptopril improved the LPS-induced learning and memory impairments in rats which were accompanied with attenuating hippocampal cytokine levels and improving the brain tissues oxidative damage criteria. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Lignans from Schisandra chinensis ameliorate cognition deficits and attenuate brain oxidative damage induced by D-galactose in rats.

    Science.gov (United States)

    Yan, Tingxu; Shang, Lei; Wang, Mengshi; Zhang, Chenning; Zhao, Xu; Bi, Kaishun; Jia, Ying

    2016-06-01

    The aim of this study was to explore the neuroprotective effects of active compounds from Schisandra chinensis (Trucz.) Baill. (Magnoliaceae) against the D-galactose (D-gal)-induced neurotoxicity in rat. The Wistar rats were subcutaneously injected with D-gal (150 mg/(kg day)) for six weeks and orally administered with water extract or 95 % ethanol extract (partitioned with petroleum ether (PE), chloroform (CF), ethyl acetate (EA) and n-Butanol (NB), respectively) of the fruits of Schisandra chinensis simultaneously. The alteration of cognitive functions was assessed by using Morris water maze and Step-down type passive avoidance test. The results demonstrated that PE fraction was the most effective fraction to ameliorate cognitive deficits. Further biochemical examination indicated that PE could attenuate the activities decreasing of superoxide dismutase (SOD), catalase (CAT), the total antioxidant (T-AOC) induced by D-gal, and maintain the normal levels of glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) in the serum, prefrontal cortex, striatum and hippocampus of the brain of related rat, selectively. Meanwhile, the compounds of PE fraction were also identified as mainly lignans, thus, these results suggest that lignans from the PE fraction of Schisandra chinensis represented a potential source of medicine for the treatment of the aging-associated neurodegenerative diseases.

  18. Indomethacin protects rats from neuronal damage induced by traumatic brain injury and suppresses hippocampal IL-1β release through the inhibition of Nogo-A expression

    Directory of Open Access Journals (Sweden)

    Chao Po-Kuan

    2012-06-01

    Full Text Available Abstract Background Nogo-A is a member of the reticulon family of membrane-associated proteins and plays an important role in axonal remodeling. The present study aimed to investigate alterations in Nogo-A expression following traumatic brain injury (TBI-induced inflammation and neuronal damage. Methods A weight-drop device was used to deliver a standard traumatic impact to rats. Western blot, RT-PCR and ELISA were used to analyze the expression of Nogo-A and IL-1β. Nogo-A antisense, and an irrelevant control oligonucleotide was intracerebroventricularly infused. We also performed H & E staining and luxol fast blue staining to evaluate the neuronal damage and demyelination resulting from TBI and various treatments. Results Based on RT-PCR and western blot analyses, the expression of Nogo-A was found to be significantly upregulated in the hippocampus beginning eight hours after TBI. In addition, TBI caused an apparent elevation in IL-1β levels and severe neuronal damage and demyelination in the tested animals. All of the TBI-associated molecular and cellular consequences could be effectively reversed by treating the animals with the anti-inflammatory drug indomethacin. More importantly, the TBI-associated stimulation in the levels of both Nogo-A and IL-1β could be effectively inhibited by a specific Nogo-A antisense oligonucleotide. Conclusions Our findings suggest that the suppression of Nogo-A expression appears to be an early response conferred by indomethacin, which then leads to decreases in the levels of IL-1β and TBI-induced neuron damage.

  19. Effect of microglia in alcohol-induced brain damage%小胶质细胞在酒精性脑损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    李锦程; 赵海苹; 罗玉敏

    2014-01-01

    Alcohol has a significant effect on the central nervous system, as the key immune effector cells in the brain, some studies proved that microglia plays an important role in the neurotoxicity of alcohol, which can lead to neuronal death and degeneration. Some investigations demonstrated that microglia is beneficial to maintain a steady state rather than causing nerve degeneration, microglia activation is the end of the damage induced by the alcohol rather than cause. This paper reviews the microglial response and related mechanism in neuronal death and degeneration caused by alcohol.%饮酒对中枢神经系统有重大影响,小胶质细胞是脑内原位免疫效应细胞,它在乙醇引起的神经毒性中有重要作用,可导致神经元死亡与退行性变;小胶质细胞有利于维持稳态而不是导致神经退行性变,小胶质细胞活化是乙醇引起损害的结果而不是损害的原因。本文对乙醇引起的神经元死亡和退行性变中小胶质细胞的反应及相应机制作一综述。

  20. Musical anhedonia after focal brain damage.

    Science.gov (United States)

    Belfi, Amy M; Evans, Erin; Heskje, Jonah; Bruss, Joel; Tranel, Daniel

    2017-03-01

    People listen to music because it is pleasurable. However, there are individual differences in the reward value of music. At the extreme low end of this continuum, individuals who derive no pleasure from music are said to have 'musical anhedonia.' Cases of acquired musical anhedonia following focal brain damage are rare, with only a handful having been reported in the scientific literature. Here, we surveyed a large sample of patients with focal brain damage to identify the frequency, specificity, and neural correlates of acquired musical anhedonia. Participants completed the Musical anhedonia Questionnaire and the Barcelona Music Reward Questionnaire (Mas-Herrero et al., 2013) to assess changes in musical enjoyment and reward following brain injury. Neuroanatomical data were analyzed with a proportional MAP-3 method to create voxelwise lesion proportion difference maps. No clear or consistent neuroanatomical correlates of musical anhedonia were identified. One patient with damage to the right-hemisphere putamen and internal capsule displayed specific and severe acquired musical anhedonia. These findings indicate that acquired musical anhedonia is very uncommon, a result which is consistent with the fact that only a small number of such cases have been reported in the literature. This rarity could have positive implications for the therapeutic potentialities of music in patients with severe neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Evoked brain potentials and disability in brain-damaged patients.

    Science.gov (United States)

    Rappaport, M; Hall, K; Hopkins, K; Belleza, T; Berrol, S; Reynolds, G

    1977-08-01

    Various measures of evoked brain potential abnormality (EPA) were correlated with disability ratings (DR) for 35 brain-damaged patients. EPA data consisted of judgements of abnormality of ipsilateral, contralateral and bilateral responses to auditory and visual stimuli reflecting activity in the brain stem, subcortex and cortex. DR data were obtained from a scale developed for this study to quantize and categorize patients with a wide range of disabilities from coma to normal functioning. EPA scores based on visual and auditory cortical responses showed significantly positive correlations with degree of disability. Visual response correlation was .49, auditory .38 and combined visual and auditory .51. It was concluded that EPA measures can reflect disability independently of clinical information. They are useful in assessing brain function in general and, specifically, in assessing impairment of sensory function. The evoked potential technique was particularly useful in patients who were not able to participate fully in their own examination. There were indications that the technique may also be valuable in monitoring progress and in predicting clinical outcome in brain-damaged patients.

  2. Feedback and neuroplasticity rehabilitation for brain damage

    Institute of Scientific and Technical Information of China (English)

    Eli Carmeli

    2014-01-01

    Neuroplasticity,also known as brain plasticity,refers to the brain tissue's ability to be repaired to reorganized and to create new connections among the nerve cells.It implies that the location of a given function in the brain (for example,certain area in the motor cortex) can displace to another area of the cortex.This transfer ability can be accomplished by sensory motor feedback training.In the case of cerebral palsy (CP) and stroke,neuroplasticity relates to unaffected nerve cells and new synaptogenesis process taking over the functions of damaged nerve cells and their connections.The aim of this overview is to explain how does neuroplasticity work and how intensive sensory motor feedback training can reorganize nerve cells.Although neurorehabilitation offers a series of therapies from the psychological to occupational,speech,teaching or re-training patients on mobility skills,this overview focuses on physical rehabilitation using a comprehensive feedback system to accelerate brain recovery.

  3. Acrylonitrile-induced oxidative DNA damage in rat astrocytes.

    Science.gov (United States)

    Pu, Xinzhu; Kamendulis, Lisa M; Klaunig, James E

    2006-10-01

    Chronic administration of acrylonitrile results in a dose-related increase in astrocytomas in rat brain, but the mechanism of acrylonitrile carcinogenicity is not fully understood. The potential of acrylonitrile or its metabolites to induce direct DNA damage as a mechanism for acrylonitrile carcinogenicity has been questioned, and recent studies indicate that the mechanism involves the induction of oxidative stress in rat brain. The present study examined the ability of acrylonitrile to induce DNA damage in the DI TNC1 rat astrocyte cell line using the alkaline Comet assay. Oxidized DNA damage also was evaluated using formamidopyrimidine DNA glycosylase treatment in the modified Comet assay. No increase in direct DNA damage was seen in astrocytes exposed to sublethal concentrations of acrylonitrile (0-1.0 mM) for 24 hr. However, acrylonitrile treatment resulted in a concentration-related increase in oxidative DNA damage after 24 hr. Antioxidant supplementation in the culture media (alpha-tocopherol, (-)-epigallocathechin-3 gallate, or trolox) reduced acrylonitrile-induced oxidative DNA damage. Depletion of glutathione using 0.1 mM DL-buthionine-[S,R]-sulfoximine increased acrylonitrile-induced oxidative DNA damage (22-46%), while cotreatment of acrylonitrile with 2.5 mM L-2-oxothiazolidine-4-carboxylic acid, a precursor for glutathione biosynthesis, significantly reduced acrylonitrile-induced oxidative DNA damage (7-47%). Cotreatment of acrylonitrile with 0.5 mM 1-aminobenzotriazole, a suicidal inhibitor of cytochrome P450, prevented the oxidative DNA damage produced by acrylonitrile. Cyanide (0.1-0.5 mM) increased oxidative DNA damage (44-160%) in astrocytes. These studies demonstrate that while acrylonitrile does not directly damage astrocyte DNA, it does increase oxidative DNA damage. The oxidative DNA damage following acrylonitrile exposure appears to arise mainly through the P450 metabolic pathway; moreover, glutathione depletion may contribute to the

  4. DNA damage induced by phenylalanine and its analogue p-chlorophenylalanine in blood and brain of rats subjected to a model of hyperphenylalaninemia.

    Science.gov (United States)

    Simon, Kellen R; Dos Santos, Rosane M; Scaini, Giselli; Leffa, Daniela D; Damiani, Adriani P; Furlanetto, Camila B; Machado, Jéssica L; Cararo, José H; Macan, Tamires P; Streck, Emilio L; Ferreira, Gustavo C; Andrade, Vanessa M; Schuck, Patrícia F

    2013-10-01

    Phenylketonuria (PKU) is a disease caused by a deficiency of phenylalanine hydroxylase (PAH), resulting in an accumulation of phenylalanine (Phe) in the brain tissue, cerebrospinal fluid, and other tissues of PKU patients. Considering that high levels of Phe are associated with neurological dysfunction and that the mechanisms underlying the neurotoxicity in PKU remain poorly understood, the main objective of this study was to investigate the in vivo and in vitro effects of Phe on DNA damage, as determined by the alkaline comet assay. The results showed that, compared to control group, the levels of DNA migration were significantly greater after acute administration of Phe, p-chlorophenylalanine (p-Cl-Phe, an inhibitor of PAH), or a combination thereof in cerebral cortex and blood, indicating DNA damage. These treatments also provoked increase of carbonyl content. Additionally, when Phe or p-Cl-Phe was present in the incubation medium, we observed an increase in the frequency and index of DNA damage in the cerebral cortex and blood, without affecting lactate dehydrogenase (LDH) release. Our in vitro and in vivo findings indicate that DNA damage occurs in the cerebral cortex and blood of rats receiving Phe, suggesting that this mechanism could be, at least in part, responsible for the neurological dysfunction in PKU patients.

  5. An investigation of the effect of thiamine pyrophosphate on cisplatin-induced oxidative stress and DNA damage in rat brain tissue compared with thiamine: thiamine and thiamine pyrophosphate effects on cisplatin neurotoxicity.

    Science.gov (United States)

    Turan, M I; Cayir, A; Cetin, N; Suleyman, H; Siltelioglu Turan, I; Tan, H

    2014-01-01

    This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine. Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses. Oxidative stress is considered responsible for cisplatin toxicity. Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD). TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels. In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1.7 ± 0.12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0.97 ± 0.03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1.55 ± 0.11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group. These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.

  6. Alcohol-related brain damage in humans.

    Directory of Open Access Journals (Sweden)

    Amaia M Erdozain

    Full Text Available Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann's area (BA 9 from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics.

  7. The neuroprotective effect of miRNA-132 against amyloid β-protein-induced neuronal damage via upregulation of brain-derived neurotrophic factor

    Directory of Open Access Journals (Sweden)

    Lei XIANG

    2016-08-01

    Full Text Available Background Brain-derived neurotrophic factor (BDNF plays a crucial role in the pathogenesis of Alzheimer's disease (AD. MicroRNA (miRNA-132, which is widely expressed in neurons, is involved in BDNF-mediated neural development by regulating the expression of target gene. This study aims to investigate the effect of miRNA-132 on BDNF and its neuroprotective effect.  Methods The hippocampal neurons were transfected by miRNA-132 after 72 h in vitro, then exposed to amyloid β-protein (Aβ on the 7th day to build AD models. The difference of miRNA-132 expression between AD group and control group was detected by real-time fluorescent quantitative polymerase chain reaction (PCR. The alterations of BDNF mRNA were observed in the neurons of different groups. Finally, the cell viability was observed by methyl thiazolyl tetrazolium (MTT assay in AD neurons transfected with miRNA-132 or incubated with BDNF. Results 1 MiRNA-132 was significantly decreased (t = 13.888, P = 0.000, and the expression of BDNF mRNA was also reduced in AD group (t = -12.274, P = 0.000. 2 Green fluorescence was clearly visible by inverted phase-contrast fluorescence microscopy after transfected with miRNA-132. BDNF mRNA was upregulated when miRNA-132 overexpression both in control group (t = 16.135, P = 0.000 and AD group (t = 8.656, P = 0.000. 3 Cell viability was obviously decreased in neurons exposed to Aβ (t = -6.023, P = 0.000, which was improved when transfected with miRNA-132 (t = 3.385, P = 0.007 or incubated with BDNF (t = 3.672, P = 0.004.  Conclusions The expression of miRNA-132 and BDNF was reduced in neuronal AD model. MiRNA-132 played an important role on neuroprotection against A β-induced neuronal damage via upregulation of BDNF. It could be expected to provide new perspective for the diagnosis and treatment of AD. DOI: 10.3969/j.issn.1672-6731.2016.07.009

  8. Zika Virus Can Damage Fetal Brain Late in Pregnancy: Study

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_161451.html Zika Virus Can Damage Fetal Brain Late in Pregnancy: Study ... WEDNESDAY, Oct. 12, 2016 (HealthDay News) -- The Zika virus may harm a baby's brain even if the ...

  9. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    Science.gov (United States)

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia.

  10. Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress.

    Science.gov (United States)

    Yang, Hongying; Fan, Shourui; Song, Dianping; Wang, Zhuo; Ma, Shungao; Li, Shuqing; Li, Xiaohong; Xu, Mian; Xu, Min; Wang, Xianmo

    2013-02-01

    The aim of this study was to investigate pathophysiological alterations and oxidative stress in various stages of streptozotocin (STZ)‑induced diabetes mellitus (DM) in rats. Male Sprague-Dawley rats (120) were randomized into DM and control groups. Body mass, plasma glucose, glycated hemoglobin (HbA1c), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, as well as aldose reductase (AR) activities, in brain tissue and serum were determined. Electron microscopy was used to observe neuron and vessel changes in the brain. In STZ‑treated rats, blood glucose, low density lipoproteins, triglycerides and total cholesterol levels increased 1.43‑3.0‑fold and high density lipoprotein, HbA1c and insulin sensitivity index increased 1.1‑1.23‑fold compared with control. At week 16 following treatment, DM rat serum H2O2 concentration was increased, indicating oxidative stress and mRNA levels of GPx and SOD were 2‑fold higher than the control. Protein GPx and SOD levels were reduced (Pblood vessels in the DM rat brains became increasingly abnormal over time with altered Golgi bodies, mitochondria and endoplasmic reticulum cisterns, concurrent with SOD inactivation and AR protein accumulation. Disease progression in rats with STZ‑induced DM included brain pathologies with vascular and neuron cell abnormalities, associated with the reduction of SOD, CAT and GPx activities and also AR accumulation.

  11. Is brain copper deficiency in Alzheimer's, Lewy body, and Creutzfeldt Jakob diseases the common key for a free radical mechanism and oxidative stress-induced damage?

    Science.gov (United States)

    Deloncle, Roger; Guillard, Olivier

    2015-01-01

    In Alzheimer's (AD), Lewy body (LBD), and Creutzfeldt Jakob (CJD) diseases, similar pathological hallmarks have been described, one of which is brain deposition of abnormal protease-resistant proteins. For these pathologies, copper bound to proteins is able to protect against free radicals by reduction from cupric Cu++ to cupreous Cu+. We have previously demonstrated in bovine brain homogenate that free radicals produce proteinase K-resistant prion after manganese is substituted for copper. Since low brain copper levels have been described in transmissible spongiform encephalopathies, in substantia nigra in Parkinson's disease, and in various brain regions in AD, LBD, and CJD, a mechanism has been proposed that may underlie the neurodegenerative processes that occur when copper protection against free radicals is impaired. In peptide sequences, the alpha acid proton near the peptide bond is highly mobile and can be pulled out by free radicals. It will produce a trivalent α-carbon radical and induce a free radical chain process that will generate a D-amino acid configuration in the peptide sequence. Since only L-amino acids are physiologically present in mammalian (human) proteins, it may be supposed that only physiological L-peptides can be recycled by physiological enzymes such as proteases. If a D-amino acid is found in the peptide sequence subsequent to deficient copper protection against free radicals, it will not be recognized and might alter the proteasome L-amino acid recycling from brain peptides. In the brain, there will result an accumulation of abnormal protease-resistant proteins such as those observed in AD, LBD, and CJD.

  12. Radio-induced brain lesions

    Directory of Open Access Journals (Sweden)

    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.

  13. Dexamethasone alleviates tumor-associated brain damage and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Zheng Fan

    Full Text Available Children and adults with the most aggressive form of brain cancer, malignant gliomas or glioblastoma, often develop cerebral edema as a life-threatening complication. This complication is routinely treated with dexamethasone (DEXA, a steroidal anti-inflammatory drug with pleiotropic action profile. Here we show that dexamethasone reduces murine and rodent glioma tumor growth in a concentration-dependent manner. Low concentrations of DEXA are already capable of inhibiting glioma cell proliferation and at higher levels induce cell death. Further, the expression of the glutamate antiporter xCT (system Xc-; SLC7a11 and VEGFA is up-regulated after DEXA treatment indicating early cellular stress responses. However, in human gliomas DEXA exerts differential cytotoxic effects, with some human glioma cells (U251, T98G resistant to DEXA, a finding corroborated by clinical data of dexamethasone non-responders. Moreover, DEXA-resistant gliomas did not show any xCT alterations, indicating that these gene expressions are associated with DEXA-induced cellular stress. Hence, siRNA-mediated xCT knockdown in glioma cells increased the susceptibility to DEXA. Interestingly, cell viability of primary human astrocytes and primary rodent neurons is not affected by DEXA. We further tested the pharmacological effects of DEXA on brain tissue and showed that DEXA reduces tumor-induced disturbances of the microenvironment such as neuronal cell death and tumor-induced angiogenesis. In conclusion, we demonstrate that DEXA inhibits glioma cell growth in a concentration and species-dependent manner. Further, DEXA executes neuroprotective effects in brains and reduces tumor-induced angiogenesis. Thus, our investigations reveal that DEXA acts pleiotropically and impacts tumor growth, tumor vasculature and tumor-associated brain damage.

  14. Brain damage in patients with manifest arterial disease

    NARCIS (Netherlands)

    Raamt, Anne Fleur van

    2006-01-01

    In this thesis we assessed whether the risk factors known to affect markers of brain damage in the general population, also effectuate brain damage in patients who already have symptomatic arterial disease. We found that elevated levels of homocysteine were related to slightly lower global cogniti

  15. Purple Sweet Potato Color Ameliorates Cognition Deficits and Attenuates Oxidative Damage and Inflammation in Aging Mouse Brain Induced by D-Galactose

    Directory of Open Access Journals (Sweden)

    Qun Shan

    2009-01-01

    Full Text Available Purple sweet potato color (PSPC, a naturally occurring anthocyanin, has a powerful antioxidant activity in vitro and in vivo. This study explores whether PSPC has the neuroprotective effect on the aging mouse brain induced by D-galactose (D-gal. The mice administrated with PSPC (100 mg/kg.day, 4 weeks, from 9th week via oral gavage showed significantly improved behavior performance in the open field and passive avoidance test compared with D-gal-treated mice (500 mg/kg.day, 8 weeks. We further investigate the mechanism involved in neuroprotective effects of PSPC on mouse brain. Interestingly, we found, PSPC decreased the expression level of glial fibrillary acidic protein (GFAP, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2, inhibited nuclear translocation of nuclear factor-kappaB (NF-κB, increased the activity of copper/zinc superoxide dismutase (Cu/Zn-SOD and catalase (CAT, and reduced the content of malondialdehyde (MDA, respectively. Our data suggested that PSPC attenuated D-gal-induced cognitive impairment partly via enhancing the antioxidant and anti-inflammatory capacity.

  16. Efficacy of Aqueous Extract of Saffron (Crocus sativus L.) in Modulating Radiation-Induced Brain and Eye Retina Damage in Rats

    OpenAIRE

    Abd El-Azime A. Sh1., Sherif N.H.2 and Eltahawy N. A

    2014-01-01

    Background: Saffron (Crocus sativus L.) is a plant of the iris family (Iridaceae). Its stigma contains crocin, anthocyanin, carotene and lycopene which are known to have pharmacological effects on various illnesses. The aim of present study was to investigate the role of aqueous extract of saffron on the radiation-induced changes in rat (eye retina, brain) tissues and blood. Material & methods: Saffron was supplemented orally, via gavages to rats at dose of 100 mg/Kg body wt/day for 2 weeks p...

  17. TOOL USE DISORDERS AFTER LEFT BRAIN DAMAGE

    Directory of Open Access Journals (Sweden)

    Josselin eBaumard

    2014-05-01

    Full Text Available In this paper we review studies that investigated tool use disorders in left-brain damaged (LBD patients over the last thirty years. Four tasks are classically used in the field of apraxia: Pantomime of tool use, single tool use, real tool use and mechanical problem solving. Our aim was to address two issues, namely, (1 the role of mechanical knowledge in real tool use and (2 the cognitive mechanisms underlying pantomime of tool use, a task widely employed by clinicians and researchers. To do so, we extracted data from 36 papers and computed the difference between healthy subjects and LBD patients. On the whole, pantomime of tool use is the most difficult task and real tool use is the easiest one. Moreover, associations seem to appear between pantomime of tool use, real tool use and mechanical problem solving. These results suggest that the loss of mechanical knowledge is critical in LBD patients, even if all of those tasks (and particularly pantomime of tool use might put differential demands on semantic memory and working memory.

  18. Experience-Dependent Neural Plasticity in the Adult Damaged Brain

    Science.gov (United States)

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

  19. Combined MRI Might Help Predict Brain Damage in Boxers

    Science.gov (United States)

    ... 2017 WEDNESDAY, Aug. 2, 2017 (HealthDay News) -- Brain injuries among pro football players are in the headlines, but pro fighters ... damage. In the boxing ring, as on the football field, recurring blows to the head can cause mild traumatic brain injury. Over time, this can lead to progressive brain ...

  20. Laser-induced damage in optical materials

    CERN Document Server

    Ristau, Detlev

    2014-01-01

    Dedicated to users and developers of high-powered systems, Laser-Induced Damage in Optical Materials focuses on the research field of laser-induced damage and explores the significant and steady growth of applications for high-power lasers in the academic, industrial, and military arenas. Written by renowned experts in the field, this book concentrates on the major topics of laser-induced damage in optical materials and most specifically addresses research in laser damage that occurs in the bulk and on the surface or the coating of optical components. It considers key issues in the field of hi

  1. Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid.

    Science.gov (United States)

    Ghasemi, Simagol; Hosseini, Mahmoud; Feizpour, Azadeh; Alipour, Fatemeh; Sadeghi, Akram; Vafaee, Farzaneh; Mohammadpour, Toktam; Soukhtanloo, Mohammad; Ebrahimzadeh Bideskan, Alireza; Beheshti, Farimah

    2017-04-01

    The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated. The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead - Ascorbic Acid (Lead-AA), (4)  Lead - Garlic (100 mg/kg, daily, gavage) (Lead-Gar). In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues. It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content.

  2. Phosphine-induced oxidative damage in rats: attenuation by melatonin.

    Science.gov (United States)

    Hsu, C; Han, B; Liu, M; Yeh, C; Casida, J E

    2000-02-15

    Phosphine (PH(3)), from hydrolysis of aluminum, magnesium and zinc phosphide, is an insecticide and rodenticide. Earlier observations on PH(3)-poisoned insects, mammals and a mammalian cell line led to the proposed involvement of oxidative damage in the toxic mechanism. This investigation focused on PH(3)-induced oxidative damage in rats and antioxidants as candidate protective agents. Male Wistar rats were treated ip with PH(3) at 2 mg/kg. Thirty min later the brain, liver, and lung were analyzed for glutathione (GSH) levels and lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals) and brain and lung for 8-hydroxydeoxyguanosine (8-OH-dGuo) in DNA. PH(3) caused a significant decrease in GSH concentration and elevation in lipid peroxidation in brain (36-42%), lung (32-38%) and liver (19-25%) and significant increase of 8-OH-dGuo in DNA of brain (70%) and liver (39%). Antioxidants administered ip 30 min before PH(3) were melatonin, vitamin C, and beta-carotene at 10, 30, and 6 mg/kg, respectively. The PH(3)-induced changes were significantly or completely blocked by melatonin while vitamin C and beta-carotene were less effective or inactive. These findings establish that PH(3) induces and melatonin protects against oxidative damage in the brain, lung and liver of rats and suggest the involvement of reactive oxygen species in the genotoxicity of PH(3).

  3. The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain?

    Science.gov (United States)

    Harper, C

    1998-02-01

    The aim of this review is to identify neuropathological changes that are directly related to the long-term use of excessive amounts of alcohol (ethanol). There is still debate as to whether alcohol per se causes brain damage. The main problem has been to identify those lesions caused by alcohol itself and those caused by other common alcohol-related factors, principally thiamin deficiency. Careful selection and classification of alcoholic cases into those with and without these complications, together with detailed quantitative neuropathological analyses, has provided us with useful data. There is brain shrinkage in uncomplicated alcoholics which can largely be accounted for by loss of white matter. Some of this damage appears to be reversible. However, alcohol-related neuronal loss has been documented in specific regions of the cerebral cortex (superior frontal association cortex), hypothalamus (supraoptic and paraventricular nuclei), and cerebellum. The data is conflicting for several regions: the hippocampus, amygdala and locus ceruleus. No change is found in the basal ganglia, nucleus basalis, or serotonergic raphe nuclei. Many of the regions that are normal in uncomplicated alcoholics are damaged in those with the Wernicke-Korsakoff syndrome. Dendritic and synaptic changes have been documented in uncomplicated alcoholics and these, together with receptor and transmitter changes, may explain functional changes and cognitive deficits that precede the more severe structural neuronal changes. The pattern of damage appears to be somewhat different and species-specific in animal models of alcohol toxicity. Pathological changes that have been found to correlate with alcohol intake include white matter loss and neuronal loss in the hypothalamus and cerebellum.

  4. Protective effect of xanthohumol against age-related brain damage.

    Science.gov (United States)

    Rancán, Lisa; Paredes, Sergio D; García, Irene; Muñoz, Pedro; García, Cruz; López de Hontanar, Guzmán; de la Fuente, Mónica; Vara, Elena; Tresguerres, Jesús A F

    2017-07-27

    It has been recently shown that xanthohumol, a flavonoid present in hops, possesses antioxidant, anti-inflammatory and chemopreventive properties. However, its role in the aging brain has not been addressed so far. Therefore, this study aimed to investigate the possible neuroprotective activity of xanthohumol against age-related inflammatory and apoptotic brain damage in male senescence-accelerated prone mice (SAMP8). Animals were divided into 4 groups: Untreated young mice, untreated old mice and old mice treated either with 1 mg kg(-1) day(-1) or 5 mg kg(-1) day(-1) xanthohumol. Young and old senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed and their brains were collected and immediately frozen in liquid nitrogen. mRNA (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, XIAP, NAIP and Bcl-2) and protein (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, BDNF, synaptophysin and synapsin) expressions were measured by RT-PCR and Western blotting, respectively. Significant increased levels of pro-inflammatory (TNF-α, IL-1β) and pro-apoptotic (AIF, BAD, BAX) markers were observed in both SAMP8 and SAMR1 old mice compared to young animals (P<.05) and also in SAMP8 untreated old mice compared to SAMR1 (P<.05). These alterations were significantly less evident in animals treated with both doses of xanthohumol (P<.05). Also, a reduced expression of synaptic markers was observed in old mice compared to young ones (P<.05) but it significantly recovered with 5 mg kg(-1) day(-1) xanthohumol treatment (P<.05). In conclusion, xanthohumol treatment modulated the inflammation and apoptosis of aged brains, exerting a protective effect on damage induced by aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Biomarkers of Alcohol Binge - drinking Induced Brain Damage in Mice%急性暴饮性饮酒对小鼠脑损伤生物标志物的影响

    Institute of Scientific and Technical Information of China (English)

    赵美清; 冯利东

    2012-01-01

    Objective To study oxyradical - related biomarkers for binge - drinking inducing alcohol - induced brain damage in mice. Methods A binge drinking model was created with a single dose of alcohol that was administered by gavage to mice. Blood alcohol levels were monitored and the brain biopsy Was performed for the pathological examination, and compared with the normal control group. The activity of SOD and the level of MDA in the mice brain were measured between the two groups of animals. Results There was no observable microscopic change in the brain after a single dose of alcohol exposure. However, the activity of SOD in the mice brain decreased and the level of MDA increased dramatically (P<0. 01). Conclusion A single dose of alcohol binge - drinking can cause oxyradical-related biomarkers change in brain which expressed as increased oxygen radicals and decreased degradation enzymes of peroxides, resulting in brain damage.%目的 研究急性暴饮性饮酒对小鼠脑组织中氧自由基相关生物学标志物的影响.方法 首先建立急性暴饮性饮酒的小鼠动物模型,检测其血液中乙醇的浓度,进行大脑病理解剖学检查,并与正常对照组比较;然后测定该动物模型以及正常动物脑组织中超氧化物歧化酶(SOD)的活性以及丙二醛(MDA)的含量水平.结果 在单次乙醇胃灌注小鼠大脑并没有观察到明显的显微镜下病理学变化,然而单次乙醇胃灌注可以使小鼠脑组织中SOD的活力显著降低(P<0.01);而使MDA含量水平显著升高(P<0.01).结论 一次性大量饮酒可以导致小鼠大脑氧自由基相关生物学标志物水平的变化,表现为降低降解自由基酶的活力和升高氧自由基的水平,从而可能造成脑损伤.

  6. Physical exercise prevents short and long-term deficits on aversive and recognition memory and attenuates brain oxidative damage induced by maternal deprivation.

    Science.gov (United States)

    Neves, Ben-Hur; Menezes, Jefferson; Souza, Mauren Assis; Mello-Carpes, Pâmela B

    2015-12-01

    It is known from previous research that physical exercise prevents long-term memory deficits induced by maternal deprivation in rats. But we could not assume similar effects of physical exercise on short-term memory, as short- and long-term memories are known to result from some different memory consolidation processes. Here we demonstrated that, in addition to long-term memory deficit, the short-term memory deficit resultant from maternal deprivation in object recognition and aversive memory tasks is also prevented by physical exercise. Additionally, one of the mechanisms by which the physical exercise influences the memory processes involves its effects attenuating the oxidative damage in the maternal deprived rats' hippocampus and prefrontal cortex.

  7. A novel rat model of blast-induced traumatic brain injury simulating different damage degree: implications for morphological, neurological, and biomarker changes

    Directory of Open Access Journals (Sweden)

    Mengdong eLiu

    2015-05-01

    Full Text Available In current military conflicts and civilian terrorism, blast-induced traumatic brain injury (bTBI is the primary cause of neurotrauma. However, the effects and mechanisms of bTBI are poorly understood. Although previous researchers have made significant contributions to establishing animal models for the simulation of bTBI, the precision and controllability of blast-induced injury in animal models must be improved. Therefore, we established a novel rat model to simulate blast-wave injury to the brain. To simulate different extents of bTBI injury, the animals were divided into moderate and severe injury groups. The miniature spherical explosives (PETN used in each group were of different sizes (2.5 mm diameter in the moderate injury group and 3.0 mm diameter in the severe injury group. A specially designed apparatus was able to precisely adjust the positions of the miniature explosives and create eight rats with bTBI simultaneously, using a single electric detonator. Neurological functions, gross pathologies, histopathological changes and the expression levels of various biomarkers were examined after the explosion. Compared with the moderate injury group, there were significantly more neurological dysfunctions, cortical contusions, intraparenchymal hemorrhages, cortical expression of S-100β, MBP, NSE, IL-8, IL-10, iNOS and HIF-1α in the severe injury group. These results demonstrate that we have created a reliable and reproducible bTBI model in rats. This model will be helpful for studying the mechanisms of bTBI and developing strategies for clinical bTBI treatment.

  8. Radiation-induced brain injury: A review

    Directory of Open Access Journals (Sweden)

    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

  9. Heart Failure Protein May Signal Early Brain Damage

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_162447.html Heart Failure Protein May Signal Early Brain Damage Higher levels ... stress. Blood levels of NT-proBNP rise when heart failure worsens and fall when it gets better. Previous ...

  10. EGb761 provides a protective effect against Aβ1-42 oligomer-induced cell damage and blood-brain barrier disruption in an in vitro bEnd.3 endothelial model.

    Directory of Open Access Journals (Sweden)

    Wen-bin Wan

    Full Text Available Alzheimer's disease (AD is the most common form of senile dementia which is characterized by abnormal amyloid beta (Aβ accumulation and deposition in brain parenchyma and cerebral capillaries, and leads to blood-brain barrier (BBB disruption. Despite great progress in understanding the etiology of AD, the underlying pathogenic mechanism of BBB damage is still unclear, and no effective treatment has been devised. The standard Ginkgo biloba extract EGb761 has been widely used as a potential cognitive enhancer for the treatment of AD. However, the cellular mechanism underlying the effect remain to be clarified. In this study, we employed an immortalized endothelial cell line (bEnd.3 and incubation of Aβ(1-42 oligomer, to mimic a monolayer BBB model under conditions found in the AD brain. We investigated the effect of EGb761 on BBB and found that Aβ1-42 oligomer-induced cell injury, apoptosis, and generation of intracellular reactive oxygen species (ROS, were attenuated by treatment with EGb761. Moreover, treatment of the cells with EGb761 decreased BBB permeability and increased tight junction scaffold protein levels including ZO-1, Claudin-5 and Occludin. We also found that the Aβ(1-42 oligomer-induced upregulation of the receptor for advanced glycation end-products (RAGE, which mediates Aβ cytotoxicity and plays an essential role in AD progression, was significantly decreased by treatment with EGb761. To our knowledge, we provide the first direct in vitro evidence of an effect of EGb761 on the brain endothelium exposed to Aβ(1-42 oligomer, and on the expression of tight junction (TJ scaffold proteins and RAGE. Our results provide a new insight into a possible mechanism of action of EGb761. This study provides a rational basis for the therapeutic application of EGb761 in the treatment of AD.

  11. Muscle damage induced by electrical stimulation.

    Science.gov (United States)

    Nosaka, Kazunori; Aldayel, Abdulaziz; Jubeau, Marc; Chen, Trevor C

    2011-10-01

    Electrical stimulation (ES) induces muscle damage that is characterised by histological alterations of muscle fibres and connective tissue, increases in circulating creatine kinase (CK) activity, decreases in muscle strength and development of delayed onset muscle soreness (DOMS). Muscle damage is induced not only by eccentric contractions with ES but also by isometric contractions evoked by ES. Muscle damage profile following 40 isometric contractions of the knee extensors is similar between pulsed current (75 Hz, 400 μs) and alternating current (2.5 kHz delivered at 75 Hz, 400 μs) ES for similar force output. When comparing maximal voluntary and ES-evoked (75 Hz, 200 μs) 50 isometric contractions of the elbow flexors, ES results in greater decreases in maximal voluntary contraction strength, increases in plasma CK activity and DOMS. It appears that the magnitude of muscle damage induced by ES-evoked isometric contractions is comparable to that induced by maximal voluntary eccentric contractions, although the volume of affected muscles in ES is not as large as that of eccentric exercise-induced muscle damage. It seems likely that the muscle damage in ES is associated with high mechanical stress on the activated muscle fibres due to the specificity of motor unit recruitment (i.e., non-selective, synchronous and spatially fixed manner). The magnitude of muscle damage induced by ES is significantly reduced when the second ES bout is performed 2-4 weeks later. It is possible to attenuate the magnitude of muscle damage by "pre-conditioning" muscles, so that muscle damage should not limit the use of ES in training and rehabilitation.

  12. Perinatal brain damage : The term infant

    NARCIS (Netherlands)

    Hagberg, Henrik; David Edwards, A.; Groenendaal, Floris

    2016-01-01

    Perinatal brain injury at term is common and often manifests with neonatal encephalopathy including seizures. The most common aetiologies are hypoxic–ischaemic encephalopathy, intracranial haemorrhage and neonatal stroke. Besides clinical and biochemical assessment the diagnostic evaluation rely

  13. Bean grain hysteresis with induced mechanical damage

    Directory of Open Access Journals (Sweden)

    Renata C. Campos

    Full Text Available ABSTRACT This study aimed to evaluate the effect of mechanical damage on the hysteresis of beans with induced mechanical damage under different conditions of temperature and relative humidity. Beans (Phaseolus vulgaris L. harvested manually with 35% water content (w.b. were used. Part of this product was subjected to induced mechanical damage by Stein Breakage Tester and controlled drying (damaged and control sample, for sorption processes. The sorption isotherms of water were analyzed for different temperature conditions: 20, 30, 40 and 50 oC; and relative humidity: 0.3; 0.4; 0.5; 0.7 and 0.9 (decimal. Equilibrium moisture content data were correlated with six mathematical models, and the Modified Oswin model was the one that best fitted to the experimental data. According to the above mentioned isotherms, it was possible to observe the phenomenon of hysteresis of damaged and control samples, and this phenomenon was more pronounced in control ones.

  14. Intrauterine infection/inflammation during pregnancy and offspring brain damages: Possible mechanisms involved

    Directory of Open Access Journals (Sweden)

    Golan Hava

    2004-04-01

    Full Text Available Abstract Intrauterine infection is considered as one of the major maternal insults during pregnancy. Intrauterine infection during pregnancy could lead to brain damage of the developmental fetus and offspring. Effects on the fetal, newborn, and adult central nervous system (CNS may include signs of neurological problems, developmental abnormalities and delays, and intellectual deficits. However, the mechanisms or pathophysiology that leads to permanent brain damage during development are complex and not fully understood. This damage may affect morphogenic and behavioral phenotypes of the developed offspring, and that mice brain damage could be mediated through a final common pathway, which includes over-stimulation of excitatory amino acid receptor, over-production of vascularization/angiogenesis, pro-inflammatory cytokines, neurotrophic factors and apoptotic-inducing factors.

  15. Captopril and Valsartan May Improve Cogniti ve Function Through Potentiation of the Brain Antioxidant Defense System and Attenuation of Oxidative/Nitrosative Damage in STZ - Induced Dementia in Rat

    Directory of Open Access Journals (Sweden)

    Yasaman Arjmand Abbassi

    2016-12-01

    Full Text Available Purpose: Previous findings have shown the crucial roles of brain renin-angiotensin system (RAS in pathogenesis of Alzheimer’s disease (AD. Since RAS inhibitors may have beneficial effects on dementia and cognitive function in elderly people, the aim of present study was to examine the neuroprotective actions of captopril and valsartan on memory function and neuronal damage in experimental model of AD. Methods: Adult forty male Wistar rats (220-280g were randomly divided into 5 groups; Control, Vehicle, Alzheimer and treatment groups. AD was induced by the injections of streptozotocin (3mg/kg, bilateral intracerebroventricular at days 1&3. Treated rats received orally captopril (50mg/kg/day and valsartan (30mg/kg/day. Memory function and histological assessments were done at termination of experiment. Finally, superoxide dismutase (SOD and catalase (CAT activities as well as malondialdehyde (MDA and NOx contents were determined. Results: There was a significant increase in the mean value of latency in Alzheimer group (66%. Captopril and valsartan considerably decreased this value in both treatment groups (45% and 72%, respectively. In Alzheimer group the activities of brain’s SOD and CAT reduced (40% and 47%, respectively in accompany with an increase in MDA and NOx contents (49% and 50%, respectively. Captopril and valsartan significantly increased the activities of brain’s SOD and CAT concomitant reduction in MDA and NOx contents. Also, histopathological damages noticeably decreased in both treatment groups. Conclusion: Our findings indicate that RAS inhibition by using captopril and valsartan potentiates the antioxidant defense system of brain and reduces oxidative/nitrosative stress in accompany with neuronal damage during AD.

  16. Irreversible brain damage caused by methamphetamine

    Directory of Open Access Journals (Sweden)

    Sebastian Moeller

    2016-03-01

    Full Text Available Methamphetamine is an addictive scene substance usage of which is increasing rapidly. While methamphetamine often causes neuropsychiatric symptoms like anxiety, psychosis and hallucinations, reports of structural ongoing cerebral alterations are rare. We here report a case of this kind of damage caused through methamphetamine use.

  17. Damage and repair of irradiated mammalian brain

    Energy Technology Data Exchange (ETDEWEB)

    Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K. (Lawrence Berkeley Lab., CA (USA); Stanford Univ., CA (USA). Medical Center; Brookside Hospital, San Pablo, CA (USA))

    1989-07-01

    We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs.

  18. Inducible HSP70 Protects Radiation-Induced Salivary Gland Damage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Lee, Su-Jae; Bae, Sang-Woo; Lee, Yun-Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung-Ho [Chonnam National University, Gwangju (Korea, Republic of)

    2006-07-01

    Irradiation (IR) delivered to the head and neck is a common treatment for malignancies. Salivary glands in the irradiation field are severely damaged, and consequently this resulted in marked salivary hypofunction. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that inducible heat shock protein 70 (HSP70i) induced radioresistance in vitro. Moreover, HSP70i localized to salivary glands by gene transfer has great potential for the treatment of salivary gland. Herein, we investigated whether HSP70 can use as radio protective molecules for radiation-induced salivary gland damage in vivo.

  19. Functionality predictors in acquired brain damage.

    Science.gov (United States)

    Huertas Hoyas, E; Pedrero Pérez, E J; Águila Maturana, A M; García López-Alberca, S; González Alted, C

    2015-01-01

    Most individuals who have survived an acquired brain injury present consequences affecting the sensorimotor, cognitive, affective or behavioural components. These deficits affect the proper performance of daily living activities. The aim of this study is to identify functional differences between individuals with unilateral acquired brain injury using functional independence, capacity, and performance of daily activities. Descriptive cross-sectional design with a sample of 58 people, with right-sided injury (n=14 TBI; n=15 stroke) or left-sided injury (n = 14 TBI, n = 15 stroke), right handed, and with a mean age of 47 years and time since onset of 4 ± 3.65 years. The functional assessment/functional independence measure (FIM/FAM) and the International Classification of Functioning (ICF) were used for the study. The data showed significant differences (P<.000), and a large size effect (dr=0.78) in the cross-sectional estimates, and point to fewer restrictions for patients with a lesion on their right side. The major differences were in the variables 'speaking' and 'receiving spoken messages' (ICF variables), and 'Expression', 'Writing' and 'intelligible speech' (FIM/FAM variables). In the linear regression analysis, the results showed that only 4 FIM/FAM variables, taken together, predict 44% of the ICF variance, which measures the ability of the individual, and up to 52% of the ICF, which measures the individual's performance. Gait alone predicts a 28% of the variance. It seems that individuals with acquired brain injury in the left hemisphere display important differences regarding functional and communication variables. The motor aspects are an important prognostic factor in functional rehabilitation. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Measuring consciousness in severely damaged brains.

    Science.gov (United States)

    Gosseries, Olivia; Di, Haibo; Laureys, Steven; Boly, Mélanie

    2014-01-01

    Significant advances have been made in the behavioral assessment and clinical management of disorders of consciousness (DOC). In addition, functional neuroimaging paradigms are now available to help assess consciousness levels in this challenging patient population. The success of these neuroimaging approaches as diagnostic markers is, however, intrinsically linked to understanding the relationships between consciousness and the brain. In this context, a combined theoretical approach to neuroimaging studies is needed. The promise of such theoretically based markers is illustrated by recent findings that used a perturbational approach to assess the levels of consciousness. Further research on the contents of consciousness in DOC is also needed.

  1. Acquired agraphia caused by focal brain damage.

    Science.gov (United States)

    Anderson, S W; Saver, J; Tranel, D; Damasio, H

    1993-03-01

    Motor and linguistic aspects of writing were evaluated in 31 subjects with focal damage in 1 of 3 regions of the left hemisphere: (1) dorsolateral frontal lobe sparing primary motor cortex (group FL), (2) parietal lobe (group PL), or (3) temporal lobe (group TL). A standard procedure was used to evaluate writing for grapheme formation, spatial arrangement, spelling, word selection, grammar, and perseveration. It was predicted that agraphia would be observed in all 3 groups, and that the most severe impairments would be associated with frontal lobe damage, particularly in aspects of writing dependent on sequencing (grapheme formation, spelling, and grammar). It was found that agraphia was common in all groups, particularly in the acute epoch, and that all groups showed considerable recovery of writing by the chronic epoch. Few differences were found between groups. However, the FL group was impaired on spelling and grammar relative to the PL group in the acute epoch and impaired on grammar relative to the TL group in the chronic epoch. The findings are consistent with the notion that writing relies on a distributed neuroanatomical network, which acts in concert to link fragments of visuomotor activity with component linguistic elements.

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2011-01-01

    Full Text Available Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO. Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

  4. Carcinoma cells misuse the host tissue damage response to invade the brain

    Science.gov (United States)

    Chuang, Han-Ning; van Rossum, Denise; Sieger, Dirk; Siam, Laila; Klemm, Florian; Bleckmann, Annalen; Bayerlová, Michaela; Farhat, Katja; Scheffel, Jörg; Schulz, Matthias; Dehghani, Faramarz; Stadelmann, Christine; Hanisch, Uwe-Karsten; Binder, Claudia; Pukrop, Tobias

    2013-01-01

    The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis. PMID:23832647

  5. Modelling of settlement induced building damage

    NARCIS (Netherlands)

    Giardina, G.

    2013-01-01

    This thesis focuses on the modelling of settlement induced damage to masonry buildings. In densely populated areas, the need for new space is nowadays producing a rapid increment of underground excavations. Due to the construction of new metro lines, tunnelling activity in urban areas is growing.

  6. In the eye of the storm: mitochondrial damage during heart and brain ischaemia.

    Science.gov (United States)

    Borutaite, Vilmante; Toleikis, Adolfas; Brown, Guy C

    2013-10-01

    We review research investigating mitochondrial damage during heart and brain ischaemia, focusing on the mechanisms and consequences of ischaemia-induced and/or reperfusion-induced: (a) inhibition of mitochondrial respiratory complex I; (b) release of cytochrome c from mitochondria; (c) changes to mitochondrial phospholipids; and (d) nitric oxide inhibition of mitochondria. Heart ischaemia causes inhibition of cytochrome oxidase and complex I, release of cytochrome c, and induction of permeability transition and hydrolysis and oxidation of mitochondrial phospholipids, but some of the mechanisms are unclear. Brain ischaemia causes inhibition of complexes I and IV, but other effects are less clear.

  7. The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke.

    Science.gov (United States)

    Wu, Long-Jun; Wu, Gongxiong; Akhavan Sharif, M Reza; Baker, Amanda; Jia, Yonghui; Fahey, Frederic H; Luo, Hongbo R; Feener, Edward P; Clapham, David E

    2012-03-04

    Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. The voltage-gated proton channel Hv1 enables NOX function by compensating cellular loss of electrons with protons. Accordingly, we investigated whether NOX-mediated brain damage in stroke can be inhibited by suppression of Hv1. We found that mouse and human brain microglia, but not neurons or astrocytes, expressed large Hv1-mediated currents. Hv1 was required for NOX-dependent ROS generation in brain microglia in situ and in vivo. Mice lacking Hv1 were protected from NOX-mediated neuronal death and brain damage 24 h after stroke. These results indicate that Hv1-dependent ROS production is responsible for a substantial fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke.

  8. DNA damages in brain cells of mice induced by joint exposure to formaldehyde and toluene%甲醛和甲苯联合染毒致小鼠脑细胞DNA损伤的研究

    Institute of Scientific and Technical Information of China (English)

    王鸿; 原福胜; 高俊宏; 王君霞; 岳红; 刘志永; 李江平

    2012-01-01

    Objective To study the combined effect of exposure to formaldehyde and toluene on DNA damage in brain of mice. Methods Thirty-six healthy clean-class Kunming mice were randomly divided into nine groups, the control group(0 mg/m3 formaldehyde+0 mg/m3 toluene), formaldehyde group(l, 5 mg/m3), toluene group(400, 2 000 mg/m3), combined group(l mg/m3 formaldehyde+400 mg/m3 toluene, 1 mg/m3 formaldehyde+2 000 mg/m3 toluene, 5 mg/m3 formaldehyde+400 mg/m3 toluene, 5 mg/m3 formaldehyde+2 000 mg/m3 toluene). 3×3 factorial analysis was used in the experiment. The treatments were conducted by static inhaling formaldehyde or(and) toluene, two hours per day for 14 days consecutively. The DNA damage in brain cells of the mice were detected with comet assay. Results When the mice were jointly exposed to formaldehyde and toluene, the percentage of tail DNA and tail moment in brain cells in exposure groups were higher than the control group (P<0.05). There was an interaction between formaldehyde and toluene on percentage of tail DNA and tail moment (P<0.05), and they have synergistic effect. Conclusion Formaldehyde and toluene may induce DNA damage in brain cells of mice. The joint toxicity of formaldehyde and toluene is considered synergistic.%目的 研究甲醛和甲苯联合染毒对小鼠脑细胞的损伤作用,探讨其联合毒性效应的类型.方法 选择健康清洁级雄性昆明小鼠36只,按3×3析因设计,将小鼠随机分为9组,每组4只,即对照组(0 mg/m3甲醛+0 mg/m3甲苯),甲醛组(1、5 mg/m3),甲苯组(400、2 000 mg/m3),联合组(1 mg/m3甲醛+400 mg/m3甲苯、1 mg/m3甲醛+2 000 mg/m3甲苯、5 mg/m3甲醛+400 mg/m3甲苯、5 mg/m3甲醛+2 000 mg/m3甲苯).采用静式吸入染毒,将小鼠暴露于不同浓度的甲醛、甲苯及两者的混合气体中,每天2h,连续14d.染毒结束后通过彗星试验测定小鼠脑细胞DNA损伤情况.结果 甲醛和甲苯单独及联合染毒可致脑细胞彗星尾部DNA含量增高,尾矩增

  9. Sepsis-induced brain dysfunction.

    Science.gov (United States)

    Adam, Nicolas; Kandelman, Stanislas; Mantz, Jean; Chrétien, Fabrice; Sharshar, Tarek

    2013-02-01

    Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. Its pathophysiology involves an ischemic process, secondary to impairment of cerebral perfusion and its determinants and a neuroinflammatory process that includes endothelial activation, alteration of the blood-brain barrier and passage of neurotoxic mediators. Microcirculatory dysfunction is common to these two processes. This brain dysfunction is associated with increased mortality, morbidity and long-term cognitive disability. Its diagnosis relies essentially on neurological examination that can lead to specific investigations, including electrophysiological testing or neuroimaging. In practice, cerebrospinal fluid analysis is indisputably required when meningitis is suspected. Hepatic, uremic or respiratory encephalopathy, metabolic disturbances, drug overdose, sedative or opioid withdrawal, alcohol withdrawal delirium or Wernicke's encephalopathy are the main differential diagnoses. Currently, treatment consists mainly of controlling sepsis. The effects of insulin therapy and steroids need to be assessed. Various drugs acting on sepsis-induced blood-brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients.

  10. [Neuroendocrine dysfunction and brain damage. A consensus statement].

    Science.gov (United States)

    Leal-Cerro, Alfonso; Rincón, María Dolores; Domingo, Manel Puig

    2009-01-01

    This consensus statement aims to enhance awareness of the incidence and risks of hypopituitarism in patients with traumatic brain injury (TBI) and/or brain hemorrhages among physicians treating patients with brain damage. The importance of this problem is related not only to the frequency of TBI but also to its prevalence in younger populations. The consequences of TBI are characterized by a series of symptoms that depend on the type of sequels related to neuroendocrine dysfunction. The signs and symptoms of hypopituitarism are often confused with those of other sequels of TBI. Consequently, patients with posttraumatic hypopituitarism may receive suboptimal rehabilitation unless the underlying hormone deficiency is identified and treated. This consensus is based on the recommendation supported by expert opinion that patients with a TBI and/or brain hemorrhage should undergo endocrine evaluation in order to assess pituitary function and, if deficiency is detected, should receive hormone replacement therapy.

  11. Patterns of damage in the mature neonatal brain

    Energy Technology Data Exchange (ETDEWEB)

    Triulzi, Fabio; Parazzini, Cecilia; Righini, Andrea [Children' s Hospital ' ' Vittore Buzzi' ' , Departments of Radiology and Neuroradiology, Milan (Italy)

    2006-07-15

    Patterns of damage in the mature neonatal brain can be subdivided into focal, multifocal and diffuse. The main cause of diffuse brain damage in the term newborn is hypoxic-ischaemic encephalopathy (HIE). HIE is still the major recognized perinatal cause of neurological morbidity in full-term newborns. MRI offers today the highest sensitivity in detecting acute anoxic injury of the neonatal brain. Conventional acquisition techniques together with modern diffusion techniques can identify typical patterns of HIE injury, even in the early course of the disease. However, even though highly suggestive, these patterns cannot be considered as pathognomonic. Perinatal metabolic disease such as kernicterus and severe hypoglycaemia should be differentiated from classic HIE. Other conditions, such as infections, non-accidental injury and rarer metabolic diseases can be misinterpreted as HIE in their early course when diffuse brain swelling is still the predominant MRI feature. Diffusion techniques can help to differentiate different types of diffuse brain oedema. Typical examples of focal injuries are arterial or venous infarctions. In arterial infarction, diffusion techniques can define more precisely than conventional imaging the extent of focal infarction, even in the hyperacute phase. Moreover, diffusion techniques provide quantitative data of acute corticospinal tract injury, especially at the level of the cerebral peduncles. Venous infarction should be suspected in every case of unexplained cerebral haematoma in the full-term newborn. In the presence of spontaneous bleeding, venous structures should always be evaluated by MR angiography. (orig.)

  12. Change of G-protein expression in the myocardial damage induced by acute brain injury%急性脑损伤致心肌损害中心肌G蛋白表达的改变

    Institute of Scientific and Technical Information of China (English)

    郭彩霞; 曾翔俊; 杜凤和; 陈步星

    2015-01-01

    Objective To test the effect of Gs-protein and Gq-protein on cardiac damage induced by acute brain injury,and the contribution ofβ1-ARB and 5-HT2A RB to G-protein.Methods The Wistar rat model of acute brain injury was built.The mRNA level of Gsαand Gqαwere evaluated with real time PCR,and the protein level of Gsαand Gqαwere detected by Western blotting assay.Results Compared with NORMgroup,the mRNA level of Gsαwas (92.6 ±24)%in SHAMgroup,(39.7 ±30)%in ABI group and (80.1 ± 1 2)% in BETA group,respectively.The mRNA level of Gsαwas significantly decreased in ABI group compared to SHAM group,but significantly increased in β1-ARB treated BETA group,and there is no difference of GsαmRNA level betweenβ1-ARB treated BETA and SHAM groups.Compared with NORM group,the protein level of Gqαwas (1 05 ±30)% in SHAM group,(1 1 0 ±1 4)% in ABI group and (1 07 ±23)% in BETA group.There was no statistical difference among three groups.Conclusion The mRNA and protein of Gsαwere significantly decreased after acute brain injury,which indicates the occurrence of myocardial damage induced by acute brain injury may be related to the inhibition in signal transduction pathway mediated Gs-protein.Gs-protein may be in the form of expression change involved in the occurrence of myocardial damage induced by acute brain injury.%目的:建立动物急性脑损伤(acute brain injury,ABI)模型,观察心肌Gs 蛋白α亚基(αsubunite of Gs ,Gsα)和Gq 蛋白α亚基(αsubunite of Gq ,Gqα)的变化,探讨Gs 和Gq 在急性脑损伤致心肌损伤中的作用及其β1肾上腺素受体阻断剂(adrenalinβ1 receptor blocker,β1-ARB)和5-羟色胺受体2A阻断剂(5-hydroxytryptamine 2A receptor blocker,5-HT2ARB)对G蛋白的影响。方法复制Wistar大鼠ABI模型(n=8)。采用数字表法随机分为正常组(NORM)、假手术对照组(SHAM)、急性脑损伤模型组(ABI)、β1-ARB组(BETA)和5-HT2A RB组(KETA组

  13. Fullerene derivatives protect endothelial cells against NO-induced damage

    Energy Technology Data Exchange (ETDEWEB)

    Lao Fang; Han Dong; Qu Ying; Liu Ying; Zhao Yuliang; Chen Chunying [CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190 (China); Li Wei [CAS Key Laboratory for Nuclear Analytical Techniques, Institute of High Energy Physics (IHEP), Chinese Academy of Sciences, Beijing 100049 (China)], E-mail: chenchy@nanoctr.cn

    2009-06-03

    Functional fullerene derivatives have been demonstrated with potent antioxidation properties. Nitric oxide (NO) is a free radical that plays a part in leading to brain damage when it is accumulated to a high concentration. The possible scavenging activity of NO by the hydroxylated fullerene derivative C{sub 60}(OH){sub 22} and malonic acid derivative C{sub 60}(C(COOH){sub 2}){sub 2} was investigated using primary rat brain cerebral microvessel endothelial cells (CMECs). Results demonstrate that sodium nitroprusside (SNP), used as an NO donor, caused a marked decrease in cell viability and an increase in apoptosis. However, fullerene derivatives can remarkably protect against the apoptosis induced by NO assault. In addition, fullerene derivatives can also prevent NO-induced depolymerization of cytoskeleton and damage of the nucleus and accelerate endothelial cell repair. Further investigation shows that the sudden increase of the intercellular reactive oxygen species (ROS) induced by NO was significantly attenuated by post-treatment with fullerene derivatives. Our results suggest that functional fullerene derivatives are potential applications for NO-related disorders.

  14. Antioxidant Formulae, Shengmai San, and LingGuiZhuGanTang, Prevent MPTP Induced Brain Dysfunction and Oxidative Damage in Mice

    OpenAIRE

    2015-01-01

    The present study was designed to evaluate the preventive effect of antioxidative traditional oriental medicine formulae, Shengmai San (SMS) and LingGuiZhuGanTang (LGZGT), against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (i.p 30 mg·kg−1 for 5 consecutive days) induced neurotoxicity. In in vitro antioxidant assays measured with Trolox and butyl hydroxyl toluene as reference antioxidant revealed that SMS has higher scavenging potential against hydroxyl radical than superoxide anion r...

  15. Behavioral evaluation of consciousness in severe brain damage.

    Science.gov (United States)

    Majerus, Steve; Gill-Thwaites, Helen; Andrews, Keith; Laureys, Steven

    2005-01-01

    This paper reviews the current state of bedside behavioral assessment in brain-damaged patients with impaired consciousness (coma, vegetative state, minimally conscious state). As misdiagnosis in this field is unfortunately very frequent, we first discuss a number of fundamental principles of clinical evaluation that should guide the assessment of consciousness in brain-damaged patients in order to avoid confusion between vegetative state and minimally conscious state. The role of standardized behavioral assessment tools is particularly stressed. The second part of this paper reviews existing behavioral assessment techniques of consciousness, showing that there are actually a large number of these scales. After a discussion of the most widely used scale, the Glasgow Coma Scale, we present several new promising tools that show higher sensitivity and reliability for detecting subtle signs of recovery of consciousness in the post-acute setting.

  16. Epileptic Encephalopathy in Children with Risk Factors for Brain Damage

    Directory of Open Access Journals (Sweden)

    Josefina Ricardo-Garcell

    2012-01-01

    Full Text Available In the study of 887 new born infants with prenatal and perinatal risk factors for brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut syndrome and another 4 children with Lennox-Gastaut syndrome that had not been preceded by West syndrome were found. In this study we present the main findings of these 15 subjects. In all infants multifactor antecedents were detected. The most frequent risk factors were prematurity and severe asphyxia; however placenta disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI direct or secondary features of periventricular leukomalacia were observed. Followup of all infants showed moderate to severe neurodevelopmental delay as well as cerebral palsy. It is concluded that prenatal and perinatal risk factors for brain damage are very important antecedents that should be taken into account to follow up those infants from an early age in order to detect and treat as early as possible an epileptic encephalopathy.

  17. Epileptic Encephalopathy in Children with Risk Factors for Brain Damage

    Science.gov (United States)

    Ricardo-Garcell, Josefina; Harmony, Thalía; Porras-Kattz, Eneida; Colmenero-Batallán, Miguel J.; Barrera-Reséndiz, Jesús E.; Fernández-Bouzas, Antonio; Cruz-Rivero, Erika

    2012-01-01

    In the study of 887 new born infants with prenatal and perinatal risk factors for brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut syndrome and another 4 children with Lennox-Gastaut syndrome that had not been preceded by West syndrome were found. In this study we present the main findings of these 15 subjects. In all infants multifactor antecedents were detected. The most frequent risk factors were prematurity and severe asphyxia; however placenta disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI direct or secondary features of periventricular leukomalacia were observed. Followup of all infants showed moderate to severe neurodevelopmental delay as well as cerebral palsy. It is concluded that prenatal and perinatal risk factors for brain damage are very important antecedents that should be taken into account to follow up those infants from an early age in order to detect and treat as early as possible an epileptic encephalopathy. PMID:22957240

  18. Oxidative damage to rat brain in iron and copper overloads.

    Science.gov (United States)

    Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Semprine, Jimena; Fuda, Julián; Torti, Horacio; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.

  19. Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice.

    Directory of Open Access Journals (Sweden)

    Ralph Timaru-Kast

    Full Text Available After traumatic brain injury (TBI elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months and old (21 months male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2% compared to young (0%. This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral

  20. PARP-1 modulates amyloid beta peptide-induced neuronal damage.

    Directory of Open Access Journals (Sweden)

    Sara Martire

    Full Text Available Amyloid beta peptide (Aβ causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose polymerase (PARP-1. To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ25-35 fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ25-35 induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ25-35 exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ25-35 induces DNA damage which in turn activates PARP-1. Challenge with Aβ25-35 is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ25-35 via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed.

  1. Do women develop alcoholic brain damage more readily than men?

    Science.gov (United States)

    Mann, K; Batra, A; Günthner, A; Schroth, G

    1992-12-01

    Chronic alcoholism is related to brain damage (i.e., volume changes) in both men and women. There is an open question whether the brains of women are more vulnerable than those of men to alcohol toxicity. The present follow-up study focuses on a direct comparison of sex-related differences in alcoholic brain shrinkage and its reversibility. In a prospective design, a random sample of 65 alcoholics of both sexes (51 males and 14 females) was studied. Computerized tomography brain scans before and after a 6-week inpatient treatment program with controlled abstinence revealed a significant re-expansion of the brain as assessed by linear measurements. By controlling for moderating variables such as age, mean daily alcohol consumption, liver dysfunction, etc. the degree of brain shrinkage was found to be similar in men and women despite significantly shorter ethanol expositions in the women. These findings corroborate the hypotheses of other investigators about basic biological differences between the two sexes as to the effects of alcohol. The hypothesis of an enhanced vulnerability of women to acute and chronic complications of alcoholism is supported.

  2. Iodine deficiency as a cause of brain damage.

    Science.gov (United States)

    Delange, F

    2001-04-01

    This editorial reviews the impact of iodine deficiency (1) on thyroid function in pregnant women and neonates and (2) on the neurointellectual development of infants and children. All degrees of iodine deficiency (mild: iodine intake of 50-99 microg/day, moderate: 20-49 microg/day, and severe: consequence. Maternal hypothyroxinaemia during early pregnancy is a key factor in the development of the neurological damage in the cretin. Selenium deficiency combined with iodine deficiency partly prevents the neurological damage but precipitates severe hypothyroidism in cretins. Iodine deficiency results in a global loss of 10-15 IQ points at a population level and constitutes the world's greatest single cause of preventable brain damage and mental retardation.

  3. Contraction-induced muscle fiber damage is increased in soleus muscle of streptozotocin-diabetic rats and is associated with elevated expression of brain-derived neurotrophic factor mRNA in muscle fibers and activated satellite cells

    NARCIS (Netherlands)

    Copray, S; Liem, R; Brouwer, N; Greenhaff, P; Habens, F; Fernyhough, P

    The expression of brain-derived neurotrophic factor (BDNF) is elevated in the soleus muscle of streptozotocin-diabetic rats. To determine whether this diabetes-induced elevation was associated with or enhanced by muscle activity we have induced high-intensity muscle contraction by electrically

  4. Contraction-induced muscle fiber damage is increased in soleus muscle of streptozotocin-diabetic rats and is associated with elevated expression of brain-derived neurotrophic factor mRNA in muscle fibers and activated satellite cells

    NARCIS (Netherlands)

    Copray, S; Liem, R; Brouwer, N; Greenhaff, P; Habens, F; Fernyhough, P

    2000-01-01

    The expression of brain-derived neurotrophic factor (BDNF) is elevated in the soleus muscle of streptozotocin-diabetic rats. To determine whether this diabetes-induced elevation was associated with or enhanced by muscle activity we have induced high-intensity muscle contraction by electrically stimu

  5. The Voltage–gated Proton Channel, Hv1, Enhances Brain Damage from Ischemic Stroke

    OpenAIRE

    Wu, Long–Jun; Wu, Gongxiong; Akhavan Sharif, M. Reza; Baker, Amanda; Jia, Yonghui; H. Fahey, Frederic; Luo, Hongbo; Feener, Edward Paul; Clapham, David Eldon

    2012-01-01

    SUMMARY Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. Here we show that NOX–mediated damage can be inhibited by suppression of the voltage-gated proton channel, Hv1. Hv1 is required for full NOX activity since it compensates for loss of NOX–exported charge. We show that Hv1 is required for NOX–dependent ROS generation in brain microglia in situ and...

  6. Tumor necrosis factor α antibody prevents brain damage of rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Kai-Zong Li; Ke-Feng Dou

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor á (TNFα) antibody on pancreatic encephalopathy in rats.METHODS:One hundred and twenty SD rats were randomly divided into normal control group,acute necrotizing pancreatitis group and TNFα antibody treated group.Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct.Serum TNFα was detected and animals were killed 12 h after drug administration.Changes in content of brain water,MDA and SOD as well as leucocyte adhesion of brain microvessels were measured.RESULTS:In TNFα antibody treated group,serum TNFálevel was decreased.Content of brain water,MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P<0.05).CONCLUSION:TNFα antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.

  7. Gut-Brain Axis in Gastric Mucosal Damage and Protection

    Science.gov (United States)

    Sgambato, Dolores; Capuano, Annalisa; Sullo, Maria Giuseppa; Miranda, Agnese; Federico, Alessandro; Romano, Marco

    2016-01-01

    Abstract: Background The gut-brain axis plays a potential role in numerous physiological and pathological conditions. Several substances link stomach with central nervous system. In particular, hypothalamo-pituitary-adrenocortical axis, thyrotropin-releasing factor-containing nerve fibers and capsaicin-sensitive nerves are principal mediators of the harmful and protective central nervous system-mediated effects on gastric mucosa. Also, existing evidence indicates that nitric oxide, prostaglandins and calcitonin gene-related peptide play a role as final effectors of gastric protection. Methods We undertook a structured search of bibliographic databases for peer-reviewed research literature with the aim of focusing on the role of gut-brain axis in gastric damage and protection. In particular, we examined manuscripts dealing with the role of steroids, thyrotropin-releasing hormone, prostaglandins, melatonin, hydrogen sulfide and peptides influencing food intake (i.e. leptin, cholecystokinin, peptide YY, central glucagon–like peptide-1, and ghrelin). Also, the role of GABAergic and glutamatergic pathways in gastric mucosal protection have been examined. Results We found and reviewed 61 peer-reviewed papers dealing with the major aspects related to the role of gut brain axis in gastric mucosal damage and protection. Conclusions A dense neuronal network links stomach with central nervous system and a number of neurotransmitters and peptides functionally and anatomically related to central nervous system play a major role in contributing to gastric mucosal integrity. Exploiting the mechanisms underlying the connection between brain and gut may lead to a better understanding of the pathophysiology of gastric mucosal injury and to an improvement in the prevention and, eventually, management of gastric damage. PMID:26903151

  8. Resveratrol Protects the Brain of Obese Mice from Oxidative Damage

    Directory of Open Access Journals (Sweden)

    Shraddha D. Rege

    2013-01-01

    Full Text Available Resveratrol (3,5,4′-trihydroxy-trans-stilbene is a polyphenolic phytoalexin that exerts cardioprotective, neuroprotective, and antioxidant effects. Recently it has been shown that obesity is associated with an increase in cerebral oxidative stress levels, which may enhance neurodegeneration. The present study evaluates the neuroprotective action of resveratrol in brain of obese (ob/ob mice. Resveratrol was administered orally at the dose of 25 mg kg−1 body weight daily for three weeks to lean and obese mice. Resveratrol had no effect on body weight or blood glucose levels in obese mice. Lipid peroxides were significantly increased in brain of obese mice. The enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and nonenzymatic antioxidants tocopherol, ascorbic acid, and glutathione were decreased in obese mice brain. Administration of resveratrol decreased lipid peroxide levels and upregulated the antioxidant activities in obese mice brain. Our findings indicate a neuroprotective effect of resveratrol by preventing oxidative damage in brain tissue of obese mice.

  9. Clinical and pathological features of alcohol-related brain damage.

    Science.gov (United States)

    Zahr, Natalie M; Kaufman, Kimberley L; Harper, Clive G

    2011-05-01

    One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B(1)) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD.

  10. Brain damages in ketamine addicts as revealed by magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Chunmei eWang

    2013-07-01

    Full Text Available Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA glutamate receptors, had been used as an anesthetic particularly for pediatric or for cardiac patients. Unfortunately, ketamine has become an abusive drug in many parts of the world while chronic and prolonged usage led to damages of many organs including the brain. However, no studies on possible damages in the brains induced by chronic ketamine abuse have been documented in the human via neuroimaging. This paper described for the first time via employing magnetic resonance imaging (MRI the changes in ketamine addicts of 0.5 to 12 years and illustrated the possible brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were recruited and the results showed that the lesions in the brains of ketamine addicts were located in many regions which appeared 2-4 years after ketamine addiction. Cortical atrophy was usually evident in the frontal, parietal or occipital cortices of addicts. Such study confirmed that many brain regions in the human were susceptible to chronic ketamine injury and presented a diffuse effect of ketamine on the brain which might differ from other central nervous system (CNS drugs, such as cocaine, heroin and methamphetamine.

  11. Genetic Damage Induced by Accidental Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Beatriz Pérez-Cadahía

    2006-01-01

    Full Text Available Petroleum is one of the main energy sources worldwide. Its transport is performed by big tankers following some established marine routes. In the last 50 years a total amount of 37 oil tankers have given rise to great spills in different parts of the world, Prestige being the last one. After the accident, a big human mobilisation took place in order to clean beaches, rocks and fauna, trying to reduce the environmental consequences of this serious catastrophe. These people were exposed to the complex mixture of compounds contained in the oil. This study aimed at determine the level of environmental exposure to volatile organic compounds (VOC, and the possible damage induced on the population involved in the different cleaning tasks by applying the genotoxicity tests sister chromatid exchanges (SCE, micronucleus (MN test, and comet assay. Four groups of individuals were included: volunteers (V, hired manual workers (MW, hired high-pressure cleaner workers (HPW and controls. The higher VOC levels were associated with V environment, followed by MW and lastly by HPW, probably due to the use of high-pressure cleaners. Oil exposure during the cleaning tasks has caused an increase in the genotoxic damage in individuals, the comet assay being the most sensitive biomarker to detect it. Sex, age and tobacco consumption have shown to influence the level of genetic damage, while the effect of using protective devices was less noticeable than expected, perhaps because the kind used was not the most adequate.

  12. Phosphine-induced oxidative damage in rats: role of glutathione.

    Science.gov (United States)

    Hsu, Ching-Hung; Chi, Bei-Ching; Liu, Ming-Yie; Li, Jih-Heng; Chen, Chiou-Jong; Chen, Ruey-Yu

    2002-09-30

    Phosphine (PH(3)), generated from aluminium, magnesium and zinc phosphide, is a widely used pesticide. PH(3) induces oxidative stress in insects, mammalian cells, animals, and humans. The involvement of glutathione (GSH) in PH(3)-induced oxidative toxicity is controversial. GSH levels in various tested tissues were reduced in aluminium phosphide-poisoned rats and humans, while the levels remained unchanged in insects and mammalian cells. This study examines the effectiveness of endogenous GSH as a protective agent against PH(3)-induced oxidative damage in rats. The association of PH(3)-induced nephrotoxicity and cardiotoxicity with free radical production was also tested. Male Wistar rats, administered intraperitoneally (I.P.) with PH(3) at 4 mg/kg, were evaluated 30 min after treatment for PH(3) toxicity to organs. PH(3) significantly decreased GSH, GSH peroxidase and catalase, while significantly increased lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals), DNA oxidation (as 8-hydroxydeoxyguaonsoine) and superoxide dismutase (SOD) levels in kidney and heart. These changes were significantly alleviated by melatonin (10 mg/kg I.P., 30 min before PH(3)), with the exception of SOD activity in heart tissue. The study also found that buthionine sulfoximine (1 g/kg I.P., 24 h before PH(3)) significantly enhanced the effect of PH(3) on GSH loss and lipid peroxidation elevation in lung. These findings indicate that (1) endogenous GSH plays a crucial role as a protective factor in modulating PH(3)-induced oxidative damage, and (2) PH(3) could injure kidney and heart (as noted earlier with brain, liver and lung) via oxidative stress and the antioxidant melatonin effectively prevents the damage.

  13. "Neuropeptides in the brain defense against distant organ damage".

    Science.gov (United States)

    Hamasaki, Mike Yoshio; Barbeiro, Hermes Vieira; Barbeiro, Denise Frediani; Cunha, Débora Maria Gomes; Koike, Marcia Kiyomi; Machado, Marcel Cerqueira César; Pinheiro da Silva, Fabiano

    2016-01-15

    Delirium, or acute confusional state, is a common manifestation in diseases that originate outside the central nervous system, affecting 30-40% of elderly hospitalized patients and up to 80% of the critically ill, even though it remains unclear if severe systemic inflammation is able or not to induce cellular disturbances and immune activation in the brain. Neuropeptides are pleotropic molecules heterogeneously distributed throughout the brain and possess a wide spectrum of functions, including regulation of the inflammatory response, so we hypothesized that they would be the major alarm system in the brain before overt microglia activation. In order to investigate this hypothesis, we induced acute pancreatitis in 8-10week old rats and collected brain tissue, 12 and 24h following pancreatic injury, to measure neuropeptide and cytokine tissue levels. We found significantly higher levels of β-endorphin, orexin and oxytocin in the brain of rats submitted to pancreatic injury, when compared to healthy controls. Interestingly, these differences were not associated with increased local cytokine levels, putting in evidence that neuropeptide release occurred independently of microglia activation and may be a pivotal alarm system to initiate neurologic reactions to distant inflammatory non-infectious aggression.

  14. Platelets recognize brain-specific glycolipid structures, respond to neurovascular damage and promote neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Ilya Sotnikov

    Full Text Available Platelets respond to vascular damage and contribute to inflammation, but their role in the neurodegenerative diseases is unknown. We found that the systemic administration of brain lipid rafts induced a massive platelet activation and degranulation resulting in a life-threatening anaphylactic-like response in mice. Platelets were engaged by the sialated glycosphingolipids (gangliosides integrated in the rigid structures of astroglial and neuronal lipid rafts. The brain-abundant gangliosides GT1b and GQ1b were specifically recognized by the platelets and this recognition involved multiple receptors with P-selectin (CD62P playing the central role. During the neuroinflammation, platelets accumulated in the central nervous system parenchyma, acquired an activated phenotype and secreted proinflammatory factors, thereby triggering immune response cascades. This study determines a new role of platelets which directly recognize a neuronal damage and communicate with the cells of the immune system in the pathogenesis of neurodegenerative diseases.

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

    Science.gov (United States)

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

    1999-01-01

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

  16. Multisensory processing after a brain damage: clues on post-injury crossmodal plasticity from neuropsychology.

    Science.gov (United States)

    Bolognini, Nadia; Convento, Silvia; Rossetti, Angela; Merabet, Lotfi B

    2013-03-01

    Current neuropsychological evidence demonstrates that damage to sensory-specific and heteromodal areas of the brain not only disrupts the ability of combining sensory information from multiple sources, but can also cause altered multisensory experiences. On the other hand, there is also evidence of behavioural benefits induced by spared multisensory mechanisms. Thus, crossmodal plasticity can be viewed in both an adaptive and maladaptive context. The emerging view is that different crossmodal plastic changes can result following damage to sensory-specific and heteromodal areas, with post-injury crossmodal plasticity representing an attempt of a multisensory system to reconnect the various senses and by-pass injured areas. Changes can be considered adaptive when there is compensation for the lesion-induced sensory impairment. Conversely, it may prove maladaptive when atypical or even illusory multisensory experiences are generated as a result of re-arranged multisensory networks. This theoretical framework posits new intriguing questions for neuropsychological research and places greater emphasis on the study of multisensory phenomena within the context of damage to large-scale brain networks, rather than just focal damage alone.

  17. Mechanisms of radiation-induced brain injury / Review

    Directory of Open Access Journals (Sweden)

    Nataša Šuštar

    2014-11-01

    Full Text Available Normal 0 21 false false false SL X-NONE X-NONE MicrosoftInternetExplorer4 Mechanisms of radiation-induced brain injury are not yet fully understood. Early failure occurs because of the effect of ionizing radiation on dividing endothelialcells and oligodendrocytes. Hypothetically, late radiation-induced brain injury is causedby chronic inflammation and oxidative stress. In the case of irradiation of thehippocampus, the failure of neurogenesis and cognitive decline could be consequencesof such pathological mechanisms. Due to lack of diagnostic tools, that could not more precisely define the brain injury after radiation, therapy, that may prevent such consequences in patients who require radiotherapy, is not currently known. This articlesummarizes research hypotheses regarding processes of the brain damage after radiation, prospects in the diagnosis and therapeutic approaches.

  18. Bacterial cytolysin during meningitis disrupts the regulation of glutamate in the brain, leading to synaptic damage.

    Directory of Open Access Journals (Sweden)

    Carolin Wippel

    Full Text Available Streptococcus pneumoniae (pneumococcal meningitis is a common bacterial infection of the brain. The cholesterol-dependent cytolysin pneumolysin represents a key factor, determining the neuropathogenic potential of the pneumococci. Here, we demonstrate selective synaptic loss within the superficial layers of the frontal neocortex of post-mortem brain samples from individuals with pneumococcal meningitis. A similar effect was observed in mice with pneumococcal meningitis only when the bacteria expressed the pore-forming cholesterol-dependent cytolysin pneumolysin. Exposure of acute mouse brain slices to only pore-competent pneumolysin at disease-relevant, non-lytic concentrations caused permanent dendritic swelling, dendritic spine elimination and synaptic loss. The NMDA glutamate receptor antagonists MK801 and D-AP5 reduced this pathology. Pneumolysin increased glutamate levels within the mouse brain slices. In mouse astrocytes, pneumolysin initiated the release of glutamate in a calcium-dependent manner. We propose that pneumolysin plays a significant synapto- and dendritotoxic role in pneumococcal meningitis by initiating glutamate release from astrocytes, leading to subsequent glutamate-dependent synaptic damage. We outline for the first time the occurrence of synaptic pathology in pneumococcal meningitis and demonstrate that a bacterial cytolysin can dysregulate the control of glutamate in the brain, inducing excitotoxic damage.

  19. Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat.

    Science.gov (United States)

    Pulsinelli, W A; Waldman, S; Rawlinson, D; Plum, F

    1982-11-01

    We compared the effects of glucose injection with those of saline or mannitol on ischemic brain damage and brain water content in a four-vessel occlusion (4-VO) rat model, which simultaneously causes severe forebrain ischemia and moderate hindbrain ischemia. Glucose given before onset of ischemia was followed by severe brain injury, with necrosis of the majority of neocortical neurons and glia, substantial neuronal damage throughout the remainder of forebrain, and severe brain edema. By comparison, saline injection before forebrain ischemia resulted in only scattered ischemic damage confined to neurons and no change in the brain water content. Mannitol injection before 4-VO or D-glucose injection during or after 4-VO produced no greater forebrain damage than did the saline injection. Morphologic damage in the cerebellum, however, was increased by D-glucose injection given either before or during 4-VO. The results demonstrate that hyperglycemia before severe brain ischemia or during moderate ischemia markedly augments morphologic brain damage.

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

    Science.gov (United States)

    Vannucci, R C

    1993-01-01

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

  1. Modeling of Corrosion-induced Concrete Damage

    DEFF Research Database (Denmark)

    Thybo, Anna Emilie A.; Michel, Alexander; Stang, Henrik

    2013-01-01

    In the present paper a finite element model is introduced to simulate corrosion-induced damage in concrete. The model takes into account the penetration of corrosion products into the concrete as well as non-uniform formation of corrosion products around the reinforcement. To ac-count for the non......-uniform formation of corrosion products at the concrete/reinforcement interface, a deterministic approach is used. The model gives good estimates of both deformations in the con-crete/reinforcement interface and crack width when compared to experimental data. Further, it is shown that non-uniform deposition...... of corrosion products affects both the time-to cover cracking and the crack width at the concrete surface....

  2. Ion irradiation induced direct damage to DNA

    CERN Document Server

    Wang, Wei; Su, Wenhui

    2008-01-01

    Ion beams have been widely applied in a few biological research fields such as radioactive breeding, health protection, and tumor therapy. Up to now many interesting and impressive achievements in biology and agriculture have been made. Over the past several decades, scientists in biology, physics, and chemistry have pursued investigations focused on understanding the mechanisms of these radiobiological effects of ion beams. From the chemical point of view, these effects are due to the ion irradiation induced biomolecular damage, direct or indirect. In this review, we will present a chemical overview of the direct effects of ion irradiation upon DNA and its components, based on a review of literature combined with recent experimental results. It is suggested that, under ion bombardment, a DNA molecule undergoes a variety of processes, including radical formation, atomic displacement, intramolecular bond-scissions, emission of fragments, fragment recombination and molecular crosslink, which may lead to genetic...

  3. 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.

  4. 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. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Performance of brain-damaged and non-brain-damaged institutionalized children on the Minnesota Percepto-Diagnostic Test.

    Science.gov (United States)

    Holland, J M; Fuller, G B; Barth, C E

    1982-01-01

    Examined the performance of 64 children on the Minnesota Percepto-Diagnostic test (MPD) who were diagnosed as either Brain-Damaged (BD) or emotionally impaired Non-Brain-Damaged (NBD). There were 31 children in the NBD group and 33 in the BD group. The MPD T-score and Actuarial Table significantly differentiated between the two groups. Seventy-four percent of the combined BD-NBD groups were identified correctly. Additional discriminant analysis on this sample yielded combined BD-NBD groups classification rates that ranged from 77% with the MPD variables Separation of Circle-Diamond (SPCD), Distortion of Circle-Diamond (DCD) and Distortion of Dots (DD) to 83% with the WISC-R three IQ scores plus the MPD T-score, SPCD and DD. The MPD T-score and Actuarial Table (MPD Two-Step Diagnosis) appeared to generalize to other populations more readily than discriminant analysis formulae, which tend to be sensitive to the samples from which they are derived.

  6. AMBIENT PARTICULATE MATTER STIMULATES OXIDATIVE STRESS IN BRAIN MICROGLIA AND DAMAGES NEURONS IN CULTURE.

    Science.gov (United States)

    Ambient particulate matter (PM) damages biological targets through oxidative stress (OS) pathways. Several reports indicate that the brain is one of those targets. Since microglia (brain macrophage) are critical to OS-mediated neurodegeneration, their response to concentrated amb...

  7. Neurotoxin-induced DNA damage is persistentin SH-SY5Y cells and LC neurons

    Science.gov (United States)

    Wang, Yan; Musich, Phillip R.; Cui, Kui; Zou, Yue; Zhu, Meng-Yang

    2015-01-01

    Degeneration of the noradrenergic neurons has been reported in the brain of patients suffering from neurodegenerative diseases. However, their pathologic characteristics during the neurodegenerative course and underlying mechanisms remain to be elucidated. In the present study, we used the neurotoxincamptothecin (CPT)to induce the DNA damage response in neuroblastoma SH-SY5Y cells, normal fibroblast cells, and primarily cultured LC and raphe neurons to examine cellular responses and repair capabilities after neurotoxin exposure. To our knowledge, the present study is the first to show that noradrenergic SH-SY5Y cells are more sensitive to CPT-induced DNA damage and deficientin DNA repair, as compared to fibroblast cells. Furthermore, similar to SH-SY5Y cells, primarily cultured LC neurons are more sensitive to CPT-induced DNA damage and show a deficiency in repairing this damage. Moreover, while N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) exposure also results in DNA damage in cultured LC neurons, neither CPT nor DSP4 induce DNA damage in neuronal cultures from the raphe nuclei. Taken together, noradrenergic SH-SY5Y cells and LC neurons are sensitive to CPT-induced DNA damage and exhibit a repair deficiency, providing a mechanistic explanation for the pathologic characteristics of LC degeneration when facing endogenous and environmental DNA-damaging insultsin vivo. PMID:25724887

  8. Line and word bisection in right-brain-damaged patients with left spatial neglect.

    Science.gov (United States)

    Veronelli, Laura; Vallar, Giuseppe; Marinelli, Chiara V; Primativo, Silvia; Arduino, Lisa S

    2014-01-01

    Right-brain-damaged patients with left unilateral spatial neglect typically set the mid-point of horizontal lines to the right of the objective center. By contrast, healthy participants exhibit a reversed bias (pseudoneglect). The same effect has been described also when bisecting orthographic strings. In particular, for this latter kind of stimulus, some recent studies have shown that visuo-perceptual characteristics, like stimulus length, may contribute to both the magnitude and the direction bias of the bisection performance (Arduino et al. in Neuropsychologia 48:2140-2146, 2010). Furthermore, word stress was shown to modulate reading performances in both healthy participants, and patients with left spatial neglect and neglect dyslexia (Cubelli and Beschin in Brain Lang 95:319-326, 2005; Rusconi et al. in Neuropsychology 18:135-140, 2004). In Experiment I, 22 right-brain-damaged patients (11 with left visuo-spatial neglect) and 11 matched neurologically unimpaired control participants were asked to set the subjective mid-point of word letter strings, and of lines of comparable length. Most patients exhibited an overall disproportionate rightward bias, sensitive to stimulus length, and similar for words and lines. Importantly, in individual patients, biases differed according to stimulus type (words vs. lines), indicating that at least partly different mechanisms may be involved. In Experiment II, the putative effects on the bisection bias of ortho-phonological information (i.e., word stress endings), arising from the non-neglected right hand side of the stimulus were investigated. The orthographic cue induced a rightward shift of the perceived mid-point in both patients and controls, with short words stressed on the antepenultimate final sequence inducing a smaller rightward deviation with respect to short words stressed on the penultimate final sequence. In conclusion, partly different mechanisms, including both visuo-spatial and lexical factors, may support

  9. 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

  10. 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.

  11. Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain.

    Science.gov (United States)

    Gong, Yu; Chai, Yi; Ding, Jian-Hua; Sun, Xiu-Lan; Hu, Gang

    2011-01-13

    Increasing evidence implicates mitochondrial failure as a crucial factor in the pathogenesis of mental disorders, such as depression. The aim of the present study was to investigate the effects of exposure to chronic mild stress (CMS), a paradigm developed in the late 1980s as an animal model of depression, on the mitochondrial function and mitochondrial ultrastructure in the mouse brain. The results showed that the CMS regime induced depressive-like symptoms in mice characterized by reduced sucrose preference and body weight. Moreover, CMS exposure was associated with a significant increase in immobility time in the tail suspension test. Exposure to the CMS paradigm inhibited mitochondrial respiration rates and dissipated mitochondrial membrane potential in hippocampus, cortex and hypothalamus of mice. In addition, we found a damaged mitochondrial ultrastructure in brains of mice exposed to CMS. These findings provide evidence for brain mitochondrial dysfunction and ultrastructural damage in a mouse model of depression. Moreover, these findings suggest that mitochondrial malfunction-induced oxidative injury could play a role in stress-related disorders such as depression.

  12. Overproduction of nitric oxide intensifies brain infarction and cerebrovascular damage through reduction of claudin-5 and ZO-1 expression in striatum of ischemic brain.

    Science.gov (United States)

    Mohammadi, Mohammad Taghi

    2016-11-01

    Nitric oxide (NO) overproduction has been demonstrated from different NO-synthase overexpression or hyperactivity after brain ischemia. Here, we examined the effects of inhibition of NO overproduction on brain infarction, cerebrovascular damage and expression of claudin-5 and zonula occludens-1 (ZO-1) in striatum of ischemic brain. The experiment was performed in three groups of rats; sham, control ischemia and ischemic treatment. Brain ischemia was induced by 60min of middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Treated rats received L-NAME 30min before induction of ischemia (1mg/kg, i.p.). Infarct volume and histopathological changes of ischemic striatum were assessed by TTC and LFB staining methods, respectively. Ultimately, quantitative RT-PCR was used for assessment of claudins-5 and ZO-1 expression. MCAO in the control group induced infarction (135±25mm(3)) at large areas of striatum in accompany with neuronal damages, whereas L-NAME significantly reduced infarction (87±16mm(3)) and neuronal injuries. The mRNA of ZO-1 and claudin-5 decreased in ischemic striatum, whereas inhibition of NO overproduction by L-NAME attenuated this reduction for these genes. Our findings indicated that NO overproduction after brain ischemia plays a crucial role in neuronal damage especially at striatal regions. Hence, inhibition of excessive NO production may save striatal cerebrovascular integrity of ischemic brain.

  13. The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk.

    Directory of Open Access Journals (Sweden)

    Denis N Silachev

    Full Text Available BACKGROUND: Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. METHODOLOGY/PRINCIPAL FINDINGS: We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated

  14. Blood-induced joint damage: novel targets for therapy

    NARCIS (Netherlands)

    van Meegeren, M.E.R.

    2012-01-01

    -induced joint damage can occur due to a trauma but also during surgery when blood leaks into the joint cavity. Besides that, it is one of the major causes of morbidity amongst haemophilia patients. The aims of this thesis were to further unravel the pathogenesis of blood-induced joint damage and to

  15. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    Science.gov (United States)

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539).

  16. Long-term prehypertension treatment with losartan effectively prevents brain damage and stroke in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    He, De-Hua; Zhang, Liang-Min; Lin, Li-Ming; Ning, Ruo-Bing; Wang, Hua-Jun; Xu, Chang-Sheng; Lin, Jin-Xiu

    2014-02-01

    Prehypertension has been associated with adverse cerebrovascular events and brain damage. The aims of this study were to investigate ⅰ) whether short‑ and long-term treatments with losartan or amlodipine for prehypertension were able to prevent blood pressure (BP)-linked brain damage, and ⅱ) whether there is a difference in the effectiveness of treatment with losartan and amlodipine in protecting BP-linked brain damage. In the present study, prehypertensive treatment with losartan and amlodipine (6 and 16 weeks treatment with each drug) was performed on 4-week‑old stroke-prone spontaneously hypertensive rats (SHRSP). The results showed that long-term (16 weeks) treatment with losartan is the most effective in lowering systolic blood pressure in the long term (up to 40 weeks follow-up). Additionally, compared with the amlodipine treatment groups, the short‑ and long-term losartan treatments protected SHRSP from stroke and improved their brains structurally and functionally more effectively, with the long-term treatment having more benefits. Mechanistically, the short‑ and long-term treatments with losartan reduced the activity of the local renin-angiotensin-aldosterone system (RAAS) in a time-dependent manner and more effectively than their respective counterpart amlodipine treatment group mainly by decreasing AT1R levels and increasing AT2R levels in the cerebral cortex. By contrast, the amlodipine treatment groups inhibited brain cell apoptosis more effectively as compared with the losartan treatment groups mainly through the suppression of local oxidative stress. Taken together, the results suggest that long-term losartan treatment for prehypertension effectively protects SHRSP from stroke-induced brain damage, and this protection is associated with reduced local RAAS activity than with brain cell apoptosis. Thus, the AT1R receptor blocker losartan is a good candidate drug that may be used in the clinic for long-term treatment on prehypertensive

  17. Changes in Connectivity after Visual Cortical Brain Damage Underlie Altered Visual Function

    Science.gov (United States)

    Bridge, Holly; Thomas, Owen; Jbabdi, Saad; Cowey, Alan

    2008-01-01

    The full extent of the brain's ability to compensate for damage or changed experience is yet to be established. One question particularly important for evaluating and understanding rehabilitation following brain damage is whether recovery involves new and aberrant neural connections or whether any change in function is due to the functional…

  18. Repeated Administration of Mercury Intensifies Brain Damage in Multiple Sclerosis through Mitochondrial Dysfunction

    Science.gov (United States)

    Kahrizi, Farzad; Salimi, Ahmad; Noorbakhsh, Farshid; Faizi, Mehrdad; Mehri, Freshteh; Naserzadeh, Parvaneh; Naderi, Nima; Pourahmad, Jalal

    2016-01-01

    In this study we investigated the additive effect of mercury on the brain mitochondrial dysfunction in experimental autoimmune encephalomyelitis (EAE) model. Experimental animals (female C57BL/6 mice) are divided into four groups (n = 8); control, Hg, EAE, EAE with Hg. EAE model of MS induced by injecting myelin oligodendrocyte glycoprotein (MOG). Neurobehavioral alterations are recorded and then mice were sacrificed at day 28 and brain mitochondria were isolated and mitochondrial toxicity parameters including mitochondrial swelling, reactive oxygen species (ROS) formation, collapse of mitochondrial membrane potential (MMP) and cytochrome c release were measured. Our results showed that repeated treatment of mercury following induction of EAE in mice significantly increased the neurobehavioral scores, as well as mitochondrial toxicity through ROS formation, mitochondrial swelling, collapse of MMP and cytochrome c release. Our findings proved that repeated exposure with mercury accelerates progression of MS through mitochondrial damage related to oxidative stress and finally apoptosis.

  19. Effect of propolis consumption on hepatotoxicity and brain damage ...

    African Journals Online (AJOL)

    user

    2013-08-14

    Aug 14, 2013 ... coefficient was followed at 480 nm in a Spectrophotometer. Plasma concentrations of total ... CPF caused functional and structural damage of liver tissue. This damage .... al., (2007). When the liver cell membrane is damaged,.

  20. Heat induced damage detection in composite materials by terahertz radiation

    Science.gov (United States)

    Radzieński, Maciej; Mieloszyk, Magdalena; Rahani, Ehsan Kabiri; Kundu, Tribikram; Ostachowicz, Wiesław

    2015-03-01

    In recent years electromagnetic Terahertz (THz) radiation or T-ray has been increasingly used for nondestructive evaluation of various materials such as polymer composites and porous foam tiles in which ultrasonic waves cannot penetrate but T-ray can. Most of these investigations have been limited to mechanical damage detection like inclusions, cracks, delaminations etc. So far only a few investigations have been reported on heat induced damage detection. Unlike mechanical damage the heat induced damage does not have a clear interface between the damaged part and the surrounding intact material from which electromagnetic waves can be reflected back. Difficulties associated with the heat induced damage detection in composite materials using T-ray are discussed in detail in this paper. T-ray measurements are compared for different levels of heat exposure of composite specimens.

  1. Candesartan and glycyrrhizin ameliorate ischemic brain damage through downregulation of the TLR signaling cascade.

    Science.gov (United States)

    Barakat, Waleed; Safwet, Nancy; El-Maraghy, Nabila N; Zakaria, Mohamed N M

    2014-02-01

    Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA). The current study was designed to investigate the protective effects of candesartan (0.15 mg/kg, orally) and glycyrrhizin (30 mg/kg, orally) experimentally-induced ischemic brain damage in C57BL/6 mice (middle cerebral artery occlusion, MCAO) in comparison to the effects of a standard neuroprotective drug (cerebrolysin, 7.5 mg/kg, IP). All drugs were administered 30 min before and 24h after MCAO. Both candesartan and glycyrrhizin ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in behaviour tests, reduction in brain infarction, neuronal degeneration, and leukocyte infiltration. In addition, MCAO induced a significant upregulation in the different elements of the TLR pathway including TLR-2 and TLR-4, Myd88, TRIF and IRF-3 and the downstream effectors TNF-α, IL-1β, IL-6 and NF-kB. All these changes were significantly ameliorated by treatment with candesartan and glycyrrhizin. The results of the current study represent a new indication for both candesartan and glycyrrhizin in the management of ischemic stroke with effects comparable to those of the standard neuroprotective drug cerebrolysin.

  2. Distinct time courses of secondary brain damage in the hippocampus following brain concussion and contusion in rats.

    Science.gov (United States)

    Nakajima, Yuko; Horiuchi, Yutaka; Kamata, Hiroshi; Yukawa, Masayoshi; Kuwabara, Masato; Tsubokawa, Takashi

    2010-07-01

    Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.

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

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yankui Guo; Yalu Li; Zhenying Yang

    2011-01-01

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

  4. Cellular Responses to Cisplatin-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Alakananda Basu

    2010-01-01

    Full Text Available Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death. This paper summarizes our current understandings regarding the mechanisms by which cisplatin induces cell death and the bases of cisplatin resistance. We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. An understanding of how various signaling pathways regulate cisplatin-induced cell death should aid in the development of more effective therapeutic strategies for the treatment of cancer.

  5. 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

  6. Chemically induced intestinal damage models in zebrafish larvae.

    Science.gov (United States)

    Oehlers, Stefan H; Flores, Maria Vega; Hall, Christopher J; Okuda, Kazuhide S; Sison, John Oliver; Crosier, Kathryn E; Crosier, Philip S

    2013-06-01

    Several intestinal damage models have been developed using zebrafish, with the aim of recapitulating aspects of human inflammatory bowel disease (IBD). These experimentally induced inflammation models have utilized immersion exposure to an array of colitogenic agents (including live bacteria, bacterial products, and chemicals) to induce varying severity of inflammation. This technical report describes methods used to generate two chemically induced intestinal damage models using either dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). Methods to monitor intestinal damage and inflammatory processes, and chemical-genetic methods to manipulate the host response to injury are also described.

  7. 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.

  8. 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.

  9. Role of IL-1alpha and IL-1beta in ischemic brain damage.

    Science.gov (United States)

    Boutin, H; LeFeuvre, R A; Horai, R; Asano, M; Iwakura, Y; Rothwell, N J

    2001-08-01

    The cytokine interleukin-1 (IL-1) has been strongly implicated in the pathogenesis of ischemic brain damage. Evidence to date suggests that the major form of IL-1 contributing to ischemic injury is IL-1beta rather than IL-1alpha, but this has not been tested directly. The objective of the present study was to compare the effects of transient cerebral ischemia [30 min middle cerebral artery occlusion (MCAO)] on neuronal injury in wild-type (WT) mice and in IL-1alpha, IL-1beta, or both IL-1alpha and IL-1beta knock-out (KO) mice. Mice lacking both forms of IL-1 exhibited dramatically reduced ischemic infarct volumes compared with wild type (total volume, 70%; cortex, 87% reduction). Ischemic damage compared with WT mice was not significantly altered in mice lacking either IL-1alpha or IL-1beta alone. IL-1beta mRNA, but not IL-1alpha or the IL-1 type 1 receptor, was strongly induced by MCAO in WT and IL-1alpha KO mice. Administration (intracerebroventricularly) of recombinant IL-1 receptor antagonist significantly reduced infarct volume in WT (-32%) and IL-1alpha KO (-48%) mice, but had no effect on injury in IL-1beta or IL-1alpha/beta KO mice. These data confirm that IL-1 plays a major role in ischemic brain injury. They also show that chronic deletion of IL-1alpha or IL-1beta fails to influence brain damage, probably because of compensatory changes in the IL-1 system in IL-1alpha KO mice and changes in IL-1-independent mediators of neuronal death in IL-1beta KO mice.

  10. Laser-Induced Thermal Damage of Skin

    Science.gov (United States)

    1977-12-01

    As with the eye model, ther- mal damage is predicted using Henriques damage integral (11). This criterion involves integrating temperature- dependent...epide•: mal layers are much larger than the coefficients for the entire skin presented in Figure 5. This observation suggests there should be twd...EXPOI"’ES INVOLVJINS MUMtPLE PULSES OTOODYCIZO 010OTO OJO SI tNGLE PUL.$LSE 19(M."ft 7.13NP#R5 xxsLlimft p DO 3 ?V 36 Ep(MgiSNPRCL) *~To so 36

  11. [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.

  12. QUANTIFYING LOCAL RADIATION-INDUCED LUNG DAMAGE FROM COMPUTED TOMOGRAPHY

    NARCIS (Netherlands)

    Ghobadi, Ghazaleh; Hogeweg, Laurens E.; Faber, Hette; Tukker, Wim G. J.; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Coppes, Robert P.; van Luijk, Peter

    2010-01-01

    Purpose: Optimal implementation of new radiotherapy techniques requires accurate predictive models for normal tissue complications. Since clinically used dose distributions are nonuniform, local tissue damage needs to be measured and related to local tissue dose. In lung, radiation-induced damage re

  13. A Plasticity Induced Anisotropic Damage Model for Sheet Forming Processes

    NARCIS (Netherlands)

    Niazi, M.S.; Meinders, V.T.; Wisselink, H.H.; Horn, ten C.H.L.J.; Klaseboer, G.; Boogaard, van den A.H.

    2013-01-01

    Plastic deformation induces damage in Advanced High Strength Steels (AHSS). Therefore damage development in these steels shall be studied and incorporated in the simulations for accurate failure predictions in forming processes and for determination of the product properties after forming. An effici

  14. 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.

  15. Simulation study of radiation damage induced by energetic helium nuclei

    CERN Document Server

    Hoang Dac Luc; Hoang Dac Dat

    2003-01-01

    High energy alpha particles produced by neutron-induced nuclear reactions can damage severely reactor materials. Simulation of this process is described using theoretical calculation and ion irradiation experiments at different displacement doses and Helium doses.

  16. Micromechanics of diffusion-induced damage evolution in reinforced polymers

    DEFF Research Database (Denmark)

    Abhilash, A.S.; Joshi, Shailendra P.; Mukherjee, Abhijit

    2011-01-01

    -induced damage provides synergistic conditions for the rapid evolution of debonding under subsequent mechanical loading. The results indicate that microstructural heterogeneity strongly affects the moisture diffusion characteristics that in turn hurt the overall load carrying capacity of a composite due...

  17. Density of oxidation-induced stacking faults in damaged silicon

    NARCIS (Netherlands)

    Kuper, F.G.; Hosson, J.Th.M. De; Verwey, J.F.

    1986-01-01

    A model for the relation between density and length of oxidation-induced stacking faults on damaged silicon surfaces is proposed, based on interactions of stacking faults with dislocations and neighboring stacking faults. The model agrees with experiments.

  18. Hypochlorite-induced damage to nucleosides

    DEFF Research Database (Denmark)

    Hawkins, C L; Davies, Michael Jonathan

    2001-01-01

    Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is a key bactericidal agent, but can also damage host tissue. As there is a strong link between chronic inflammation and some cancers, we have investigated...

  19. 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.

  20. Cordycepin attenuates traumatic brain injury-induced impairments of blood-brain barrier integrity in rats.

    Science.gov (United States)

    Yuan, Jing; Wang, Aihua; He, Yan; Si, Zhihua; Xu, Shan; Zhang, Shanchao; Wang, Kun; Wang, Dawei; Liu, Yiming

    2016-10-01

    Loss of blood-brain barrier (BBB) integrity is a downstream event caused by traumatic brain injury (TBI). BBB integrity is affected by certain physiological conditions, including inflammation and oxidative stress. Cordycepin is a susbtance with anti-inflammatory and anti-oxidative effects. Therefore, it is necessary to investigate whether cordycepin affects TBI-induced impairments of BBB integrity. Using TBI rats as the in vivo model and applying multiple techniques, including stroke severity evaluation, Evans blue assessment, quantitative real-time PCR, Western blotting and ELISA, we investigated the dose-dependent protective effects of cordycepin on the TBI-induced impairments of BBB integrity. Cordycepin treatment attenuated the TBI-induced impairments in a dose-dependent manner, and played a role in protecting BBB integrity. Cordycepin was able to alleviate TBI-induced loss of tight junction proteins zonula occludens protein-1 (ZO-1) and occludin, which are important for BBB integrity. Moreover, cordycepin suppressed pro-inflammatory factors, including IL-1β, iNOS, MPO and MMP-9, and promoted anti-inflammation-associated factors arginase 1 and IL-10. Furthermore, cordycepin inhibited NADPH oxidase (NOX) expression and activity following TBI, probably through NOX1, but not NOX2 and NOX4. Cordycepin has protective effects against brain damages induced by TBI. The protection of cordycepin on BBB integrity was probably achieved through recovery of tight junction proteins, inhibition of local inflammation, and prevention of NOX activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Quercitrin protects skin from UVB-induced oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Yuanqin [Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Yao, Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J. [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY (United States); Gao, Ning [Department of Pharmacognos, College of Pharmacy, 3rd Military Medical University, Chongqing (China); Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States)

    2013-06-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

  2. Detection of spatial frequency in brain-damaged patients: influence of hemispheric asymmetries and hemineglect

    Directory of Open Access Journals (Sweden)

    Natanael Antonio Dos Santos

    2013-04-01

    Full Text Available Hemispheric specialization for spatial frequency processing was investigated by measuring the contrast sensitivity curves of sine-wave gratings in 30 left or right brain-damaged patients using different spatial frequencies compared with healthy participants. The results showed that left brain-damaged patients were selectively impaired in processing high frequencies, whereas right brain-damaged patients were more impaired in the processing low frequencies, regardless of the presence of visuo-spatial neglect. These visual processing results can be interpreted in terms of spatial frequency discrimination, with both hemispheres participating in this process in different ways.

  3. The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats.

    Science.gov (United States)

    Otsuka, Shotaro; Sakakima, Harutoshi; Sumizono, Megumi; Takada, Seiya; Terashi, Takuto; Yoshida, Yoshihiro

    2016-04-15

    Preconditioning exercise can exert neuroprotective effects after stroke. However, the mechanism underlying these neuroprotective effects by preconditioning exercise remains unclear. We investigated the neuroprotective effects of preconditioning exercise on brain damage and the expression levels of the midkine (MK) and brain-derived neurotrophic factor (BDNF) after brain ischemia. Animals were assigned to one of 4 groups: exercise and ischemia (Ex), no exercise and ischemia (No-Ex), exercise and no ischemia (Ex-only), and no exercise and intact (Control). Rats ran on a treadmill for 30 min once a day at a speed of 25 m/min for 5 days a week for 3 weeks. After the exercise program, stroke was induced by a 60 min left middle cerebral artery occlusion using an intraluminal filament. The infarct volume, motor function, neurological deficits, and the cellular expressions levels of MK, BDNF, GFAP, PECAM-1, caspase 3, and nitrotyrosine (NT) were evaluated 48 h after the induction of ischemia. The infarct volume, neurological deficits and motor function in the Ex group were significantly improved compared to that of the No-Ex group. The expression levels of MK, BDNF, GFAP, and PECAM-1 were enhanced in the Ex group compared to the expression levels in the No-Ex group after brain ischemia, while the expression levels of activated caspase 3 and NT were reduced in the area surrounding the necrotic lesion. Our findings suggest that preconditioning exercise reduced the infract volume and ameliorated motor function, enhanced expression levels of MK and BDNF, increased astrocyte proliferation, increased angiogenesis, and reduced neuronal apoptosis and oxidative stress.

  4. Simulations of explosion-induced damage to underground rock chambers

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    A numerical approach is presented to study the explosion-induced pressure load on an underground rock chamber wall and its resultant damage to the rock chamber.Numerical simulations are carried out by using a modified version of the commercial software AUTODYN.Three different criteria,i.e.a peak particle velocity (PPV) criterion,an effective strain (ES) criterion,and a damage criterion,are employed to examine the explosion-induced damaged zones of the underground rock chamber.The results show that the charg...

  5. Vision restoration after brain and retina damage: the "residual vision activation theory".

    Science.gov (United States)

    Sabel, Bernhard A; Henrich-Noack, Petra; Fedorov, Anton; Gall, Carolin

    2011-01-01

    Vision loss after retinal or cerebral visual injury (CVI) was long considered to be irreversible. However, there is considerable potential for vision restoration and recovery even in adulthood. Here, we propose the "residual vision activation theory" of how visual functions can be reactivated and restored. CVI is usually not complete, but some structures are typically spared by the damage. They include (i) areas of partial damage at the visual field border, (ii) "islands" of surviving tissue inside the blind field, (iii) extrastriate pathways unaffected by the damage, and (iv) downstream, higher-level neuronal networks. However, residual structures have a triple handicap to be fully functional: (i) fewer neurons, (ii) lack of sufficient attentional resources because of the dominant intact hemisphere caused by excitation/inhibition dysbalance, and (iii) disturbance in their temporal processing. Because of this resulting activation loss, residual structures are unable to contribute much to everyday vision, and their "non-use" further impairs synaptic strength. However, residual structures can be reactivated by engaging them in repetitive stimulation by different means: (i) visual experience, (ii) visual training, or (iii) noninvasive electrical brain current stimulation. These methods lead to strengthening of synaptic transmission and synchronization of partially damaged structures (within-systems plasticity) and downstream neuronal networks (network plasticity). Just as in normal perceptual learning, synaptic plasticity can improve vision and lead to vision restoration. This can be induced at any time after the lesion, at all ages and in all types of visual field impairments after retinal or brain damage (stroke, neurotrauma, glaucoma, amblyopia, age-related macular degeneration). If and to what extent vision restoration can be achieved is a function of the amount of residual tissue and its activation state. However, sustained improvements require repetitive

  6. Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

    Science.gov (United States)

    Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

    2013-05-01

    Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults.

  7. Laser-Induced Damage Initiation and Growth of Optical Materials

    Directory of Open Access Journals (Sweden)

    Jingxia Yu

    2014-01-01

    Full Text Available The lifetime of optical components is determined by the combination of laser-induced damage initiation probability and damage propagation rate during subsequent laser shots. This paper reviews both theoretical and experimental investigations on laser-induced damage initiation and growth at the surface of optics. The damage mechanism is generally considered as thermal absorption and electron avalanche, which play dominant roles for the different laser pulse durations. The typical damage morphology in the surface of components observed in experiments is also closely related to the damage mechanism. The damage crater in thermal absorption process, which can be estimated by thermal diffusion model, is typical distortion, melting, and ablation debris often with an elevated rim caused by melted material flow and resolidification. However, damage initiated by electron avalanche is often accompanied by generation of plasma, crush, and fracture, which can be explained by thermal explosion model. Damage growth at rear surface of components is extremely severe which can be explained by several models, such as fireball growth, impact crater, brittle fracture, and electric field enhancement. All the physical effects are not independent but mutually coupling. Developing theoretical models of multiphysics coupling are an important trend for future theoretical research. Meanwhile, more attention should be paid to integrated analysis both in theory and experiment.

  8. Bleomycin and radiation-induced lung damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Collis, C.H.; Down, J.D.; Pearson, A.E.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1983-01-01

    Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction.

  9. Difference in volatiles of poplar induced by various damages

    Institute of Scientific and Technical Information of China (English)

    HUZeng-hui; YANGDi; SHENYing-bai

    2004-01-01

    Three treatments including mechanical damage, Lymantria dispar attacking and daubing oral secretions of the insects on mechanically damaged cut were conducted on Populus simoniixPopulus pyramibalis c.v. in order to find the genuine reason leading to effective resistance response of tree to insects attacking. The release situation of the induced volatiles of the plant was analyzed by TCT-GC/MS at 24 hours after damages. The results indicated that some of the volatiles such as (Z)-3-hexenyl acetate, decanal, 3-hexenyl isovalerate, nonanal, ocimene, and 2-cyanobutane can be induced by both insects attacking and mechanical damage, while 2,6-dimethyl-1,3,5,7-octatetraene, 2-methyl-6-methylene-1,7-octadien-3-one, caryophyllene,Isovaleronitrile, diethyl-methyl-benzamide, and dicapryl phthalate were only induced by insects attacking. Such difference in volatiles was attributed to that there existed active components in oral sections of the larvae of Lymantria dispar

  10. Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

    Science.gov (United States)

    Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L

    2014-07-01

    Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased

  11. Intranasal delivery of obidoxime to the brain prevents mortality and CNS damage from organophosphate poisoning.

    Science.gov (United States)

    Krishnan, Jishnu K S; Arun, Peethambaran; Appu, Abhilash P; Vijayakumar, Nivetha; Figueiredo, Taíza H; Braga, Maria F M; Baskota, Sudikshya; Olsen, Cara H; Farkas, Natalia; Dagata, John; Frey, William H; Moffett, John R; Namboodiri, Aryan M A

    2016-03-01

    Intranasal delivery is an emerging method for bypassing the blood brain barrier (BBB) and targeting therapeutics to the CNS. Oximes are used to counteract the effects of organophosphate poisoning, but they do not readily cross the BBB. Therefore, they cannot effectively counteract the central neuropathologies caused by cholinergic over-activation when administered peripherally. For these reasons we examined intranasal administration of oximes in an animal model of severe organophosphate poisoning to determine their effectiveness in reducing mortality and seizure-induced neuronal degeneration. Using the paraoxon model of organophosphate poisoning, we administered the standard treatment (intramuscular pralidoxime plus atropine sulphate) to all animals and then compared the effectiveness of intranasal application of obidoxime (OBD) to saline in the control groups. Intranasally administered OBD was effective in partially reducing paraoxon-induced acetylcholinesterase inhibition in the brain and substantially reduced seizure severity and duration. Further, intranasal OBD completely prevented mortality, which was 41% in the animals given standard treatment plus intranasal saline. Fluoro-Jade-B staining revealed extensive neuronal degeneration in the surviving saline-treated animals 24h after paraoxon administration, whereas no detectable degenerating neurons were observed in any of the animals given intranasal OBD 30min before or 5min after paraoxon administration. These findings demonstrate that intranasally administered oximes bypass the BBB more effectively than those administered peripherally and provide an effective method for protecting the brain from organophosphates. The addition of intranasally administered oximes to the current treatment regimen for organophosphate poisoning would improve efficacy, reducing both brain damage and mortality.

  12. Laser induced damage in optical materials: 1989

    Science.gov (United States)

    Bennett, H. E.; Chase, L. L.; Guenther, A. H.; Newnam, B. E.; Soileau, M. J.

    1990-10-01

    The 21st Annual Symposium on Optical Materials for High Power Lasers was divided into sessions concerning Materials and Measurements, Mirrors and Surfaces, Thin Films, and, finally, Fundamental Mechanisms. As in previous years, the emphasis of the papers presented was directed toward new frontiers and new developments. Particular emphasis was given to materials for high power apparatus. The wavelength range of the prime interest included surface characterization, thin film substrate boundaries, and advances in fundamental laser matter threshold interactions and mechanisms. The scalling of damage thresholds with pulse duration, focal area, and wavelength was discussed in detail.

  13. Visual scanning and matching dysfunction in brain-damaged patients with drawing impairment.

    Science.gov (United States)

    Belleza, T; Rappaport, M; Hopkins, H K; Hall, K

    1979-03-01

    Visual matching and visual exploration were examined in 7 normal subjects and 20 brain-damaged patients with drawing impairment measured by the Bender Gestalt Visual-Motor Test. Right brain-damaged patients made significantly more errors of rotation and integration than left brain-damaged patients. Selecteded Bender figures were also used as stimuli for both visual matching and visual exploration tests. The ability to match Bender figures was found to be impaired in right but not left brain-damaged patients. All patients showed eye movement and fixation patterns different from those normals. Patients essentially had more fixations and shorter fixation durations. Significant intercorrelations were found between the total Bender Gestalt score and visual matching and visual exploration scores. These findings indicate that visual matching and visual exploration measures can be used to evaluate perceptual impairment in individuals who do not have adequate motor responses or where impaired motor responses may confound interpretations about visual cognitive impairment.

  14. A neurocorrective approach for MMPI-2 use for brain-damaged patients

    NARCIS (Netherlands)

    Balen, H.G.G. van; Mey, H.R.A. De; Limbeek, J. van

    1999-01-01

    Conventional administration of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) to aetiologically distinct brain-damaged out-patients (n = 137) revealed significant indications of psychological maladjustment. An adjustment for the endorsement of aetiology-specific items pertaining to

  15. Experimental Investigation of DNA Damage Induced by Heavy Ions

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    DNA is considered the critical target for radiobiological effects. It is highly important to study DNAdamage induced by ionizing radiation. Especially DNA double strand breaks have been identified as themost initial damage. In this experiment, DNA double strand breaks induced by heavy ions wereinvestigated with atomic force microscopy (AFM).

  16. Damage of vascular endothelial barrier induced by explosive blast and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Wang; Jing Chen

    2016-01-01

    In recent years,injuries induced by explosive blast have got more and more attention owing to weapon development and frequent terrorist activities.Tear.bleeding and edema of tissues and organs are the main manifestations of blast shock wave damage.Vascular endothelial barrier is the main defense of tissues and organs' integrity.This article aims to discuss possible mechanisms of endothelial barrier damage induced by explosive blast and main manifestations of blood brain barrier,blood-air barrier,and intestinal vascular barrier impairments.In addition,the main regulatory factors of vascular permeability are also summarized so as to provide theoretical basis for prevention and cure of vascular endothelial barrier damage resulting from explosive blast.

  17. Spontaneous perseverative turning in rats with radiation-induced hippocampal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mickley, G.A.; Ferguson, J.L.; Nemeth, T.J.; Mulvihill, M.A.; Alderks, C.E. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1989-08-01

    This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage.

  18. Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

    Directory of Open Access Journals (Sweden)

    José A. Hernández

    2016-01-01

    Full Text Available The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol-related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms.

  19. Swimming training attenuates oxidative damage and increases enzymatic but not non-enzymatic antioxidant defenses in the rat brain

    Directory of Open Access Journals (Sweden)

    L.F. Nonato

    Full Text Available Although it is well known that physical training ameliorates brain oxidative function after injuries by enhancing the levels of neurotrophic factors and oxidative status, there is little evidence addressing the influence of exercise training itself on brain oxidative damage and data is conflicting. This study investigated the effect of well-established swimming training protocol on lipid peroxidation and components of antioxidant system in the rat brain. Male Wistar rats were randomized into trained (5 days/week, 8 weeks, 30 min; n=8 and non-trained (n=7 groups. Forty-eight hours after the last session of exercise, animals were euthanized and the brain was collected for oxidative stress analysis. Swimming training decreased thiobarbituric acid reactive substances (TBARS levels (P0.05. Moreover, the swimming training promoted metabolic adaptations, such as increased maximal workload capacity (P<0.05 and maintenance of body weight. In this context, the reduced TBARS content and increased SOD antioxidant activity induced by 8 weeks of swimming training are key factors in promoting brain resistance. In conclusion, swimming training attenuated oxidative damage and increased enzymatic antioxidant but not non-enzymatic status in the rat brain.

  20. Moringa Oleifera Lam Mitigates Oxidative Damage and Brain Infarct Volume in Focal Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2012-01-01

    Full Text Available Problem statement: At present, the therapeutic outcome of cerebral ischemia is still not in the satisfaction level. Therefore, the preventive strategy is considered. Based on the protective effect against oxidative damage of Moringa oleifera Lam. Leaves extract, we hypothesized that this plant extract might protect against cerebral ischemia, one of the challenge problems nowadays. In order to test this hypothesis, we aimed to determine the protective effect of M.oleifera leaves extract in animal model of focal cerebral ischemia induced by permanent occlusion of right middle cerebral artery. Approach: Male Wistar rats, weighing 300-350 g, were orally given the extract once daily at doses of 100, 200 and 400 mg kg-1 BW at a period of 2 weeks, then, they were permanently occluded the right Middle Cerebral Artery (MCAO. The animals were assessed the cerebral infarction volume and oxidative damage markers including MDA level and the activities of SOD, CAT and GSHPx enzymes at 24 h after occlusion. Results: Rats subjected to M.oleifera extract at all doses used in this study significantly decreased brain infarct volume both at cortical and subcortical structures in accompany with the elevation of SOD activity in both hippocampus and striatum while only the rats exposed to the extract at doses of 100 and 400 mg kg-1 BW showed the increased GSHPx activity in hippocampus. No the changes were observed. Therefore, our results demonstrates the potential benefit of M.oleifera leaves to decrease oxidative stress damage and brain infarct volume. Conclusion: This study is the first study to demonstrate the neuroprotective effect against focal cerebral ischemia of M.oleifera leaves. It suggests that M.oleifera may be served as natural resource for developing neuroprotectant against focal cerebral ischemia. However, the precise underlying mechanism and possible active ingredient are still required further study.

  1. Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Quan-Guang Zhang

    Full Text Available BACKGROUND: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O(2(-, and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI. METHODOLOGY/PRINCIPAL FINDINGS: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O(2(- induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI. CONCLUSIONS/SIGNIFICANCE: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.

  2. Hypochlorite-induced damage to proteins

    DEFF Research Database (Denmark)

    Hawkins, C L; Davies, Michael Jonathan

    1998-01-01

    Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl damages proteins by reaction with amino acid side-chains or backbone cleavage. Little information is available about the mechanisms and intermediates involved...... in these reactions. EPR spin trapping has been employed to identify radicals on proteins, peptides and amino acids after treatment with HOCl. Reaction with HOCl gives both high- and low-molecular-mass nitrogen-centred, protein-derived radicals; the yield of the latter increases with both higher HOCl:protein ratios...... and enzymic digestion. These radicals, which arise from lysine side-chain amino groups, react with ascorbate, glutathione and Trolox. Reaction of HOCl-treated proteins with excess methionine eliminates radical formation, which is consistent with lysine-derived chloramines (via homolysis of N-Cl bonds) being...

  3. 45. Damage effects of sulfur dioxide inhalation on DNA of brain cells from mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The damage effects of sulfur dioxide (SO2) inhalation on DNA of brain cells from mice were studied with the single cell microgel electrophoresis tecknique (Comet test). The results show that SO2 inhalation caused the damage effects to DNA of the mouse brain cells in a dose-dependent manner. The results indicate that even under SO2 inhalation at low concentrations as 7 mg SO2/m3, The brain cells with DNA damaged also reached to 98.8%, it implies the brain cells of mammalian animals are very sensitive to SO2 inhalation. The results also indicate that DNA damage of the brain cells from male mice is more serious than that from female mice, that remains to be further studied. These results led us to conclusion SO2 pollution even at low concentrations also has a potential risk to damage genetic material DNA of brain cells from mammalian animals. It might be explained by our conclusion that the recently published epidemiological studies of workers exposed to SO2 or it's derivatives (bi)sulfite) found increased mortality for brain cancer.

  4. White Matter Damage and Cognitive Impairment after Traumatic Brain Injury

    Science.gov (United States)

    Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James

    2011-01-01

    White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…

  5. Secondary Damage after Traumatic Brain Injury: Epidemiology, Pathophysiology and Therapy

    NARCIS (Netherlands)

    D.C. Engel (Doortje Caroline)

    2008-01-01

    textabstractTraumatic brain injury (TBI) is defined as a microscopic or macroscopic injury to the brain caused by external physical forces. Road traffic accidents, falls, sports injuries (i.e. boxing), recreational accidents (i.e. parachute jumping), the use of firearms, assault, child abuse, and se

  6. Secondary Damage after Traumatic Brain Injury: Epidemiology, Pathophysiology and Therapy

    NARCIS (Netherlands)

    D.C. Engel (Doortje Caroline)

    2008-01-01

    textabstractTraumatic brain injury (TBI) is defined as a microscopic or macroscopic injury to the brain caused by external physical forces. Road traffic accidents, falls, sports injuries (i.e. boxing), recreational accidents (i.e. parachute jumping), the use of firearms, assault, child abuse,

  7. Intraperitoneal administration of thioredoxin decreases brain damage from ischemic stroke.

    Science.gov (United States)

    Wang, Bin; Tian, Shilai; Wang, Jiayi; Han, Feng; Zhao, Lei; Wang, Rencong; Ning, Weidong; Chen, Wei; Qu, Yan

    2015-07-30

    Recent studies demonstrate that Thioredixin (Trx) possesses a neuronal protective effect and closely relates to oxidative stress and apoptosis of cerebral ischemia injury. The present study was conducted to validate the neuroprotective effect of recombinant human Trx-1 (rhTrx-1) and its potential mechanisms against ischemia injury at middle cerebral artery occlusion (MCAO) in mice. rhTrx-1 was administrated intraperitoneally at a dose of 5, 10 and 20mg/kg 30 min before MCAO in mice, and its neuronal protective effect was evaluated by neurological deficit score, brain dry-wet weight, 2,3,5-triphenyltetrazolium chloride (TTC) staining. The protein carbonyl content and HO-1 were detected to investigate its potential anti-oxidative and anti-inflammatory property, and the anti-apoptotic ability of rhTrx-1 was assessed by casepase-3 and TUNEL staining. The results demonstrated that rhTrx-1 significantly improved neurological functions and reduced cerebral infarction and apoptotic cell death at 24h after MCAO. Moreover, rhTrx-1 resulted in a significant decrease in carbonyl contents and HO-1 against oxidative stress, which turned to be fast reduction during the first 24h and tended to be stable from 24h to 72h after MCAO. The study shows that rhTrx-1 exerts an neuroprotective effect in cerebral ischemia injury. The anti-oxidative, anti-apoptotic and anti-inflammatory properties of rhTrx-1 are more likely to succeed as a therapeutic approach to diminish oxidative stress-induced neuronal apoptotic cell death in acute ischemic stroke.

  8. Oxidative stress and DNA damages induced by cadmium accumulation

    Institute of Scientific and Technical Information of China (English)

    LIN Ai-jun; ZHANG Xu-hong; CHEN Mei-mei; CAO Qing

    2007-01-01

    Experimental evidence shows that cadmium (Cd) could induce oxidative stress and then causes DNA damage in animal cells, however, whether such effect exists in plants is still unclear. In the present study, Vicia faba plants was exposed to 5 and 10 mg/L Cd for 4 d to investigate the distribution of Cd in plant, the metal effects on the cell lipids, antioxidative enzymes and DNA damages in leaves. Cd induced an increase in Cd concentrations in plants. An enhanced level of lipid peroxidation in leaves and an enhanced concentration of H2O2 in root tissues suggested that Cd caused oxidative stress in Vicia faba. Compared with control, Cd-induced enhancement in superoxide dismutase activity was significant at 5 mg/L than at 10 mg/kg in leaves, by contrast, catalase and peroxidaseactivities were significantly suppressed by Cd addition. DNA damage was detected by neutral/neutral, alkaline/neutral and alkaline/alkaline Comet assay. Increased levels of DNA damages induced by Cd occurred with reference to oxidative stress in leaves, therefore, oxidative stress induced by Cd accumulation in plants contributed to DNA damages and was possibly an important mechanism of Cd-phytotoxicity in Vicia faba plants.

  9. The Use of Computers and Video Games in Brain Damage Therapy.

    Science.gov (United States)

    Lorimer, David

    The use of computer assisted therapy (CAT) in the rehabilitation of individuals with brain damage is examined. Hardware considerations are explored, and the variety of software programs available for brain injury rehabilitation is discussed. Structured testing and treatment programs in time measurement, memory, and direction finding are described,…

  10. The Use of Computers and Video Games in Brain Damage Therapy.

    Science.gov (United States)

    Lorimer, David

    The use of computer assisted therapy (CAT) in the rehabilitation of individuals with brain damage is examined. Hardware considerations are explored, and the variety of software programs available for brain injury rehabilitation is discussed. Structured testing and treatment programs in time measurement, memory, and direction finding are described,…

  11. The immune system mediates blood-brain barrier damage; Possible implications for pathophysiology of neuropsychiatric illnesses

    NARCIS (Netherlands)

    VanderWerf, YD; DeJongste, MJL; terHorst, GJ

    1995-01-01

    The immune system mediates blood-brain barrier damage; possible implications for pathophysiology of neuropsychiatric illnesses. In this investigation the effects of immune activation on the brain are characterized In order to study this, we used a model for chronic immune activation, the myocardial

  12. Inducible repair of oxidative DNA damage in Escherichia coli.

    Science.gov (United States)

    Demple, B; Halbrook, J

    Hydrogen peroxide is lethal to many cell types, including the bacterium Escherichia coli. Peroxides yield transient radical species that can damage DNA and cause mutations. Such partially reduced oxygen species are occasionally released during cellular respiration and are generated by lethal and mutagenic ionizing radiation. Because cells live in an environment where the threat of oxidative DNA damage is continual, cellular mechanisms may have evolved to avoid and repair this damage. Enzymes are known which evidently perform these functions. We report here that resistance to hydrogen peroxide toxicity can be induced in E. coli, that this novel induction is specific and occurs, in part, at the level of DNA repair.

  13. Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury.

    Science.gov (United States)

    Endesfelder, Stefanie; Weichelt, Ulrike; Strauß, Evelyn; Schlör, Anja; Sifringer, Marco; Scheuer, Till; Bührer, Christoph; Schmitz, Thomas

    2017-01-18

    Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28-32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

  14. Exposure to 1800 MHz radiofrequency radiation induces oxidative damage to mitochondrial DNA in primary cultured neurons.

    Science.gov (United States)

    Xu, Shangcheng; Zhou, Zhou; Zhang, Lei; Yu, Zhengping; Zhang, Wei; Wang, Yuan; Wang, Xubu; Li, Maoquan; Chen, Yang; Chen, Chunhai; He, Mindi; Zhang, Guangbin; Zhong, Min

    2010-01-22

    Increasing evidence indicates that oxidative stress may be involved in the adverse effects of radiofrequency (RF) radiation on the brain. Because mitochondrial DNA (mtDNA) defects are closely associated with various nervous system diseases and mtDNA is particularly susceptible to oxidative stress, the purpose of this study was to determine whether radiofrequency radiation can cause oxidative damage to mtDNA. In this study, we exposed primary cultured cortical neurons to pulsed RF electromagnetic fields at a frequency of 1800 MHz modulated by 217 Hz at an average special absorption rate (SAR) of 2 W/kg. At 24 h after exposure, we found that RF radiation induced a significant increase in the levels of 8-hydroxyguanine (8-OHdG), a common biomarker of DNA oxidative damage, in the mitochondria of neurons. Concomitant with this finding, the copy number of mtDNA and the levels of mitochondrial RNA (mtRNA) transcripts showed an obvious reduction after RF exposure. Each of these mtDNA disturbances could be reversed by pretreatment with melatonin, which is known to be an efficient antioxidant in the brain. Together, these results suggested that 1800 MHz RF radiation could cause oxidative damage to mtDNA in primary cultured neurons. Oxidative damage to mtDNA may account for the neurotoxicity of RF radiation in the brain.

  15. Quercitrin protects skin from UVB-induced oxidative damage.

    Science.gov (United States)

    Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

    2013-06-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin.

  16. 促甲状腺激素释放激素类似物 YM14673对大鼠脑损伤性脑水肿的作用及机制%Effect and mechanism of YM14673,an analog of thyrotropin-releasing hormone,to cerebral edema induced by brain damage in rats

    Institute of Scientific and Technical Information of China (English)

    张绍东; 翟晶; 张辉; 张家瑾

    2004-01-01

    BACKGROUND:As an analog of thyrotropin-releasing hormone(TRH), YM14673 has protective effects on brain.Many researches aim to explore wether the protective effects on brain of YM14673 are realized by the inhibition of cerebral edema. OBJECTIVE:To observe the effects of analog of TRH-YM14673 on blood brain barrier after brain damage. DESIGN:Randomized case control study. SETTING and MATERIALS:Experimental site:Beijing Institute of Neurosurgery.Sixty Wistar rats were randomly divided into sham-operation group,saline group,administrative group I(0.1 mg/kg)and administrative group II(1 mg/kg)with each of 15 rats. INTERVENTIONS:Acute brain damage model of rats were made.Evans blue was injected into femoral vein to test the change of permeability of blood-brain barrier in advance.Rats of sham-operation group were opened bone window without any strike.Rats of other groups were taken strike.Saline or YM14673 solution was injected after strike. Rats were executed after 24 hours to assay the water content of brain and the Evans blue content in brain tissue and plasma.MAIN OUTCOME MEASURES:①Changes of water contents in both hemispheres in rats of each group; ②Changes of Evans blue content in both hemispheres and plasma of rats. RESULTS:After brain damage occurred,the water content in brain tissue of saline group was much higher than that of sham-operation group[Left hemisphere:saline group( 79.57± 0.47)%, sham- operation group(78.29 ± 0.63)%, t=3.98,P0.05).The Evans blue content of brain remarkably increased after acute brain damage. YM14673 did not influence the contents.There was no difference on Evans blue content in plasma between groups. CONCLUSION:YM14673 can relieve the cerebral edema induced by acute brain damage.However,there is no effect on increasing the permeability of blood-brain barrier.%背景: YM14673为促甲状腺激素释放激素( thyrotropin-releasing hormone,TRH)类似物 ,具有脑保护作用.目前的许多研究都在探讨其脑保护作用

  17. Obesity-Induced Hypertension: Brain Signaling Pathways

    Science.gov (United States)

    da Silva, Alexandre A.; Wang, Zhen; Fang, Taolin; Aberdein, Nicola; de Lara Rodriguez, Cecilia E. P.; Hall, John E.

    2017-01-01

    Obesity greatly increases the risk for cardiovascular, metabolic, and renal diseases and is one of the most significant and preventable causes of increased blood pressure (BP) in patients with essential hypertension. This review high-lights recent advances in our understanding of central nervous system (CNS) signaling pathways that contribute to the etiology and pathogenesis of obesity-induced hypertension. We discuss the role of excess adiposity and activation of the brain leptin-melanocortin system in causing increased sympathetic activity in obesity. In addition, we highlight other potential brain mechanisms by which increased weight gain modulates metabolic and cardiovascular functions. Unraveling the CNS mechanisms responsible for increased sympathetic activation and hypertension and how circulating hormones activate brain signaling pathways to control BP offer potentially important therapeutic targets for obesity and hypertension. PMID:27262997

  18. Crosstalk between microglia and T cells contributes to brain damage and recovery after ischemic stroke.

    Science.gov (United States)

    Wang, Sunwei; Zhang, He; Xu, Yun

    2016-06-01

    To summarize available knowledge regarding the crosstalk, thereby providing a more detailed explanation for the mechanism of brain damage and recovery after ischemic stroke. An extensive review of the literature on the crosstalk between microglia and T cells in ischemic stroke was performed. We review the relevant publications in PubMed database. After cerebral ischemia, microglia are activated and peripheral T cells infiltrated into the brain. The crosstalk between microglia and T cells has both pro-inflammatory and anti-inflammatory effects in the inflammation after stroke. The crosstalk between M1 and Th1/Th17 cells promotes immune response after stroke and contributes to brain damage, while the crosstalk between M2 and Th2/Treg cells plays an anti-inflammatory role and contributes to brain recovery. Meanwhile, the crosstalk can be regulated by many factors, in both contact dependent and non-contact dependent way. Inflammation mediated by microglia crosstalking to T cells contributes to brain damage and recovery after ischemic stroke. Extensive evidence supports a critical role for the crosstalk of microglia and T cells in the prognosis of brain injury after ischemic stroke. The regulation of the crosstalk may provide a potential therapeutic target for improving the ischemic brain damage.

  19. Role of inter-hemispheric transfer in generating visual evoked potentials in V1-damaged brain hemispheres.

    Science.gov (United States)

    Kavcic, Voyko; Triplett, Regina L; Das, Anasuya; Martin, Tim; Huxlin, Krystel R

    2015-02-01

    Partial cortical blindness is a visual deficit caused by unilateral damage to the primary visual cortex, a condition previously considered beyond hopes of rehabilitation. However, recent data demonstrate that patients may recover both simple and global motion discrimination following intensive training in their blind field. The present experiments characterized motion-induced neural activity of cortically blind (CB) subjects prior to the onset of visual rehabilitation. This was done to provide information about visual processing capabilities available to mediate training-induced visual improvements. Visual Evoked Potentials (VEPs) were recorded from two experimental groups consisting of 9 CB subjects and 9 age-matched, visually-intact controls. VEPs were collected following lateralized stimulus presentation to each of the 4 visual field quadrants. VEP waveforms were examined for both stimulus-onset (SO) and motion-onset (MO) related components in postero-lateral electrodes. While stimulus presentation to intact regions of the visual field elicited normal SO-P1, SO-N1, SO-P2 and MO-N2 amplitudes and latencies in contralateral brain regions of CB subjects, these components were not observed contralateral to stimulus presentation in blind quadrants of the visual field. In damaged brain hemispheres, SO-VEPs were only recorded following stimulus presentation to intact visual field quadrants, via inter-hemispheric transfer. MO-VEPs were only recorded from damaged left brain hemispheres, possibly reflecting a native left/right asymmetry in inter-hemispheric connections. The present findings suggest that damaged brain hemispheres contain areas capable of responding to visual stimulation. However, in the absence of training or rehabilitation, these areas only generate detectable VEPs in response to stimulation of the intact hemifield of vision.

  20. Methionine restriction decreases endogenous oxidative molecular damage and increases mitochondrial biogenesis and uncoupling protein 4 in rat brain.

    Science.gov (United States)

    Naudí, Alba; Caro, Pilar; Jové, Mariona; Gómez, José; Boada, Jordi; Ayala, Victoria; Portero-Otín, Manuel; Barja, Gustavo; Pamplona, Reinald

    2007-12-01

    Aging plays a central role in the occurrence of neurodegenerative diseases. Caloric restriction (CR) mitigates oxidative stress by decreasing the rate of generation of endogenous damage, a mechanism that can contribute to the slowing of the aging rate induced by this intervention. Various reports have recently linked methionine to aging, and methionine restriction (MetR) without energy restriction also increases life span. We have thus hypothesized that MetR can be responsible, at least in part, for the decrease in endogenous oxidative damage in CR. In this investigation we subjected male rats to exactly the same dietary protocol of MetR that is known to increase their life span. We have found that MetR: (1) decreases the mitochondrial complex I content and activity, as well as complex III content, while the complex II and IV, the mitochondrial flavoprotein apoptosis-inducing factor (AIF) and ATP content are unchanged; (2) increases the mitochondrial biogenesis factor PGC-1alpha; (3) increases the resistance of brain to metabolic and oxidative stress by increasing mitochondrial uncoupling protein 4 uncoupling protein 4 (UCP4); and (4) decreases mitochondrial oxidative DNA damage and all five different markers of protein oxidation measured and lowers membrane unsaturation in rat brain. No changes were detected for protein amino acid composition. These beneficial MetR-induced changes likely derived from metabolic reprogramming at the cellular and tissue level can play a key role in the protection against aging-associated neurodegenerative disorders.

  1. Energy metabolisme and brain damage : Investigations by positron emission tomography (PET); the role of ketone bodies in cerebral protection

    NARCIS (Netherlands)

    Prenen, Gerardus Hyacinthus Maria

    1992-01-01

    In a general sense this thesis comprises three subjects: a) the changes in energy metabolism of the brain during cerebral pathology, b) the effect of alterations in energy metabolism on the extent of brain damage, and c) measures to prevent or limit brain damage. In this context the formation of

  2. Magnetic resonance imaging of post-ischemic blood-brain barrier damage with PEGylated iron oxide nanoparticles

    Science.gov (United States)

    Liu, Dong-Fang; Qian, Cheng; An, Yan-Li; Chang, Di; Ju, Sheng-Hong; Teng, Gao-Jun

    2014-11-01

    Blood-brain barrier (BBB) damage during ischemia may induce devastating consequences like cerebral edema and hemorrhagic transformation. This study presents a novel strategy for dynamically imaging of BBB damage with PEGylated supermagnetic iron oxide nanoparticles (SPIONs) as contrast agents. The employment of SPIONs as contrast agents made it possible to dynamically image the BBB permeability alterations and ischemic lesions simultaneously with T2-weighted MRI, and the monitoring could last up to 24 h with a single administration of PEGylated SPIONs in vivo. The ability of the PEGylated SPIONs to highlight BBB damage by MRI was demonstrated by the colocalization of PEGylated SPIONs with Gd-DTPA after intravenous injection of SPION-PEG/Gd-DTPA into a mouse. The immunohistochemical staining also confirmed the leakage of SPION-PEG from cerebral vessels into parenchyma. This study provides a novel and convenient route for imaging BBB alteration in the experimental ischemic stroke model.

  3. Heat Induced Damage Detection by Terahertz (THz) Radiation

    Science.gov (United States)

    Rahani, Ehsan Kabiri; Kundu, Tribikram; Wu, Ziran; Xin, Hao

    2011-06-01

    Terahertz (THz) and sub-terahertz imaging and spectroscopy are becoming increasingly popular nondestructive evaluation techniques for damage detection and characterization of materials. THz radiation is being used for inspecting ceramic foam tiles used in TPS (Thermal Protection System), thick polymer composites and polymer tiles that are not good conductors of ultrasonic waves. Capability of THz electromagnetic waves in detecting heat induced damage in porous materials is investigated in this paper. Porous pumice stone blocks are subjected to long time heat exposures to produce heat induced damage in the block. The dielectric properties extracted from THz TDS (Time Domain Spectroscopy) measurements are compared for different levels of heat exposure. Experimental results show noticeable and consistent change in dielectric properties with increasing levels of heat exposure, well before its melting point.

  4. HSP25 Protects Radiation-Induced Salivary Gland Damage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae June; Lee, Yoon Jin; Kwon, Hee Choong; Lee, Su Jae; Bae, Sang Woo; Lee, Yun Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung Ho [Chonnam National Univ., Gwangju (Korea, Republic of)

    2005-07-01

    Irradiation (IR) is a central treatment modality administered for head and neck malignancies. A significant consequence of this IR treatment is irreversible damage to salivary gland in the IR field. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that heat shock protein 25 (HSP25) induced radioresistance in vitro. HSP25 interferes negatively with apoptosis through several pathways which involve its direct interaction with cytochrome c, protein kinase c delta or Akt. And localized gene transfer to salivary glands has great potential for the treatment of salivary gland. Herein, we investigated whether HSP25 can use as radio protective molecules for radiation-induced salivary gland damage in vivo.

  5. Shock-induced damage in rocks: Application to impact cratering

    Science.gov (United States)

    Ai, Huirong

    Shock-induced damage beneath impact craters is studied in this work. Two representative terrestrial rocks, San Marcos granite and Bedford limestone, are chosen as test target. Impacts into the rock targets with different combinations of projectile material, size, impact angle, and impact velocity are carried out at cm scale in the laboratory. Shock-induced damage and fracturing would cause large-scale compressional wave velocity reduction in the recovered target beneath the impact crater. The shock-induced damage is measured by mapping the compressional wave velocity reduction in the recovered target. A cm scale nondestructive tomography technique is developed for this purpose. This technique is proved to be effective in mapping the damage in San Marcos granite, and the inverted velocity profile is in very good agreement with the result from dicing method and cut open directly. Both compressional velocity and attenuation are measured in three orthogonal directions on cubes prepared from one granite target impacted by a lead bullet at 1200 m/s. Anisotropy is observed from both results, but the attenuation seems to be a more useful parameter than acoustic velocity in studying orientation of cracks. Our experiments indicate that the shock-induced damage is a function of impact conditions including projectile type and size, impact velocity, and target properties. Combined with other crater phenomena such as crater diameter, depth, ejecta, etc., shock-induced damage would be used as an important yet not well recognized constraint for impact history. The shock-induced damage is also calculated numerically to be compared with the experiments for a few representative shots. The Johnson-Holmquist strength and failure model, initially developed for ceramics, is applied to geological materials. Strength is a complicated function of pressure, strain, strain rate, and damage. The JH model, coupled with a crack softening model, is used to describe both the inelastic response of

  6. Potential role of punicalagin against oxidative stress induced testicular damage

    Directory of Open Access Journals (Sweden)

    Faiza Rao

    2016-01-01

    Full Text Available Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98% on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  7. Inferencing Processes after Right Hemisphere Brain Damage: Maintenance of Inferences

    Science.gov (United States)

    Blake, Margaret Lehman

    2009-01-01

    Purpose: This study was designed to replicate and extend a previous study of inferencing in which some adults with right hemisphere damage (RHD) generated but did not maintain predictive inferences over time (M. Lehman-Blake & C. Tompkins, 2001). Two hypotheses were tested: (a) inferences were deactivated, and (b) selection of previously generated…

  8. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    Science.gov (United States)

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population.

  9. Prostacyclin infusion may prevent secondary damage in pericontusional brain tissue

    DEFF Research Database (Denmark)

    Reinstrup, Peter; Nordström, Carl-Henrik

    2011-01-01

    Prostacyclin is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation, and has been suggested as therapy for cerebral ischemia. A case of focal traumatic brain lesion that was monitored using intracerebral microdialysis, and bedside analysis and display is reported here....

  10. Prenatal Alcohol Exposure Damages Brain Signal Transduction System

    Science.gov (United States)

    2004-09-01

    Chem. 279: 41807- 41814. 9 Available online at www.sciencedirect.com SCIENCE DIRECT @ ANALYTICAL BIOCHEMISTRY ACADEMIC PRESS Analytical Biochemistry...Mol Brain Res 40:177-187. frontal cortex. Neurobiol Learn Mem 76:151-182. Available online at www.sciencedirect.com PHARMACOLOGY SCIENCE DIRECT & BIOCHEMISTRY

  11. Alcohol Alert: Alcohol's Damaging Effects on the Brain

    Science.gov (United States)

    ... 44). Markers such as the P3 can help identify people who may be at greatest risk for developing problems with alcohol. END OF SIDEBAR ... Meta–analysis of P300 amplitude from males at risk for alcoholism. Psychological Bulletin 115:55–73, ... appeared in the journal Alcohol Research & Health, “Alcoholic Brain Damage” (Vol. 27, ...

  12. Brain damage and addictive behavior: a neuropsychological and electroencephalogram investigation with pathologic gamblers.

    Science.gov (United States)

    Regard, Marianne; Knoch, Daria; Gütling, Eva; Landis, Theodor

    2003-03-01

    Gambling is a form of nonsubstance addiction classified as an impulse control disorder. Pathologic gamblers are considered healthy with respect to their cognitive status. Lesions of the frontolimbic systems, mostly of the right hemisphere, are associated with addictive behavior. Because gamblers are not regarded as "brain-lesioned" and gambling is nontoxic, gambling is a model to test whether addicted "healthy" people are relatively impaired in frontolimbic neuropsychological functions. Twenty-one nonsubstance dependent gamblers and nineteen healthy subjects underwent a behavioral neurologic interview centered on incidence, origin, and symptoms of possible brain damage, a neuropsychological examination, and an electroencephalogram. Seventeen gamblers (81%) had a positive medical history for brain damage (mainly traumatic head injury, pre- or perinatal complications). The gamblers, compared with the controls, were significantly more impaired in concentration, memory, and executive functions, and evidenced a higher prevalence of non-right-handedness (43%) and, non-left-hemisphere language dominance (52%). Electroencephalogram (EEG) revealed dysfunctional activity in 65% of the gamblers, compared with 26% of controls. This study shows that the "healthy" gamblers are indeed brain-damaged. Compared with a matched control population, pathologic gamblers evidenced more brain injuries, more fronto-temporo-limbic neuropsychological dysfunctions and more EEG abnormalities. The authors thus conjecture that addictive gambling may be a consequence of brain damage, especially of the frontolimbic systems, a finding that may well have medicolegal consequences.

  13. Cardiac Arrest Alters Regional Ubiquitin Levels in Association with the Blood-Brain Barrier Breakdown and Neuronal Damages in the Porcine Brain.

    Science.gov (United States)

    Sharma, Hari S; Patnaik, Ranjana; Sharma, Aruna; Lafuente, José Vicente; Miclescu, Adriana; Wiklund, Lars

    2015-10-01

    The possibility that ubiquitin expression is altered in cardiac arrest-associated neuropathology was examined in a porcine model using immunohistochemical and biochemical methods. Our observations show that cardiac arrest induces progressive increase in ubiquitin expression in the cortex and hippocampus in a selective and specific manner as compared to corresponding control brains using enzyme-linked immunoassay technique (enzyme-linked immunosorbent assay (ELISA)). Furthermore, immunohistochemical studies showed ubiquitin expression in the neurons exhibiting immunoreaction in the cytoplasm and karyoplasm of distorted or damaged cells. Separate Nissl and ubiquitin staining showed damaged and distorted neurons and in the same cortical region ubiquitin expression indicating that ubiquitin expression after cardiac arrest represents dying neurons. The finding that methylene blue treatment markedly induced neuroprotection following identical cardiac arrest and reduced ubiquitin expression strengthens this view. Taken together, our observations are the first to show that cardiac arrest enhanced ubiquitin expression in the brain that is related to the magnitude of neuronal injury and the finding that methylene blue reduced ubiquitin expression points to its role in cell damage, not reported earlier.

  14. Amyloid β-induced erythrocytic damage and its attenuation by carotenoids.

    Science.gov (United States)

    Nakagawa, Kiyotaka; Kiko, Takehiro; Miyazawa, Taiki; Sookwong, Phumon; Tsuduki, Tsuyoshi; Satoh, Akira; Miyazawa, Teruo

    2011-04-20

    The presence of amyloid β-peptide (Aβ) in human blood has recently been established, and it has been hypothesized that Aβ readily contacts red blood cells (RBC) and oxidatively impairs RBC functions. In this study, we conducted in vitro and in vivo studies, which provide evidence that Aβ induces oxidative injury to RBC by binding to them, causing RBC phospholipid peroxidation and diminishing RBC endogenous carotenoids, especially xanthophylls. This type of damage is likely to injure the vasculature, potentially reducing oxygen delivery to the brain and facilitating Alzheimer's disease (AD). As a preventive strategy, because the Aβ-induced RBC damage could be attenuated by treatment of RBC with xanthophylls, we suggest that xanthophylls may contribute to the prevention of AD.

  15. Protective effects of honokiol against methylglyoxal-induced osteoblast damage.

    Science.gov (United States)

    Suh, Kwang Sik; Chon, Suk; Choi, Eun Mi

    2016-01-25

    Honokiol is an active compound isolated from Magnolia officinalis that has been used without notable side effects in traditional medicine. We investigated the effects of honokiol against methylglyoxal (MG)-induced cytotoxicity in MC3T3-E1 osteoblast cells and the possible molecular mechanism(s) involved. The results showed that honokiol alleviated MG-induced cell death and the production of intracellular ROS, mitochondrial superoxide, cardiolipin peroxidation, and inflammatory cytokines. MG induction of the soluble receptor for advanced glycation end product (AGE) was reduced by pretreatment with honokiol. Furthermore, honokiol increased the levels of Nrf2 and increased the levels of glutathione and the activity of glyoxalase I. Pretreatment with honokiol prior to MG exposure reduced MG-induced mitochondrial dysfunction and alleviated MG-induced reduction of nitric oxide and PGC1α levels, suggesting that honokiol may induce mitochondrial biogenesis. It was concluded that honokiol could be useful in the attenuation of MG-induced cell damage.

  16. 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.

  17. Methylmercury Causes Blood-Brain Barrier Damage in Rats via Upregulation of Vascular Endothelial Growth Factor Expression

    Science.gov (United States)

    Takahashi, Tetsuya; Fujimura, Masatake; Koyama, Misaki; Kanazawa, Masato; Usuki, Fusako; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2017-01-01

    Clinical manifestations of methylmercury (MeHg) intoxication include cerebellar ataxia, concentric constriction of visual fields, and sensory and auditory disturbances. The symptoms depend on the site of MeHg damage, such as the cerebellum and occipital lobes. However, the underlying mechanism of MeHg-induced tissue vulnerability remains to be elucidated. In the present study, we used a rat model of subacute MeHg intoxication to investigate possible MeHg-induced blood-brain barrier (BBB) damage. The model was established by exposing the rats to 20-ppm MeHg for up to 4 weeks; the rats exhibited severe cerebellar pathological changes, although there were no significant differences in mercury content among the different brain regions. BBB damage in the cerebellum after MeHg exposure was confirmed based on extravasation of endogenous immunoglobulin G (IgG) and decreased expression of rat endothelial cell antigen-1. Furthermore, expression of vascular endothelial growth factor (VEGF), a potent angiogenic growth factor, increased markedly in the cerebellum and mildly in the occipital lobe following MeHg exposure. VEGF expression was detected mainly in astrocytes of the BBB. Intravenous administration of anti-VEGF neutralizing antibody mildly reduced the rate of hind-limb crossing signs observed in MeHg-exposed rats. In conclusion, we demonstrated for the first time that MeHg induces BBB damage via upregulation of VEGF expression at the BBB in vivo. Further studies are required in order to determine whether treatment targeted at VEGF can ameliorate MeHg-induced toxicity. PMID:28118383

  18. Zebrafish fin regeneration after cryoinjury-induced tissue damage

    Directory of Open Access Journals (Sweden)

    Bérénice Chassot

    2016-06-01

    Full Text Available Although fin regeneration following an amputation procedure has been well characterized, little is known about the impact of prolonged tissue damage on the execution of the regenerative programme in the zebrafish appendages. To induce histolytic processes in the caudal fin, we developed a new cryolesion model that combines the detrimental effects of freezing/thawing and ischemia. In contrast to the common transection model, the damaged part of the fin was spontaneously shed within two days after cryoinjury. The remaining stump contained a distorted margin with a mixture of dead material and healthy cells that concomitantly induced two opposing processes of tissue debris degradation and cellular proliferation, respectively. Between two and seven days after cryoinjury, this reparative/proliferative phase was morphologically featured by displaced fragments of broken bones. A blastemal marker msxB was induced in the intact mesenchyme below the damaged stump margin. Live imaging of epithelial and osteoblastic transgenic reporter lines revealed that the tissue-specific regenerative programmes were initiated after the clearance of damaged material. Despite histolytic perturbation during the first week after cryoinjury, the fin regeneration resumed and was completed without further alteration in comparison to the simple amputation model. This model reveals the powerful ability of the zebrafish to restore the original appendage architecture after the extended histolysis of the stump.

  19. Damage induced by femtosecond laser in optical dielectric films

    Institute of Scientific and Technical Information of China (English)

    Caihua Huang; Yiyu Xue; Zhilin Xia; Yuanan Zhao; Fangfang Yang; Peitao Guo

    2009-01-01

    Both the nature of avalanche ionization (AI) and the role of multi-photon ionization (MPI) in the studies of laser-induced damage have remained controversial up to now. According to the model proposed by Stuart et al., we study the role of MPI and AI in laser-induced damage in two dielectric films, fused silica (FS) and barium aluminum borosilicate (BBS), irradiated by 780-nm laser pulse with the pulse width range of 0.01 鈥? 5 ps. The effects of MPI and initial electron density on seed electron generation are numerically analyzed. For FS, laser-induced damage is dominated by AI for the entire pulse width regime due to the wider band-gap. While for BBS, MPI becomes the leading power in damage for the pulse width r less than about 0.03 ps. MPI may result in a sharp rise of threshold fluence Fth on 蟿, and AI may lead to a mild increase or even a constant value of Fth on 蟿. MPI serves the production of seed electrons for AI when the electron density for AI is approached or exceeded before the end of MPI. This also means that the effect of initial electron can be neglected when MPI dominates the seed electron generation. The threshold fluence Fth decreases with the increasing initial electron density when the latter exceeds a certain critical value.

  20. Obesity Exacerbates Sepsis-Induced Oxidative Damage in Organs.

    Science.gov (United States)

    Petronilho, Fabricia; Giustina, Amanda Della; Nascimento, Diego Zapelini; Zarbato, Graciela Freitas; Vieira, Andriele Aparecida; Florentino, Drielly; Danielski, Lucinéia Gainski; Goldim, Mariana Pereira; Rezin, Gislaine Tezza; Barichello, Tatiana

    2016-12-01

    Sepsis progression is linked to the imbalance between reactive oxygen species and antioxidant enzymes. Sepsis affects multiple organs, but when associated with a chronic inflammatory disease, such as obesity, it may be exacerbated. We hypothesized that obesity could aggravate the oxidative damage to peripheral organs of rats submitted to an animal model of sepsis. Male Wistar rats aged 8 weeks received hypercaloric nutrition for 2 months to induce obesity. Sepsis was induced by cecal ligation and puncture (CLP) procedure, and sham-operated rats were considered as control group. The experimental groups were divided into sham + eutrophic, sham + obese, CLP + eutrophic, and CLP + obese. Twelve and 24 h after surgery, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the liver, lung, kidney, and heart. The data indicate that obese rats subjected to sepsis present oxidative stress mainly in the lung and liver. This alteration reflected an oxidative damage to lipids and proteins and an imbalance of SOD and CAT levels, especially 24 h after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate sepsis-induced damage in peripheral organs.

  1. The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain repair.

    Directory of Open Access Journals (Sweden)

    Davide Lecca

    Full Text Available Deciphering the mechanisms regulating the generation of new neurons and new oligodendrocytes, the myelinating cells of the central nervous system, is of paramount importance to address new strategies to replace endogenous damaged cells in the adult brain and foster repair in neurodegenerative diseases. Upon brain injury, the extracellular concentrations of nucleotides and cysteinyl-leukotrienes (cysLTs, two families of endogenous signaling molecules, are markedly increased at the site of damage, suggesting that they may act as "danger signals" to alert responses to tissue damage and start repair. Here we show that, in brain telencephalon, GPR17, a recently deorphanized receptor for both uracil nucleotides and cysLTs (e.g., UDP-glucose and LTD(4, is normally present on neurons and on a subset of parenchymal quiescent oligodendrocyte precursor cells. We also show that induction of brain injury using an established focal ischemia model in the rodent induces profound spatiotemporal-dependent changes of GPR17. In the lesioned area, we observed an early and transient up-regulation of GPR17 in neurons expressing the cellular stress marker heat shock protein 70. Magnetic Resonance Imaging in living mice showed that the in vivo pharmacological or biotechnological knock down of GPR17 markedly prevents brain infarct evolution, suggesting GPR17 as a mediator of neuronal death at this early ischemic stage. At later times after ischemia, GPR17 immuno-labeling appeared on microglia/macrophages infiltrating the lesioned area to indicate that GPR17 may also acts as a player in the remodeling of brain circuitries by microglia. At this later stage, parenchymal GPR17+ oligodendrocyte progenitors started proliferating in the peri-injured area, suggesting initiation of remyelination. To confirm a specific role for GPR17 in oligodendrocyte differentiation, the in vitro exposure of cortical pre-oligodendrocytes to the GPR17 endogenous ligands UDP-glucose and LTD(4

  2. 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.

  3. The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

    Science.gov (United States)

    Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

    2008-10-01

    To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

  4. Contribution of endogenous and exogenous damage to the total radiation-induced damage in the bacterial spore

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, G.P.; Samuni, A.; Czapski, G.

    1980-01-01

    Radical scavengers such as polyethylene glycol 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous damage to the total radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous.

  5. Brain parenchymal damage in neuromyelitis optica spectrum disorder - A multimodal MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Pache, F.; Paul, F. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Zimmermann, H.; Lacheta, A.; Papazoglou, S.; Kuchling, J.; Wuerfel, J.; Brandt, A.U. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Finke, C. [Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Humboldt-Universitaet zu Berlin, Berlin School of Mind and Brain, Berlin (Germany); Hamm, B. [Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Ruprecht, K. [Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Scheel, M. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany)

    2016-12-15

    To investigate different brain regions for grey (GM) and white matter (WM) damage in a well-defined cohort of neuromyelitis optica spectrum disorder (NMOSD) patients and compare advanced MRI techniques (VBM, Subcortical and cortical analyses (Freesurfer), and DTI) for their ability to detect damage in NMOSD. We analyzed 21 NMOSD patients and 21 age and gender matched control subjects. VBM (GW/WM) and DTI whole brain (TBSS) analyses were performed at different statistical thresholds to reflect different statistical approaches in previous studies. In an automated atlas-based approach, Freesurfer and DTI results were compared between NMOSD and controls. DTI TBSS and DTI atlas based analysis demonstrated microstructural impairment only within the optic radiation or in regions associated with the optic radiation (posterior thalamic radiation p < 0.001, 6.9 % reduction of fractional anisotropy). VBM demonstrated widespread brain GM and WM reduction, but only at exploratory statistical thresholds, with no differences remaining after correction for multiple comparisons. Freesurfer analysis demonstrated no group differences. NMOSD specific parenchymal brain damage is predominantly located in the optic radiation, likely due to a secondary degeneration caused by ON. In comparison, DTI appears to be the most reliable and sensitive technique for brain damage detection in NMOSD. (orig.)

  6. The impact of unilateral brain damage on anticipatory grip force scaling when lifting everyday objects.

    Science.gov (United States)

    Eidenmüller, S; Randerath, J; Goldenberg, G; Li, Y; Hermsdörfer, J

    2014-08-01

    The scaling of our finger forces according to the properties of manipulated objects is an elementary prerequisite of skilled motor behavior. Lesions of the motor-dominant left brain may impair several aspects of motor planning. For example, limb-apraxia, a tool-use disorder after left brain damage is thought to be caused by deficient recall or integration of tool-use knowledge into an action plan. The aim of the present study was to investigate whether left brain damage affects anticipatory force scaling when lifting everyday objects. We examined 26 stroke patients with unilateral brain damage (16 with left brain damage, ten with right brain damage) and 21 healthy control subjects. Limb apraxia was assessed by testing pantomime of familiar tool-use and imitation of meaningless hand postures. Participants grasped and lifted twelve randomly presented everyday objects. Grip force was measured with help of sensors fixed on thumb, index and middle-finger. The maximum rate of grip force was determined to quantify the precision of anticipation of object properties. Regression analysis yielded clear deficits of anticipation in the group of patients with left brain damage, while the comparison of patient with right brain damage with their respective control group did not reveal comparable deficits. Lesion-analyses indicate that brain structures typically associated with a tool-use network in the left hemisphere play an essential role for anticipatory grip force scaling, especially the left inferior frontal gyrus (IFG) and the premotor cortex (PMC). Furthermore, significant correlations of impaired anticipation with limb apraxia scores suggest shared representations. However, the presence of dissociations, implicates also independent processes. Overall, our findings suggest that the left hemisphere is engaged in anticipatory grip force scaling for lifting everyday objects. The underlying neural substrate is not restricted to a single region or stream; instead it may rely on

  7. Whole brain radiation-induced cognitive impairment: pathophysiological mechanisms and therapeutic targets.

    Science.gov (United States)

    Lee, Yong Woo; Cho, Hyung Joon; Lee, Won Hee; Sonntag, William E

    2012-07-01

    Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tu-mor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cel-lular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the iden-tification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defin-ing a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy.

  8. Evidence for a therapeutic effect of Braintone on ischemic brain damage***

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Qin; Yu Luo; Weiwei Gu; Lei Yang; Xikun Shen; Zhenlun Gu; Huiling Zhang; Xiumei Gao

    2013-01-01

    This study used a novel combination of in vivo and in vitro experiments to show that Braintone had neuroprotective effects and clarified the molecular mechanisms underlying its efficacy. The Chinese herbal extract Braintone is composed of Radix Rhodiolase Essence, Radix Notoginseng Essence, Folium Ginkgo Essence and Rhizoma Chuanxiong. In vivo experiments showed that cerebral in-farction volume was reduced, hemispheric water content decreased, and neurological deficits were al eviated in a rat model of permanent middle cerebral artery occlusion after administration of 87.5, 175 or 350 mg/kg Braintone for 7 consecutive days. Western blot analysis showed that Braintone enhanced the expression of hypoxia-inducible factor 1α, heme oxygenase-1 and vascular endothe-lial growth factor in the ischemic cortex of these rats. The 350 mg/kg dose of Braintone produced the most dramatic effects. For the in vitro experiments, prior to oxygen-glucose deprivation, rats were intragastrical y injected with 440, 880 or 1 760 mg/kg Braintone to prepare a Braintone-co-ntaining serum, which was used to pre-treat human umbilical vein endothelial cel s for 24 hours. Human umbilical vein endothelial cel injury was al eviated with this pre-treatment. Western blot and real-time PCR analysis showed that the Braintone-containing serum increased the levels of hypox-ia-inducible factor 1α mRNA and protein, heme oxygenase-1 protein and vascular endothelial growth factor mRNA in oxygen-glucose deprived human umbilical vein endothelial cel s. The 1 760 mg/kg dose produced the greatest increases in expression. Col ectively, these experimental findings suggest that Braintone has neuroprotective effects on ischemia-induced brain damage via the up-regulation of hypoxia-inducible factor 1α, heme oxygenase-1 and vascular endothelial growth factor expression in vascular endothelial cel s.

  9. Radiation induced crystallinity damage in poly(L-lactic acid)

    CERN Document Server

    Kantoglu, O

    2002-01-01

    The radiation-induced crystallinity damage in poly(L-lactic acid) (PLLA) in the presence of air and in vacuum, is studied. From the heat of fusion enthalpy values of gamma irradiated samples, some changes on the thermal properties were determined. To identify these changes, first the glass transition temperature (T sub g) of L-lactic acid polymers irradiated to various doses in air and vacuum have been investigated and it is found that it is independent of irradiation atmosphere and dose. The fraction of damaged units of PLLA per unit of absorbed energy has been measured. For this purpose, SAXS and differential scanning calorimetry methods were used, and the radiation yield of number of damaged units (G(-u)) is found to be 0.74 and 0.58 for PLLA samples irradiated in vacuum and air, respectively.

  10. 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.

  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. Inhibitory action of antioxidants (ascorbic acid or α-tocopherol on seizures and brain damage induced by pilocarpine in rats Ação inibitória de antioxidantes (ácido ascórbico e α-tocoferol nas convulsões e dano cerebral em ratos induzidos pela pilocarpina

    Directory of Open Access Journals (Sweden)

    Adriana da Rocha Tomé

    2010-06-01

    Full Text Available Temporal lobe epilepsy is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. The objectives of this work were to comparatively study the inhibitory action of antioxidants (ascorbic acid or α-tocopherol on behavioral changes and brain damage induced by high doses of pilocarpine, aiming to further clarify the mechanism of action of these antioxidant compounds. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (250 or 500 mg/kg, i.p. and α-tocopherol (200 or 400 mg/kg, i.p. on the behavior and brain lesions observed after seizures induced by pilocarpine (400 mg/kg, i.p., P400 model in rats. Ascorbic acid or α-tocopherol injections prior to pilocarpine suppressed behavioral seizure episodes. These findings suggested that free radicals can be produced during brain damage induced by seizures. In the P400 model, ascorbic acid and α-tocopherol significantly decreased cerebral damage percentage. Antioxidant compounds can exert neuroprotective effects associated with inhibition of free radical production. These results highlighted the promising therapeutic potential of ascorbic acid and α-tocopherol in treatments for neurodegenerative diseases.A epilepsia de lobo temporal é a mais comum forma de epilepsia em humanos. O estresse oxidativo é um dos mecanismos de morte celular induzida pelas crises convulsivas. Os compostos antioxidantes apresentam efeitos neuroprotetores devido à sua capacidade de inibir a produção de radicais livres. Os objetivos do presente trabalho foram estudar de forma comparativa a ação inibitória de antioxidantes (ácido ascórbico e α-tocoferol sobre as alterações comportamentais e histopatológicas no hipocampo de ratos após convulsões induzidas pela pilocarpina. A fim de determinar os efeitos neuroprotetores

  13. Ketamine/Xylazine-Induced Corneal Damage in Mice.

    Directory of Open Access Journals (Sweden)

    Demelza Koehn

    Full Text Available We have observed that the commonly used ketamine/xylazine anesthesia mix can induce a focally severe and permanent corneal opacity. The purpose of this study was to establish the clinical and histological features of this deleterious side effect, its sensitivity with respect to age and anesthesia protocol, and approaches for avoiding it.Young C57BL/6J, C57BLKS/J, and SJL/J mice were treated with permutations of anesthesia protocols and compared using slit-lamp exams, optical coherence tomography, histologic analyses, and telemetric measurements of body temperature.Ketamine/xylazine induces corneal damage in mice with a variable frequency. Among 12 experimental cohorts, corneal damage associated with ketamine/xylazine was observed in 9 of them. Despite various treatments to avoid corneal dehydration during anesthesia, the frequency of corneas experiencing damage among responding cohorts was 42% (26% inclusive of all cohorts, which is significantly greater than the natural prevalence (5%. The damage was consistent with band keratopathy. It appeared as a white or gray horizontal band located proximal to the pupil and was positive for subepithelial calcium deposition with von Kossa stain.The sum of our clinical and histological observations is consistent with ketamine/xylazine-induced band keratopathy in mice. This finding is relevant for mouse studies involving the eye and/or vision-dependent behavioral assays, which would both be prone to artifact without appreciation of the damage caused by ketamine/xylazine anesthesia. Use of yohimbine is suggested as a practical means of avoiding this complication.

  14. 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.

  15. Laser induced damage studies in mercury cadmium telluride

    Science.gov (United States)

    Garg, Amit; Kapoor, Avinashi; Tripathi, K. N.; Bansal, S. K.

    2007-10-01

    We have investigated laser induced damage at 1.06 μm laser wavelength in diamond paste polished (mirror finish) and carborundum polished Hg0.8Cd0.2Te (MCT) samples with increasing fluence as well as number of pulses. Evolution of damage morphology in two types of samples is quite different. In case of diamond paste polished samples, evolution of damage morphological features is consistent with Hg evaporation with transport of Cd/Te globules towards the periphery of the molten region. Cd/Te globules get accumulated with successive laser pulses at the periphery indicating an accumulation effect. Real time reflectivity (RTR) measurement has been done to understand melt pool dynamics. RTR measurements along with the thermal profile of the melt pool are in good agreement with thermal melting model of laser irradiated MCT samples. In case of carborundum polished samples, laser damage threshold is significantly reduced. Damage morphological features are significantly influenced by surface microstructural condition. From comparison of the morphological features in the two cases, it can be inferred that laser processing of MCT for device applications depends significantly on surface preparation conditions.

  16. Statistical analysis of vibration-induced bone and joint damages.

    Science.gov (United States)

    Schenk, T

    1995-01-01

    Vibration-induced damages to bones and joints are still occupational diseases with insufficient knowledge about causing and moderating factors and resulting damages. For a better understanding of these relationships also retrospective analyses of already acknowledged occupational diseases may be used. Already recorded detailed data for 203 in 1970 to 1979 acknowledged occupational diseases in the building industry and the building material industry of the GDR are the basis for the here described investigations. The data were gathered from the original documents of the occupational diseases and scaled in cooperation of an industrial engineer and an industrial physician. For the purposes of this investigations the data are to distinguish between data which describe the conditions of the work place (e.g. material, tools and posture), the exposure parameters (e.g. beginning of exposure and latency period) and the disease (e.g. anamnestical and radiological data). These data are treated for the use with sophisticated computerized statistical methods. The following analyses were carried out. Investigation of the connections between the several characteristics, which describe the occupational disease (health damages), including the comparison of the severity of the damages at the individual joints. Investigation of the side dependence of the damages. Investigation of the influence of the age at the beginning of the exposure and the age at the acknowledgement of the occupational disease and herewith of the exposure duration. Investigation of the effect of different occupational and exposure conditions.

  17. 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.

  18. Induced hyperthermia in brain tissue in vivo.

    Science.gov (United States)

    Terzis, A J; Nowak, G; Mueller, E; Rentzsch, O; Arnold, H

    1994-01-01

    Concerning hypothermia treatment, knowledge of time-temperature and of temperature distributions within tumor volumes is essential in order to obtain the maximal therapeutic effect. New techniques are being developed to overcome these difficulties. Two different heat sources, a contact Nd:YAG laser system and an automatically controlled high-frequency current system were investigated on 15 rabbits. Changes of the intracerebral temperature were registered at 4 different distances from the energy source. The intracerebral temperature was increased to 42.5 degrees C at a distance of 5 mm to the heat source and maintained at this level for a period of 60 min. The contact Nd:YAG laser system reached 42.5 degrees C at 3 W of output power. Using higher laser output power, brain tissue herniation (brain edema) through the burrhole was observed. The automatically controlled high-frequency current system reached 42.5 degrees C at 18.75 W of output current. A very small herniation of brain tissue could be observed using higher output current. Both heat sources presented an exponential decrease of the temperature profile depending on the distance. The tissue heat clearance was compensated for by intermittent laser or high-frequency current application. Both systems proved efficient for inducing hyperthermia as needed for antitumoral therapy.

  19. 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.

  20. Effects of Lipoic Acid on Acrylamide Induced Testicular Damage

    OpenAIRE

    Lebda, Mohamed; Gad, Shereen; Gaafar, Hossam

    2014-01-01

    Introduction: Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha-lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress. Aim of the study: This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues. Material and methods: Forty adult male rats were divided into ...

  1. Anchor-induced chondral damage in the hip

    OpenAIRE

    Matsuda, Dean K.; Bharam, Srino; White, Brian J.; Matsuda, Nicole A.; SAFRAN, Marc

    2015-01-01

    The purpose of this study is to investigate the outcomes from anchor-induced chondral damage of the hip, both with and without frank chondral penetration. A multicenter retrospective case series was performed of patients with chondral deformation or penetration during initial hip arthroscopic surgery. Intra-operative findings, post-surgical clinical courses, hip outcome scores and descriptions of arthroscopic treatment in cases requiring revision surgery and anchor removal are reported. Five ...

  2. 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 ...

  3. Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion.

    Science.gov (United States)

    Juvekar, Ashish; Hu, Hai; Yadegarynia, Sina; Lyssiotis, Costas A; Ullas, Soumya; Lien, Evan C; Bellinger, Gary; Son, Jaekyoung; Hok, Rosanna C; Seth, Pankaj; Daly, Michele B; Kim, Baek; Scully, Ralph; Asara, John M; Cantley, Lewis C; Wulf, Gerburg M

    2016-07-26

    We previously reported that combining a phosphoinositide 3-kinase (PI3K) inhibitor with a poly-ADP Rib polymerase (PARP)-inhibitor enhanced DNA damage and cell death in breast cancers that have genetic aberrations in BRCA1 and TP53. Here, we show that enhanced DNA damage induced by PI3K inhibitors in this mutational background is a consequence of impaired production of nucleotides needed for DNA synthesis and DNA repair. Inhibition of PI3K causes a reduction in all four nucleotide triphosphates, whereas inhibition of the protein kinase AKT is less effective than inhibition of PI3K in suppressing nucleotide synthesis and inducing DNA damage. Carbon flux studies reveal that PI3K inhibition disproportionately affects the nonoxidative pentose phosphate pathway that delivers Rib-5-phosphate required for base ribosylation. In vivo in a mouse model of BRCA1-linked triple-negative breast cancer (K14-Cre BRCA1(f/f)p53(f/f)), the PI3K inhibitor BKM120 led to a precipitous drop in DNA synthesis within 8 h of drug treatment, whereas DNA synthesis in normal tissues was less affected. In this mouse model, combined PI3K and PARP inhibition was superior to either agent alone to induce durable remissions of established tumors.

  4. Stochastics of diffusion induced damage in intercalation materials

    Science.gov (United States)

    Barai, Pallab; Mukherjee, Partha P.

    2016-10-01

    Fundamental understanding of the underlying diffusion-mechanics interplay in the intercalation electrode materials is critical toward improved life and performance of lithium-ion batteries for electric vehicles. Especially, diffusion induced microcrack formation in brittle, intercalation active materials, with emphasis on the grain/grain-boundary (GB) level implications, has been fundamentally investigated based on a stochastic modeling approach. Quasistatic damage evolution has been analyzed under lithium concentration gradient induced stress. Scaling of total amount of microcrack formation shows a power law variation with respect to the system size. Difference between the global and local roughness exponent indicates the existence of anomalous scaling. The deterioration of stiffness with respect to microcrack density displays two distinct regions of damage propagation; namely, diffused damage evolution and stress concentration driven localized crack propagation. Polycrystalline material microstructures with different grain sizes have been considered to study the diffusion-induced fracture in grain and GB regions. Intergranular crack paths are observed within microstructures containing softer GB region, whereas, transgranular crack paths have been observed in microstructures with relatively strong GB region. Increased tortuosity of the spanning crack has been attributed as the reason behind attaining increased fracture strength in polycrystalline materials with smaller grain sizes.

  5. Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

    Science.gov (United States)

    Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

    2015-01-01

    Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

  6. Reduced hypertension-induced end-organ damage in mice lacking cardiac and renal angiotensinogen synthesis.

    Science.gov (United States)

    Kang, Ningling; Walther, Thomas; Tian, Xiao-Li; Bohlender, Jürgen; Fukamizu, Akiyoshi; Ganten, Detlev; Bader, Michael

    2002-06-01

    Hypertension-induced damage of kidney and heart is of major clinical relevance, but its pathophysiology is only partially understood. As there is considerable evidence for involvement of angiotensin II, we generated a new mouse model by breeding angiotensinogen (AOGEN) deficient mice with transgenic animals expressing the rat AOGEN gene only in brain and liver. This genetic manipulation overcame the hypotension of AOGEN-deficient mice and even caused hypertension indistinguishable in its extent from the parent transgenic mice with an intact endogenous AOGEN gene. In contrast to normal mice, however, crossbred animals lacked detectable expression of AOGEN in kidney and heart. As a consequence they showed markedly reduced cardiac hypertrophy and fibrosis. Furthermore, hypertension-induced alterations in kidney histology and function were less pronounced in crossbred mice than in equally hypertensive animals expressing AOGEN locally. The dysmorphogenesis observed in kidneys from AOGEN-deficient mice was absent in mice expressing this gene only in liver and brain. Our results support an important role of local AOGEN expression in hypertension-induced end-organ damage but not in the development of the kidney.

  7. L-DEPRENYL REDUCES BRAIN-DAMAGE IN RATS EXPOSED TO TRANSIENT HYPOXIA-ISCHEMIA

    NARCIS (Netherlands)

    KNOLLEMA, S; AUKEMA, W; HOM, H; KORF, J; TERHORST, GJ

    1995-01-01

    Background and Purpose L-Deprenyl (Selegiline) protects animal brains against toxic substances such as 1-methyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine. Experiments were conducted to test whether L-deprenyl prevents or reduces cerebral damage in a transient hypoxia/ischemia rat model. Metho

  8. What does brain damage tell us about the mechanisms of sleep?

    National Research Council Canada - National Science Library

    Evans, B M

    2002-01-01

    ... the damaged brain. WAKEFULNESS, RAPID EYE MOVEMENT (REM) SLEEP AND NON-REM SLEEP Wakefulness is characterized by a state of arousal with an activated cerebral cortex, high cerebral blood-flow and glucose metabolism, and fast activity in the electroence-- phalogram (EEG); autonomic activity and muscular tone are also high. Non-REM sleep begins at sleep ons...

  9. Reflecting on Co-Creating a Smart Learning Ecosystem for Adolescents with Congenital Brain Damage

    DEFF Research Database (Denmark)

    2017-01-01

    . In this paper we present a first part of an ongoing collaboration with a special needs education facility for adolescents with congenital and acquired brain damage, that is interested in exploring the transformation of the institutional space into a smart learning ecosystem. We exemplify our research approach...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  11. 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.

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

    Science.gov (United States)

    Kitamura, O

    1994-01-01

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

  13. Advanced neuroprotection for brain ischemia: an alternative approach to minimize stroke damage.

    Science.gov (United States)

    Ayuso, Maria Irene; Montaner, Joan

    2015-01-01

    Despite decades of research on neuroprotectants in the fight against ischemic stroke, no successful results have been obtained and new alternative approaches are urgently needed. Translation of effective candidate drugs in experimental studies to patients has systematically failed. However, some of those treatments or neuroprotectant diets which demonstrated only beneficial effects if given before (but not after) ischemia induction and discarded for conventional neuroprotection, could be rescued in order to apply an 'advanced neuroprotection strategy' (ADNES). Herein, the authors discuss how re-profiling those neuroprotective candidate drugs and diets with the best potential, some of which are mentioned in this article as an ADNES, may be a good approach for developing successful treatments that protect the brain against ischemic damage. This novel approach would try to protect the brain of patients who are at high risk of suffering a stroke, before damage occurs, in order to minimize brain injury by having the neuroprotectant drug or diet 'on board' if unfortunately stroke occurs.

  14. Processing of Basic Speech Acts Following Localized Brain Damage: A New Light on the Neuroanatomy of Language

    Science.gov (United States)

    Soroker, N.; Kasher, A.; Giora, R.; Batori, G.; Corn, C.; Gil, M.; Zaidel, E.

    2005-01-01

    We examined the effect of localized brain lesions on processing of the basic speech acts (BSAs) of question, assertion, request, and command. Both left and right cerebral damage produced significant deficits relative to normal controls, and left brain damaged patients performed worse than patients with right-sided lesions. This finding argues…

  15. Prevention of downhill walking-induced muscle damage by non-damaging downhill walking.

    Science.gov (United States)

    Maeo, Sumiaki; Yamamoto, Masayoshi; Kanehisa, Hiroaki; Nosaka, Kazunori

    2017-01-01

    Mountain trekking involves level, uphill, and downhill walking (DW). Prolonged DW induces damage to leg muscles, reducing force generating ability and muscle coordination. These increase risks for more serious injuries and accidents in mountain trekking, thus a strategy to minimize muscle damage is warranted. It has been shown that low-intensity eccentric contractions confer protective effect on muscle damage induced by high-intensity eccentric contractions. This study tested the hypothesis that 5-min non-damaging DW would attenuate muscle damage induced by 40-min DW, but 5-min level walking (LW) would not. Untrained young men were allocated (n = 12/group) to either a control or one of the two preconditioning groups (PRE-DW or PRE-LW). The PRE-DW and PRE-LW groups performed 5-min DW (-28%) and 5-min LW, respectively, at 5 km/h with a load of 10% body mass, 1 week before 40-min DW (-28%, 5 km/h, 10% load). The control group performed 40-min DW only. Maximal knee extension strength, plasma creatine kinase (CK) activity, and muscle soreness (0-100 mm visual analogue scale) were measured before and 24 h after 5-min DW and 5-min LW, and before and 24, 48, and 72 h after 40-min DW. No significant changes in any variables were evident after 5-min DW and 5-min LW. After 40-min DW, the control and PRE-LW groups showed significant (P<0.05) changes in the variables without significant differences between groups (control vs. PRE-LW; peak strength reduction: -19.2 ± 6.9% vs. -18.7 ± 11.0%, peak CK: 635.5 ± 306.0 vs. 639.6 ± 405.4 U/L, peak soreness: 81.4 ± 14.8 vs. 72.0 ± 29.2 mm). These changes were significantly (P<0.05) attenuated (47-64%) for the PRE-DW group (-9.9 ± 9.6%, 339.3 ± 148.4 U/L, 27.8 ± 16.8 mm). The results supported the hypothesis and suggest that performing small volume of downhill walking is crucial in preparation for trekking.

  16. Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

    Science.gov (United States)

    Rendon, Cesar A.; Lilge, Lothar

    2004-10-01

    In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

  17. Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid.

    Science.gov (United States)

    Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R; Masliah, Eliezer; Lipton, Stuart A

    2015-06-01

    Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain barrier to up-regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human-induced pluripotent stem cell-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain. Cyanide, a potential bioterrorist agent, can produce a chronic delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both in vitro and in vivo models through activation of the Nrf2/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid-derived 2)-like 2). © 2015 International Society for Neurochemistry.

  18. Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model

    Science.gov (United States)

    Lin, Wei-Ting; Chen, Ran-Chou; Lu, Wen-Wei; Liu, Shing-Hwa; Yang, Feng-Yi

    2015-04-01

    The protein expressions of neurotrophic factors can be enhanced by low-intensity pulsed ultrasound (LIPUS) stimulation in the brain. The purpose of this study was to demonstrate the protective effect of LIPUS stimulation against aluminum-induced cerebral damage in Alzheimer's disease rat model. LIPUS was administered 7 days before each aluminum chloride (AlCl3) administration, and concomitantly given with AlCl3 daily for a period of 6 weeks. Neurotrophic factors in hippocampus were measured by western blot analysis. Behavioral changes in the Morris water maze and elevated plus maze were examined in rats after administration of AlCl3. Various biochemical analyses were performed to evaluate the extent of brain damages. LIPUS is capable of prompting levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor (VEGF) in rat brain. AlCl3 administration resulted in a significant increase in the aluminum concentration, acetylcholinesterase activity and beta-amyloid (Aβ) deposition in AlCl3 treated rats. LIPUS stimulation significantly attenuated aluminum concentration, acetylcholinesterase activity, Aβ deposition and karyopyknosis in AlCl3 treated rats. Furthermore, LIPUS significantly improved memory retention in AlCl3-induced memory impairment. These experimental results indicate that LIPUS has neuroprotective effects against AlCl3-induced cerebral damages and cognitive dysfunction.

  19. Retinal damage induced by commercial light emitting diodes (LEDs).

    Science.gov (United States)

    Jaadane, Imene; Boulenguez, Pierre; Chahory, Sabine; Carré, Samuel; Savoldelli, Michèle; Jonet, Laurent; Behar-Cohen, Francine; Martinsons, Christophe; Torriglia, Alicia

    2015-07-01

    Spectra of "white LEDs" are characterized by an intense emission in the blue region of the visible spectrum, absent in daylight spectra. This blue component and the high intensity of emission are the main sources of concern about the health risks of LEDs with respect to their toxicity to the eye and the retina. The aim of our study was to elucidate the role of blue light from LEDs in retinal damage. Commercially available white LEDs and four different blue LEDs (507, 473, 467, and 449nm) were used for exposure experiments on Wistar rats. Immunohistochemical stain, transmission electron microscopy, and Western blot were used to exam the retinas. We evaluated LED-induced retinal cell damage by studying oxidative stress, stress response pathways, and the identification of cell death pathways. LED light caused a state of suffering of the retina with oxidative damage and retinal injury. We observed a loss of photoreceptors and the activation of caspase-independent apoptosis, necroptosis, and necrosis. A wavelength dependence of the effects was observed. Phototoxicity of LEDs on the retina is characterized by a strong damage of photoreceptors and by the induction of necrosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Investigation of cutting-induced damage in CMC bend bars

    Directory of Open Access Journals (Sweden)

    Neubrand A.

    2015-01-01

    Full Text Available Ceramic matrix composites (“CMC” with a strong fibre-matrix interface can be made damage-tolerant by introducing a highly porous matrix. Such composites typically have only a low interlaminar shear strength, which can potentially promote damage when preparing specimens or components by cutting. In order to investigate the damage induced by different cutting methods, waterjet cutting with and without abrasives, laser-cutting, wire eroding and cutoff grinding were used to cut plates of two different CMCs with a matrix porosity up to 35 vol.-%. For each combination of cutting method and composite, the flexural and interlaminar shear strength of the resulting specimens was determined. Additionally, the integrity of the regions near the cut surfaces was investigated by high-resolution x-ray computer tomography. It could be shown that the geometrical quality of the cut is strongly affected by the cutting method employed. Laser cut and waterjet cut specimens showed damage and delaminations near the cut surface leading to a reduced interlaminar shear strength of short bend bars in extreme cases.

  1. Ghrelin attenuates gastrointestinal epithelial damage induced by doxorubicin

    Institute of Scientific and Technical Information of China (English)

    Mohamed A Fahim; Hazem Kataya; Rkia El-Kharrag; Dena AM Amer; Basel al-Ramadi; Sherif M Karam

    2011-01-01

    AIM: To examine the influence of ghrelin on the regenerative potential of gastrointestinal (GI) epithelium.METHODS: Damage to GI epithelium was induced in mice by two intravenous injections of doxorubicin (10 and 6 mg/kg). Some of the doxorubicin-treated mice received a continuous subcutaneous infusion of ghrelin (1.25 μg/h) for 10 d via implanted mini-osmotic pumps. To label dividing stem cells in the S-phase of the cell cycle, all mice received a single intraperitoneal injection of 5'-bromo-2'-deoxyuridine (BrdU) one hour before sacrifice. The stomach along with the duodenum were then removed and processed for histological examination and immunohistochemistry using anti-BrdU antibody. RESULTS: The results showed dramatic damage to the GI epithelium 3 d after administration of chemotherapy which began to recover by day 10. In ghrelin-treated mice, attenuation of GI mucosal damage was evident in the tissues examined post-chemotherapy. Immunohistochemical analysis showed an increase in the number of BrdU-labeled cells and an alteration in their distribution along the epithelial lining in response to damage by doxorubicin. In mice treated with both doxorubicin and ghrelin, the number of BrdU-labeled cells was reduced when compared with mice treated with doxorubicin alone. CONCLUSION: The present study suggests that ghrelin enhances the regenerative potential of the GI epithelium in doxorubicin-treated mice, at least in part, by modulating cell proliferation.

  2. Natural polyphenols may ameliorate damage induced by copper overload.

    Science.gov (United States)

    Arnal, Nathalie; Tacconi de Alaniz, María J; Marra, Carlos Alberto

    2012-02-01

    The effect of the simultaneous exposure to transition metals and natural antioxidants frequently present in food is a question that needs further investigation. We aimed to explore the possible use of the natural polyphenols caffeic acid (CA), resveratrol (RES) and curcumin (CUR) to prevent damages induced by copper-overload on cellular molecules in HepG2 and A-549 human cells in culture. Exposure to 100μM/24h copper (Cu) caused extensive pro-oxidative damage evidenced by increased TBARS, protein carbonyls and nitrite productions in both cell types. Damage was aggravated by simultaneous incubation with 100μM of CA or RES, and it was also reflected in a decrease on cellular viability explored by trypan blue dye exclusion test and LDH leakage. Co-incubation with CUR produced opposite effects demonstrating a protective action which restored the level of biomarkers and cellular viability almost to control values. Thus, while CA and RES might aggravate the oxidative/nitrative damage of Cu, CUR should be considered as a putative protective agent. These results could stimulate further research on the possible use of natural polyphenols as neutralizing substances against the transition metal over-exposure in specific populations such as professional agrochemical sprayers and women using Cu-intrauterine devices.

  3. A different story on "Theory of Mind" deficit in adults with right hemisphere brain damage.

    Science.gov (United States)

    Tompkins, Connie A; Scharp, Victoria L; Fassbinder, Wiltrud; Meigh, Kimberly M; Armstrong, Elizabeth M

    2008-01-01

    BACKGROUND: Difficulties in social cognition and interaction can characterise adults with unilateral right hemisphere brain damage (RHD). Some pertinent evidence involves their apparently poor reasoning from a "Theory of Mind" perspective, which requires a capacity to attribute thoughts, beliefs, and intentions in order to understand other people's behaviour. Theory of Mind is typically assessed with tasks that induce conflicting mental representations. Prior research with a commonly used text task reported that adults with RHD were less accurate in drawing causal inferences about mental states than at making non-mental-state causal inferences from control texts. However, the Theory of Mind and control texts differed in the number and nature of competing discourse entity representations. This stimulus discrepancy, together with the explicit measure of causal inferencing, likely put the adults with RHD at a disadvantage on the Theory of Mind texts. AIMS: This study revisited the question of Theory of Mind deficit in adults with RHD. The aforementioned Theory of Mind texts were used but new control texts were written to address stimulus discrepancies, and causal inferencing was assessed relatively implicitly. Adults with RHD were hypothesised not to display a Theory of Mind deficit under these conditions. METHODS #ENTITYSTARTX00026; PROCEDURES: The participants were 22 adults with unilateral RHD from cerebrovascular accident, and 38 adults without brain damage. Participants listened to spoken texts that targeted either mental-state or non-mental-state causal inferences. Each text was followed by spoken True/False probe sentences, to gauge target inference comprehension. Both accuracy and RT data were recorded. Data were analysed with mixed, two-way Analyses of Variance (Group by Text Type). OUTCOMES #ENTITYSTARTX00026; RESULTS: There was a main effect of Text Type in both accuracy and RT analyses, with a performance advantage for the Theory of Mind

  4. Leaf damage induces twining in a climbing plant.

    Science.gov (United States)

    Gianoli, Ernesto; Molina-Montenegro, Marco A

    2005-08-01

    Successful climbing by vines not only prevents shading by neighbouring vegetation, but also may place the vines beyond ground herbivores. Here we tested the hypothesis that herbivory might enhance climbing in a vine species, and that such induced climbing should be greater in the shade. We assessed field herbivory in climbing and prostrate ramets of the twining vine Convolvulus arvensis. We evaluated plant climbing after mechanical damage in a glasshouse under both sun and shade conditions, and determined whether control and damaged plants differed in growth rate or photosynthetic capacity. Plants experienced greater herbivory when growing prostrate than when climbing onto companion plants, in both an open habitat and a shaded understorey. Experimental plants increased their twining rate on a stake after suffering leaf damage, in both high- and low-light conditions, and this induced climbing was not coupled to an increase in growth rate. Increased photosynthesis was associated with enhanced twining rate only in the shade. Herbivory may be an ecological factor promoting the evolution of a climbing habit in plants.

  5. Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2014-10-01

    Full Text Available Viruses are the causative agents of 10%–15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer.

  6. Ginsenoside Rb1 attenuates activated microglia-induced neuronal damage

    Institute of Scientific and Technical Information of China (English)

    Lining Ke; Wei Guo; Jianwen Xu; Guodong Zhang; Wei Wang; Wenhua Huang

    2014-01-01

    The microglia-mediated inlfammatory reaction promotes neuronal damage under cerebral isch-emia/hypoxia conditions. We therefore speculated that inhibition of hypoxia-induced microglial activation may alleviate neuronal damage. To test this hypothesis, we co-cultured ginsenoside Rb1, an active component of ginseng, and cortical neurons. Ginsenoside Rb1 protected neuronal morphology and structure in a single hypoxic culture system and in a hypoxic co-culture system with microglia, and reduced neuronal apoptosis and caspase-3 production. The protective effect was observable prior to placing in co-culture. Additionally, ginsenoside Rb1 inhibited levels of tumor necrosis factor-αin a co-culture system containing activated N9 microglial cells. Ginse-noside Rb1 also signiifcantly decreased nitric oxide and superoxide production induced by N9 microglia. Our ifndings indicate that ginsenoside Rb1 attenuates damage to cerebral cortex neu-rons by downregulation of nitric oxide, superoxide, and tumor necrosis factor-αexpression in hypoxia-activated microglia.

  7. Chlorambucil induced chromosome damage in juvenile chronic arthritis.

    Science.gov (United States)

    Palmer, R G; Varonos, S; Doré, C J; Denman, A M; Ansell, B M

    1985-01-01

    Sister chromatid exchanges, a sensitive measure of chromosome damage, were counted in peripheral blood lymphocytes from 23 patients with juvenile chronic arthritis receiving long term, low dose chlorambucil treatment. Thirty five patients with juvenile chronic arthritis who had not been treated with cytotoxic drugs served as controls. All of the treated patients have cells with abnormal sister chromatid exchange frequencies. Damage is related to the daily dose and may, in part, be determined by the duration of treatment. Sister chromatid exchanges from nine patients who had received chlorambucil at some time in the past remained high for at least five months after stopping the drug. Long term follow up will determine whether sister chromatid exchange analysis can help predict those most at risk of drug induced malignancies. Images Fig. 1 PMID:4073932

  8. Lithium and valproate modulate antioxidant enzymes and prevent ouabain-induced oxidative damage in an animal model of mania.

    Science.gov (United States)

    Jornada, Luciano K; Valvassori, Samira S; Steckert, Amanda V; Moretti, Morgana; Mina, Francielle; Ferreira, Camila L; Arent, Camila O; Dal-Pizzol, Felipe; Quevedo, João

    2011-02-01

    In this study, we assessed the oxidative stress parameters in rats submitted to an animal model of mania induced by ouabain (OUA), which included the use of lithium (Li) and valproate (VPA). Li and VPA treatment reversed and prevented the OUA-induced damage in these structures, however, this effect varies depending on the brain region and treatment regimen. Moreover, the activity of the antioxidant enzymes, namely, superoxide dismutase (SOD) and catalase (CAT) was found to be increased and decreased, respectively, in the brain of OUA-administered rats. Li and VPA modulated SOD and CAT activities in OUA-subjected rats in both experimental models. Our results support the notion that Li and VPA exert antioxidant-like properties in the brain of rats submitted to animal model of mania induced by ouabain.

  9. Effect of Contraction Velocity on Selected Muscle Damage Indices Following Acute Eccentric Exercise-Induced Muscle Damage: A Review

    Directory of Open Access Journals (Sweden)

    Farzaneh Movaseghi

    2016-12-01

    Full Text Available Background & Objective: Eccentric muscle action is mechanically more efficient but employs a unique activation strategy which predisposes the muscle to damage. Type II muscle fibers are more susceptible than type I fibers to muscle damage; hence, velocity probably interferes with mechanical stress and thus may modulate muscle damage. The purpose of this review study was to investigate the effect of contraction velocity on selected muscle damage indices following acute eccentric exercise-induced muscle damage. Material & Method: Looking up related articles published in valid scientific databases such as PubMed, Springer, Elsevier, Science Direct, and SID with standard keywords and according to the research criteria, 16 studies (1980 to 2015 were selected. Results: Ten studies showed that high velocity eccentric exercise induced greater muscle damage. Five studies showed no differences between velocities, and a single study indicated a greater magnitude of muscle damage following slow eccentric exercise. Conclusion: Thus, greater magnitude of damage is induced by contractions performed at a higher velocity. However, considering differences during tension in the majority of studies, focusing on elbow flexor muscles and muscle damage profile variety in various muscle groups, and more animal and human studies in other muscular groups are necessary to confirm how the velocity of acute eccentric exercise would affect the muscle damage.

  10. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age

    OpenAIRE

    Sutherland, Greg T.; Sheedy, Donna; Kril, Jillian J.

    2013-01-01

    The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic n...

  11. Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis

    Directory of Open Access Journals (Sweden)

    Yijun Zheng

    2016-01-01

    Full Text Available Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc., survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis.

  12. No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 days.

    Science.gov (United States)

    Witt, Kristine L; Malarkey, David E; Hobbs, Cheryl A; Davis, Jeffrey P; Kissling, Grace E; Caspary, William; Travlos, Gregory; Recio, Leslie

    2010-01-01

    Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. [2007]: Prog Neuropsychopharmacol Biol Psychiatry 31:1282-1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats.

  13. Oxidative Stress in Ischemic Brain Damage: Mechanisms of Cell Death and Potential Molecular Targets for Neuroprotection

    Science.gov (United States)

    Chen, Hai; Yoshioka, Hideyuki; Kim, Gab Seok; Jung, Joo Eun; Okami, Nobuya; Sakata, Hiroyuki; Maier, Carolina M.; Narasimhan, Purnima; Goeders, Christina E.

    2011-01-01

    Abstract Significant amounts of oxygen free radicals (oxidants) are generated during cerebral ischemia/reperfusion, and oxidative stress plays an important role in brain damage after stroke. In addition to oxidizing macromolecules, leading to cell injury, oxidants are also involved in cell death/survival signal pathways and cause mitochondrial dysfunction. Experimental data from laboratory animals that either overexpress (transgenic) or are deficient in (knock-out) antioxidant proteins, mainly superoxide dismutase, have provided strong evidence of the role of oxidative stress in ischemic brain damage. In addition to mitochondria, recent reports demonstrate that NADPH oxidase (NOX), an important pro-oxidant enzyme, is also involved in the generation of oxidants in the brain after stroke. Inhibition of NOX is neuroprotective against cerebral ischemia. We propose that superoxide dismutase and NOX activity in the brain is a major determinant for ischemic damage/repair and that these major anti- and pro-oxidant enzymes are potential endogenous molecular targets for stroke therapy. Antioxid. Redox Signal. 14, 1505–1517. PMID:20812869

  14. 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

    Background Although traumatic brain injury can lead to opening the blood-brain barrier and leaking of blood substances (including water) into brain tissue,few studies of brain antigens leaking into the blood and the pathways have been reported.Brain antigens result in damage to brain tissues by stimulating the immune system to produce anti-brain antibodies,but no treatment has been reported to reduce the production of anti-brain antibodies and protect the brain tissue.The aim of the study is to confirm the relationship between immune injury and arachnoid granulations following traumatic brain injury,and provide some new methods to inhibit the immune injury.Methods In part one,methylene blue was injected into the rabbits' cisterna magna after traumatic brain injury,and concentrations of methylene blue and tumor necrosis factor (TNF)-α in blood were detected to determine the permeability of arachnoid granulations.In part two,umbilical cord mesenchymal stem cells and immature dendritic cells were injected into veins,and concentrations of interleukin 1 (IL-1),IL-10,interferon (IFN)-y,transforming growth factor (TGF)-β,anti-brain antibodies (ABAb),and IL-12 were measured by ELISA on days 1,3,7,14 and 21 after injury,and the numbers of leukocytes in the blood were counted.Twenty-one days after injury,expression of glutamate in brain tissue was determined by immunohistochemical staining,and neuronal degeneration was detected by H&E staining.Results In part one,blood concentrations of methylene blue and TNF-α in the traumatic brain injury group were higher than in the control group (P <0.05).Concentrations of methylene blue and TNF-α in the trauma cerebrospinal fluid (CSF)injected group were higher than in the control cerebrospinal fluid injected group (P <0.05).In part two,concentrations of IL-1,IFN-y,ABAb,IL-12,expression of glutamate (Glu),neuronal degeneration and number of peripheral blood leukocytes were lower in the group with cell treatment compared to the

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

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan Xia; Yi-xin Xia

    2011-01-01

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

  16. Uptake of radiolabeled ions in normal and ischemia-damaged brain.

    Science.gov (United States)

    Dienel, G A; Pulsinelli, W A

    1986-05-01

    The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (63Ni, 99TcO4, 22Na, and [3H]tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater than in normal tissue. The concentrations of 65Zn, 59Fe, 32PO4, and 147Pm in postischemic brain were similar to or less than those in normal brain. The concentration of [14C]EDTA was increased in injured and uninjured brain of postischemic rats. Autoradiographic analysis of the distribution patterns of some of these ions in normal animals showed that 99TcO4, 22Na, 65Zn, and 59Fe were distributed more uniformly throughout the brain than were 32PO4, 63Ni, and 147Pm. At 24 or 48 hours after ischemia, 63Ni, 99TcO4, and 22Na were preferentially concentrated in the damaged striatum and hippocampus, whereas 65Zn, 59Fe, 32PO4, and 147Pm did not accumulate in irreversibly injured tissue. Of the radiochemicals tested to date, Ni, TcO4, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography.

  17. The effects of chronic smoking on the pathology of alcohol-related brain damage.

    Science.gov (United States)

    McCorkindale, A N; Sheedy, D; Kril, J J; Sutherland, G T

    2016-06-01

    Both pathological and neuroimaging studies demonstrate that chronic alcohol abuse causes brain atrophy with widespread white matter loss limited gray matter loss. Recent neuroimaging studies suggest that tobacco smoking also causes brain atrophy in both alcoholics and neurologically normal individuals; however, this has not been confirmed pathologically. In this study, the effects of smoking and the potential additive effects of concomitant alcohol and tobacco consumption were investigated in autopsied human brains. A total of 44 cases and controls were divided into four groups: 16 non-smoking controls, nine smoking controls, eight non-smoking alcoholics, and 11 smoking alcoholics. The volumes of 26 gray and white matter regions were measured using an established point-counting technique. The results showed trends for widespread white matter loss in alcoholics (p smoking alone had no effect on brain atrophy and the combination of smoking and alcohol showed no additional effect. Neuronal density was analyzed as a more sensitive assay of gray matter integrity. Similar to the volumetric analysis, there was a reduction in neurons (29%) in the prefrontal cortex of alcoholics, albeit this was only a trend when adjusted for potential confounders (p smoking or combinatorial effects on neuronal density in any of the three regions examined. These results do not support the hypothesis that smoking exacerbates alcohol-related brain damage. The trends here support previous studies that alcohol-related brain damage is characterized by focal neuronal loss and generalized white matter atrophy. These disparate effects suggest that two different pathogenic mechanisms may be operating in the alcoholic brain. Future studies using ultrastructural or molecular techniques will be required to determine if smoking has more subtle effects on the brain and how chronic alcohol consumption leads to widespread white matter loss.

  18. 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.

  19. Proton induced radiation damage in fast crystal scintillators

    Science.gov (United States)

    Yang, Fan; Zhang, Liyuan; Zhu, Ren-Yuan; Kapustinsky, Jon; Nelson, Ron; Wang, Zhehui

    2016-07-01

    This paper reports proton induced radiation damage in fast crystal scintillators. A 20 cm long LYSO crystal, a 15 cm long CeF3 crystal and four liquid scintillator based sealed quartz capillaries were irradiated by 800 MeV protons at Los Alamos up to 3.3 ×1014 p /cm2. Four 1.5 mm thick LYSO plates were irradiated by 24 GeV protons at CERN up to 6.9 ×1015 p /cm2. The results show an excellent radiation hardness of LYSO crystals against charged hadrons.

  20. Laser beam shaping for studying thermally induced damage

    CSIR Research Space (South Africa)

    Masina, BN

    2011-08-01

    Full Text Available for studying thermally induced damage Bathusile N. Masinaa, Richard Bodkinc, Bonex Mwakikungad and Andrew Forbesa,b?, aCSIR National Laser Centre, P. O. Box 395, Pretoria 0001, South Africa bSchool of Physics, University of KwaZulu-Natal, Private Bag X... from the blackbody at each wavelength, it is possible to determine the temperature of the blackbody or of the object by fitting the blackbody spectrum to the measured light. The advantage of using the blackbody emission is that there is no physical...

  1. Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration

    Science.gov (United States)

    Holubiec, Mariana Inés; Tornatore, Tamara Logica; Rivière, Stéphanie; Kölliker-Frers, Rodolfo Alberto; Tau, Julia; Blanco, Eduardo; Galeano, Pablo; Lillig, Christopher Horst

    2017-01-01

    The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury. PMID:28706574

  2. Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Romero

    2017-01-01

    Full Text Available The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury.

  3. Detection of brain damage: neuropsychological assessment in a Spanish speaking population.

    Science.gov (United States)

    Ostrosky-Solis, F; Quintanar, L; Ardila, A

    1989-12-01

    We developed a neuropsychological battery for assessment of cognitive processes that was standardized in 150 neurologically intact subjects from different socioeducational levels in Mexico City (Ostrosky et al., 1985, 1986). The present study was designed to explore the capacity of this neuropsychological battery to discriminate a brain-injured population from a normal one. Thirty-four patients attending the neurological service of two hospitals institutions in Mexico City were studied. The reasons for going to the hospital included both neurological and neuropsychological symptoms. The group was divided into two subgroups: twenty-four patients who showed brain damage confirmed by brain scans, and ten patients with a normal brain scan. A control group of 19 normal subjects was also studied and paired with the other groups by sex, age and sociocultural level. The results show that the neuropsychological battery was able to recognize 83.3% of the patients with scanographically confirmed brain damage: the total percentage of successful diagnosis was 88.2% and there were no false positives. These results indicate that neuropsychological assessment is a powerful diagnostic procedure that also evaluates the patient's cognitive-behavioral activity and can help to predict the possibilities for rehabilitation and return to work.

  4. MicroRNA-103-1 selectively downregulates brain NCX1 and its inhibition by anti-miRNA ameliorates stroke damage and neurological deficits.

    Science.gov (United States)

    Vinciguerra, Antonio; Formisano, Luigi; Cerullo, Pierpaolo; Guida, Natascia; Cuomo, Ornella; Esposito, Alba; Di Renzo, Gianfranco; Annunziato, Lucio; Pignataro, Giuseppe

    2014-10-01

    Na(+)/Ca2+ exchanger (NCX) is a plasma membrane transporter that, by regulating Ca2+ and Na(+) homeostasis, contributes to brain stroke damage. The objectives of this study were to investigate whether there might be miRNAs in the brain able to regulate NCX1 expression and, thereafter, to set up a valid therapeutic strategy able to reduce stroke-induced brain damage by regulating NCX1 expression. Thus, we tested whether miR-103-1, a microRNA belonging to the miR-103/107 family that on the basis of sequence analysis might be a potential NCX1 regulator, could control NCX1 expression. The role of miR-103-1 was assessed in a rat model of transient cerebral ischemia by evaluating the effect of the correspondent antimiRNA on both brain infarct volume and neurological deficits. NCX1 expression was dramatically reduced when cortical neurons were exposed to miR-103-1. This alleged tight regulation of NCX1 by miR-103-1 was further corroborated by luciferase assay. Notably, antimiR-103-1 prevented NCX1 protein downregulation induced by the increase in miR-103-1 after brain ischemia, thereby reducing brain damage and neurological deficits. Overall, the identification of a microRNA able to selectively regulate NCX1 in the brain clarifies a new important molecular mechanism of NCX1 regulation in the brain and offers the opportunity to develop a new therapeutic strategy for stroke.

  5. Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation

    DEFF Research Database (Denmark)

    Undén, Johan; Strandberg, Karin; Malm, Jan

    2009-01-01

    INTRODUCTION: A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as novel...... diagnostic tools for stroke subtypes. METHODS: Ninety-seven stroke patients were prospectively investigated in a multicenter design with blood levels of brain biomarkers S100B, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) as well as a coagulation biomarker, activated protein C......: This exploratory study indicated that blood levels of biomarkers GFAP and APC-PCI, prior to neuroimaging, may rule out ICH in a mixed stroke population....

  6. Bee products prevent agrichemical-induced oxidative damage in fish.

    Directory of Open Access Journals (Sweden)

    Daiane Ferreira

    Full Text Available In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™ and a group that was exposed to 0.88 mg L(-1 of TEB alone (corresponding to 16.6% of the 96-h LC50. We show that waterborne bee products, including royal jelly (RJ, honey (H, bee pollen (BP and propolis (P, reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD, catalase (CAT and glutathione-S-transferase (GST are increased.

  7. Quercetin protection against ciprofloxacin induced liver damage in rats.

    Science.gov (United States)

    Taslidere, E; Dogan, Z; Elbe, H; Vardi, N; Cetin, A; Turkoz, Y

    2016-01-01

    Ciprofloxacin is a common, broad spectrum antibacterial agent; however, evidence is accumulating that ciprofloxacin may cause liver damage. Quercetin is a free radical scavenger and antioxidant. We investigated histological changes in hepatic tissue of rats caused by ciprofloxacin and the effects of quercetin on these changes using histochemical and biochemical methods. We divided 28 adult female Wistar albino rats into four equal groups: control, quercetin treated, ciprofloxacin treated, and ciprofloxacin + quercetin treated. At the end of the experiment, liver samples were processed for light microscopic examination and biochemical measurements. Sections were prepared and stained with hematoxylin and eosin, and a histopathologic damage score was calculated. The sections from the control group appeared normal. Hemorrhage, inflammatory cell infiltration and intracellular vacuolization were observed in the ciprofloxacin group. The histopathological findings were reduced in the group treated with quercetin. Significant differences were found between the control and ciprofloxacin groups, and between the ciprofloxacin and ciprofloxacin + quercetin groups. Quercetin administration reduced liver injury caused by ciprofloxacin in rats. We suggest that quercetin may be useful for preventing ciprofloxacin induced liver damage.

  8. The AID-induced DNA damage response in chromatin

    DEFF Research Database (Denmark)

    Daniel, Jeremy A; Nussenzweig, André

    2013-01-01

    with somatic hypermutation and class switch recombination, chromatin must be made accessible for activation-induced cytidine deaminase (AID)-mediated deamination of cytosines in DNA. These lesions are recognized and removed by various DNA repair pathways but, if not handled properly, can lead to formation......Chemical modifications to the DNA and histone protein components of chromatin can modulate gene expression and genome stability. Understanding the physiological impact of changes in chromatin structure remains an important question in biology. As one example, in order to generate antibody diversity...... of oncogenic chromosomal translocations. In this review, we focus the discussion on how chromatin-modifying activities and -binding proteins contribute to the native chromatin environment in which AID-induced DNA damage is targeted and repaired. Outstanding questions remain regarding the direct roles...

  9. Anchor-induced chondral damage in the hip

    Science.gov (United States)

    Matsuda, Dean K.; Bharam, Srino; White, Brian J.; Matsuda, Nicole A.; Safran, Marc

    2015-01-01

    The purpose of this study is to investigate the outcomes from anchor-induced chondral damage of the hip, both with and without frank chondral penetration. A multicenter retrospective case series was performed of patients with chondral deformation or penetration during initial hip arthroscopic surgery. Intra-operative findings, post-surgical clinical courses, hip outcome scores and descriptions of arthroscopic treatment in cases requiring revision surgery and anchor removal are reported. Five patients (three females) of mean age 32 years (range, 16–41 years) had documented anchor-induced chondral damage with mean 3.5 years (range, 1.5–6.0 years) follow-up. The 1 o'clock position (four cases) and anterior and mid-anterior portals (two cases each) were most commonly implicated. Two cases of anchor-induced acetabular chondral deformation without frank penetration had successful clinical and radiographic outcomes, while one case progressed from deformation to chondral penetration with clinical worsening. Of the cases that underwent revision hip arthroscopy, all three had confirmed exposed hard anchors which were removed. Two patients have had clinical improvement and one patient underwent early total hip arthroplasty. Anchor-induced chondral deformation without frank chondral penetration may be treated with close clinical and radiographic monitoring with a low threshold for revision surgery and anchor removal. Chondral penetration should be treated with immediate removal of offending hard anchor implants. Preventative measures include distal-based portals, small diameter and short anchors, removable hard anchors, soft suture-based anchors, curved drill and anchor insertion instrumentation and attention to safe trajectories while visualizing the acetabular articular surface. PMID:27011815

  10. Anchor-induced chondral damage in the hip.

    Science.gov (United States)

    Matsuda, Dean K; Bharam, Srino; White, Brian J; Matsuda, Nicole A; Safran, Marc

    2015-01-01

    The purpose of this study is to investigate the outcomes from anchor-induced chondral damage of the hip, both with and without frank chondral penetration. A multicenter retrospective case series was performed of patients with chondral deformation or penetration during initial hip arthroscopic surgery. Intra-operative findings, post-surgical clinical courses, hip outcome scores and descriptions of arthroscopic treatment in cases requiring revision surgery and anchor removal are reported. Five patients (three females) of mean age 32 years (range, 16-41 years) had documented anchor-induced chondral damage with mean 3.5 years (range, 1.5-6.0 years) follow-up. The 1 o'clock position (four cases) and anterior and mid-anterior portals (two cases each) were most commonly implicated. Two cases of anchor-induced acetabular chondral deformation without frank penetration had successful clinical and radiographic outcomes, while one case progressed from deformation to chondral penetration with clinical worsening. Of the cases that underwent revision hip arthroscopy, all three had confirmed exposed hard anchors which were removed. Two patients have had clinical improvement and one patient underwent early total hip arthroplasty. Anchor-induced chondral deformation without frank chondral penetration may be treated with close clinical and radiographic monitoring with a low threshold for revision surgery and anchor removal. Chondral penetration should be treated with immediate removal of offending hard anchor implants. Preventative measures include distal-based portals, small diameter and short anchors, removable hard anchors, soft suture-based anchors, curved drill and anchor insertion instrumentation and attention to safe trajectories while visualizing the acetabular articular surface.

  11. Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model

    OpenAIRE

    Lin, Wei-Ting; Chen, Ran-Chou; Lu, Wen-Wei; Liu,Shing-Hwa; Yang, Feng-Yi

    2015-01-01

    The protein expressions of neurotrophic factors can be enhanced by low-intensity pulsed ultrasound (LIPUS) stimulation in the brain. The purpose of this study was to demonstrate the protective effect of LIPUS stimulation against aluminum-induced cerebral damage in Alzheimer's disease rat model. LIPUS was administered 7 days before each aluminum chloride (AlCl3) administration, and concomitantly given with AlCl3 daily for a period of 6 weeks. Neurotrophic factors in hippocampus were measured b...

  12. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

    2011-10-15

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced

  13. [Perinatal brain damage--from neuroprotection to neuroregeneration using cord blood stem cells].

    Science.gov (United States)

    Jensen, Arne; Vaihinger, Hans-Martin; Meier, Carola

    2003-12-15

    Per year, approximately 1,000 children in Germany suffer from brain damage due to hypoxic-ischemic insults during the perinatal period. Based on the severity and localization of the insult, these children develop either spastic pareses, choreoathetosis, ataxia, or sensomotoric dysfunctions. A close cooperation between obstetricians, pediatricians, neuropediatricians, physical therapists, developmental psychologists, and other specialists is required, as the strain these disorders have on the children and their families is tremendous. The costs resulting per birthyear for the community are estimated on 1 million Euro. Clinical concepts to decrease the cerebral morbidity in perinatology departments have proven to be effective over the last decade. However, since brain damage cannot be prevented every time, it is essential that therapeutic measures, which have a neuroprotective effect after the insult, are being developed. Experimental pilots regarding these matters are promising. Current experiments are focused on the possible application of cord blood-derived stem cells for neuroregeneration.

  14. 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.

  15. Scaling Relations for Intercalation Induced Damage in Electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chien-Fan; Barai, Pallab; Smith, Kandler; Mukherjee, Partha P.

    2016-06-01

    Mechanical degradation, owing to intercalation induced stress and microcrack formation, is a key contributor to the electrode performance decay in lithium-ion batteries (LIBs). The stress generation and formation of microcracks are caused by the solid state diffusion of lithium in the active particles. In this work, scaling relations are constructed for diffusion induced damage in intercalation electrodes based on an extensive set of numerical experiments with a particle-level description of microcrack formation under disparate operating and cycling conditions, such as temperature, particle size, C-rate, and drive cycle. The microcrack formation and evolution in active particles is simulated based on a stochastic methodology. A reduced order scaling law is constructed based on an extensive set of data from the numerical experiments. The scaling relations include combinatorial constructs of concentration gradient, cumulative strain energy, and microcrack formation. The reduced order relations are further employed to study the influence of mechanical degradation on cell performance and validated against the high order model for the case of damage evolution during variable current vehicle drive cycle profiles.

  16. DAMAGE OF SILICONE RUBBER INDUCED BY PROTON IRRADIATION

    Institute of Scientific and Technical Information of China (English)

    Li-xin Zhang; Shi-qin Yang; Shi-yu He

    2003-01-01

    In this paper, the damage to methyl silicone rubber induced by irradiation with protons of 150 keV energy was studied. The surface morphology, tensile strength, Shore hardness, cross-linking density and glass transition temperature were examined. Positron annihilation lifetime spectrum analysis (PALS) was perfomed to reveal the damage mechanisms of the rubber. The results showed that tensile strength and Shore hardness of the rubber increased first and then decreased with increasing irradiation fluence. The PALS characteristics τ3 and I3, as well as the free volume Vf, decreased with increasing irradiation fluence up to 1015 cm-2, and then increased slowly. It indicates that proton irradiation causes a decrease of free volume in the methyl silicone rubber when the fluence is less than l015 cm-2, while the free volume increases when the fluence is greater than 1015 cm-2. The results on cross-linking density indicate that the cross-linking induced by proton irradiation is dominant at smaller proton fluences, increasing the tensile strength and Shore hardness of the rubber, while the degradation of rubber dominates at greater fluence, leading to a decrease of tensile strength and Shore hardness.

  17. Defense mechanisms against radiation induced teratogenic damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kato, F.; Ootsuyama, A.; Nomoto, S.; Norimura, T. [Univ. of Occupational and Environmental Health, Kitakyushu, (Japan)

    2002-07-01

    Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair.

  18. Rhubarb extract has a protective role against radiation-induced brain injury and neuronal cell apoptosis.

    Science.gov (United States)

    Lu, Kui; Zhang, Cheng; Wu, Wenjun; Zhou, Min; Tang, Yamei; Peng, Ying

    2015-08-01

    Oxidative stress caused by ionizing radiation is involved in neuronal damage in a number of disorders, including trauma, stroke, Alzheimer's disease and amyotrophic lateral sclerosis. Ionizing radiation can lead to the formation of free radicals, which cause neuronal apoptosis and have important roles in the development of some types of chronic brain disease. The present study evaluated the effects of varying concentrations (2, 5 and 10 µg/ml) of ethanolic rhubarb extract on the neuronal damage caused by irradiation in primary neuronal cultures obtained from the cortices of rat embryos aged 20 days. Brain damage was induced with a single dose of γ-irradiation that induced DNA fragmentation, increased lactate dehydrogenase release in neuronal cells and acted as a trigger for microglial cell proliferation. Treatment with rhubarb extract significantly decreased radiation-induced lactate dehydrogenase release and DNA fragmentation, which are important in the process of cell apoptosis. The rhubarb extract exhibited dose-dependent inhibition of lactate dehydrogenase release and neuronal cell apoptosis that were induced by the administration of ionizing radiation. The effect of a 10 µg/ml dose of rhubarb extract on the generation of reactive oxygen species (ROS) induced by radiation was also investigated. This dose led to significant inhibition of ROS generation. In conclusion, the present study showed a protective role of rhubarb extract against irradiation-induced apoptotic neuronal cell death and ROS generation.

  19. Neuropsychological Rehabilitation Treatments of Executive Functions in Patients with Brain Damage: Characterization and Effectiveness A Review

    OpenAIRE

    Martínez Martínez, Adriana Marcela; Pontificia Universidad Javeriana; Martínez Villar, Susana; Aguilar Mejia, Oscar Mauricio; Pontificia Universidad Javeriana; Mariño García, Daniela

    2014-01-01

    This paper analyses the effectiveness of rehabilitation programs for executive functions in adults with brain damage. We consider an effective treatment when the program shows results with a statistically significant difference in the neuropsychological assessment after intervention (p < 0.05). Moreover, others criteria were considered such as improvement on daily life scales, the transfer of strategies on daily life conditions and the persistence of these for at least six months. The article...

  20. Changes in the permeability of blood brain barrier and endothelial cell damage after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Ke Liu; Jiansheng Li

    2006-01-01

    OBJECTIVE: To investigate the effect of endothelial cells on the permeability of blood brain barrier (BBB) after brain injury and its effect mechanism.DATA SOURCES: We searched for the articles of permeability of BBB and endothelial cell injury after brain ischemia, which were published between January 1982 and December 2005, with the key words of "cerebral ischemia damage,blood brain barrier ( BBB),permeability,effect of endothelial cell (EC) and its variation mechanism"in English.STUDY SELECTION: The materials were primarily selected. The articles related to the changes in the permeability of BBB and the effect of endothelial cells as well as the change mechanism after cerebral ischemia damage were chosen. Repetitive studies or review articles were excluded.DATA EXTRACTION: Totally 55 related articles were collected, and 35 were excluded due to repetitive or review articles, finally 20 articles were involved.DATA SYNTHESIS: The content or viewpoints of involved literatures were analyzed. Cerebral ischemia had damage for endothelial cells, such as the inflow of a lot of Ca2+, the production of nitrogen monoxide and oxygen free radical, and aggravated destruction of BBB. After acceptors of inflammatory mediators on cerebrovascular endothelial cell membrane, such as histamine, bradykinin , 5-hydroxytryptamine and so on are activated, endothelial cells shrink and the permeability of BBB increases. Its mechanism involves in the inflow of extracellular Ca2+and the release of intracellular Ca2+ in the cells. Glycocalyx molecule on the surface of endothelial cell, having structural polytropy, is the determinative factor of the permeability of BBB. VEGF, intensively increasing the vasopermeability and mainly effecting on postcapillary vein and veinlet, is the strongest known blood vessel permeation reagent. Its chronic overexpression in the brain can lead the destruction of BBB.CONCLUSION: The injury of endothelial cell participants in the pathological mechanism of BBB

  1. Effects of maintenance electroshock on the oxidative damage parameters in the rat brain.

    Science.gov (United States)

    Jornada, Luciano K; Feier, Gustavo; Barichello, Tatiana; Vitali, Angeles M; Reinke, Adalisa; Gavioli, Elaine C; Dal-Pizzol, Felipe; Quevedo, João

    2007-03-01

    Although several advances have occurred over the past 20 years concerning refining the use and administration of electroconvulsive therapy to minimize side effects of this treatment, little progress has been made in understanding the mechanisms underlying its therapeutic or adverse effects. This work was performed in order to determine the level of oxidative damage at different times after the maintenance electroconvulsive shock (ECS). Male Wistar rats (250-300 g) received a protocol mimicking therapeutic of maintenance or simulated ECS (Sham) and were subsequently sacrificed immediately after, 48 h and 7 days after the last maintenance electroconvulsive shock. We measured oxidative damage parameters (thiobarbituric acid reactive species for lipid peroxidation and protein carbonyls for protein damage, respectively) in hippocampus, cortex, cerebellum and striatum. We demonstrated no alteration in the lipid peroxidation and protein damage in the four structures studied immediately after, 48 h and 7 days after a last maintenance electroconvulsive shock. Our findings, for the first time, demonstrated that after ECS maintenance we did protocol minimal oxidative damage in the brain regions, predominating absence of damage on the findings.

  2. Melatonin Improves Outcomes of Heatstroke in Mice by Reducing Brain Inflammation and Oxidative Damage and Multiple Organ Dysfunction

    Directory of Open Access Journals (Sweden)

    Yu-Feng Tian

    2013-01-01

    Full Text Available We report here that when untreated mice underwent heat stress, they displayed thermoregulatory deficit (e.g., animals display hypothermia during room temperature exposure, brain (or hypothalamic inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment (e.g., decreased plasma levels of both adrenocorticotrophic hormone and corticosterone during heat stress, multiple organ dysfunction or failure, and lethality. Melatonin therapy significantly reduced the thermoregulatory deficit, brain inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment, multiple organ dysfunction, and lethality caused by heat stroke. Our data indicate that melatonin may improve outcomes of heat stroke by reducing brain inflammation, oxidative damage, and multiple organ dysfunction.

  3. Radial bisection of words and lines in right-brain-damaged patients with spatial neglect.

    Science.gov (United States)

    Veronelli, Laura; Arduino, Lisa S; Girelli, Luisa; Vallar, Giuseppe

    2017-09-01

    The bisection of lines positioned radially (with the two ends of the line close and far, with respect to the participant's body) has been less investigated than that of lines placed horizontally (with their two ends left and right, with respect to the body's midsagittal plane). In horizontal bisection, patients with left neglect typically show a rightward bias for both lines and words, greater with longer stimuli. As for radial bisection, available data indicate that neurologically unimpaired participants make a distal error, while results from right-brain-damaged patients with left spatial neglect are contradictory. We investigated the bisection of radially oriented words, with the prediction that, during bisection, linguistic material would be recoded to its canonical left-to-right format in reading, with the performance of neglect patients being similar to that for horizontal words. Thirteen right-brain-damaged patients (seven with left spatial neglect) and fourteen healthy controls were asked to manually bisect 40 radial and 40 horizontal words (5-10 letters), and 80 lines, 40 radial and 40 horizontal, of comparable length. Right-brain-damaged patients with spatial neglect exhibited a proximal bias in the bisection of short radial words, with the proximal part corresponding to the final right part of horizontally oriented words. This proximal error was not found in patients without neglect and healthy controls. For bisection, short radial words may be recoded to the canonical orthographic horizontal format, unveiling the impact of left neglect on radially oriented stimuli. © 2015 The British Psychological Society.

  4. Protective role for type 4 metabotropic glutamate receptors against ischemic brain damage.

    Science.gov (United States)

    Moyanova, Slavianka G; Mastroiacovo, Federica; Kortenska, Lidia V; Mitreva, Rumiana G; Fardone, Erminia; Santolini, Ines; Sobrado, Mónica; Battaglia, Giuseppe; Bruno, Valeria; Nicoletti, Ferdinando; Ngomba, Richard T

    2011-04-01

    We examined the influence of type 4 metabotropic glutamate (mGlu4) receptors on ischemic brain damage using the permanent middle cerebral artery occlusion (MCAO) model in mice and the endothelin-1 (Et-1) model of transient focal ischemia in rats. Mice lacking mGlu4 receptors showed a 25% to 30% increase in infarct volume after MCAO as compared with wild-type littermates. In normal mice, systemic injection of the selective mGlu4 receptor enhancer, N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-caboxamide (PHCCC; 10  mg/kg, subcutaneous, administered once 30  minutes before MCAO), reduced the extent of ischemic brain damage by 35% to 45%. The drug was inactive in mGlu4 receptor knockout mice. In the Et-1 model, PHCCC administered only once 20  minutes after ischemia reduced the infarct volume to a larger extent in the caudate/putamen than in the cerebral cortex. Ischemic rats treated with PHCCC showed a faster recovery of neuronal function, as shown by electrocorticographic recording and by a battery of specific tests, which assess sensorimotor deficits. These data indicate that activation of mGlu4 receptors limit the development of brain damage after permanent or transient focal ischemia. These findings are promising because selective mGlu4 receptor enhancers are under clinical development for the treatment of Parkinson's disease and other central nervous system disorders.

  5. Does alcohol damage the adolescent brain? Neuroanatomical and neuropsychological consequences of adolescent drinking

    Directory of Open Access Journals (Sweden)

    Fleming RL

    2015-12-01

    Full Text Available Rebekah L Fleming1,2 1Durham VA Medical Center, 2Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA Abstract: Alcohol drinking is a significant risk factor for morbidity and mortality in adolescents worldwide. Adolescents frequently binge drink, and this pattern of use is associated with poor school performance, injuries, violence, drug use, and a variety of poor psychosocial outcomes in adulthood. These associations have raised concerns that alcohol drinking may damage the adolescent brain and lead to impaired cognition and behavior. Similar to the neurotoxicity seen in adult alcoholics, magnetic resonance imaging studies of brain anatomy in adolescent drinkers have shown that alcohol disrupts the development of temporal and frontal cortices and myelinated fiber tracts throughout the brain. Although adult brains show some recovery with abstinence, at present, no studies have examined brain recovery in adolescents. Studies of neuropsychological function have found deficits in attention and visuospatial ability that show dose-dependent correlations with alcohol exposure and withdrawal symptoms, but visuospatial performance recovers with short-term abstinence. Differences in executive function and decision-making have also been found, but the available evidence suggests that these are not primarily the result of alcohol exposure; instead, they reflect premorbid factors that increase risk-taking and substance use. Nevertheless, alcohol drinking by adolescents remains an important concern because of the potential for brain injury in addition to the many negative consequences associated with acute intoxication. Keywords: adolescence, binge drinking, alcohol, magnetic resonance imaging, neuropsychological function

  6. Frontal White Matter Damage Impairs Response Inhibition in Children Following Traumatic Brain Injury

    Science.gov (United States)

    Lipszyc, Jonathan; Levin, Harvey; Hanten, Gerri; Hunter, Jill; Dennis, Maureen; Schachar, Russell

    2014-01-01

    Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition. PMID:24618405

  7. Ischemic Preconditioning Blunts Muscle Damage Responses Induced by Eccentric Exercise.

    Science.gov (United States)

    Franz, Alexander; Behringer, Michael; Harmsen, Jan-Frieder; Mayer, Constantin; Krauspe, Rüdiger; Zilkens, Christoph; Schumann, Moritz

    2017-08-22

    Ischemic preconditioning (IPC) is known to reduce muscle damage induced by ischemia and reperfusion-injury (I/R-Injury) during surgery. Due to similarities between the pathophysiological formation of I/R-injury and eccentric exercise-induced muscle damage (EIMD), as characterized by an intracellular accumulation of Ca, an increased production of reactive oxygen species and increased pro-inflammatory signaling, the purpose of the present study was to investigate whether IPC performed prior to eccentric exercise may also protect against EIMD. Nineteen healthy men were matched to an eccentric only (ECC) (n=9) or eccentric proceeded by IPC group (IPC+ECC) (n=10). The exercise protocol consisted of bilateral biceps curls (3x10 repetitions at 80% of the concentric 1RM). In IPC+ECC, IPC was applied bilaterally at the upper arms by a tourniquet (200 mmHg) immediately prior to the exercise (3x5 minutes of occlusion, separated by 5 minutes of reperfusion). Creatine Kinase (CK), arm circumference, subjective pain (VAS score) and radial displacement (Tensiomyography, Dm) were assessed before IPC, pre-exercise, post-exercise, 20 minutes-, 2 hours-, 24 hours-, 48 hours- and 72 hours post-exercise. CK differed from baseline only in ECC at 48h (pexercise. After 24h, 48h and 72h, CK was increased in ECC compared to IPC+ECC (between groups: 24h: p=0.004, 48h: pexercise, when compared to IPC+ECC (between groups: all pexercise days in ECC (all peccentric exercise of the elbow flexors blunts EIMD and exercise-induced pain, while maintaining the contractile properties of the muscle.

  8. TRPM2 channels mediate acetaminophen-induced liver damage.

    Science.gov (United States)

    Kheradpezhouh, Ehsan; Ma, Linlin; Morphett, Arthur; Barritt, Greg J; Rychkov, Grigori Y

    2014-02-25

    Acetaminophen (paracetamol) is the most frequently used analgesic and antipyretic drug available over the counter. At the same time, acetaminophen overdose is the most common cause of acute liver failure and the leading cause of chronic liver damage requiring liver transplantation in developed countries. Acetaminophen overdose causes a multitude of interrelated biochemical reactions in hepatocytes including the formation of reactive oxygen species, deregulation of Ca(2+) homeostasis, covalent modification and oxidation of proteins, lipid peroxidation, and DNA fragmentation. Although an increase in intracellular Ca(2+) concentration in hepatocytes is a known consequence of acetaminophen overdose, its importance in acetaminophen-induced liver toxicity is not well understood, primarily due to lack of knowledge about the source of the Ca(2+) rise. Here we report that the channel responsible for Ca(2+) entry in hepatocytes in acetaminophen overdose is the Transient Receptor Potential Melanostatine 2 (TRPM2) cation channel. We show by whole-cell patch clamping that treatment of hepatocytes with acetaminophen results in activation of a cation current similar to that activated by H2O2 or the intracellular application of ADP ribose. siRNA-mediated knockdown of TRPM2 in hepatocytes inhibits activation of the current by either acetaminophen or H2O2. In TRPM2 knockout mice, acetaminophen-induced liver damage, assessed by the blood concentration of liver enzymes and liver histology, is significantly diminished compared with wild-type mice. The presented data strongly suggest that TRPM2 channels are essential in the mechanism of acetaminophen-induced hepatocellular death.

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

    Institute of Scientific and Technical Information of China (English)

    Jieying Lin; Niyang Lin

    2006-01-01

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

  10. Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Wei-Ming Lin

    2014-01-01

    Full Text Available The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI. However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.

  11. Effect of lacosamide on structural damage and functional recovery after traumatic brain injury in rats.

    Science.gov (United States)

    Pitkänen, A; Immonen, R; Ndode-Ekane, X; Gröhn, O; Stöhr, T; Nissinen, J

    2014-05-01

    In a subgroup of patients, traumatic brain injury (TBI) results in the occurrence of acute epileptic seizures or even status epilepticus, which are treated with antiepileptic drugs (AEDs). Recent experimental data, however, suggest that administration of AEDs at the early post-injury phase can compromise the recovery process. The present study was designed to assess the profile of a novel anticonvulsant, lacosamide (Vimpat) on post-TBI structural, motor and cognitive outcomes. Moderate TBI was induced by lateral fluid-percussion injury in adult rats. Treatment with 0.9% saline or lacosamide (30 mg/kg, i.p.) was started at 30 min post-injury and continued at 8h intervals for 3d (total daily dose 90 mg/kg/d). Rats were randomly assigned to 4 treatment groups: sham-operated controls treated with vehicle (Sham-Veh) or lacosamide (Sham-LCM) and injured animals treated with vehicle (TBI-Veh) or lacosamide (TBI-LCM). As functional outcomes we tested motor recovery with composite neuroscore and beam-walking at 2, 7, and 15 d post-injury. Cognitive recovery was tested with the Morris water-maze at 12-14 d post-TBI. To assess the structural outcome, animals underwent magnetic resonance imaging (MRI) at 2 d post-TBI. At 16d post-TBI, rats were perfused for histology to analyze cortical and hippocampal neurodegeneration and axonal damage. Our data show that at 2 d post-TBI, both the TBI-Veh and TBI-LCM groups were equally impaired in neuroscore. Thereafter, motor recovery occurred similarly during the first week. At 2 wk post-TBI, recovery of the TBI-LCM group lagged behind that in the TBI-VEH group (p<0.05). Performance in beam-walking did not differ between the TBI-Veh and TBI-LCM groups. Both TBI groups were similarly impaired in the Morris water-maze at 2 wk post-TBI. MRI and histology did not reveal any differences in the cortical or hippocampal damage between the TBI-Veh and TBI-LCM groups. Taken together, acute treatment with LCM had no protective effects on post

  12. 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

  13. 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.

  14. Influence of a brief episode of anesthesia during the induction of experimental brain trauma on secondary brain damage and inflammation.

    Directory of Open Access Journals (Sweden)

    Clara Luh

    Full Text Available It is unclear whether a single, brief, 15-minute episode of background anesthesia already modulates delayed secondary processes after experimental brain injury. Therefore, this study was designed to characterize three anesthesia protocols for their effect on molecular and histological study endpoints. Mice were randomly separated into groups that received sevoflurane (sevo, isoflurane (iso or an intraperitoneal anesthetic combination (midazolam, fentanyl and medetomidine; comb prior to traumatic brain injury (controlled cortical impact, CCI; 8 m/s, 1 mm impact depth, 3 mm diameter. Twenty-four hours after insult, histological brain damage, neurological function (via neurological severity score, cerebral inflammation (via real-time RT-PCR for IL6, COX-2, iNOS and microglia (via immunohistochemical staining for Iba1 were determined. Fifteen minutes after CCI, the brain contusion volume did not differ between the anesthetic regimens (sevo = 17.9±5.5 mm(3; iso = 20.5±3.7 mm(3; comb = 19.5±4.6 mm(3. Within 24 hours after injury, lesion size increased in all groups (sevo = 45.3±9.0 mm(3; iso = 31.5±4.0 mm(3; comb = 44.2±6.2 mm(3. Sevo and comb anesthesia resulted in a significantly larger contusion compared to iso, which was in line with the significantly better neurological function with iso (sevo = 4.6±1.3 pts.; iso = 3.9±0.8 pts.; comb = 5.1±1.6 pts.. The expression of inflammatory marker genes was not significantly different at 15 minutes and 24 hours after CCI. In contrast, significantly more Iba1-positive cells were present in the pericontusional region after sevo compared to comb anesthesia (sevo = 181±48/mm(3; iso = 150±36/mm(3; comb = 113±40/mm(3. A brief episode of anesthesia, which is sufficient for surgical preparations of mice for procedures such as delivering traumatic brain injury, already has a significant impact on the extent of secondary brain damage.

  15. Earthquake-induced Landslidingand Ground Damage In New Zealand

    Science.gov (United States)

    Hancox, G. T.; Perrin, N. D.; Dellow, G. D.

    A study of landsliding caused by 22 historical earthquakes in New Zealand was completed at the end of 1997 (Hancox et al., 1997). The main aims of that study were to determine: (a) the nature and extent of landsliding and other ground damage (sand boils, subsidence and lateral spreading due to soil liquefaction) caused by historical earthquakes; (b) relationships between landsliding and earthquake magnitude, epicentre, faulting, geology and topography; (c) improved environmental criteria and ground classes for assigning MM intensities and seismic hazard assessments in N.Z. The data and results of the 1997 study have recently been summarised and expanded (Hancox et al., in press), and are described in this paper. Relationships developed from these studies indicate that the minimum magnitude for earthquake-induced landsliding (EIL) in N.Z. is about M 5, with significant landsliding occurring at M 6 or greater. The minimum MM intensity for landsliding is MM6, while the most common intensities for significant landsliding are MM7-8. The intensity threshold for soil liquefaction in New Zealand was found to be MM7 for sand boils, and MM8 for lateral spreading, although such effects may also occur at one intensity level lower in highly susceptible materials. The minimum magnitude for liquefaction phenomena in N.Z. is about M 6, compared to M 5 overseas where highly susceptible soils are probably more widespread. Revised environmental response criteria (landsliding, subsidence, liquefaction-induced sand boils and lateral spreading) have also been established for the New Zealand MM Intensity Scale, and provisional landslide susceptibility Ground Classes developed for assigning MM intensities in areas where there are few buildings. Other new data presented include a size/frequency distribution model for earthquake-induced landslides over the last 150 years and a preliminary EIL Opportunity model for N.Z. The application of EIL data and relationships for seismic hazard

  16. DNA damage and mutations induced by arachidonic acid peroxidation.

    Science.gov (United States)

    Lim, Punnajit; Sadre-Bazzaz, Kianoush; Shurter, Jesse; Sarasin, Alain; Termini, John

    2003-12-30

    Endogenous cellular oxidation of omega6-polyunsaturated fatty acids (PUFAs) has long been recognized as a contributing factor in the development of various cancers. The accrual of DNA damage as a result of reaction with free radical and electrophilic aldehyde products of lipid peroxidation is believed to be involved; however, the genotoxic and mutation-inducing potential of specific membrane PUFAs remains poorly defined. In the present study we have examined the ability of peroxidizing arachidonic acid (AA, 20:4omega6) to induce DNA strand breaks, base modifications, and mutations. The time-dependent induction of single-strand breaks and oxidative base modifications by AA in genomic DNA was quantified using denaturing glyoxal gel electrophoresis. Mutation spectra were determined in XP-G fibroblasts and a repair-proficient line corrected for this defect by c-DNA complementation (XP-G(+)). Mutation frequencies were elevated from approximately 5- to 30-fold over the background following reaction of DNA with AA for various times. The XPG gene product was found to be involved in the suppression of mutations after extended reaction of DNA with AA. Arachidonic acid-induced base substitutions were consistent with the presence of both oxidized and aldehyde base adducts in DNA. The frequency of multiple-base substitutions induced by AA was significantly reduced upon correction for the XPG defect (14% vs 2%, P = 0.0015). Evidence is also presented which suggests that the induced frequency of multiple mutations is lesion dependent. These results are compared to published data for mutations stimulated by alpha,beta-unsaturated aldehydes identified as products of lipid peroxidation.

  17. Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2

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    Little Morgan R

    2010-06-01

    Full Text Available Abstract Background Using a murine model of herpes simplex virus (HSV-1 encephalitis, our laboratory has determined that induction of proinflammatory mediators in response to viral infection is largely mediated through a Toll-like receptor-2 (TLR2-dependent mechanism. Published studies have shown that, like other inflammatory mediators, reactive oxygen species (ROS are generated during viral brain infection. It is increasingly clear that ROS are responsible for facilitating secondary tissue damage during central nervous system infection and may contribute to neurotoxicity associated with herpes encephalitis. Methods Purified microglial cell and mixed neural cell cultures were prepared from C57B/6 and TLR2-/- mice. Intracellular ROS production in cultured murine microglia was measured via 2', 7'-Dichlorofluorescin diacetate (DCFH-DA oxidation. An assay for 8-isoprostane, a marker of lipid peroxidation, was utilized to measure free radical-associated cellular damage. Mixed neural cultures obtained from β-actin promoter-luciferase transgenic mice were used to detect neurotoxicity induced by HSV-infected microglia. Results Stimulation with HSV-1 elevated intracellular ROS in wild-type microglial cell cultures, while TLR2-/- microglia displayed delayed and attenuated ROS production following viral infection. HSV-infected TLR2-/- microglia produced less neuronal oxidative damage to mixed neural cell cultures in comparison to HSV-infected wild-type microglia. Further, HSV-infected TLR2-/- microglia were found to be less cytotoxic to cultured neurons compared to HSV-infected wild-type microglia. These effects were associated with decreased activation of p38 MAPK and p42/p44 ERK in TLR2-/- mice. Conclusions These studies demonstrate the importance of microglial cell TLR2 in inducing oxidative stress and neuronal damage in response to viral infection.

  18. Knee proprioception after exercise-induced muscle damage.

    Science.gov (United States)

    Torres, R; Vasques, J; Duarte, J A; Cabri, J M H

    2010-06-01

    The purpose of the present study was to investigate whether exercise-induced quadriceps muscle damage affects knee proprioception such as joint position sense (JPS), force sense and the threshold to detect passive movement (TTDPM). Fourteen young men performed sets of eccentric quadriceps contractions at a target of 60% of the maximal concentric peak torque until exhaustion; the exercise was interrupted whenever the subject could not complete two sets. Muscle soreness, JPS, the TTDPM and force sense were examined before the exercise as well as one, 24, 48, 72 and 96 h after exercise. The results were compared using one-way repeated-measure ANOVA. Plasma CK activity, collected at the same times, was analyzed by the Friedman's test to discriminate differences between baseline values and each of the other assessment moments (pknee flexion and force sense were significantly decreased up to 48 h, whereas TTDPM decreased significantly at only one hour and 24 h after exercise, at 30 and 70 degrees of the knee flexion, respectively. The results allow the conclusion that eccentric exercise leading to muscle damage alters joint proprioception, suggesting that there might be impairment in the intrafusal fibres of spindle muscles and in the tendon organs.

  19. Protection of cadmium chloride induced DNA damage by Lamiaceae plants

    Institute of Scientific and Technical Information of China (English)

    Ramaraj Thirugnanasampandan; Rajarajeswaran Jayakumar

    2011-01-01

    Objective: To analyze the total phenolic content, DNA protecting and radical scavenging activity of ethanolic leaf extracts of three Lamiaceae plants, i.e. Anisomelos malabarica (A. malabarica), Leucas aspera (L. aspera) and Ocimum basilicum (O. basilicum). Methods: The total polyphenols and flavonoids were analyzed in the ethanolic leaf extracts of the lamiaceae plants. To determine the DNA protecting activity, various concentrations of the plant extracts were prepared and treated on cultured HepG2 human lung cancer cells. The pretreated cells were exposed to H2O2 to induce DNA damage through oxidative stress. Comet assay was done and the tail length of individual comets was measured. Nitric oxide and superoxide anion scavenging activities of lamiaceae plants were analyzed. Results: Among the three plant extracts, the highest amount of total phenolic content was found in O. basilicum (189.33 mg/g), whereas A. malabarica showed high levels of flavonoids (10.66 mg/g). O. basilicum also showed high levels of DNA protecting (85%) and radical scavenging activity. Conclusions: The results of this study shows that bioactive phenols present in lamiaceae plants may prevent carcinogenesis through scavenging free radicals and inhibiting DNA damage.

  20. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2011-01-01

    Full Text Available Reactive oxygen species (ROS, including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress.

  1. X-Ray induced DNA damage – why use plants?

    Directory of Open Access Journals (Sweden)

    John William Einset

    2015-06-01

    Full Text Available The comet assay was used to monitor DNA repair after X-ray exposures caused by 0.2-15 Gy. A clear distinction in the time course of DNA repair after 2 Gy was observed with an early ‘rapid phase’, lasting 20-40 minutes, being followed by a ‘slow phase’ which actually consists of a period of negligible repair and then rapid repair during 140-160 minutes. The fact that homozygous mutants for both ATM and BRCA1 fail to repair DNA completely during 3 hours after 2 Gy exposures indicates that repair processes occurring during the ‘slow phase’ involve ds breaks in DNA. Both BRCA1 and Rad51 expression are strongly upregulated by X-rays in Arabidopsis. Rye grass, Norway spruce and Sawara cypress also have ‘slow phase’ repair similar to Arabidopsis, suggesting that the requisite enzymes have to be induced in these plants as well. To look at the effect of genome size in relation to sensitivity to DNA damage, we exposed isolated nuclei from Norway spruce (19.2 Gbp genome, celery (14.1 Gbp, spinach (12.6 Gbp Sawara cypress (8.9 Gbp, lettuce (2.6 Gbp and Arabidopsis (0.135 Gbp to X-rays. After a 1 Gy exposure, a linear relationship was seen between % tails and genome size, confirming the idea that larger genomes are more sensitive to X-ray damage.

  2. Limits for Beam-Induced Damage: Reckless or too Cautious?

    CERN Document Server

    Bertarelli, A; Carra, F; Cerutti, F; Dallocchio, A; Mariani, N; Peroni, L; Scapin, M

    2011-01-01

    Accidental events implying direct beam impacts on collimators are of the utmost importance as they may lead to serious limitations of the overall LHC Performance. In order to assess damage threshold of components impacted by high energy density beams, entailing changes of phase and extreme pressures, state-of-the-art numerical simulation methods are required. In this paper, a review of the different dynamic response regimes induced by particle beams is given along with an indication of the most suited tools to treat each regime. Particular attention is paid to the most critical case, that of shock waves, for which standard Finite Element codes are totally unfit. A novel category of numerical tools, named Hydrocodes, has been adapted and used to analyse the consequences of an asynchronous beam abort on Phase 1 Tertiary Collimators (TCT). A number of simulations has been carried out with varying beam energy, number of bunches and bunch sizes allowing to identify different damage levels for the TCT up to catastr...

  3. Limits for Beam Induced Damage: Reckless or too Cautious?

    CERN Document Server

    Bertarelli, A; Carra, F; Cerutti, F; Dallocchio, A; Mariani, N; Peroni, L; Scapin, M

    2011-01-01

    Accidental events implying direct beam impacts on collimators are of the utmost importance as they may lead to serious limitations of the overall LHC Performance. In order to assess damage threshold of components impacted by high energy density beams, entailing changes of phase and extreme pressures, state-of-the-art numerical simulation methods are required. In this paper, a review of the different dynamic response regimes induced by particle beams is given along with an indication of the most suited tools to treat each regime. Particular attention is paid to the most critical case, that of shock waves, for which standard Finite Element codes are totally unfit. A novel category of numerical tools, named Hydrocodes, has been adapted and used to analyse the consequences of an asynchronous beam abort on Phase 1 Tertiary Collimators (TCT). A number of simulations has been carried out with varying beam energy, number of bunches and bunch sizes allowing to identify different damage levels for the TCT up to catastr...

  4. A Programmed Training Technique That Uses Reinforcement to Facilitate Acquisition and Retention in Brain-Damaged Patients

    Science.gov (United States)

    Dolan, Michael P.; Norton, James C.

    1977-01-01

    Hospitalized brain-damaged patients were Ss in a study designed to evaluate the effectiveness of a treatment technique used with contingent reinforcement to facilitate acquisition and retention of environmentally relevant information. (Editor)

  5. Sonic-boom-induced building structure responses including damage.

    Science.gov (United States)

    Clarkson, B. L.; Mayes, W. H.

    1972-01-01

    Concepts of sonic-boom pressure loading of building structures and the associated responses are reviewed, and results of pertinent theoretical and experimental research programs are summarized. The significance of sonic-boom load time histories, including waveshape effects, are illustrated with the aid of simple structural elements such as beams and plates. Also included are discussions of the significance of such other phenomena as three-dimensional loading effects, air cavity coupling, multimodal responses, and structural nonlinearities. Measured deflection, acceleration, and strain data from laboratory models and full-scale building tests are summarized, and these data are compared, where possible, with predicted values. Damage complaint and claim experience due both to controlled and uncontrolled supersonic flights over communities are summarized with particular reference to residential, commercial, and historic buildings. Sonic-boom-induced building responses are compared with those from other impulsive loadings due to natural and cultural events and from laboratory simulation tests.

  6. Relationship between skull asymmetry and CT findings. Supine head position preference and brain damage

    Energy Technology Data Exchange (ETDEWEB)

    Yamori, Yuriko; Yuge, Mariko; Kanda, Toyoko; Ashida, Hiromi; Fukase, Hiroshi

    1987-07-01

    In order to clarify the relationship between brain damage and skull asymmetry or supine head position preference, we classified CT findings of 330 cases with cerebral palsy or risk of motor disturbance into 6 groups according to skull shape. Those were severe (I, n = 37) and mild (II, n = 114) grades in the right occipital flatness, severe (III, n = 34) and mild (IV, n = 58) grades in the left occipital flatness, long skull with temporal flatness (V, n = 33) and symmetric round skull (control, n = 54). It was considered that the asymmetry of cortical atrophy in appearance was formed physicaly by skull asymmetry but that the asymmetric dilatation in appearance of lateral ventricle was related to the asymmetry of brain damage. The severity and the asymmetry of brain damage were tend to increase the grade of skull asymmetry. The incidence of cases with the right occipital flatness was 1.6 times more frequently than the left sided. The incidence of cases whose left (lateral) ventricle was larger than the right was 4.1 times more than the cases whose right ventricle was larger than the left. The cases with occipital flatness in the contralateral side of the larger lateral ventricle were found more than the cases with occipital flatness in the ipsilateral side of the larger ventricle, that is to say, the direction of supine head position preference during early infant was suspected to be the more severely disturbed side of body. These results suggest that the supine head position preference to the right in newborn babies and infants with scoliosis or cerebral palsy might be the result of transient or permanent asymmetric (left > right) brain dysfunction.

  7. Bisecting real and fake body parts: effects of prism adaptation after right brain damage.

    Science.gov (United States)

    Bolognini, Nadia; Casanova, Debora; Maravita, Angelo; Vallar, Giuseppe

    2012-01-01

    The representation of body parts holds a special status in the brain, due to their prototypical shape and the contribution of multisensory (visual and somatosensory-proprioceptive) information. In a previous study (Sposito et al., 2010), we showed that patients with left unilateral spatial neglect exhibit a rightward bias in setting the midpoint of their left forearm, which becomes larger when bisecting a cylindrical object comparable in size. This body part advantage, found also in control participants, suggests partly different processes for computing the extent of body parts and objects. In this study we tested 16 right-brain-damaged patients, and 10 unimpaired participants, on a manual bisection task of their own (real) left forearm, or a size-matched fake forearm. We then explored the effects of adaptation to rightward displacing prism exposure, which brings about leftward aftereffects. We found that all participants showed prism adaptation (PA) and aftereffects, with right-brain-damaged patients exhibiting a reduction of the rightward bias for both real and fake forearm, with no overall differences between them. Second, correlation analyses highlighted the role of visual and proprioceptive information for the metrics of body parts. Third, single-patient analyses showed dissociations between real and fake forearm bisections, and the effects of PA, as well as a more frequent impairment with fake body parts. In sum, the rightward bias shown by right-brain-damaged patients in bisecting body parts is reduced by prism exposure, as other components of the neglect syndrome; discrete spatial representations for real and fake body parts, for which visual and proprioceptive codes play different roles, are likely to exist. Multisensory information seems to render self bodily segments more resistant to the disruption brought about by right-hemisphere injury.

  8. Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate.

    Science.gov (United States)

    Ayyappan, Prathapan; Palayyan, Salin Raj; Kozhiparambil Gopalan, Raghu

    2016-01-01

    Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications.

  9. Ecabet sodium alleviates neomycin-induced hair cell damage.

    Science.gov (United States)

    Rah, Yoon Chan; Choi, June; Yoo, Myung Hoon; Yum, Gunhwee; Park, Saemi; Oh, Kyoung Ho; Lee, Seung Hoon; Kwon, Soon Young; Cho, Seung Hyun; Kim, Suhyun; Park, Hae-Chul

    2015-12-01

    Ecabet sodium (ES) is currently applied to some clinical gastrointestinal disease primarily by the inhibition of the ROS production. In this study, the protective role of ES was evaluated against the neomycin-induced hair cell loss using zebrafish experimental animal model. Zebrafish larvae (5-7 dpf), were treated with each of the following concentrations of ES: 5, 10, 20, 40, and 80 μg/mL for 1 h, followed by 125 μM neomycin for 1h. The positive control group was established by 125 μM neomycin-only treatment (1h) and the negative control group with no additional chemicals was also established. Hair cells inside four neuromasts ( SO1, SO2, O1, OC1) were assessed using fluorescence microscopy (n = 10). Hair cell survival was calculated as the mean number of viable hair cells for each group. Apoptosis and mitochondrial damage were investigated using special staining (TUNEL and DASPEI assay, respectively), and compared among groups. Ultrastructural changes were evaluated using scanning electron microscopy. Pre-treatment group with ES increased the mean number of viable hair cells as a dose-dependent manner achieving almost same number of viable hair cells with 40 μM/ml ES treatment (12.98 ± 2.59 cells) comparing to that of the negative control group (14.15 ± 1.39 cells, p = 0.72) and significantly more number of viable hair cells than that of the positive control group (7.45 ± 0.91 cells, p neomycin treatment than the negative control group and significantly decreased down to 105% with the pre-treatment with 40 μM/ml ES (n = 40, p = 0.04). A significantly less number of TUNEL-positive cells (reflecting apoptosis, p neomycin-induced hair cell loss possibly by reducing apoptosis, mitochondrial damages, and the ROS generation.

  10. Role of Oxidative Damage in Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

  11. Pyrosequencing: applicability for studying DNA damage-induced mutagenesis.

    Science.gov (United States)

    Minko, Irina G; Earley, Lauriel F; Larlee, Kimberly E; Lin, Ying-Chih; Lloyd, R Stephen

    2014-10-01

    Site-specifically modified DNAs are routinely used in the study of DNA damage-induced mutagenesis. These analyses involve the creation of DNA vectors containing a lesion at a pre-determined position, DNA replication, and detection of mutations at the target site. The final step has previously required the isolation of individual DNA clones, hybridization with radioactively labeled probes, and verification of mutations by Sanger sequencing. In the search for an alternative procedure that would allow direct quantification of sequence variants in a mixed population of DNA molecules, we evaluated the applicability of pyrosequencing to site-specific mutagenesis assays. The progeny DNAs were analyzed that originated from replication of N(6) -(deoxy-D-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine (MeFapy-dG)-containing vectors in primate cells, with the lesion being positioned in the 5'-GCNGG-3' sequence context. Pyrosequencing detected ∼8% G to T transversions and ∼3.5% G to A transitions, a result that was in excellent agreement with frequencies previously measured by the standard procedure (Earley LF et al. [2013]: Chem Res Toxicol 26:1108-1114). However, ∼3.5% G to C transversions and ∼2.0% deletions could not be detected by pyrosequencing. Consistent with these observations, the sensitivity of pyrosequencing for measuring the single deoxynucleotide variants differed depending on the deoxynucleotide identity, and in the given sequence contexts, was determined to be ∼1-2% for A and T and ∼5% for C. Pyrosequencing of other DNA isolates that were obtained following replication of MeFapy-dG-containing vectors in primate cells or Escherichia coli, identified several additional limitations. Collectively, our data demonstrated that pyrosequencing can be used for studying DNA damage-induced mutagenesis as an effective complementary experimental approach to current protocols.

  12. Shortwave UV-induced damage as part of the solar damage spectrum is not a major contributor to mitochondrial dysfunction.

    Science.gov (United States)

    Gebhard, Daniel; Matt, Katja; Burger, Katharina; Bergemann, Jörg

    2014-06-01

    Because of the absence of a nucleotide excision repair in mitochondria, ultraviolet (UV)-induced bulky mitochondrial DNA (mtDNA) lesions persist for several days before they would eventually be removed by mitophagy. Long persistence of this damage might disturb mitochondrial functions, thereby contributing to skin ageing. In this study, we examined the influence of shortwave UV-induced damage on mitochondrial parameters in normal human skin fibroblasts. We irradiated cells with either sun-simulating light (SSL) or with ultraviolet C to generate bulky DNA lesions. At equivalent antiproliferative doses, both irradiation regimes induced gene expression of mitochondrial transcription factor A (TFAM) and matrix metallopeptidase 1 (MMP-1). Only irradiation with SSL, however, caused significant changes in mtDNA copy number and a decrease in mitochondrial respiration. Our results indicate that shortwave UV-induced damage as part of the solar spectrum is not a major contributor to mitochondrial dysfunction.

  13. Influence of Ambient Temperature on Nanosecond and Picosecond Laser-Induced Bulk Damage of Fused Silica

    Directory of Open Access Journals (Sweden)

    L. Yang

    2014-01-01

    Full Text Available The nanosecond (ns and picosecond (ps pulsed laser-induced damage behaviors of fused silica under cryogenic and room temperature have been investigated. The laser-induced damage threshold (LIDT and damage probability are used to understand the damage behavior at different ambient temperatures. The results show that the LIDTs for both ns and ps slightly increased at cryogenic temperature compared to that at room temperature. Meanwhile, the damage probability has an inverse trend; that is, the damage probability at low temperature is smaller than that at room temperature. A theoretical model based on heated crystal lattice is well consistent with the experimental results.

  14. Early transient mild hypothermia attenuates neurological deficits and brain damage after experimental subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Lilla, Nadine; Rinne, Christoph; Weiland, Judith; Linsenmann, Thomas; Ernestus, Ralf-Ingo; Westermaier, Thomas

    2017-09-23

    Metabolic exhaustion in ischemic tissue is the basis for a detrimental cascade of cell damage. In the acute stage of subarachnoid hemorrhage (SAH), a sequence of global and focal ischemia occurs, threatening brain tissue to undergo ischemic damage. This study was conducted to investigate whether early therapy with moderate hypothermia can offer neuroprotection after experimental SAH. 20 male Sprague-Dawley rats were subjected to SAH and treated by active cooling (34° C) or served as controls by continuous maintenance of normothermia (37.0° C). Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local cerebral blood flow (CBF) over both hemispheres were continuously measured. Neurological assessment was performed 24 hours later. Hippocampal damage was assessed by hematoxylin and eosin and Caspase-3 staining. By a slight increase of MABP in the cooling phase and a significant reduction of ICP, hypothermia improved cerebral perfusion pressure (CPP) in the first 60 minutes after SAH. Accordingly, a trend to increased CBF was observed during this period. The rate of injured neurons was significantly reduced in hypothermia-treated animals compared to normothermic controls. The results of this series cannot finally answer whether this form of treatment permanently attenuates or only delays ischemic damage. In the latter case, slowing down metabolic exhaustion by hypothermia may still be a valuable treatment during this state of ischemic brain damage and prolong the therapeutic window for possible causal treatments of the acute perfusion deficit. Therefore, it may be useful as a first-tier therapy in suspected SAH. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Calcium antagonists decrease capillary wall damage in aging hypertensive rat brain

    NARCIS (Netherlands)

    Farkas, E.; de Jong, G.I.; Apro, E.; Keuker, J.I.H.; Luiten, P.G.M.

    2001-01-01

    Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillar

  16. Uptake of radiolabeled ions in normal and ischemia-damaged brain

    Energy Technology Data Exchange (ETDEWEB)

    Dienel, G.A.; Pulsinelli, W.A.

    1986-05-01

    The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (/sup 63/Ni, /sup 99/TcO/sub 4/, /sup 22/Na, and (/sup 3/H)tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater than in normal tissue. The concentrations of /sup 65/Zn, /sup 59/Fe, /sup 32/PO/sub 4/, and /sup 147/Pm in postischemic brain were similar to or less than those in normal brain. The concentration of (14C)EDTA was increased in injured and uninjured brain of postischemic rats. Autoradiographic analysis of the distribution patterns of some of these ions in normal animals showed that /sup 99/TcO/sub 4/, /sup 22/Na, /sup 65/Zn, and /sup 59/Fe were distributed more uniformly throughout the brain than were /sup 32/PO/sub 4/, /sup 63/Ni, and /sup 147/Pm. At 24 or 48 hours after ischemia, /sup 63/Ni, /sup 99/TcO/sub 4/, and /sup 22/Na were preferentially concentrated in the damaged striatum and hippocampus, whereas /sup 65/Zn, /sup 59/Fe, /sup 32/PO/sub 4/, and /sup 147/Pm did not accumulate in irreversibly injured tissue. Of the radiochemicals tested to date, Ni, TcO/sub 4/, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography.

  17. Frequency and Type of Situational Awareness Errors Contributing to Death and Brain Damage: A Closed Claims Analysis.

    Science.gov (United States)

    Schulz, Christian M; Burden, Amanda; Posner, Karen L; Mincer, Shawn L; Steadman, Randolph; Wagner, Klaus J; Domino, Karen B

    2017-08-01

    Situational awareness errors may play an important role in the genesis of patient harm. The authors examined closed anesthesia malpractice claims for death or brain damage to determine the frequency and type of situational awareness errors. Surgical and procedural anesthesia death and brain damage claims in the Anesthesia Closed Claims Project database were analyzed. Situational awareness error was defined as failure to perceive relevant clinical information, failure to comprehend the meaning of available information, or failure to project, anticipate, or plan. Patient and case characteristics, primary damaging events, and anesthesia payments in claims with situational awareness errors were compared to other death and brain damage claims from 2002 to 2013. Anesthesiologist situational awareness errors contributed to death or brain damage in 198 of 266 claims (74%). Respiratory system damaging events were more common in claims with situational awareness errors (56%) than other claims (21%, P situational awareness error claims compared to 46% in other claims (P = 0.001), with no significant difference in payment size. Among 198 claims with anesthesia situational awareness error, perception errors were most common (42%), whereas comprehension errors (29%) and projection errors (29%) were relatively less common. Situational awareness error definitions were operationalized for reliable application to real-world anesthesia cases. Situational awareness errors may have contributed to catastrophic outcomes in three quarters of recent anesthesia malpractice claims.Situational awareness errors resulting in death or brain damage remain prevalent causes of malpractice claims in the 21st century.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  19. Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation.

    Directory of Open Access Journals (Sweden)

    Xurui Zhang

    Full Text Available Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92-1 cells. By measuring senescence associated-β-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research.

  20. 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

  1. 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.

  2. 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 ...

  3. 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.

  4. Exenatide Induces Impairment of Autophagy Flux to Damage Rat Pancreas.

    Science.gov (United States)

    Li, Zhiqiang; Huang, Lihua; Yu, Xiao; Yu, Can; Zhu, Hongwei; Li, Xia; Han, Duo; Huang, Hui

    2017-01-01

    The study aimed to explore the alteration of autophagy in rat pancreas treated with exenatide. Normal Sprague-Dawley rats and diabetes-model rats induced by 2-month high-sugar and high-fat diet and streptozotocin injection were subcutaneously injected with exenatide, respectively, for 10 weeks, with homologous rats treated with saline as control. Meanwhile, AR42J cells, pancreatic acinar cell line, were cultured with exenatide at doses of 5 pM for 3 days. The pancreas was disposed, and several sections were stained with hematoxylin-eosin. Immunohistochemistry was used to measure the expressions of glucagon-like peptide 1 receptor (GLP-1R) and cysteine-aspartic acid protease-3 in rat pancreas, and Western blot was used to test the expressions of GLP-1R, light chain 3B-I and -II, and p62 in rat pancreas and AR42J cells. The data were expressed as mean (standard deviation) and analyzed by unpaired Student's t-test. Exenatide can induce pathological changes in rat pancreas. The GLP-1R, p62, light chain 3B-II, and cysteine-aspartic acid protease-3 in rat pancreas and AR42J cells treated with exenatide were significantly overexpressed. Exenatide can activate and upregulate its receptor, GLP-1R, then impair autophagy flux and activate apoptosis in the pancreatic acinar cell, thus damaging rat pancreas.

  5. Chromium-induced membrane damage: protective role of ascorbic acid

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80 - 100gbody weight). It has been observed that the intoxication with chromium ( i. p. ) at the dose of 0.8 mg/100g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospbolipid of both liver and kidney. The alkaline pbosphatase, total ATPase and Na + -K + -ATPase activities were significantly decreased in both liver and kidney after chromium treatment,except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid ( i.p. at the dose of 0.5 mg,/100g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

  6. Protective effects of C-phycocyanin against kainic acid-induced neuronal damage in rat hippocampus.

    Science.gov (United States)

    Rimbau, V; Camins, A; Romay, C; González, R; Pallàs, M

    1999-12-03

    The neuroprotective role of C-phycocyanin was examined in kainate-injured brains of rats. The effect of three different treatments with C-phycocyanin was studied. The incidence of neurobehavioral changes was significantly lower in animals receiving C-phycocyanin. These animals also gained significantly more weight than the animals only receiving kainic acid, whereas their weight gain did not differed significantly from controls. Equivalent results were found when the neuronal damage in the hippocampus was evaluated through changes in peripheral benzodiazepine receptors (microglial marker) and heat shock protein 27 kD expression (astroglial marker). Our results are consistent with the oxygen radical scavenging properties of C-phycocyanin described elsewhere. Our findings and the virtual lack of toxicity of C-phycocyanin suggest this drug could be used to treat oxidative stress-induced neuronal injury in neurodegenerative diseases, such as Alzheimer's and Parkinson's.

  7. PREDICTION OF SPECIFIC DAMAGE OR INFARCTION FROM THE MEASUREMENT OF TISSUE IMPEDANCE FOLLOWING REPETITIVE BRAIN ISCHEMIA IN THE RAT

    NARCIS (Netherlands)

    KLEIN, HC; KROPVANGASTEL, W; GO, KG; KORF, J

    The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of

  8. The Relationship between Localized Brain Damage and Agraphia%脑不同部位损害与失写症

    Institute of Scientific and Technical Information of China (English)

    谢秋幼; 孙红宇; 刘晓加

    2001-01-01

    Writing behavior is affected by many factors and depends on the functional integrity of the nervous system. Its neuropsychological mechanism remains unknown. The agraphic features involving different parts of brain damage are dissimilar. The neuroanatomic location of agraphia and its possible brain mechanism are reviewed.

  9. Myostatin induces DNA damage in skeletal muscle of streptozotocin-induced type 1 diabetic mice.

    Science.gov (United States)

    Sriram, Sandhya; Subramanian, Subha; Juvvuna, Prasanna Kumar; McFarlane, Craig; Salerno, Monica Senna; Kambadur, Ravi; Sharma, Mridula

    2014-02-28

    One of the features of uncontrolled type 1 diabetes is oxidative stress that induces DNA damage and cell death. Skeletal muscle atrophy is also considerable in type 1 diabetes, however, the signaling mechanisms that induce oxidative stress culminating in muscle atrophy are not fully known. Here, we show that in Streptozotocin-induced diabetic wild type mice, hypo-phosphorylation of Akt, resulted in activation of Foxa2 transcription factor in the muscle. Foxa2 transcriptionally up-regulated Myostatin, contributing to exaggerated oxidative stress leading to DNA damage via p63/REDD1 pathway in skeletal muscle of Streptozotocin-treated wild type mice. In Myostatin(-/-) mice however, Streptozotocin treatment did not reduce Akt phosphorylation despite reduced IRS-1 signaling. Moreover, Foxa2 levels remained unaltered in Myostatin(-/-) mice, while levels of p63/REDD1 were higher compared with wild type mice. Consistent with these results, relatively less DNA damage and muscle atrophy was observed in Myostatin(-/-) muscle in response to Streptozotocin treatment. Taken together, our results for the first time show the role of Foxa2 in Myostatin regulation in skeletal muscle in diabetic mice. Altogether, these results demonstrate the mechanism by which Myostatin contributes to DNA damage in skeletal muscle of the diabetic mice that would lead to myofiber degeneration.

  10. Brain oscillations in bipolar disorder and lithium-induced changes.

    Science.gov (United States)

    Atagün, Murat İlhan

    2016-01-01

    Electroencephalography (EEG) studies in patients with bipolar disorder have revealed lower amplitudes in brain oscillations. The aim of this review is to describe lithium-induced EEG changes in bipolar disorder and to discuss potential underlying factors. A literature survey about lithium-induced EEG changes in bipolar disorder was performed. Lithium consistently enhances magnitudes of brain oscillations in slow frequencies (delta and theta) in both resting-state EEG studies as well as event-related oscillations studies. Enhancement of magnitudes of beta oscillations is specific to event-related oscillations. Correlation between serum lithium levels and brain oscillations has been reported. Lithium-induced changes in brain oscillations might correspond to lithium-induced alterations in neurotransmitters, signaling cascades, plasticity, brain structure, or biophysical properties of lithium. Therefore, lithium-induced changes in brain oscillations could be promising biomarkers to assess the molecular mechanisms leading to variability in efficacy. Since the variability of lithium response in bipolar disorder is due to the genetic differences in the mechanisms involving lithium, it would be highly promising to assess the lithium-induced EEG changes as biomarkers in genetic studies.

  11. Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Juanjuan; Zhang, Yu [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentaoboy@sina.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Luo, YunBo [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Hao, Junran [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Shen, Xiao Li [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Yang, Xuan [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Li, Xiaohong [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Huang, Kunlun, E-mail: hkl009@163.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

    2013-04-15

    Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by

  12. l-Theanine attenuates cadmium-induced neurotoxicity through the inhibition of oxidative damage and tau hyperphosphorylation.

    Science.gov (United States)

    Ben, Peiling; Zhang, Zhengping; Zhu, Yanyan; Xiong, Aiying; Gao, Yanhong; Mu, Jianyun; Yin, Zhimin; Luo, Lan

    2016-12-01

    Cadmium (Cd) has long been known to induce neurological degenerative disorders. We studied effects of l-theanine, one of the major amino acid components in green tea, on Cd-induced brain injury in mice. Male ICR mice were intraperitoneally injected with l-theanine (100 or 200mg/kg/day) or saline and after one hour these mice were orally administrated with CdCl2 (3.75-6mg/kg). The treatment was conducted for 8 weeks. l-Theanine significantly reduced Cd level in the mouse brain and plasma. Cd-induced neuronal cell death in the mouse cortex and hippocampus were apparently inhibited by l-theanine treatment. l-Theanine also decreased the levels of malondialdehyde (MDA) and ROS, and obviously elevated the levels of glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the mouse brain. Hyperphosphorylation of tau protein is proposed to be an early event for the evolution of tau pathology, and may play an important role in Cd-induced neurodegeneration. Our results showed that l-theanine significantly suppressed Cd-induced tau protein hyperphosphorylation at Ser199, Ser202, and Ser396. Mechanism study showed that l-theanine inhibited the activation of glycogen synthase kinase-3β (GSK-3β) which contributed to the hyperphosphorylation of tau and Cd-induced cytotoxicity. Furthermore, l-theanine reduced Cd-induced cytotoxicity possibly by interfering with the Akt/mTOR signaling pathway. In conclusion, our study indicated that l-theanine protected mice against Cd-induced neurotoxicity through reducing brain Cd level and relieved oxidative damage and tau hyperphosphorylation. Our foundings provide a novel insight into the potential use of l-theanine as prophylactic and therapeutic agents for Cd-induced neurodegenerative diseases.

  13. 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

  14. 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.

  15. ERK inhibition with PD184161 mitigates brain damage in a mouse model of stroke.

    Science.gov (United States)

    Gladbach, Amadeus; van Eersel, Janet; Bi, Mian; Ke, Yazi D; Ittner, Lars M

    2014-05-01

    Ischemic stroke is a leading cause of death. It has previously been shown that blocking activation of extracellular signal-regulated kinase (ERK) with the MEK inhibitor U0126 mitigates brain damage in rodent models of ischemic stroke. Here we show that the newer MEK inhibitor PD184161 reduces cell death and altered gene expression in cultured neurons and mice undergoing excitotoxicity, and has similar protective effects in a mouse model of stroke. This further supports ERK inhibition as a potential treatment for stroke.

  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. Robustness of various metals against high THz field induced damage

    DEFF Research Database (Denmark)

    Zhu, Jianfei; Iwaszczuk, Krzysztof; Tarekegne, Abebe Tilahun;

    2016-01-01

    We investigate various metals for their robustness against damage caused by strong THz field. Even though the damage process is not of a thermal nature we observe a correlation between robustness and the melting temperature. Influence of the substrate material on the damage pattern is also studied....

  18. Radiation damage of insulating crystals induced by electronic excitation

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Noriaki

    1988-05-01

    A review is given on radiation damage of insulating crystals arising from energy imparted to solids into electronic excitation. Emphasis is placed in describing the mechanism. The role of the exciton-phonon interaction in the production of radiation damage is described and the radiation damage processes in a few typical insulators such as alkali halides, alkali earth fluorides and silicon dioxide are described.

  19. Fatigue-induced damage of high-strength steels

    Science.gov (United States)

    Shetulov, D. I.; Myl'nikov, V. V.

    2014-03-01

    The issues on the estimation of the surface damage of the products produced from high-strength alloys are considered. Mathematical relationships for a numerical calculation of the surface damage are given. The peculiarities of the evaluation of the surface damage are investigated, as applied to high-strength alloys.

  20. Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate.

    Science.gov (United States)

    Tovar-y-Romo, Luis B; Penagos-Puig, Andrés; Ramírez-Jarquín, Josué O

    2016-01-01

    Neuronal survival depends on multiple factors that comprise a well-fueled energy metabolism, trophic input, clearance of toxic substances, appropriate redox environment, integrity of blood-brain barrier, suppression of programmed cell death pathways and cell cycle arrest. Disturbances of brain homeostasis lead to acute or chronic alterations that might ultimately cause neuronal death with consequent impairment of neurological function. Although we understand most of these processes well when they occur independently from one another, we still lack a clear grasp of the concerted cellular and molecular mechanisms activated upon neuronal damage that intervene in protecting damaged neurons from death. In this review, we summarize a handful of endogenously activated mechanisms that balance molecular cues so as to determine whether neurons recover from injury or die. We center our discussion on mechanisms that have been identified to participate in stroke, although we consider different scenarios of chronic neurodegeneration as well. We discuss two central processes that are involved in endogenous repair and that, when not regulated, could lead to tissue damage, namely, trophic support and neuroinflammation. We emphasize the need to construct integrated models of neuronal degeneration and survival that, in the end, converge in neuronal fate after injury. Under neurodegenerative conditions, endogenously activated mechanisms balance out molecular cues that determine whether neurons contend toxicity or die. Many processes involved in endogenous repair may as well lead to tissue damage depending on the strength of stimuli. Signaling mediated by trophic factors and neuroinflammation are examples of these processes as they regulate different mechanisms that mediate neuronal demise including necrosis, apoptosis, necroptosis, pyroptosis and autophagy. In this review, we discuss recent findings on balanced regulation and their involvement in neuronal death.

  1. Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke.

    Science.gov (United States)

    Zavaglia, Melissa; Forkert, Nils D; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C

    2015-01-01

    Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a 'map of stroke'.

  2. Implications of astrocytes in mediating the protective effects of Selective Estrogen Receptor Modulators upon brain damage

    Directory of Open Access Journals (Sweden)

    George E. Barreto

    2015-04-01

    Full Text Available Selective Estrogen Receptor Modulators (SERMs are steroidal or non-steroidal compounds that are already used in clinical practice for the treatment of breast cancer, osteoporosis and menopausal symptoms. While SERMs actions in the breast, bone, and uterus have been well characterized, their actions in the brain are less well understood. Previous works have demonstrated the beneficial effects of SERMs in different chronic neurodegenerative diseases like Alzheimer, Parkinson’s disease and Multiple sclerosis, as well as acute degeneration as stroke and traumatic brain injury. Moreover, these compounds exhibit similar protective actions as those of estradiol in the Central Nervous System, overt any secondary effect. For these reasons, in the past few years, there has been a growing interest in the neuroprotective effects exerted directly or indirectly by SERMs in the SNC. In this context, astrocytes play an important role in the maintenance of brain metabolism, and antioxidant support to neurons, thus indicating that better protection of astrocytes are an important asset targeting neuronal protection. Moreover, various clinical and experimental studies have reported that astrocytes are essential for the neuroprotective effects of SERMs during neuronal injuries, as these cells express different estrogen receptors in cell membrane, demonstrating that part of SERMs effects upon injury may be mediated by astrocytes. The present work highlights the current evidence on the protective mechanisms of SERMs, such as tamoxifen and raloxifene, in the SNC, and their modulation of astrocytic properties as promising therapeutic targets during brain damage.

  3. The effects of pre-exercise vibration stimulation on the exercise-induced muscle damage

    Science.gov (United States)

    Kim, Ji-Yun; Kang, Da-Haeng; Lee, Joon-Hee; O, Se-Min; Jeon, Jae-Keun

    2017-01-01

    [Purpose] To investigate the effects of pre-induced muscle damage vibration stimulation on the pressure-pain threshold and muscle-fatigue-related metabolites of exercise-induced muscle damage. [Subjects and Methods] Thirty healthy, adult male subjects were randomly assigned to the pre-induced muscle damage vibration stimulation group, post-induced muscle damage vibration stimulation group, or control group (n=10 per group). To investigate the effects of pre-induced muscle damage vibration stimulation, changes in the pressure-pain threshold (lb), creatine kinase level (U/L), and lactate dehydrogenase level (U/L) were measured and analyzed at baseline and at 24 hours, 48 hours, and 72 hours after exercise. [Results] The pressure-pain thresholds and concentrations of creatine kinase and lactate dehydrogenase varied significantly in each group and during each measurement period. There were interactions between the measurement periods and groups, and results of the post-hoc test showed that the pre-induced muscle damage vibration stimulation group had the highest efficacy among the groups. [Conclusion] Pre-induced muscle damage vibration stimulation is more effective than post-induced muscle damage vibration stimulation for preventing muscle damage. PMID:28210056

  4. Prevalence, and Intellectual Outcome of Unilateral Focal Cortical Brain Damage as a Function of Age, Sex and Aetiology

    Directory of Open Access Journals (Sweden)

    C. M. J. Braun

    2002-01-01

    Full Text Available Neurologists and neuropsychologists are aware that aging men are more at risk than women for brain damage, principally because of the well known male-predominant risk for cardiovascular disease and related cerebrovascular accidents. However, a disproportion in prevalence of brain damage between the sexes in childhood may be less suspected. Furthermore, sex-specific risk for other aetiologies of brain damage may be little known, whether in the pediatric or adult populations. Proposals of a sex difference in cognitive recovery from brain damage have also been controversial. Six hundred and thirty five “consecutive” cases with cortical focal lesions including cases of all ages and both sexes were reviewed. Aetiology of the lesion was determined for each case as was postlesion IQ. Risk was highly male prevalent in all age groups, with a predominance of cardiovascular aetiology explaining much of the adult male prevalence. However, several other aetiological categories were significantly male prevalent in juveniles (mitotic, traumatic, dysplasic and adults (mitotic, traumatic. There was no sex difference in outcome (i.e., postlesion IQ of these cortical brain lesions for the cohort as a whole, after statistical removal of the influence of lesion extent, aetiology and presence of epilepsy. Mechanisms potentially responsible for sex differences in prevalence, aetiology of brain damage, and recovery, are reviewed and discussed.

  5. Methylphenidate and Amphetamine Do Not Induce Cytogenetic Damage in Lymphocytes of Children with ADHD

    Science.gov (United States)

    Witt, Kristine L.; Shelby, Michael D.; Itchon-Ramos, Nilda; Faircloth, Melissa; Kissling, Grace E.; Chrisman, Allan K.; Ravi, Hima; Murli, Hemalatha; Mattison, Donald R.; Kollins, Scott H.

    2008-01-01

    The inducement of chromosomal damage in lymphocytes among children with attention deficit hyperactivity disorder receiving treatment with methylphenidate- or amphetamine-based drugs is investigated. Findings did not reveal significant increases in cytogenetic damage related to the treatment. The risk for cytogenetic damage posed by such products…

  6. 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.

  7. H2O2-mediated DNA damage and repair in the brain cells in the aging rats detected by comet assay

    Institute of Scientific and Technical Information of China (English)

    Suming ZhangM.D., Ph.D; Zongchao Han, M.D.; Siyu Fang, M.D.; Ruan Yang, M.D; Wei Wang, M.D., Ph. D

    2000-01-01

    Objective: To identify the relation between DNA damage susceptibility/ DNA repair capability and aging process after insults, an observation of H2O2_induced DNA damage and the kinetics of DNA repair in senescent murine brain cells with the alkaline single cell gel electrophoresis (SCGE/Comet assay) was made. Methods: The dissociated brain cells harvested in the area of the cerebral cortex, hippocampus, basal gang]ion from 3-month (n=10), 8-month (n=8) and 26-month (n=5) old rats were respectively treated with H2O2 in gradient doses for 10 min, or without H2O2 as controls. The cells embedded in agarose were lysed, helix-untied, electrophoresed, stained with a fluorescence DNA binding stain, viewed under a fluorescence microscope. Individual image was optically recorded. The frequency of the tailed cells and the grade of tails wereused to analyze single strand breaks of DNA and injury intensity. Results: By the cell and DNA image like comets, a linear increase was noticed in vulnerability of DNA both to H2O2 doses and to the age. Regarding the damaged region of the brain, the cortex cells were more vulnerable to the insult than the hippocampus/basal ganglionic cells. Whatever aging or not the cells were, the maximum of ratio of DNA repair was only within 1 hour during the incubation for 0.5-4 hours after the insults. Furthermore, the more aging, the less ratio of DNA repair of sick cells. Conclusion: The DNA damagesusceptibility and the DNA repair capability of individual cells, whatever its age is, can be detected by this brain cell injury model. Comet assay is a sensitive way to find out DNA damage and repair of the cells. It should be more difficult for the cells to cope with an acute and excessive than with a persistent, chronic and mild DNA damage which is more related to an accumulating injury, the aging.

  8. SHI induced damage in electrical properties of silicon NPN BJTs

    Science.gov (United States)

    Kumar, M. Vinay; Kumar, Santhosh; Yashoda, T.; Krishnaveni, S.

    2016-05-01

    The investigation of radiation damage in Si microelectronic circuitry and devices are being carried out by various research groups globally. In particular the Si Bipolar junction transistors are very sensitive to high energetic radiation. In the present study, radiation response of NPN Bipolar junction transistor (2N3773) has been examined for 60 MeV B4+ ion. Key electrical properties like Gummel, dc current gain and capacitance - voltage (C-V) characteristics of 60 MeV B4+ ion irradiated transistor were studied before and after irradiation. Ion irradiation and subsequent electrical characterizations were performed at room temperature. Current voltage (I-V) measurements showed the increase in collector current for VBE ≤ 0.4 V as a function of fluence, which is due to B4+ ion induced surface leakage currents. Base current is observed to be more sensitive than collector current and gain appears to be degraded with ion fluence. Also, C-V measurements shows that both built in potential and doping concentration increased significantly after irradiation.

  9. Time evolution of damage in thermally induced creep rupture

    KAUST Repository

    Yoshioka, N.

    2012-01-01

    We investigate the time evolution of a bundle of fibers subject to a constant external load. Breaking events are initiated by thermally induced stress fluctuations followed by load redistribution which subsequently leads to an avalanche of breakings. We compare analytic results obtained in the mean-field limit to the computer simulations of localized load redistribution to reveal the effect of the range of interaction on the time evolution. Focusing on the waiting times between consecutive bursts we show that the time evolution has two distinct forms: at high load values the breaking process continuously accelerates towards macroscopic failure, however, for low loads and high enough temperatures the acceleration is preceded by a slow-down. Analyzing the structural entropy and the location of consecutive bursts we show that in the presence of stress concentration the early acceleration is the consequence of damage localization. The distribution of waiting times has a power law form with an exponent switching between 1 and 2 as the load and temperature are varied.

  10. Retinal Damage Induced by Internal Limiting Membrane Removal

    Directory of Open Access Journals (Sweden)

    Rachel Gelman

    2015-01-01

    Full Text Available The internal limiting membrane (ILM, the basement membrane of the Müller cells, serves as the interface between the vitreous body and the retinal nerve fiber layer. It has a fundamental role in the development, structure, and function of the retina, although it also is a pathologic component in the various vitreoretinal disorders, most notably in macular holes. It was not until understanding of the evolution of idiopathic macular holes and the advent of idiopathic macular hole surgery that the idea of adjuvant ILM peeling in the treatment of tractional maculopathies was explored. Today intentional ILM peeling is a commonly applied surgical technique among vitreoretinal surgeons as it has been found to increase the rate of successful macular hole closure and improve surgical outcomes in other vitreoretinal diseases. Though ILM peeling has refined surgery for tractional maculopathies, like all surgical procedures it is not immune to perioperative risk. The essential role of the ILM to the integrity of the retina and risk of trauma to retinal tissue spurs suspicion with regard to its routine removal. Several authors have investigated the retinal damage induced by ILM peeling and these complications have been manifested across many different diagnostic studies.

  11. Novel DNA damage checkpoint in mitosis: Mitotic DNA damage induces re-replication without cell division in various cancer cells.

    Science.gov (United States)

    Hyun, Sun-Yi; Rosen, Eliot M; Jang, Young-Joo

    2012-07-06

    DNA damage induces multiple checkpoint pathways to arrest cell cycle progression until damage is repaired. In our previous reports, when DNA damage occurred in prometaphase, cells were accumulated in 4 N-DNA G1 phase, and mitosis-specific kinases were inactivated in dependent on ATM/Chk1 after a short incubation for repair. We investigated whether or not mitotic DNA damage causes cells to skip-over late mitotic periods under prolonged incubation in a time-lapse study. 4 N-DNA-damaged cells re-replicated without cell division and accumulated in 8 N-DNA content, and the activities of apoptotic factors were increased. The inhibition of DNA replication reduced the 8 N-DNA cell population dramatically. Induction of replication without cell division was not observed upon depletion of Chk1 or ATM. Finally, mitotic DNA damage induces mitotic slippage and that cells enter G1 phase with 4 N-DNA content and then DNA replication is occurred to 8 N-DNA content before completion of mitosis in the ATM/Chk1-dependent manner, followed by caspase-dependent apoptosis during long-term repair. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Laser-Induced Damage Growth on Larger-Aperture Fused Silica Optical Components at 351 nm

    Institute of Scientific and Technical Information of China (English)

    HUANG Wan-Qing; ZHANG Xiao-Min; HAN Wei; WANG Fang; XIANG Yong; LI Fu-Quan; FENG Bin; JING Feng; WEI Xiao-Feng; ZHENG Wan-Guo

    2009-01-01

    Laser-induced damage is a key lifetime limiter for optics in high-power laser facility. Damage initiation and growth under 351 nm high-fluence laser irradiation are observed on larger-aperture fused silica optics. The input surface of one fused silica component is damaged most severely and an explanation is presented. Obscurations and the area of a scratch on it are found to grow exponentially with the shot number. The area of damage site grows linearly. Micrographs of damage sites support the micro-explosion damage model which could be used to qualitatively explain the phenomena.

  13. Piano training in youths with hand motor impairments after damage to the developing brain.

    Science.gov (United States)

    Lampe, Renée; Thienel, Anna; Mitternacht, Jürgen; Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana

    2015-01-01

    Damage to the developing brain may lead to impairment of the hand motor function and negatively impact on patients' quality of life. Development of manual dexterity and finger and hand motor function may be promoted by learning to play the piano. The latter brings together music with the intensive training of hand coordination and fine finger mobility. We investigated if learning to play the piano helped to improve hand motor skills in 18 youths with hand motor disorders resulting from damage during early brain development. Participants trained 35-40 minutes twice a week for 18 months with a professional piano teacher. With the use of a Musical Instrument Digital Interface piano, the uniformity of finger strokes could be objectively assessed from the timing of keystrokes. The analysis showed a significant improvement in the uniformity of keystrokes during the training. Furthermore, the youths showed strong motivation and engagement during the study. This is nevertheless an open study, and further studies remain needed to exclude effects of growth and concomitant therapies on the improvements observed and clarify which patients will more likely benefit from learning to play the piano.

  14. Defective pantomime of object use in left brain damage: apraxia or asymbolia?

    Science.gov (United States)

    Goldenberg, Georg; Hartmann, Karoline; Schlott, Isa

    2003-01-01

    Disturbance of pantomime of object use in patients with left brain damage (LBD) and aphasia has been firmly established but its nature remains controversial. It may be due to an inability to perform movements from memory without external support by objects (apraxia) or to an inability to produce signs referring to absent objects and actions (asymbolia). The need to perform movements without external support is shared with imitation of gestures, and the demand to designate absent objects with drawing from memory. Both of these tasks have been found to be impaired in LBD. We examined pantomime of object use, drawing objects from memory, imitation of meaningless gestures, and aphasia in 40 patients with LBD and aphasia and compared them to healthy controls and to patients with right brain damage (RBD). Whereas drawing showed comparable sensitivity to LBD and RBD, pantomime was distinctly more disturbed in LBD than in RBD patients. Pantomime was worse than drawing in LBD but better than drawing in RBD. In the LBD group scores on pantomime showed significant correlations of very similar strength to drawing, imitation, and all language tests. Multidimensional scaling of the correlational structure placed pantomime in an intermediate position between verbal and non-verbal tests. We conclude that neither apraxia nor asymbolia can satisfactorily explain our results. It seems as if pantomime of object use taps a central aspect of left hemisphere function which is compromised by any LBD. We propose that this may be the ability to select and combine distinctive features of objects and actions.

  15. FeTPPS Reduces Secondary Damage and Improves Neurobehavioral Functions after Traumatic Brain Injury

    Science.gov (United States)

    Bruschetta, Giuseppe; Impellizzeri, Daniela; Campolo, Michela; Casili, Giovanna; Di Paola, Rosanna; Paterniti, Irene; Esposito, Emanuela; Cuzzocrea, Salvatore

    2017-01-01

    Traumatic brain injury (TBI) determinate a cascade of events that rapidly lead to neuron's damage and death. We already reported that administration of FeTPPS, a 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrin iron III chloride peroxynitrite decomposition catalyst, possessed evident neuroprotective effects in a experimental model of spinal cord damage. The present study evaluated the neuroprotective property of FeTPPS in TBI, using a clinically validated model of TBI, the controlled cortical impact injury (CCI). We observe that treatment with FeTPPS (30 mg/kg, i.p.) reduced: the state of brain inflammation and the tissue hurt (histological score), myeloperoxidase activity, nitric oxide production, glial fibrillary acidic protein (GFAP) and pro-inflammatory cytokines expression and apoptosis process. Moreover, treatment with FeTPPS re-established motor-cognitive function after CCI and it resulted in a reduction of lesion volumes. Our results established that FeTPPS treatment decreases the growth of inflammatory process and the tissue injury associated with TBI. Thus our study confirmed the neuroprotective role of FeTPPS treatment on TBI.

  16. Assessment of hand after brain damage with the aim of functional surgery.

    Science.gov (United States)

    Romain, M; Benaim, C; Allieu, Y; Pelissier, J; Chammas, M

    1999-01-01

    The semiology of the hand after brain damage is really rich. Its clinical evaluation remains quite difficult and must be integrated in the neuro-orthopedic and cognitive context. Deficiency, neuropsychological, analytic and functional status, must be assessed before any surgical decision aiming the improvement of prehension. Neuropsychological evaluation precise the hemispheric specialization: right hemisphere lesions conduct to unilateral spatial neglect while left hemispherical lesions determine language troubles and gesture impairment (apraxia). The analytical evaluation describes motor and sensitive function and assesses spasticity and pain. Concerning the functional assessment, the Enjalbert's score seems to be the most adapted to the upper limb. The assessment of hand deficiency and its origin is necessary to orientate the surgical decision and includes the Zancolli classification for the fingers and wrist and the House classification for the thumb. These classification used for cerebral palsy seems to be insufficient for all the different situations occurring after brain damage. A new classification is proposed based on 3 parameters: fingers extension, thumb abduction and supination. Surgical decision should be examined only after an adapted rehabilitation program.

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

    Science.gov (United States)

    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.

  18. Effect of Vacuum on the Laser-Induced Damage of Anti-Reflection Coatings

    Institute of Scientific and Technical Information of China (English)

    LING Xiu-Lan; ZHAO Yuan-An; LI Da-Wei; ZHOU Ming; SHAO Jian-Da; FAN Zheng-Xiu

    2009-01-01

    In the comparison of damage modifications, absorption measurement and energy dispersive x-ray analysis, the effect of vacuum on the laser-induced damage of anti-reflection coatings is analyzed. It is found that vacuum decreases the laser-induced damage threshold of the films. The low laser-induced damage threshold in vacuum environments as opposed to air environments is attributed to water absorption and the formation of the O/Si,O/Zr sub-stoichiometry in the course of laser irradiation.

  19. Mild hyperthermia worsens the neuropathological damage associated with mild traumatic brain injury in rats.

    Science.gov (United States)

    Sakurai, Atsushi; Atkins, Coleen M; Alonso, Ofelia F; Bramlett, Helen M; Dietrich, W Dalton

    2012-01-20

    The effects of slight variations in brain temperature on the pathophysiological consequences of acute brain injury have been extensively described in models of moderate and severe traumatic brain injury (TBI). In contrast, limited information is available regarding the potential consequences of temperature elevations on outcome following mild TBI (mTBI) or concussions. One potential confounding variable with mTBI is the presence of elevated body temperature that occurs in the civilian or military populations due to hot environments combined with exercise or other forms of physical exertion. We therefore determined the histopathological effects of pre- and post-traumatic hyperthermia (39°C) on mTBI. Adult male Sprague-Dawley rats were divided into 3 groups: pre/post-traumatic hyperthermia, post-traumatic hyperthermia alone for 2 h, and normothermia (37°C). The pre/post-hyperthermia group was treated with hyperthermia starting 15 min before mild parasagittal fluid-percussion brain injury (1.4-1.6 atm), with the temperature elevation extending for 2 h after trauma. At 72 h after mTBI, the rats were perfusion-fixed for quantitative histopathological evaluation. Contusion areas and volumes were significantly larger in the pre/post-hyperthermia treatment group compared to the post-hyperthermia and normothermic groups. In addition, pre/post-traumatic hyperthermia caused the most severe loss of NeuN-positive cells in the dentate hilus compared to normothermia. These neuropathological results demonstrate that relatively mild elevations in temperature associated with peri-traumatic events may affect the long-term functional consequences of mTBI. Because individuals exhibiting mildly elevated core temperatures may be predisposed to aggravated brain damage after mTBI or concussion, precautions should be introduced to target this important physiological variable.

  20. Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke.

    Science.gov (United States)

    Frankowski, Jan C; DeMars, Kelly M; Ahmad, Abdullah S; Hawkins, Kimberly E; Yang, Changjun; Leclerc, Jenna L; Doré, Sylvain; Candelario-Jalil, Eduardo

    2015-12-09

    Cyclooxygenase-2 (COX-2) is activated in response to ischemia and significantly contributes to the neuroinflammatory process. Accumulation of COX-2-derived prostaglandin E2 (PGE2) parallels the substantial increase in stroke-mediated blood-brain barrier (BBB) breakdown. Disruption of the BBB is a serious consequence of ischemic stroke, and is mainly mediated by matrix metalloproteinases (MMPs). This study aimed to investigate the role of PGE2 EP1 receptor in neurovascular injury in stroke. We hypothesized that pharmacological blockade or genetic deletion of EP1 protects against BBB damage and hemorrhagic transformation by decreasing the levels and activity of MMP-3 and MMP-9. We found that post-ischemic treatment with the EP1 antagonist, SC-51089, or EP1 genetic deletion results in a significant reduction in BBB disruption and reduced hemorrhagic transformation in an experimental model of transient focal cerebral ischemia. These neurovascular protective effects of EP1 inactivation are associated with a significant reduction in MMP-9/-3, less peripheral neutrophil infiltration, and a preservation of tight junction proteins (ZO-1 and occludin) composing the BBB. Our study identifies the EP1 signaling pathway as an important link between neuroinflammation and MMP-mediated BBB breakdown in ischemic stroke. Targeting the EP1 receptor could represent a novel approach to diminish the devastating consequences of stroke-induced neurovascular damage.

  1. Microglial Hv1 proton channel promotes cuprizone-induced demyelination through oxidative damage.

    Science.gov (United States)

    Liu, Junli; Tian, Daishi; Murugan, Madhuvika; Eyo, Ukpong B; Dreyfus, Cheryl F; Wang, Wei; Wu, Long-Jun

    2015-10-01

    NADPH oxidase (NOX)-dependent reactive oxygen species (ROS) production in inflammatory cells including microglia plays an important role in demyelination and free radical-mediated tissue injury in multiple sclerosis (MS). However, the mechanism underlying microglial ROS production and demyelination remains largely unknown. The voltage-gated proton channel, Hv1, is selectively expressed in microglia and is required for NOX-dependent ROS generation in the brain. In the present study, we sought to determine the role of microglial Hv1 proton channels in a mouse model of cuprizone-induced demyelination, a model for MS. Following cuprizone exposure, wild-type mice presented obvious demyelination, decreased myelin basic protein expression, loss of mature oligodendrocytes, and impaired motor coordination in comparison to mice on a normal chow diet. However, mice lacking Hv1 (Hv1(-/-) ) are partially protected from demyelination and motor deficits compared with those in wild-type mice. These rescued phenotypes in Hv1(-/-) mice in cuprizone-induced demyelination is accompanied by reduced ROS production, ameliorated microglial activation, increased oligodendrocyte progenitor cell (NG2) proliferation, and increased number of mature oligodendrocytes. These results demonstrate that the Hv1 proton channel is required for cuprizone-induced microglial oxidative damage and subsequent demyelination. Our study suggests that the microglial Hv1 proton channel is a unique target for controlling NOX-dependent ROS production in the pathogenesis of MS.

  2. Pilot Study of Propofol-induced Slow Waves as a Pharmacologic Test for Brain Dysfunction after Brain Injury.

    Science.gov (United States)

    Kortelainen, Jukka; Väyrynen, Eero; Huuskonen, Usko; Laurila, Jouko; Koskenkari, Juha; Backman, Janne T; Alahuhta, Seppo; Seppänen, Tapio; Ala-Kokko, Tero

    2017-01-01

    Slow waves (less than 1 Hz) are the most important electroencephalogram signatures of nonrapid eye movement sleep. While considered to have a substantial importance in, for example, providing conditions for single-cell rest and preventing long-term neural damage, a disturbance in this neurophysiologic phenomenon is a potential indicator of brain dysfunction. Since, in healthy individuals, slow waves can be induced with anesthetics, the authors tested the possible association between hypoxic brain injury and slow-wave activity in comatose postcardiac arrest patients (n = 10) using controlled propofol exposure. The slow-wave activity was determined by calculating the low-frequency (less than 1 Hz) power of the electroencephalograms recorded approximately 48 h after cardiac arrest. To define the association between the slow waves and the potential brain injury, the patients' neurologic recovery was then followed up for 6 months. In the patients with good neurologic outcome (n = 6), the low-frequency power of electroencephalogram representing the slow-wave activity was found to substantially increase (mean ± SD, 190 ± 83%) due to the administration of propofol. By contrast, the patients with poor neurologic outcome (n = 4) were unable to generate propofol-induced slow waves. In this experimental pilot study, the comatose postcardiac arrest patients with poor neurologic outcome were unable to generate normal propofol-induced electroencephalographic slow-wave activity 48 h after cardiac arrest. The finding might offer potential for developing a pharmacologic test for prognostication of brain injury by measuring the electroencephalographic response to propofol.

  3. D-galactose-induced brain ageing model

    DEFF Research Database (Denmark)

    Sadigh-Eteghad, Saeed; Majdi, Alireza; McCann, Sarah K.

    2017-01-01

    Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent...

  4. Laser-induced damage tests based on a marker-based watershed algorithm with gray control

    Institute of Scientific and Technical Information of China (English)

    Yajing; Guo; Shunxing; Tang; Xiuqing; Jiang; Yujie; Peng; Baoqiang; Zhu; Zunqi; Lin

    2014-01-01

    An effective damage test method based on a marker-based watershed algorithm with gray control(MWGC) is proposed to study the properties of damage induced by near-field laser irradiation for large-aperture laser facilities.Damage tests were performed on fused silica samples and information on the size of damage sites was obtained by this new algorithm,which can effectively suppress the issue of over-segmentation of images resulting from non-uniform illumination in darkfield imaging.Experimental analysis and results show that the lateral damage growth on the exit surface is exponential,and the number of damage sites decreases sharply with damage site size in the damage site distribution statistics.The average damage growth coefficients fitted according to the experimental results for Corning-7980 and Heraeus-Suprasil312 samples at 351 nm are 1.10 ± 0.31 and 0.60 ± 0.09,respectively.

  5. Selective deficit of second language: a case study of a brain-damaged Arabic-Hebrew bilingual patient

    Directory of Open Access Journals (Sweden)

    Ibrahim Raphiq

    2009-03-01

    Full Text Available Abstract Background An understanding of how two languages are represented in the human brain is best obtained from studies of bilingual patients who have sustained brain damage. The primary goal of the present study was to determine whether one or both languages of an Arabic-Hebrew bilingual individual are disrupted following brain damage. I present a case study of a bilingual patient, proficient in Arabic and Hebrew, who had sustained brain damage as a result of an intracranial hemorrhage related to herpes encephalitis. Methods The patient's performance on several linguistic tasks carried out in the first language (Arabic and in the second language (Hebrew was assessed, and his performance in the two languages was compared. Results The patient displayed somewhat different symptomatologies in the two languages. The results revealed dissociation between the two languages in terms of both the types and the magnitude of errors, pointing to aphasic symptoms in both languages, with Hebrew being the more impaired. Further analysis disclosed that this dissociation was apparently caused not by damage to his semantic system, but rather by damage at the lexical level. Conclusion The results suggest that the principles governing the organization of lexical representations in the brain are not similar for the two languages.

  6. Intrauterine infection and neonatal brain damage%宫内感染与新生儿脑损伤

    Institute of Scientific and Technical Information of China (English)

    石晶; 母得志

    2015-01-01

    宫内感染是导致新生儿脑损伤及神经系统功能障碍的重要危险因素。病毒、细菌和原虫可感染子宫腔并导致胎儿和新生儿脑损伤。炎症反应是宫内感染致新生儿脑损伤的重要致病因素,不同孕期宫内感染导致不同类型脑损害。临床医师应重视孕期宫内感染的预防,有必要进一步加强临床和基础研究,探索宫内感染致新生儿脑损伤的有效干预措施。%Intrauterine infection is an important risk factor for neonatal brain damage and neurological dysfunction. Viruses, bacteria, and protozoa can cause intrauterine infection which results in neonatal brain damage. The inlfammatory response is an important pathogenic factor for neonatal brain damage caused by intrauterine infection. Intrauterine infection in different periods of pregnancy might cause different types of brain damage in neonates. Clinicians should pay attention to the prevention of intrauterine infection during pregnancy. It is necessary to further strengthen the clinical and basic research to explore effective interventions for neonatal brain damage caused by intrauterine infection.

  7. Microcavitation as a Neuronal Damage Mechanism in Blast Traumatic Brain Injury

    Science.gov (United States)

    Franck, Christian; Estrada, Jonathan

    2015-11-01

    Blast traumatic brain injury (bTBI) is a leading cause of injury in the armed forces. Diffuse axonal injury, the hallmark feature of blunt TBI, has been investigated in direct mechanical loading conditions. However, recent evidence suggests inertial cavitation as a possible bTBI mechanism, particularly in the case of exposure to blasts. Cavitation damage to free surfaces has been well-studied, but bubble interactions within confined 3D environments, in particular their stress and strain signatures are not well understood. The structural damage due to cavitation in living tissues - particularly at the cellular level - are incompletely understood, in part due to the rapid bubble formation and deformation strain rates of up to ~ 105-106 s-1. This project aims to characterize material damage in 2D and 3D cell culture environments by utilizing a novel high-speed red-blue diffraction assisted image correlation method at speeds of up to 106 frames per second. We gratefully acknowledge funding from the Office of Naval Research (POC: Dr. Tim Bentley).

  8. Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Martina Svensson

    2016-12-01

    Full Text Available Physical exercise is known to be a beneficial factor by increasing the cellular stress tolerance. In ischemic stroke, physical exercise is suggested to both limit the brain injury and facilitate behavioral recovery. In this study we investigated the effect of physical exercise on brain damage following global cerebral ischemia in mice. We aimed to study the effects of 4.5 weeks of forced treadmill running prior to ischemia on neuronal damage, neuroinflammation and its effect on general stress by measuring corticosterone in feces. We subjected C57bl/6 mice (n = 63 to either treadmill running or a sedentary program prior to induction of global ischemia. Anxious, depressive, and cognitive behaviors were analyzed. Stress levels were analyzed using a corticosterone ELISA. Inflammatory and neurological outcomes were analyzed using immunohistochemistry, multiplex electrochemoluminescence ELISA and Western blot. To our surprise, we found that forced treadmill running induced a stress response, with increased anxiety in the Open Field test and increased levels of corticosterone. In accordance, mice subjected to forced exercise prior to ischemia developed larger neuronal damage in the hippocampus and showed higher cytokine levels in the brain and blood compared to non-exercised mice. The extent of neuronal damage correlated with increased corticosterone levels. To compare forced treadmill with voluntary wheel running, we used a different set of mice that exercised freely on running wheels. These mice did not show any anxiety or increased corticosterone levels. Altogether, our results indicate that exercise pre-conditioning may not be beneficial if the animals are forced to run as it can induce a detrimental stress response.

  9. α-Synuclein-Induced Synapse Damage in Cultured Neurons Is Mediated by Cholesterol-Sensitive Activation of Cytoplasmic Phospholipase A2

    Directory of Open Access Journals (Sweden)

    Clive Bate

    2015-03-01

    Full Text Available The accumulation of aggregated forms of the α-synuclein (αSN is associated with the pathogenesis of Parkinson’s disease (PD and Dementia with Lewy Bodies. The loss of synapses is an important event in the pathogenesis of these diseases. Here we show that aggregated recombinant human αSN, but not βSN, triggered synapse damage in cultured neurons as measured by the loss of synaptic proteins. Pre-treatment with the selective cytoplasmic phospholipase A2 (cPLA2 inhibitors AACOCF3 and MAFP protected neurons against αSN-induced synapse damage. Synapse damage was associated with the αSN-induced activation of synaptic cPLA2 and the production of prostaglandin E2. The activation of cPLA2 is the first step in the generation of platelet-activating factor (PAF and PAF receptor antagonists (ginkgolide B or Hexa-PAF also protect neurons against αSN-induced synapse damage. αSN-induced synapse damage was also reduced in neurons pre-treated with the cholesterol synthesis inhibitor (squalestatin. These results are consistent with the hypothesis that αSN triggered synapse damage via hyperactivation of cPLA2. They also indicate that αSN-induced activation of cPLA2 is influenced by the cholesterol content of membranes. Inhibitors of this pathway that can cross the blood brain barrier may protect against the synapse damage seen during PD.

  10. Elevated global SUMOylation in Ubc9 transgenic mice protects their brains against focal cerebral ischemic damage.

    Directory of Open Access Journals (Sweden)

    Yang-Ja Lee

    Full Text Available We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects against ischemic brain damage, we have generated transgenic mice in which Ubc9 is expressed strongly in all tissues under the chicken β-actin promoter. Ubc9 expression levels in 10 founder lines ranged from 2 to 30 times the endogenous level, and lines that expressed Ubc9 at modestly increased levels showed robust resistance to brain ischemia compared to wild type mice. The infarction size was inversely correlated with the Ubc9 expression levels for up to five times the endogenous level. Although further increases showed no additional benefit, the Ubc9 expression level was highly correlated with global SUMO-1 conjugation levels (and SUMO-2,3 levels to a lesser extent up to a five-fold Ubc9 increase. Most importantly, there were striking reciprocal relationships between SUMO-1 (and SUMO-2,3 conjugation levels and cerebral infarction volumes among all tested animals, suggesting that the limit in cytoprotection by global SUMOylation remains undefined. These results support efforts to further augment global protein SUMOylation in brain ischemia.

  11. Coefficient of variation of R-R intervals in severe brain damage.

    Science.gov (United States)

    Nezu, A; Kimura, S; Kobayashi, T; Osaka, H; Uehara, S

    1996-01-01

    The coefficient of variation of R-R intervals (CVRR) was studied in 18 children having severe brain damage with a mean +/- standard deviation (s.d.) age of 8.4 +/- 5.9 years, who were divided into ten patients complicated with respiratory insufficiency (RI group) and eight patients with severe athetotic cerebral palsy (SA group). CVRR was obtained in the resting supine position, and was compared with that in 22 neurologically normal controls. CVRR in the RI group (mean +/- S.D., 2.19 +/- 1.28%) was significantly lower than that in controls (5.56 +/- 1.53%), while CVRR in the SA group (11.30 +/- 3.91%) was significantly higher than that in controls (both P < 0.01, ANOVA). In particular, the four patients with brain death showed extremely low CVRR of 1.00-1.29%. Since CVRR was 4.09% in the patient aged 4 years with birth injury of the upper cervical spinal cord causing absence of spontaneous respiration, the extremely low CVRR in patients with brain death may be directly related to brainstem dysfunction. The cause of the high CVRR in the SA group was not determined. Thus, CVRR may be useful for quantitative evaluation of severe neurological disorder.

  12. The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model

    Science.gov (United States)

    Xiao, Jinglei; Tan, Yongchang; Li, Yinjiao; Luo, Yan

    2016-01-01

    Background Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study available concerning its protective role in hypoxia-ischemia-induced immature brain damage. Therefore, we investigated whether C16 protects against neonatal hypoxia-ischemia injuries in a neonatal rat model. Material/Methods Postnatal day 7 (P7) rats were used to establish classical hypoxia-ischemia animal models, and C16 postconditioning with 100 ug/kg was performed immediately after hypoxia. Western blot analysis was performed to quantify the phosphorylation of the PKR at 0 h, 3 h, 6 h, 12 h, 24 h, and phosphorylation of NF-κB 24h after hypoxia exposure. The TTC stain for infarction area and TUNEL stain for apoptotic cells were assayed 24 h after the brain hypoxia. Gene expression of IL-1β, IL-6, and TNF-α was performed at 3 h, 6 h, 12 h, and 24 h. Results The level of PKR autophosphorylation was increased dramatically, especially at 3 h (C16 group vs. HI group, P<0.01). Intraperitoneal C16 administration reduced the infarct volume and apoptosis ratio after this insult (C16 group vs. HI group<0.01), and C16 reduced proinflammatory cytokines mRNA expression, partly through inhibiting NF-κB activation (C16 group vs. HI group<0.05). Conclusions C16 can protect immature rats against hypoxia-ischemia-induced brain damage by modulating neuroinflammation. PMID:28008894

  13. 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

  14. Blast-Induced Damage on Millisecond Blasting Model Test with Multicircle Vertical Blastholes

    Directory of Open Access Journals (Sweden)

    Qin-yong Ma

    2015-01-01

    Full Text Available To investigate the blast-induced damage effect on surrounding rock in vertical shaft excavation, 4 kinds of millisecond blasting model tests with three-circle blastholes were designed and carried out with excavation blasting in vertical shaft as the background. The longitudinal wave velocity on the side of concrete model was also measured before and after blasting. Then blast damage factor was then calculated by measuring longitudinal wave velocity before and after blasting. The test results show that the blast-induced damage factor attenuated gradually with the centre of three-circle blastholes as centre. With the threshold value of 0.19 for blast-induced damage factor, blast-induced damage zones for 4 kinds of model tests are described and there is an inverted cone blast-induced damage zone in concrete model. And analyses of cutting effect and blast-induced damage zone indicate that in order to minimize the blast-induced damage effect and ensure the cutting effect the reasonable blasting scheme for three-circle blastholes is the inner two-circle blastholes initiated simultaneously and the outer third circle blastholes initiated in a 25 ms delay.

  15. 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...

  16. Resveratrol ameliorates hypoxia/ischemia-induced brain injury in the neonatal rat via the miR-96/Bax axis.

    Science.gov (United States)

    Bian, Hongen; Shan, Haijun; Chen, Tuanying

    2017-07-18

    This study was aimed to investigate the mechanism of resveratrol on amelioration of hypoxia/ischemia (H/I)-induced brain injury. The RT-PCR and western blot were used to detect the mRNA and protein expressions, respectively. The PC12 cell induced by OGD/R was as in vitro H/I brain injury model. The luciferase reporter assay was used to prove the relationship between Bax and miR-96, and the cell apoptosis was detected by MTT assay. The loss of MBP+ area in neonatal rats analyzed by immunohistochemistry was to evaluate the extent of brain injury. The miR-96 expression was decreased in the hippocampus and cerebral cortex of neonatal rats with H/I brain injury and the oxygenglucose deprivation/re-oxygenation (OGD/R)-induced PC12 cell, while Bax expression was opposite. And then the H/I rats and OGD/R-induced PC12 cell were treated with resveratrol (RSV); the results showed that the RSV could reverse the miR-96 and Bax expressions. Next, the luciferase reporter assay proved that Bax was a target of miR-96. We used the miR-96 inhibitor to suppress miR-96 expression in OGD/R-induced PC12 cell, and found that RSV regulated Bax expression and prevented OGD/R-induced PC12 cell apoptosis via miR-96. In addition, the immunohistochemistry was used to analyze the loss of MBP+ area in neonatal rats, and the result showed that the RSV significantly reduced the brain damage, increased miR-96 expression, and decreased Bax expression, while inhibition of miR-96 aggravated the brain damage and reversed the effect of RSV. Resveratrol ameliorates hypoxia/ischemia-induced brain injury in neonatal rat via the miR-96/ Bax axis.

  17. 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.

  18. 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.

  19. 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.

  20. Sunlight-induced DNA damage in human mononuclear cells

    DEFF Research Database (Denmark)

    Møller, Peter; Wallin, Hakan; Holst, Erik

    2002-01-01

    of sunlight was comparable to the interindividual variation, indicating that sunlight exposure and the individual's background were the two most important determinants for the basal level of DNA damage. Influence of other lifestyle factors such as exercise, intake of foods, infections, and age could......In this study of 301 blood samples from 21 subjects, we found markedly higher levels of DNA damage (nonpyrimidine dimer types) in the summer than in the winter detected by single-cell gel electrophoresis. The level of DNA damage was influenced by the average daily influx of sunlight ... to blood sampling. The 3 and 6 day periods before sampling influenced DNA damage the most. The importance of sunlight was further emphasized by a positive association of the DNA damage level to the amount of time the subjects had spent in the sun over a 3 day period prior to the sampling. The effect...

  1. 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.

  2. Using induced pluripotent stem cells derived neurons to model brain diseases

    Directory of Open Access Journals (Sweden)

    Cindy E McKinney

    2017-01-01

    Full Text Available The ability to use induced pluripotent stem cells (iPSC to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders. Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology. iPSC derived neurons, or other neural cell types, provide the ability to access pathology in cells derived directly from a patient's blood sample or skin biopsy where availability of brain tissue is limiting. Thus, utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future. Many brain diseases across the spectrum of neurodevelopment, neurodegenerative and neuropsychiatric are being approached by iPSC models. The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells. In this mini-review, the importance of iPSC cell models validated for pluripotency, germline competency and function assessments is discussed. Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.

  3. No inherent left and right side in human 'mental number line': evidence from right brain damage.

    Science.gov (United States)

    Aiello, Marilena; Jacquin-Courtois, Sophie; Merola, Sheila; Ottaviani, Teresa; Tomaiuolo, Francesco; Bueti, Domenica; Rossetti, Yves; Doricchi, Fabrizio

    2012-08-01

    Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial

  4. The discrepancy between the absence of copper deposition and the presence of neuronal damage in the brain of Atp7b(-/-) mice.

    Science.gov (United States)

    Dong, Yi; Shi, Sheng-Sheng; Chen, Sheng; Ni, Wang; Zhu, Min; Wu, Zhi-Ying

    2015-02-01

    Wilson's disease (WD) is caused by mutations within the copper-transporting ATPase (ATP7B), characterized by copper deposition in various organs, principally the liver and the brain. With the availability of Atp7b(-/-) mice, the valid animal model of WD, the mechanism underlying copper-induced hepatocyte necrosis has been well understood. Nonetheless, little is known about the adverse impact of copper accumulation on the brain in WD. Therefore, the aim of this study was to identify copper disturbances according to various brain compartments and further dissect the causal relationship between copper storage and neuronal damage using Atp7b(-/-) mice. Copper levels in the liver, whole brain, brain compartments and basal ganglia mitochondria of Atp7b(-/-) mice and age-matched controls were measured by atomic absorption spectroscopy. Delicate electron microscopic studies on hepatocytes and neurons in the basal ganglia were performed. Here we further confirmed the remarkably elevated copper content and abnormal ultrastructure findings in livers of Atp7b(-/-) mice. Interestingly, we found the ultrastructure abnormalities in neurons of the basal ganglia of Atp7b(-/-) mice, whereas copper deposition was not detected in the whole brain, even within the basal ganglia and its mitochondria. The disparity provided a new understanding of neuronal dysfunction in WD, and strongly indicated that copper might not be the sole causative player and other unidentified pathogenic factors could enhance the toxic effects of copper on neurons in WD.

  5. 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.

  6. Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

    Directory of Open Access Journals (Sweden)

    Francesca Colciaghi

    Full Text Available Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

  7. Effects of memantine, an N-methyl-D-aspartate receptor antagonist, on fatigue and neuronal brain damage in a rat model of combined (physical and mental) fatigue.

    Science.gov (United States)

    Morimoto, Yasuo; Zhang, Qian; Adachi, Koji

    2012-01-01

    Most of the fatigue in everyday life is a combination of physical and mental fatigue. Recently, an animal model of combined fatigue was designed by housing rats in a cage filled with water. We have previously hypothesized that mental fatigue is caused partly by neuronal brain damage through the activation of N-methyl-D-aspartate (NMDA) receptors by quinolinic acid (QUIN), a metabolite of tryptophan (TRP). Therefore, we investigated whether the same mechanism also participates in combined fatigue. Rats were housed for 5 d under water-immersed conditions, and the extent of fatigue was evaluated by a weight-loaded forced swimming test. The swimming time of the water-immersed group was shorter than that of the control group, indicating that rats were fatigued by water-immersion. However, unexpectedly, the blood and brain levels of QUIN in the water-immersed group were lower than those of the control group. QUIN levels in both the blood and brains of a food-restricted nonimmersed group, where body weight was matched with the water-immersed group, were also decreased, suggesting that decreased QUIN in the water-immersed group originated from a reduced intake of TRP-containing food. On the other hand, hippocampal neuronal damage was shown in the water-immersed group, similar to that seen in other fatigue models where QUIN increased. Memantine, an NMDA receptor antagonist, inhibited not only the reduction in swimming times but also the neuronal damage induced by water-immersion. These results suggest that neuronal brain damage by an endogenous NMDA receptor agonist other than QUIN participates in combined fatigue by water immersion.

  8. 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.

  9. Insights into the epigenetic mechanisms involving histone lysine methylation and demethylation in ischemia induced damage and repair has therapeutic implication.

    Science.gov (United States)

    Chakravarty, Sumana; Jhelum, Priya; Bhat, Unis Ahmad; Rajan, Wenson D; Maitra, Swati; Pathak, Salil S; Patel, Anant B; Kumar, Arvind

    2017-01-01

    Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. Therapeutic interventions to minimize ischemia-induced neural damage are limited due to poor understanding of molecular mechanisms mediating complex pathophysiology in stroke. Recently, epigenetic mechanisms mostly histone lysine (K) acetylation and deacetylation have been implicated in ischemic brain damage and have expanded the dimensions of potential therapeutic intervention to the systemic/local administration of histone deacetylase inhibitors. However, the role of other epigenetic mechanisms such as histone lysine methylation and demethylation in stroke-induced damage and subsequent recovery process is elusive. Here, we established an Internal Carotid Artery Occlusion (ICAO) model in CD1 mouse that resulted in mild to moderate level of ischemic damage to the striatum, as suggested by magnetic resonance imaging (MRI), TUNEL and histopathological staining along with an evaluation of neurological deficit score (NDS), grip strength and rotarod performance. The molecular investigations show dysregulation of a number of histone lysine methylases (KMTs) and few of histone lysine demethylases (KDMs) post-ICAO with significant global attenuation in the transcriptionally repressive epigenetic mark H3K9me2 in the striatum. Administration of Dimethyloxalylglycine (DMOG), an inhibitor of KDM4 or JMJD2 class of histone lysine demethylases, significantly ameliorated stroke-induced NDS by restoring perturbed H3K9me2 levels in the ischemia-affected striatum. Overall, these results highlight the novel role of epigenetic regulatory mechanisms controlling the epigenetic mark H3K9me2 in mediating the stroke-induced striatal damage and subsequent repair following mild to moderate cerebral ischemia.

  10. Helium vs. Proton Induced Displacement Damage in Electronic Materials

    Science.gov (United States)

    Ringo, Sawnese; Barghouty, A. F.

    2010-01-01

    In this project, the specific effects of displacement damage due to the passage of protons and helium nuclei on some typical electronic materials will be evaluated and contrasted. As the electronic material absorbs the energetic proton and helium momentum, degradation of performance occurs, eventually leading to overall failure. Helium nuclei traveling at the same speed as protons are expected to impart more to the material displacement damage; due to the larger mass, and thus momentum, of helium nuclei compared to protons. Damage due to displacement of atoms in their crystalline structure can change the physical properties and hence performance of the electronic materials.

  11. A single dose of PPARγ agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats.

    Science.gov (United States)

    Pilipović, Kristina; Župan, Željko; Dolenec, Petra; Mršić-Pelčić, Jasenka; Župan, Gordana

    2015-06-03

    Neuroprotective actions of the peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been observed in various animal models of the brain injuries. In this study we examined the effects of a single dose of pioglitazone on oxidative and inflammatory parameters as well as on neurodegeneration and the edema formation in the rat parietal cortex following traumatic brain injury (TBI) induced by the lateral fluid percussion injury (LFPI) method. Pioglitazone was administered in a dose of 1mg/kg at 10min after the brain trauma. The animals of the control group were sham-operated and injected by vehicle. The rats were decapitated 24h after LFPI and their parietal cortices were analyzed by biochemical and histological methods. Cortical edema was evaluated in rats sacrificed 48h following TBI. Brain trauma caused statistically significant oxidative damage of lipids and proteins, an increase of glutathione peroxidase (GSH-Px) activity, the cyclooxygenase-2 (COX-2) overexpression, reactive astrocytosis, the microglia activation, neurodegeneration, and edema, but it did not influence the superoxide dismutase activity and the expressions of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in the rat parietal cortex. Pioglitazone significantly decreased the cortical lipid and protein oxidative damage, increased the GSH-Px activity and reduced microglial reaction. Although a certain degree of the TBI-induced COX-2 overexpression, neurodegeneration and edema decrease was detected in pioglitazone treated rats, it was not significant. In the injured animals, cortical reactive astrocytosis was unchanged by the tested PPARγ agonist. These findings demonstrate that pioglitazone, administered only in a single dose, early following LFPI, reduced cortical oxidative damage, increased antioxidant defense and had limited anti-inflammatory effect, suggesting the need for further studies of this drug in the treatment of TBI.

  12. Processing of basic speech acts following localized brain damage: a new light on the neuroanatomy of language.

    Science.gov (United States)

    Soroker, Nachum; Kasher, Asa; Giora, Rachel; Batori, Gila; Corn, Cecilia; Gil, Mali; Zaidel, Eran

    2005-03-01

    We examined the effect of localized brain lesions on processing of the basic speech acts (BSAs) of question, assertion, request, and command. Both left and right cerebral damage produced significant deficits relative to normal controls, and left brain damaged patients performed worse than patients with right-sided lesions. This finding argues against the common conjecture that the right hemisphere of most right-handers plays a dominant role in natural language pragmatics. In right-hemisphere damaged patients, there was no correlation between location and extent of lesion in perisylvian cortex and performance on BSAs. By contrast, processing of the different BSAs by left hemisphere-damaged patients was strongly affected by perisylvian lesion location, with each BSA showing a distinct pattern of localization. This finding raises the possibility that the classical left perisylvian localization of language functions, as measured by clinical aphasia batteries, partly reflects the localization of the BSAs required to perform these functions.

  13. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    Science.gov (United States)

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2015-05-01

    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment.

  14. Chromatin remodeling in the UV-induced DNA damage response

    NARCIS (Netherlands)

    Ö.Z. Aydin (Özge)

    2014-01-01

    markdownabstract__Abstract__ DNA damage interferes with transcription and replication, causing cell death, chromosomal aberrations or mutations, eventually leading to aging and tumorigenesis (Hoeijmakers, 2009). The integrity of DNA is protected by a network of DNA repair and associated signalling

  15. Damage induced by paracetamol compared with N-acetylcysteine

    Directory of Open Access Journals (Sweden)

    Abdullah Kisaoglu

    2014-09-01

    Conclusion: Thiamine pyrophosphate and N-acetylcysteine had a similar positive effect on oxidative damage caused by paracetamol hepatotoxicity. These findings show that TPP may be beneficial in paracetamol hepatotoxicity.

  16. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

    OpenAIRE

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary ...

  17. Biomarkers of Brain Damage and Postoperative Cognitive Disorders in Orthopedic Patients: An Update.

    Science.gov (United States)

    Tomaszewski, Dariusz

    2015-01-01

    The incidence of postoperative cognitive dysfunction (POCD) in orthopedic patients varies from 16% to 45%, although it can be as high as 72%. As a consequence, the hospitalization time of patients who developed POCD was longer, the outcome and quality of life were worsened, and prolonged medical and social assistance were necessary. In this review the short description of such biomarkers of brain damage as the S100B protein, NSE, GFAP, Tau protein, metalloproteinases, ubiquitin C terminal hydrolase, microtubule-associated protein, myelin basic protein, α-II spectrin breakdown products, and microRNA was made. The role of thromboembolic material in the development of cognitive decline was also discussed. Special attention was paid to optimization of surgical and anesthetic procedures in the prevention of postoperative cognitive decline.

  18. Biomarkers of Brain Damage and Postoperative Cognitive Disorders in Orthopedic Patients: An Update

    Directory of Open Access Journals (Sweden)

    Dariusz Tomaszewski

    2015-01-01

    Full Text Available The incidence of postoperative cognitive dysfunction (POCD in orthopedic patients varies from 16% to 45%, although it can be as high as 72%. As a consequence, the hospitalization time of patients who developed POCD was longer, the outcome and quality of life were worsened, and prolonged medical and social assistance were necessary. In this review the short description of such biomarkers of brain damage as the S100B protein, NSE, GFAP, Tau protein, metalloproteinases, ubiquitin C terminal hydrolase, microtubule-associated protein, myelin basic protein, α-II spectrin breakdown products, and microRNA was made. The role of thromboembolic material in the development of cognitive decline was also discussed. Special attention was paid to optimization of surgical and anesthetic procedures in the prevention of postoperative cognitive decline.

  19. Continuous cytokine exposure of colonic epithelial cells induces DNA damage

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole Haagen

    2005-01-01

    Chronic inflammatory diseases of the intestinal tract are associated with an increased risk of colorectal cancer. As an example ulcerative colitis (UC) is associated with a production of reactive oxygen species (ROS), including nitrogen monoxide (NO), which is produced in high amounts by inducibl...... nitrogen oxide synthase (iNOS). NO as well as other ROS are potential DNA damaging agents. The aim was to determine the effect of long-term cytokine exposure on NO formation and DNA damage in epithelial cells....

  20. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    Directory of Open Access Journals (Sweden)

    Mónica Millán

    2008-01-01

    Full Text Available Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA.

  1. Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

    Science.gov (United States)

    Flores-Palacios, Alejandro; Corona-López, Angélica María; Rios, María Yolanda; Aguilar-Guadarrama, Berenice; Toledo-Hernández, Víctor Hugo; Rodríguez-López, Verónica; Valencia-Díaz, Susana

    2015-01-01

    Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC) 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound) and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load) that may be caused by a high load of epiphytes than to damage caused by the xylophages. PMID:26625350

  2. Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

    Directory of Open Access Journals (Sweden)

    Alejandro Flores-Palacios

    Full Text Available Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load that may be caused by a high load of epiphytes than to damage caused by the xylophages.

  3. Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

    Science.gov (United States)

    Flores-Palacios, Alejandro; Corona-López, Angélica María; Rios, María Yolanda; Aguilar-Guadarrama, Berenice; Toledo-Hernández, Víctor Hugo; Rodríguez-López, Verónica; Valencia-Díaz, Susana

    2015-01-01

    Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC) 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound) and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load) that may be caused by a high load of epiphytes than to damage caused by the xylophages.

  4. Reappraisal generation after acquired brain damage: The role of laterality and cognitive control

    Science.gov (United States)

    Salas, Christian E.; Gross, James J.; Turnbull, Oliver H.

    2014-01-01

    In the past decade, there has been growing interest in the neuroanatomical and neuropsychological bases of reappraisal. Findings suggest that reappraisal activates a set of areas in the left hemisphere (LH), which are commonly associated with language abilities and verbally mediated cognitive control. The main goal of this study was to investigate whether individuals with focal damage to the LH (n = 8) were more markedly impaired on a reappraisal generation task than individuals with right hemisphere lesions (RH, n = 8), and healthy controls (HC, n = 14). The reappraisal generation task consisted of a set of ten pictures from the IAPS, depicting negative events of different sorts. Participants were asked to quickly generate as many positive reinterpretations as possible for each picture. Two scores were derived from this task, namely difficulty and productivity. A second goal of this study was to explore which cognitive control processes were associated with performance on the reappraisal task. For this purpose, participants were assessed on several measures of cognitive control. Findings indicated that reappraisal difficulty – defined as the time taken to generate a first reappraisal – did not differ between LH and RH groups. However, differences were found between patients with brain injury (LH + RH) and HC, suggesting that brain damage in either hemisphere influences reappraisal difficulty. No differences in reappraisal productivity were found across groups, suggesting that neurological groups and HC are equally productive when time constraints are not considered. Finally, only two cognitive control processes inhibition and verbal fluency- were inversely associated with reappraisal difficulty. Implications for the neuroanatomical and neuropsychological bases of reappraisal generation are discussed, and implications for neuro-rehabilitation are considered. PMID:24711799

  5. Piano training in youths with hand motor impairments after damage to the developing brain

    Directory of Open Access Journals (Sweden)

    Lampe R

    2015-08-01

    Full Text Available Renée Lampe,1,* Anna Thienel,2 Jürgen Mitternacht,1 Tobias Blumenstein,1 Varvara Turova,1 Ana Alves-Pinto1,* 1Research Unit for Paediatric Neuroorthopaedics and Cerebral Palsy, Orthopaedics Department, Klinikum Rechts der Isar, Technische Universität München, 2Department Sonderpädagogik, Ludwig Maximilians-Universität München, Munich, Germany *These authors contributed equally to this work Abstract: Damage to the developing brain may lead to impairment of the hand motor function and negatively impact on patients’ quality of life. Development of manual dexterity and finger and hand motor function may be promoted by learning to play the piano. The latter brings together music with the intensive training of hand coordination and fine finger mobility. We investigated if learning to play the piano helped to improve hand motor skills in 18 youths with hand motor disorders resulting from damage during early brain development. Participants trained 35–40 minutes twice a week for 18 months with a professional piano teacher. With the use of a Musical Instrument Digital Interface piano, the uniformity of finger strokes could be objectively assessed from the timing of keystrokes. The analysis showed a significant improvement in the uniformity of keystrokes during the training. Furthermore, the youths showed strong motivation and engagement during the study. This is nevertheless an open study, and further studies remain needed to exclude effects of growth and concomitant therapies on the improvements observed and clarify which patients will more likely benefit from learning to play the piano. Keywords: manual skill, cerebral palsy, neurodevelopmental disorder, music, rehabilitation

  6. DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Maronpot, Robert R; Torres-Jardon, Ricardo; Henríquez-Roldán, Carlos; Schoonhoven, Robert; Acuña-Ayala, Hilda; Villarreal-Calderón, Anna; Nakamura, Jun; Fernando, Reshan; Reed, William; Azzarelli, Biagio; Swenberg, James A

    2003-01-01

    Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant gases affect people in urban areas and those exposed to fires, disasters, and wars. Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NFkappaB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid(1-42) in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days-10 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex. Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer

  7. The perception of positive and negative facial expressions in unilateral brain-damaged patients: A meta-analysis.

    Science.gov (United States)

    Abbott, Jacenta D; Cumming, Geoff; Fidler, Fiona; Lindell, Annukka K

    2013-01-01

    How the brain is lateralised for emotion processing remains a key question in contemporary neuropsychological research. The right hemisphere hypothesis asserts that the right hemisphere dominates emotion processing, whereas the valence hypothesis holds that positive emotion is processed in the left hemisphere and negative emotion is controlled by the right hemisphere. A meta-analysis was conducted to assess unilateral brain-damaged individuals' performance on tasks of facial emotion perception according to valence. A systematic search of the literature identified seven articles that met the conservative selection criteria and could be included in a meta-analysis. A total of 12 meta-analyses of facial expression perception were constructed assessing identification and labelling tasks according to valence and the side of brain damage. The results demonstrated that both left and right hemisphere damage leads to impairments in emotion perception (identification and labelling) irrespective of valence. Importantly, right hemisphere damage prompted more pronounced emotion perception impairment than left hemisphere damage, across valence, suggesting right hemisphere dominance for emotion perception. Furthermore, right hemisphere damage was associated with a larger tendency for impaired perception of negative than positive emotion across identification and labelling tasks. Overall the findings support Adolphs, Jansari, and Tranel (2001) model whereby the right hemisphere preferentially processes negative facial expressions and both hemispheres process positive facial expressions.

  8. Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

    Science.gov (United States)

    Baumert, Philipp; Lake, Mark J; Stewart, Claire E; Drust, Barry; Erskine, Robert M

    2016-09-01

    Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage.

  9. 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.

  10. Theoretical analysis for temperature dependence of laser- induced damage threshold of optical thin films

    Science.gov (United States)

    Mikami, K.; Motokoshi, S.; Somekawa, T.; Jitsuno, T.; Fujita, M.; Tanaka, KA; Azechi, H.

    2016-03-01

    The temperature dependence of the laser-induced damage threshold on optical coatings was studied in detail for laser pulses from 123 K to 473 K at different temperatures. The laser-induced damage threshold increased with decreasing temperatures when we tested long pulses (200 ps and 4 ns). The temperature dependence, however, was reversed for pulses shorter than a few picoseconds (100 fs testing). We propose a scaling model with a flowchart that includes three separate processes: free-electron generation, electron multiplication, and electron heating. Furthermore, we calculated the temperature dependence of laser-induced damage thresholds at different temperatures. Our calculation results agreed well with the experimental results.

  11. Selective impairment of self body-parts processing in right brain-damaged patients.

    Science.gov (United States)

    Frassinetti, Francesca; Maini, Manuela; Benassi, Mariagrazia; Avanzi, Stefano; Cantagallo, Anna; Farnè, Alessandro

    2010-03-01

    To investigate whether the processing of the visual appearance of one's own body, that is the corporeal self is a unified or modular function we submitted eight right brain-damaged (RBD) patients and a group of fourteen age-matched neurologically healthy subjects, to a visual matching-to-sample task testing for corporeal self processing. If corporeal self processing is a unique function (i.e., body- and face-parts are processed by the same network), patients impaired in self body-parts (i.e., showing no self-advantage) should be impaired also in self face-parts; alternatively, if corporeal self processing is a modular function (i.e., body- and face-parts are processed by different networks), patients impaired in self body-parts should be unimpaired in self face-parts, unless the face-module is also damaged by the lesion. Results showed that healthy participants were more accurate in processing pictures representing their own as compared to other people's body- and face-parts, showing the so-called self-advantage. The patients' findings revealed a simple dissociation, in that patients who were impaired in the processing of self-related body-parts showed a preserved self-advantage when processing self-related face-parts, thus providing initial evidence of a modular representation of the corporeal self.

  12. The DNA damage response molecule MCPH1 in brain development and beyond

    Institute of Scientific and Technical Information of China (English)

    Xiaoqian Liu; Zhong-Wei Zhou; Zhao-Qi Wang

    2016-01-01

    Microcephalin (MCPH1) is identified as being responsible for the neurodevelopmental disorder primary microcephaly type 1,which is characterized by a smaller-than-normal brain size and mental retardation.MCPH1 has originally been identified as an important regulator of telomere integrity and of cell cycle control.Genetic and cellular studies show that MCPH1 controls neurogenesis by coordinating the cell cycle and the centrosome cycle and thereby regulating the division mode of neuroprogenitors to prevent the exhaustion of the progenitor pool and thereby microcephaly.In addition to its role in neurogenesis,MCPH1 plays a role in gonad development.MCPH1 also functions as a tumor suppressor in several human cancers as well as in mouse models.Here,we review the role of MCPH1 in DNA damage response,cell cycle control,chromosome condensation and chromatin remodeling.We also summarize the studies on the biological functions of MCPH1 in brain size determination and in pathologies,including infertility and cancer.

  13. Multifocal brain damage due to lacquer sniffing: the first case report of Thailand.

    Science.gov (United States)

    Poungvarin, N

    1991-07-01

    The first patient of multifocal brain damage due to lacquer sniffing was reported in Thailand. He was a 24-year-old man who had a 5 year history of lacquer sniffing (toluene abuse). He had difficulty in walking and had tremor for 1 year which became progressively worse and he was finally confined to bed. Examination revealed marked cerebellar signs of both upper and lower extremities with scanning speech. Five of his friends who were lacquer abusers also had similar symptoms and were confined to bed. Investigations showed marked atrophy of both cerebellar hemispheres, vermis, brainstem and less atrophy of both cerebral hemispheres in both computerized brain scanning and magnetic resonance imaging. Diffuse toxic demyelination of white matter and excess iron deposition over both thalami, basal ganglia and cerebral cortex were demonstrated on magnetic resonance imaging. Brainstem evoked response showed abnormal response of both sides. Nerve conduction velocity, electromyographic study and electroencephalogram were normal. Psychometric tests revealed dull normal or below average IQ-test of 82. He was admitted for 2 months with gradual recovery of neurological deficits. After six months of abstinence from lacquer and daily physical rehabilitation. This report of toluene abuse is not only public health problem but also reflects the socioeconomic status as well as political unawareness of this condition in the Thai community.

  14. 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.

  15. Exercise-induced muscle damage and the potential protective role of estrogen.

    Science.gov (United States)

    Kendall, Becky; Eston, Roger

    2002-01-01

    Exercise-induced muscle damage is a well documented phenomenon that often follows unaccustomed and sustained metabolically demanding activities. This is a well researched, but poorly understood area, including the actual mechanisms involved in the muscle damage and repair cycle. An integrated model of muscle damage has been proposed by Armstrong and is generally accepted. A more recent aspect of exercise-induced muscle damage to be investigated is the potential of estrogen to have a protective effect against skeletal muscle damage. Estrogen has been demonstrated to have a potent antioxidant capacity that plays a protective role in cardiac muscle, but whether this antioxidant capacity has the ability to protect skeletal muscle is not fully understood. In both human and rat studies, females have been shown to have lower creatine kinase (CK) activity following both eccentric and sustained exercise compared with males. As CK is often used as an indirect marker of muscle damage, it has been suggested that female muscle may sustain less damage. However, these findings may be more indicative of the membrane stabilising effect of estrogen as some studies have shown no histological differences in male and female muscle following a damaging protocol. More recently, investigations into the potential effect of estrogen on muscle damage have explored the possible role that estrogen may play in the inflammatory response following muscle damage. In light of these studies, it may be suggested that if estrogen inhibits the vital inflammatory response process associated with the muscle damage and repair cycle, it has a negative role in restoring normal muscle function after muscle damage has occurred. This review is presented in two sections: firstly, the processes involved in the muscle damage and repair cycle are reviewed; and secondly, the possible effects that estrogen has upon these processes and muscle damage in general is discussed. The muscle damage and repair cycle is

  16. Laser Induced Damage Studies in Borosilicate Glass Using nanosecond and sub nanosecond pulses

    CERN Document Server

    Rastogi, Vinay; Munda, D S

    2016-01-01

    The damage mechanism induced by laser pulse of different duration in borosilicate glass widely used for making confinement geometry targets which are important for laser driven shock multiplication and elongation of pressure pulse, is studied. We measured the front and rear surface damage threshold of borosilicate glass and their dependency on laser parameters. In this paper, we also study the thermal effects on the damage diameters, generated at the time of plasma formation. These induced damage width, geometries and microstructure changes are measured and analyzed with optical microscope, scanning electron microscope and Raman spectroscopy. The results show that at low energies symmetrical damages are found and these damage width increases nonlinearly with laser intensity. The emitted optical spectrum during the process of breakdown is also investigated and is used for the characterization of emitted plasma such as plasma temperature and free electron density. Optical emission lines from Si I at 500 nm, Si ...

  17. Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation-induced DNA damage in PC12 cells

    Directory of Open Access Journals (Sweden)

    Beheshteh Babazadeh

    2012-06-01

    Full Text Available Objective: The discovery and development of natural products with potent antioxidant properties has been one of the most interesting and promising approaches in the search for treatment of CNS injuries. The most significant consequence of the oxidative stress is thought to be the DNA modifications, which can become permanent via the formation of mutations and other types of genomic instability resulting cellular dysfunction. Serum/glucose deprivation (SGD has served as an excellent in vitro model for the understanding of the molecular mechanisms of neuronal damage during ischemia and for the development of neuroprotective drugs against ischemia-induced brain injury. Nigella sativa (N. sativa seeds and thymoquinone (TQ, its most abundant constituent, have been shown to possess anti-inflammatory, antioxidant, chemopreventive and anti-neoplastic effects both in vitro and in vivo. Therefore, in this study we investigated genoprotective effects of N. sativa and TQ on DNA damage of PC12 cells under SGD condition. Materials and Methods: PC12 cells were cultured in DMEM medium containing 10% (v/v fetal bovine serum, 100 units/ml penicillin, and 100 µg/ml streptomycin. Initially cells were pretreated with different concentrations of N. sativa extract (NSE, (10, 50, 250 µg/ml and TQ (1, 5, 10 µg/ml for 6 h and then deprived of serum/glucose (SGD for 18 h. The alkaline comet assay was used to evaluate the effect of these compounds on DNA damage following ischemic insult. The amount of DNA in the comet tail (% tail DNA was measured as an indicator of DNA damage. Results: A significant increase in the % tail DNA was seen in nuclei of cells following SGD induced  DNA damage (p0.05. NSE and TQ pretreatment resulted in a significant decrease in DNA damage following ischemic insult (p

  18. Lesion correlates of impairments in actual tool use following unilateral brain damage.

    Science.gov (United States)

    Salazar-López, E; Schwaiger, B J; Hermsdörfer, J

    2016-04-01

    To understand how the brain controls actions involving tools, tests have been developed employing different paradigms such as pantomime, imitation and real tool use. The relevant areas have been localized in the premotor cortex, the middle temporal gyrus and the superior and inferior parietal lobe. This study employs Voxel Lesion Symptom Mapping to relate the functional impairment in actual tool use with extent and localization of the structural damage in the left (LBD, N=31) and right (RBD, N=19) hemisphere in chronic stroke patients. A series of 12 tools was presented to participants in a carousel. In addition, a non-tool condition tested the prescribed manipulation of a bar. The execution was scored according to an apraxic error scale based on the dimensions grasp, movement, direction and space. Results in the LBD group show that the ventro-dorsal stream constitutes the core of the defective network responsible for impaired tool use; it is composed of the inferior parietal lobe, the supramarginal and angular gyrus and the dorsal premotor cortex. In addition, involvement of regions in the temporal lobe, the rolandic operculum, the ventral premotor cortex and the middle occipital gyrus provide evidence of the role of the ventral stream in this task. Brain areas related to the use of the bar largely overlapped with this network. For patients with RBD data were less conclusive; however, a trend for the involvement of the temporal lobe in apraxic errors was manifested. Skilled bar manipulation depended on the same temporal area in these patients. Therefore, actual tool use depends on a well described left fronto-parietal-temporal network. RBD affects actual tool use, however the underlying neural processes may be more widely distributed and more heterogeneous. Goal directed manipulation of non-tool objects seems to involve very similar brain areas as tool use, suggesting that both types of manipulation share identical processes and neural representations. Copyright

  19. Residual force enhancement following eccentric induced muscle damage.

    Science.gov (United States)

    Power, Geoffrey A; Rice, Charles L; Vandervoort, Anthony A

    2012-06-26

    During lengthening of an activated skeletal muscle, the force maintained following the stretch is greater than the isometric force at the same muscle length. This is termed residual force enhancement (RFE), but it is unknown how muscle damage following repeated eccentric contractions affects RFE. Using the dorsiflexors, we hypothesised muscle damage will impair the force generating sarcomeric structures leading to a reduction in RFE. Following reference maximal voluntary isometric contractions (MVC) in 8 young men (26.5±2.8y) a stretch was performed at 30°/s over a 30° ankle excursion ending at the same muscle length as the reference MVCs (30° plantar flexion). Surface electromyography (EMG) of the tibialis anterior and soleus muscles was recorded during all tasks. The damage protocol involved 4 sets of 25 isokinetic (30°/s) lengthening contractions. The same measures were collected at baseline and immediately post lengthening contractions, and for up to 10min recovery. Following the lengthening contraction task, there was a 30.3±6.4% decrease in eccentric torque (Pmuscle damage (Pmuscle function compared to isometric actions succeeding damage. Thus, active force of cross-bridges is decreased because of impaired excitation-contraction coupling but force generated during stretch remains intact because force contribution from stretched sarcomeric structures is less impaired.

  20. Stress-induced DNA damage biomarkers: applications and limitations

    Science.gov (United States)

    Nikitaki, Zacharenia; Hellweg, Christine E.; Georgakilas, Alexandros G.; Ravanat, Jean-Luc

    2015-01-01

    A variety of environmental stresses like chemicals, UV and ionizing radiation and organism's endogenous processes such as replication stress and metabolism can lead to the generation of reactive oxygen and nitrogen species (ROS/RNS) that can attack cellular vital components like DNA, proteins and lipid membranes. Among them, much attention has been focused on DNA since DNA damage plays a role in several biological disorders and aging processes. Thus, DNA damage can be used as a biomarker in a reliable and accurate way to quantify for example radiation exposure and can indicate its possible long term effects and cancer risk. Based on the type of DNA lesions detected one can hypothesize on the most probable mechanisms involved in the formation of these lesions for example in the case of UV and ionizing radiation (e.g., X- or α-, γ-rays, energetic ions, neutrons). In this review we describe the most accepted chemical pathways for DNA damage induction and the different types of DNA lesions, i.e., single, complex DNA lesions etc. that can be used as DNA damage biomarkers. We critically compare DNA damage detection methods and their limitations. In addition, we suggest the use of DNA repair gene products as biomarkes for identification of different types of stresses i.e., radiation, oxidative, or replication stress, based on bioinformatic approaches and meta-analysis of literature data. PMID:26082923

  1. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  2. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment.

    Science.gov (United States)

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

    2014-02-01

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

  3. 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.

    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

  4. 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 (

  5. 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

  6. Detection of DNA damage induced by heavy ion irradiation in the individual cells with comet assay

    Science.gov (United States)

    Wada, S.; Natsuhori, M.; Ito, N.; Funayama, T.; Kobayashi, Y.

    2003-05-01

    Investigating the biological effects of high-LET heavy ion irradiation at low fluence is important to evaluate the risk of charged particles. Especially it is important to detect radiation damage induced by the precise number of heavy ions in the individual cells. Thus we studied the relationship between the number of ions traversing the cell and DNA damage produced by the ion irradiation. We applied comet assay to measure the DNA damage in the individual cells. Cells attached on the ion track detector CR-39 were irradiated with ion beams at TIARA, JAERI-Takasaki. After irradiation, the cells were stained with ethidium bromide and the opposite side of the CR-39 was etched. We observed that the heavy ions with higher LET values induced the heavier DNA damage. The result indicated that the amount of DNA damage induced by one particle increased with the LET values of the heavy ions.

  7. Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2017-01-01

    Full Text Available CeO2 nanoparticles (CeO2 NPs which are used as a diesel fuel additive are emitted in the particulate phase in the exhaust, posing a health concern. However, limited information exists regarding the in vivo acute toxicity of CeO2 NPs on multiple organs. Presently, we investigated the acute (24 h effects of intratracheally instilled CeO2 NPs in mice (0.5 mg/kg on oxidative stress, inflammation, and DNA damage in major organs including lung, heart, liver, kidneys, spleen, and brain. Lipid peroxidation measured by malondialdehyde production was increased in the lungs only, and reactive oxygen species were increased in the lung, heart, kidney, and brain. Superoxide dismutase activity was decreased in the lung, liver, and kidney, whereas glutathione increased in lung but it decreased in the kidney. Total nitric oxide was increased in the lung and spleen but it decreased in the heart. Tumour necrosis factor-α increased in all organs studied. Interleukin- (IL- 6 increased in the lung, heart, liver, kidney, and spleen. IL-1β augmented in the lung, heart, kidney, and spleen. Moreover, CeO2 NPs induced DNA damage, assessed by COMET assay, in all organs studied. Collectively, these findings indicate that pulmonary exposure to CeO2 NPs causes oxidative stress, inflammation, and DNA damage in multiple organs.

  8. 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.

  9. 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.

  10. Explosive-induced shock damage in copper and recompression of the damaged region

    Science.gov (United States)

    Turley, W. D.; Stevens, G. D.; Hixson, R. S.; Cerreta, E. K.; Daykin, E. P.; Graeve, O. A.; La Lone, B. M.; Novitskaya, E.; Perez, C.; Rigg, P. A.; Veeser, L. R.

    2016-08-01

    We have studied the dynamic spall process for copper samples in contact with detonating low-performance explosives. When a triangular shaped shock wave from detonation moves through a sample and reflects from the free surface, tension develops immediately, one or more damaged layers can form, and a spall scab can separate from the sample and move ahead of the remaining target material. For dynamic experiments, we used time-resolved velocimetry and x-ray radiography. Soft-recovered samples were analyzed using optical imaging and microscopy. Computer simulations were used to guide experiment design. We observe that for some target thicknesses the spall scab continues to run ahead of the rest of the sample, but for thinner samples, the detonation product gases accelerate the sample enough for it to impact the spall scab several microseconds or more after the initial damage formation. Our data also show signatures in the form of a late-time reshock in the time-resolved data, which support this computational prediction. A primary goal of this research was to study the wave interactions and damage processes for explosives-loaded copper and to look for evidence of this postulated recompression event. We found both experimentally and computationally that we could tailor the magnitude of the initial and recompression shocks by varying the explosive drive and the copper sample thickness; thin samples had a large recompression after spall, whereas thick samples did not recompress at all. Samples that did not recompress had spall scabs that completely separated from the sample, whereas samples with recompression remained intact. This suggests that the hypothesized recompression process closes voids in the damage layer or otherwise halts the spall formation process. This is a somewhat surprising and, in some ways controversial, result, and the one that warrants further research in the shock compression community.

  11. Hybrid molecular dynamics simulation for plasma induced damage analysis

    Science.gov (United States)

    Matsukuma, Masaaki

    2016-09-01

    In order to enable further device size reduction (also known as Moore's law) and improved power performance, the semiconductor industry is introducing new materials and device structures into the semiconductor fabrication process. Materials now include III-V compounds, germanium, cobalt, ruthenium, hafnium, and others. The device structure in both memory and logic has been evolving from planar to three dimensional (3D). One such device is the FinFET, where the transistor gate is a vertical fin made either of silicon, silicon-germanium or germanium. These changes have brought renewed interests in the structural damages caused by energetic ion bombardment of the fin sidewalls which are exposed to the ion flux from the plasma during the fin-strip off step. Better control of the physical damage of the 3D devices requires a better understanding of the damage formation mechanisms on such new materials and structures. In this study, the damage formation processes by ion bombardment have been simulated for Si and Ge substrate by Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid simulations and compared to the results from the classical molecular dynamics (MD) simulations. In our QM/MM simulations, the highly reactive region in which the structural damage is created is simulated with the Density Functional based Tight Binding (DFTB) method and the region remote from the primary region is simulated using classical MD with the Stillinger-Weber and Moliere potentials. The learn on the fly method is also used to reduce the computational load. Hence our QM/MM simulation is much faster than the full QC-MD simulations and the original QM/MM simulations. The amorphous layers profile simulated with QM/MM have obvious differences in their thickness for silicon and germanium substrate. The profile of damaged structure in the germanium substrate is characterized by a deeper tail then in silicon. These traits are also observed in the results from the mass selected ion beam