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Sample records for ethanol-induced motor impairment

  1. Central adenosinergic system involvement in ethanol-induced motor incoordination in mice

    Energy Technology Data Exchange (ETDEWEB)

    Dar, M.S. (East Carolina Univ., Greenville, NC (USA))

    1990-12-01

    To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v. adenosine agonists, N6-(R-phenylisopropyl)adenosine (R-PIA), N6-(S-phenylisopropyl)adenosine, 5'-(N-cyclopropyl)-carboxamidoadenosine, antagonists, theophylline and 8-p-(sulfophenyl)theophylline as well as enprofylline on ethanol-(i.p.)-induced motor incoordination was evaluated by rotorod. Adenosine agonists and antagonists dose dependently accentuated and attenuated, respectively, ethanol-induced motor incoordination, thereby suggesting a central mechanism of adenosine modulation of this effect of ethanol and confirmed our previous reports in which adenosine agonists and antagonists were given i.p. Enprofylline, a weak adenosine antagonist but potent inhibitor of cyclic AMP phosphodiesterase, did not alter ethanol's motor incoordination, further supporting involvement of brain adenosine receptor mechanism(s) in ethanol-adenosine interactions. Results from R-PIA and N6-(S-phenylisopropyl)adenosine experiments showed nearly a 40-fold greater potency of R-vs. S-diastereoisomer, suggesting predominance of adenosine A1 subtype. However, 5'-(N-cyclopropyl)-carboxamidoadenosine data indicate complexity of the mechanism(s) and point toward an additional involvement of a yet unknown subtype of adenosine A2. No effect of ethanol on blood or brain levels of (3H)R-PIA was noted and sufficient amount of the latter entered the brain to suggest adenosine receptor activation adequate to produce behavioral interaction with ethanol. There was no escape of i.c.v.-administered (3H)R-PIA from brain to the peripheral circulation ruling out a peripheral and supporting a central mechanism of ethanol-adenosine interaction.

  2. Zonal differences in ethanol-induced impairments in receptor-mediated endocytosis of asialoglycoproteins in isolated rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Casey, C.A.; Kragskow, S.L.; Sorrell, M.F.; Tuma, D.J. (Department of Veterans Affairs Medical Center, Omaha, NE (USA))

    1991-02-01

    We have shown previously that ethanol-induced defects in receptor-mediated endocytosis of asialoorosomucoid occurred as early as 1 wk after ethanol feeding. This study was undertaken as an initial attempt to establish a possible role of defective receptor-mediated endocytosis in liver injury by investigating whether differences exist in the effects of ethanol on receptor-mediated endocytosis in hepatocytes isolated from different regions of the liver. Perivenule cells, present in the distal half of the liver, are thought to be more susceptible to ethanol-induced liver injury than are the periportal cells located in the proximal half of the liver acini. For these studies, we fed male Sprague-Dawley rats for 7 days with liquid diets containing either ethanol (36% of calories) or isocaloric carbohydrate. Perivenule and periportal hepatocytes were then isolated using a digitonin-collagenase perfusion method. In control animals, cells isolated from the perivenule region bound significantly more ligand than did cells from the periportal region. Amounts of ligand internalized and degraded were also greater in perivenule than in periportal cells in these animals. After ethanol feeding, cells isolated from both the perivenule and periportal regions bound significantly less ligand than their respective controls. This impairment in surface and total binding was more pronounced in perivenule than in periportal cells. Internalization and degradation of the ligand were also more adversely affected in the centrilobular region as shown by decreases of greater than 60% in perivenule cells and by only 20% to 30% in periportal cells of ethanol-fed animals compared with controls.

  3. The Neuroprotective Effects of Carvacrol on Ethanol-Induced Hippocampal Neurons Impairment via the Antioxidative and Antiapoptotic Pathways

    Directory of Open Access Journals (Sweden)

    Peng Wang

    2017-01-01

    Full Text Available Chronic alcohol consumption causes hippocampal neuronal impairment, which is associated with oxidative stress and apoptosis. Carvacrol is a major monoterpenic phenol found in essential oils from the family Labiatae and has antioxidative stress and antiapoptosis actions. However, the protective effects of carvacrol in ethanol-induced hippocampal neuronal impairment have not been fully understood. We explored the neuroprotective effects of carvacrol in vivo and in vitro. Male C57BL/6 mice were exposed to 35% ethanol for 4 weeks to establish ethanol model in vivo, and hippocampal neuron injury was simulated by 200 mM ethanol in vitro. Morris water maze test was performed to evaluate the cognitive dysfunction. The oxidative stress injury of hippocampal neurons was evaluated by measuring the levels of oxidative stress biomarkers. Histopathological examinations and western blot were performed to evaluate the apoptosis of neurons. The results showed that carvacrol attenuates the cognitive dysfunction, oxidative stress, and apoptosis of the mice treated with ethanol and decreases hippocampal neurons apoptosis induced by ethanol in vitro. In addition, western blot analysis revealed that carvacrol modulates the protein expression of Bcl-2, Bax, caspase-3, and p-ERK, without influence of p-JNK and p-p38. Our results suggest that carvacrol alleviates ethanol-mediated hippocampal neuronal impairment by antioxidative and antiapoptotic effects.

  4. Comparison of the impact of melatonin on chronic ethanol-induced learning and memory impairment between young and aged rats.

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    Baydas, Giyasettin; Yasar, Abdullah; Tuzcu, Mehmet

    2005-11-01

    Chronic alcohol exposure causes functional and structural changes in nervous system which have all been associated with learning and memory impairments. Furthermore, alcohol consumption has been shown to alter the pattern of neural cell adhesion molecules (NCAM) which are involved in memory processes. In the current work, we investigated the effects of melatonin on learning and memory deficits induced by alcohol exposure in young and aged rats. A group of young rats (3 months old) were administered ethanol for 45 days and half of them were co-treated with melatonin. Similar treatments were performed in the aged (19 months old) rats. Morris water maze test and passive avoidance task were used to assess cognitive performance. Lipid peroxidation (LPO) and glutathione (GSH) levels were determined to characterize the level of oxidative stress in the hippocampus and cortex. NCAM levels were determined by Western blotting in the hippocampal homogenates. There was a significant elevation in LPO levels and a reduction in GSH levels in aged and alcohol-exposed rats. Furthermore, both young and aged rats displayed some cognitive impairment when given with alcohol for 45 days. Co-administration of melatonin with ethanol significantly reduced LPO and elevated GSH levels while improving the learning and memory deficits induced by ethanol; the aged rats exhibited a greater response to melatonin supplementation. Moreover, melatonin modulated NCAM expression in hippocampus. Present findings indicate that exposure to ethanol induces learning and memory deficits probably by generating reactive oxygen species and downregulating NCAM 180 in hippocampus of aged rats. Melatonin improves learning and memory deficits and the behavioral responses of rats to melatonin supplementation are age dependent.

  5. Different genes influence toluene- and ethanol-induced locomotor impairment in C. elegans*

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    Davies, Andrew G.; Friedberg, Ryan I.; Gupta, Hersh; Chan, Chung-Lung; Shelton, Keith L.; Bettinger, Jill C.

    2011-01-01

    Background The abused volatile solvent toluene shares many behavioral effects with classic central nervous system depressants such as ethanol. Similarities between toluene and ethanol have also been demonstrated using in vitro electrophysiology. Together, these studies suggest that toluene and ethanol may be acting, at least in part, via common mechanisms. Methods We used the genetic model, C. elegans, to examine the behavioral effects of toluene in a simple system, and used mutant strains known to have altered responses to other CNS depressants to examine the involvement of those genes in the motor effects induced by toluene. Results Toluene vapor brings about an altered pattern of locomotion in wild-type worms that is visibly distinct from that generated by ethanol. Mutants of the slo-1, rab-3 and unc-64 genes that are resistant to ethanol or the volatile anesthetic halothane show no resistance to toluene. A mutation in the unc-79 gene results in hypersensitivity to ethanol, halothane and toluene indicating a possible convergence of mechanisms of the three compounds. We screened for, and isolated, two mutations that generate resistance to the locomotor depressing effects of toluene and do not alter sensitivity to ethanol. Conclusions In C. elegans, ethanol and toluene have distinct behavioral effects and minimal overlap in terms of the genes responsible for these effects. These findings demonstrate that the C. elegans model system provides a unique and sensitive means of delineating both the commonalities as well as the differences in the neurochemical effects of classical CNS depressants and abused volatile inhalants. PMID:21945072

  6. Effects of different exercise protocols on ethanol-induced spatial memory impairment in adult male rats.

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    Hashemi Nosrat Abadi, T; Vaghef, L; Babri, S; Mahmood-Alilo, M; Beirami, M

    2013-06-01

    Chronic ethanol consumption is often accompanied by numerous cognitive deficits and may lead to long-lasting impairments in spatial learning and memory. The aim of the present study was to evaluate the therapeutic potential of regular treadmill exercise on hippocampal-dependent memory in ethanol-treated rats. Spatial memory was tested in a Morris Water Maze task. Adult male Wistar rats were exposed to ethanol (4 g/kg, 20% v/v for 4 weeks) and effects of three exercise protocols (pre-ethanol, post-ethanol and pre-to-post-ethanol treatment) were examined. Results showed that ethanol exposure resulted in longer escape latencies during the acquisition phase of the Morris Water Maze task. Moreover, all three exercise protocols significantly decreased the latency to locate the hidden platform. During the probe trial, ethanol led to decreased time spent in the target quadrant. In contrast, performance on the probe trial was significantly better in the rats that had done the post- and pre-to-post-ethanol, but not pre-ethanol, exercises. These findings suggest that treadmill running can attenuate the adverse effects of chronic ethanol exposure on spatial memory, and may serve as a non-pharmacological alcohol abuse treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver

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    Tao Zeng

    2018-04-01

    Full Text Available Protein kinase B (PKB/Akt plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD. Previous studies suggest that cytochrome P4502E1 (CYP2E1 plays causal roles in the pathogenesis of alcoholic fatty liver (AFL. We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver. Chronic ethanol exposure had no effects on the protein levels of phosphatidylinositol 3 kinase (PI3K and phosphatase and tensin homologue deleted on chromosome ten (PTEN, and led to a slight decrease of phosphoinositide-dependent protein kinase 1 (PDK-1 protein level. Ethanol exposure resulted in increased levels of malondialdehyde (MDA and 4-hydroxynonenal (4-HNE-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ, an efficient CYP2E1 inhibitor. Interestingly, N-acetyl-L-cysteine (NAC significantly attenuated chronic ethanol-induced hepatic fat accumulation and the decline of Akt phosphorylation at Thr308. In the in vitro studies, Akt phosphorylation was suppressed in CYP2E1-expressing HepG2 (CYP2E1-HepG2 cells compared with the negative control HepG2 (NC-HepG2 cells, and 4-HNE treatment led to significant decrease of Akt phosphorylation at Thr308 in wild type HepG2 cells. Lastly, pharmacological activation of Akt by insulin-like growth factor-1 (IGF-1 significantly alleviated chronic ethanol-induced fatty liver in mice. Collectively, these results indicate that CYP2E1-induced oxidative stress may be responsible for ethanol-induced suppression of Akt phosphorylation and pharmacological modulation of Akt in liver may be an effective strategy for the treatment of ethanol-induced fatty liver. Keywords

  8. Effects of electroacupuncture on ethanol-induced impairments of spatial learning and memory and Fos expression in the hippocampus in rats.

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    Lu, Bin; Ma, Zhao; Cheng, Fei; Zhao, Yan; Zhang, Xin; Mao, Huijuan; Shen, Xueyong; Liu, Sheng

    2014-07-25

    It is well established that alcohol impairs spatial learning and memory. Here, we investigated the effects of electroacupuncture (EA) at ST36 or nonacupoint on ethanol-induced learning and memory impairment and the expression of Fos in the hippocampus. Ethanol (5g/kg) was administered intragastrically once a day for 5 consecutive days; 2Hz EA was administered immediately after ethanol exposure. After a 2-day ethanol abstinence, for 6 consecutive days, the rats were submitted to Morris water maze training. Probe trials were performed on 1 day after the final training session. We also applied immunohistochemistry to detect Fos-positive nuclei in the hippocampus. We found that 5-day ethanol exposure markedly decreased spatial learning and memory abilities in the Morris water maze task as indicated by escape latency and time in the target quadrant. EA treatment shortened the time of reaching platform and increased times traveled in the target quadrant (Plearning and memory, which may be involved in the hippocampal CA1 area. EA treatment may provide a novel nonpharmacological strategy for ethanol-induced learning and memory impairment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. ETHANOL-INDUCED LOCOMOTOR ACTIVITY IN ADOLESCENT RATS AND THE RELATIONSHIP WITH ETHANOL-INDUCED CONDITIONED PLACE PREFERENCE AND CONDITIONED TASTE AVERSION

    OpenAIRE

    Acevedo, María Belén; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.; Pautassi, Ricardo Marcos

    2012-01-01

    Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol’s motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference by ethanol at this age. The present study assessed age-related differences in ethanol’s motor stimulating effects and analysed the association between ethanol-induced LMA and conventional measures of ethanol-induced rein...

  10. Striatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption.

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    Bahi, Amine; Dreyer, Jean-Luc

    2013-07-01

    Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Motor development in visually impaired children

    National Research Council Canada - National Science Library

    Hallemans, Ann

    2016-01-01

    ..., a visual impairment affects their overall development, including their motor development and skill acquisition. Different studies report a delay in gross motor milestones such as head control, sitting, standing, crawling, and walking during the first year of life. Vision appears to be key to normal postural and motor development in infants. W...

  12. Attention Deficit Hyperactivity Disorder and Motor Impairment.

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    Goulardins, Juliana B; Marques, Juliana C B; De Oliveira, Jorge A

    2017-04-01

    Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder during childhood, affecting approximately 3-6% of school-aged children; its cardinal symptoms of high activity, impulsivity, and behavioral distractibility might be assumed to have close relationships to interferences with motor skills. A separate body of literature attests to ways that motor problems can severely impact children's daily lives, as motor problems may occur in 30-50% of children with ADHD. This article critically reviews research on motor impairment in children with ADHD, notable differences in motor performance of individuals with ADHD compared with age-matched controls, and possible neural underpinnings of this impairment. We discuss the highly prevalent link between ADHD and developmental coordination disorder (DCD) and the lack of a clear research consensus about motor difficulties in ADHD. Despite increasing evidence and diagnostic classifications that define DCD by motor impairment, the role of ADHD symptoms in DCD has not been delineated. Similarly, while ADHD may predispose children to motor problems, it is unclear whether any such motor difficulties observed in this population are inherent to ADHD or are mediated by comorbid DCD. Future research should address the exact nature and long-term consequences of motor impairment in children with ADHD and elucidate effective treatment strategies for these disorders together and apart.

  13. Motor Impairments in Angelman Syndrome

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    J Gordon Millichap

    2004-04-01

    Full Text Available Of 33 children and adolescents (median age 6 years investigated for learning disability, epilepsy, and motor dysfunction to detect suspected Angelman syndrome (AS, in a study at Goteborg University, Sweden, 23 fulfilled criteria for AS.

  14. Serial practice impairs motor skill consolidation.

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    Neville, Kristin-Marie; Trempe, Maxime

    2017-09-01

    Recent reports have revealed that motor skill learning is impaired if two skills are practiced one after the other, that is before the first skill has had the time to become consolidated. This suggests that motor skills should be practiced in isolation from one another to minimize interference. At the moment, little is known about the effect of practice schedules high in contextual interference on motor skill consolidation. In Experiment 1, we investigated whether a serial practice schedule impairs motor skill consolidation. Participants had to learn two distinct sequences of finger movements (A and B) under either a blocked practice schedule or a serial practice schedule before being retested the following day. A control group also practiced Sequence A only. Our results revealed that a blocked practice schedule led to no interference between the sequences, whereas a serial practice schedule impaired the consolidation of Sequence B. In Experiment 2, we investigated the origin of the interference caused by a serial practice schedule by replacing the physical practice of Sequence A with either the observation of a model performing Sequence A or by asking participants to produce random finger movements. Our results revealed that both tasks interfered with the consolidation of Sequence B. Thus, we suggest that a serial practice schedule impairs motor skill consolidation through a conflict in the brain networks involved in the acquisition of the cognitive representation of the sequence and its execution.

  15. Impaired Visual Motor Coordination in Obese Adults.

    LENUS (Irish Health Repository)

    Gaul, David

    2016-09-01

    Objective. To investigate whether obesity alters the sensory motor integration process and movement outcome during a visual rhythmic coordination task. Methods. 88 participants (44 obese and 44 matched control) sat on a chair equipped with a wrist pendulum oscillating in the sagittal plane. The task was to swing the pendulum in synchrony with a moving visual stimulus displayed on a screen. Results. Obese participants demonstrated significantly (p < 0.01) higher values for continuous relative phase (CRP) indicating poorer level of coordination, increased movement variability (p < 0.05), and a larger amplitude (p < 0.05) than their healthy weight counterparts. Conclusion. These results highlight the existence of visual sensory integration deficiencies for obese participants. The obese group have greater difficulty in synchronizing their movement with a visual stimulus. Considering that visual motor coordination is an essential component of many activities of daily living, any impairment could significantly affect quality of life.

  16. Lentiviral vector-mediated dopamine d3 receptor modulation in the rat brain impairs alcohol intake and ethanol-induced conditioned place preference.

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    Bahi, Amine; Dreyer, Jean-Luc

    2014-09-01

    It has been reported that dopamine D3 receptor (D3R) knockout mice display similar ethanol (EtOH) consumption compared to wild types. In addition, studies with D3R pharmacological targeting were inconclusive. In the current study, we used both gain- and loss-of-function approaches to test the effects of central D3R manipulation on voluntary alcohol intake and EtOH-induced conditioned place preference (CPP) in rats. To this aim, we developed a lentiviral-mediated gene transfer approach to examine whether D3R knockdown (LV-siD3R) or overexpression (LV-D3R) in the nucleus accumbens (NAcc) is sufficient to modulate voluntary alcohol consumption and EtOH-CPP. Using the standard 2-bottle choice drinking paradigm and an unbiased CPP procedure, our results indicated that, like the D3R selective antagonist SB-277011-A, LV-siD3R attenuated voluntary alcohol consumption. In contrast, LV-D3R increased EtOH intake with no effect on total fluid intake. Similarly, the D3R agonist 7-OH-DPAT also exacerbated EtOH intake. Interestingly, neither pharmacological nor genetic manipulation of D3R activity affected saccharin and quinine consumption and preference. More importantly, we report that LV-siD3R blocked, whereas LV-D3R exacerbated, EtOH-CPP. These results support the notion that the D3R plays an important role in alcohol reward in rats and suggest that a key threshold range of D3R levels is associated with impaired alcohol consumption. Taken together, these findings demonstrate that the D3R is an essential component of the molecular pathways underlying the reinforcing properties of alcohol. Thus, medications targeting the D3Rs may be beneficial to tackle EtOH abuse and alcoholism in humans. Copyright © 2014 by the Research Society on Alcoholism.

  17. Motor Imagery Impairment in Postacute Stroke Patients

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    Niclas Braun

    2017-01-01

    Full Text Available Not much is known about how well stroke patients are able to perform motor imagery (MI and which MI abilities are preserved after stroke. We therefore applied three different MI tasks (one mental chronometry task, one mental rotation task, and one EEG-based neurofeedback task to a sample of postacute stroke patients (n=20 and age-matched healthy controls (n=20 for addressing the following questions: First, which of the MI tasks indicate impairment in stroke patients and are impairments restricted to the paretic side? Second, is there a relationship between MI impairment and sensory loss or paresis severity? And third, do the results of the different MI tasks converge? Significant differences between the stroke and control groups were found in all three MI tasks. However, only the mental chronometry task and EEG analysis revealed paresis side-specific effects. Moreover, sensitivity loss contributed to a performance drop in the mental rotation task. The findings indicate that although MI abilities may be impaired after stroke, most patients retain their ability for MI EEG-based neurofeedback. Interestingly, performance in the different MI measures did not strongly correlate, neither in stroke patients nor in healthy controls. We conclude that one MI measure is not sufficient to fully assess an individual’s MI abilities.

  18. AMPA receptor potentiation can prevent ethanol-induced intoxication.

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    Jones, Nicholas; Messenger, Marcus J; O'Neill, Michael J; Oldershaw, Anna; Gilmour, Gary; Simmons, Rosa M A; Iyengar, Smriti; Libri, Vincenzo; Tricklebank, Mark; Williams, Steve C R

    2008-06-01

    We present a substantial series of behavioral and imaging experiments, which demonstrate, for the first time, that increasing AMPA receptor-mediated neurotransmission via administration of potent and selective biarylsulfonamide AMPA potentiators LY404187 and LY451395 reverses the central effects of an acutely intoxicating dose of ethanol in the rat. Using pharmacological magnetic resonance imaging (phMRI), we observed that LY404187 attenuated ethanol-induced reductions in blood oxygenation level dependent (BOLD) in the anesthetized rat brain. A similar attenuation was apparent when measuring local cerebral glucose utilization (LCGU) via C14-2-deoxyglucose autoradiography in freely moving conscious rats. Both LY404187 and LY451395 significantly and dose-dependently reversed ethanol-induced deficits in both motor coordination and disruptions in an operant task where animals were trained to press a lever for food reward. Both prophylactic and acute intervention treatment with LY404187 reversed ethanol-induced deficits in motor coordination. Given that LY451395 and related AMPA receptor potentiators/ampakines are tolerated in both healthy volunteers and elderly patients, these data suggest that such compounds may form a potential management strategy for acute alcohol intoxication.

  19. Procedural Motor Learning in Children with Specific Language Impairment

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    Sanjeevan, Teenu; Mainela-Arnold, Elina

    2017-01-01

    Purpose: Specific language impairment (SLI) is a developmental disorder that affects language and motor development in the absence of a clear cause. An explanation for these impairments is offered by the procedural deficit hypothesis (PDH), which argues that motor difficulties in SLI are due to deficits in procedural memory. The aim of this study…

  20. Limb distribution, motor impairment, and functional classification of cerebral palsy

    NARCIS (Netherlands)

    Gorter, J.A.; Rosenbaum, P.L.

    2004-01-01

    This study explored the relationships between the Gross Motor Function Classification System (GMFCS), limb distribution, and type of motor impairment. Data used were collected in the Ontario Motor Growth study, a longitudinal cohort study with a population-based sample of children with cerebral

  1. Neuropsychological investigation of motor impairments in autism.

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    Duffield, Tyler C; Trontel, Haley G; Bigler, Erin D; Froehlich, Alyson; Prigge, Molly B; Travers, Brittany; Green, Ryan R; Cariello, Annahir N; Cooperrider, Jason; Nielsen, Jared; Alexander, Andrew; Anderson, Jeffrey; Fletcher, P Thomas; Lange, Nicholas; Zielinski, Brandon; Lainhart, Janet

    2013-01-01

    It is unclear how standardized neuropsychological measures of motor function relate to brain volumes of motor regions in autism spectrum disorder (ASD). An all-male sample composed of 59 ASD and 30 controls (ages 5-33 years) completed three measures of motor function: strength of grip (SOG), finger tapping test (FTT), and grooved pegboard test (GPT). Likewise, all participants underwent magnetic resonance imaging with region of interest (ROI) volumes obtained to include the following regions: motor cortex (precentral gyrus), somatosensory cortex (postcentral gyrus), thalamus, basal ganglia, cerebellum, and caudal middle frontal gyrus. These traditional neuropsychological measures of motor function are assumed to differ in motor complexity, with GPT requiring the most followed by FTT and SOG. Performance by ASD participants on the GPT and FTT differed significantly from that of controls, with the largest effect size differences observed on the more complex GPT task. Differences on the SOG task between the two groups were nonsignificant. Since more complex motor tasks tap more complex networks, poorer GPT performance by those with ASD may reflect less efficient motor networks. There was no gross pathology observed in classic motor areas of the brain in ASD, as ROI volumes did not differ, but FTT was negatively related to motor cortex volume in ASD. The results suggest a hierarchical motor disruption in ASD, with difficulties evident only in more complex tasks as well as a potential anomalous size-function relation in motor cortex in ASD.

  2. Tracking motor impairments in the progression of Huntington's disease.

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    Long, Jeffery D; Paulsen, Jane S; Marder, Karen; Zhang, Ying; Kim, Ji-In; Mills, James A

    2014-03-01

    The Unified Huntington's Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene-expanded participants from the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntington's disease research and the planning of clinical trials of efficacy are discussed. © 2013 International Parkinson and Movement Disorder Society.

  3. Children with motor impairment related to cerebral palsy: Prevalence, severity and concurrent impairments in China.

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    He, Ping; Chen, Gong; Wang, Zhenjie; Guo, Chao; Zheng, Xiaoying

    2017-05-01

    Cerebral palsy (CP) is the most common cause of motor impairment in childhood. This study aimed to examine the prevalence, severity and concurrent impairments of CP-related motor impairment among Chinese children. Children with CP-related motor impairment aged 0-17 years were identified through a national population-based survey based on World Health Organization International Classification of Functioning, Disability and Health. Logistic regression models allowing for weights were used to examine individual and family factors in relation to CP-related motor impairment. The weighted prevalence of CP-related motor impairment was 1.25 per 1000 children (95% confidence interval (CI): 1.16, 1.35) in China. Male children, children in multiples and in families where adults suffered from CP, were more likely to be affected by CP-related motor impairment. For mild, moderate, severe and extremely severe groups of motor impairment, weighted proportions of CP were 14.12% (95%CI: 11.70, 16.95), 20.35% (95%CI: 17.48, 23.56), 27.44% (95%CI: 24.25, 30.87) and 38.09% (95%CI: 34.55, 41.76), respectively; and weighted proportions of concurrent visual, hearing and cognitive impairment were 5.00% (95%CI: 3.59, 6.91), 6.98% (95%CI: 5.34, 9.08) and 71.06% (95%CI: 67.57, 74.31), respectively. Gender, multiple births and family adults with CP were significantly associated with CP-related motor impairment in Chinese children. Proportions of CP and concurrent impairments that increased with severity of motor impairment were observed. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  4. The correlation between motor impairments and event-related desynchronization during motor imagery in ALS patients

    Directory of Open Access Journals (Sweden)

    Kasahara Takashi

    2012-06-01

    Full Text Available Abstract Background The event-related desynchronization (ERD in EEG is known to appear during motor imagery, and is thought to reflect cortical processing for motor preparation. The aim of this study is to examine the modulation of ERD with motor impairment in ALS patients. ERD during hand motor imagery was obtained from 8 ALS patients with a variety of motor impairments. ERD was also obtained from age-matched 11 healthy control subjects with the same motor task. The magnitude and frequency of ERD were compared between groups for characterization of ALS specific changes. Results The ERD of ALS patients were significantly smaller than those of control subjects. Bulbar function and ERD were negatively correlated in ALS patients. Motor function of the upper extremities did was uncorrelated with ERD. Conclusions ALS patients with worsened bulbar scales may show smaller ERD. Motor function of the upper extremities did was uncorrelated with ERD.

  5. Early role of the κ opioid receptor in ethanol-induced reinforcement.

    Science.gov (United States)

    Pautassi, Ricardo Marcos; Nizhnikov, Michael E; Acevedo, Ma Belén; Spear, Norman E

    2012-03-20

    Effects of early ethanol exposure on later ethanol intake emphasize the importance of understanding the neurobiology of ethanol-induced reinforcement early in life. Infant rats exhibit ethanol-induced appetitive conditioning and ethanol-induced locomotor activation, which have been linked in theory and may have mechanisms in common. The appetitive effects of ethanol are significantly modulated by μ and δ opioid receptors, whereas μ but not δ receptors are involved in the motor stimulant effects of ethanol during early development. The involvement of the κ opioid receptor (KOR) system in the motivational effects of ethanol has been much less explored. The present study assessed, in preweanling (infant) rats, the modulatory role of the KOR system in several paradigms sensitive to ethanol-induced reinforcement. Kappa opioid activation and blockade were examined in second-order conditioned place preference with varied timing before conditioning and with varied ethanol doses. The role of KOR on ethanol-induced locomotion and ethanol-induced taste conditioning was also explored. The experiments were based on the assumption that ethanol concurrently induces appetitive and aversive effects and that the latter may be mediated by activation of kappa receptors. The main result was that blockade of kappa function facilitated the expression of appetitive ethanol reinforcement in terms of tactile and taste conditioning. The effects of kappa activation on ethanol conditioning seemed to be independent from ethanol's stimulant effects. Kappa opioid activation potentiated the motor depressing effects of ethanol but enhanced motor activity in control subjects. Overall, the results support the hypothesis that a reduced function of the KOR system in nondependent subjects should attenuate the aversive consequences of ethanol. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Impairments of Motor Function While Multitasking in HIV.

    Science.gov (United States)

    Kronemer, Sharif I; Mandel, Jordan A; Sacktor, Ned C; Marvel, Cherie L

    2017-01-01

    Human immunodeficiency virus (HIV) became a treatable illness with the introduction of combination antiretroviral therapy (CART). As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND). The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing). Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

  7. Impairments of Motor Function While Multitasking in HIV

    Directory of Open Access Journals (Sweden)

    Cherie L. Marvel

    2017-04-01

    Full Text Available Human immunodeficiency virus (HIV became a treatable illness with the introduction of combination antiretroviral therapy (CART. As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND. The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing. Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

  8. Motor impairment and its relationship to fitness in children.

    Science.gov (United States)

    Morris, Martyn; Dawes, Helen; Howells, Ken; Janssen, Roel

    2013-01-01

    The aim of this work was to explore the physiological and perceptual limits to exercise in children with varying degrees of motor impairment, and the relationships to measures of health. In a group comparison design, 35 boys aged 12-15 years completed the Movement ABC test for the assessment of motor impairment, followed by an incremental cycle ergometer test to exhaustion for the assessment of maximal oxygen uptake (VO2peak), respiratory exchange ratio (RER), heart rate (HR) and rating of perceived exertion (RPE). Ten participants classified as having either high or no motor impairment also performed a maximal voluntary isometric contraction (MVIC) for the assessment of lower limb extensor strength. 18 boys were classified as having high motor impairment. There was a significant difference in peak (34.9 vs 48.5 mL kg/min), workload (12.5 vs 10.0 mL W), maximal HR (176 vs 188 bpm), maximal oxygen pulse (12.1 vs 15.9 mL beat) and MVIC (5.7 vs 9.1 Nm kg) between the high and non-motor impaired participants, respectively, (pmotor impairment. The lower maximal HR, coupled with reduced movement efficiency and muscle strength reported in this group, suggests that exercise is limited by impairment at the muscular level. This finding was supported by high RER values despite low maximal HR values attained at exercise cessation and reduced maximal strength. Perception of effort is not heightened in children with high motor impairment and future-exercise interventions should be focused on improving muscular condition in these participants to enable them to be better prepared to engage in physical activity for health.

  9. Motor Output Variability Impairs Driving Ability in Older Adults.

    Science.gov (United States)

    Lodha, Neha; Moon, Hwasil; Kim, Changki; Onushko, Tanya; Christou, Evangelos A

    2016-12-01

    The functional declines with aging relate to deficits in motor control and strength. In this study, we determine whether older adults exhibit impaired driving as a consequence of declines in motor control or strength. Young and older adults performed the following tasks: (i) maximum voluntary contractions of ankle dorsiflexion and plantarflexion; (ii) sinusoidal tracking with isolated ankle dorsiflexion; and (iii) a reactive driving task that required responding to unexpected brake lights of the car ahead. We quantified motor control with ankle force variability, gas position variability, and brake force variability. We quantified reactive driving performance with a combination of gas pedal error, premotor and motor response times, and brake pedal error. Reactive driving performance was ~30% more impaired (t = 3.38; p driving (gas pedal variability: t = 1.87; p driving were strongly correlated to greater motor output variability (R 2 = .48; p .05). This study provides novel evidence that age-related declines in motor control but not strength impair reactive driving. These findings have implications on rehabilitation and suggest that interventions should focus on improving motor control to enhance driving-related function in older adults. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Impairments of Motor Function While Multitasking in HIV

    OpenAIRE

    Kronemer, Sharif I.; Mandel, Jordan A.; Sacktor, Ned C.; Marvel, Cherie L.

    2017-01-01

    Human immunodeficiency virus (HIV) became a treatable illness with the introduction of combination antiretroviral therapy (CART). As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND). The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking p...

  11. Oral motor deficits in speech-impaired children with autism.

    Science.gov (United States)

    Belmonte, Matthew K; Saxena-Chandhok, Tanushree; Cherian, Ruth; Muneer, Reema; George, Lisa; Karanth, Prathibha

    2013-01-01

    Absence of communicative speech in autism has been presumed to reflect a fundamental deficit in the use of language, but at least in a subpopulation may instead stem from motor and oral motor issues. Clinical reports of disparity between receptive vs. expressive speech/language abilities reinforce this hypothesis. Our early-intervention clinic develops skills prerequisite to learning and communication, including sitting, attending, and pointing or reference, in children below 6 years of age. In a cohort of 31 children, gross and fine motor skills and activities of daily living as well as receptive and expressive speech were assessed at intake and after 6 and 10 months of intervention. Oral motor skills were evaluated separately within the first 5 months of the child's enrolment in the intervention programme and again at 10 months of intervention. Assessment used a clinician-rated structured report, normed against samples of 360 (for motor and speech skills) and 90 (for oral motor skills) typically developing children matched for age, cultural environment and socio-economic status. In the full sample, oral and other motor skills correlated with receptive and expressive language both in terms of pre-intervention measures and in terms of learning rates during the intervention. A motor-impaired group comprising a third of the sample was discriminated by an uneven profile of skills with oral motor and expressive language deficits out of proportion to the receptive language deficit. This group learnt language more slowly, and ended intervention lagging in oral motor skills. In individuals incapable of the degree of motor sequencing and timing necessary for speech movements, receptive language may outstrip expressive speech. Our data suggest that autistic motor difficulties could range from more basic skills such as pointing to more refined skills such as articulation, and need to be assessed and addressed across this entire range in each individual.

  12. Oral Motor Deficits in Speech-Impaired Children with Autism

    Directory of Open Access Journals (Sweden)

    Matthew K Belmonte

    2013-07-01

    Full Text Available Absence of communicative speech in autism has been presumed to reflect a fundamental deficit in the use of language, but at least in a subpopulation may instead stem from motor and oral motor issues. Clinical reports of disparity between receptive versus expressive speech / language abilities reinforce this hypothesis. Our early-intervention clinic develops skills prerequisite to learning and communication, including sitting, attending, and pointing or reference, in children below 6 years of age. In a cohort of 31 children, gross and fine motor skills and activities of daily living as well as receptive and expressive speech were assessed at intake and after 6 and 10 months of intervention. Oral motor skills were evaluated separately within the first 5 months of the child's enrolment in the intervention programme and again at 10 months of intervention. Assessment used a clinician-rated structured report, normed against samples of 360 (for motor and speech skills and 90 (for oral motor skills typically developing children matched for age, cultural environment and socio-economic status. In the full sample, oral and other motor skills correlated with receptive and expressive language both in terms of pre-intervention measures and in terms of learning rates during the intervention. A motor-impaired group comprising a third of the sample was discriminated by an uneven profile of skills with oral motor and expressive language deficits out of proportion to the receptive language deficit. This group learnt language more slowly, and ended intervention lagging in oral motor skills. In individuals incapable of the degree of motor sequencing and timing necessary for speech movements, receptive language may outstrip expressive speech. Our data suggest that autistic motor difficulties could range from more basic skills such as pointing to more refined skills such as articulation, and need to be assessed and addressed across this entire range in each individual.

  13. The turmeric protective properties at ethanol-induced behavioral disorders.

    Directory of Open Access Journals (Sweden)

    Goldina I.A.

    2017-03-01

    Full Text Available The aim of the study was to determine the effect of mechanically modified turmeric extract on the parameters of orienting-exploratory behavior in mice with chronic ethanol consumption. Material and methods. Mice behavior was assessed in the "open field" test. In the both control groups the animals received water or 10% ethanol solution; in the test group — turmeric extract in 10% ethanol solution. Amount of blood mononuclear cells, thymocytes, and splenocytes were estimated. Results. Analysis of the behavioral parameters in animals after chronic exposure to ethanol showed suppression of motor and exploratory components of the behavior. In mice that received both ethanol and turmeric extract recorded behavior parameters were significantly higher than in the group of animals who received ethanol only. It was shown that the turmeric extract enhances the amount of blood immune cells. Conclusion. Mechanically modified turmeric extract possesses protective properties against ethanol-induced behavioral disorders.

  14. Factors associated with the severity of motor impairment in children ...

    African Journals Online (AJOL)

    Background. Cerebral palsy (CP) is a heterogeneous condition that is well known to cause impairments with varying degrees of severity. The gross motor function classification system (GMFCS) is widely used to assess ambulatory function in CP, but little is known about the factors that account for the variations in gross ...

  15. The nature of hand motor impairment after stroke and its treatment.

    Science.gov (United States)

    Raghavan, Preeti

    2007-06-01

    Hand motor impairments may be viewed as 1) a deficit in motor execution, resulting from weakness, spasticity, and abnormal muscle synergies, and/or 2) a deficit in higher-order processes, such as motor planning and motor learning, which lead to poorly formed sensorimotor associations that lead to impaired motor control. Although weakness and spasticity impede motor execution, strengthening and tone reduction represent simplistic solutions to the deficit in motor control after stroke. Deficits in hand motor control are better appreciated by examining the coordination of fingertip forces and movements during natural movements, and suggest that impairments in motor learning and planning are fundamental impediments to motor recovery following stroke. However, despite an explosion in the number of therapeutic protocols based on the principles of motor learning, little is known about the types of motor learning impairment that occur after stroke and how lesion location may influence motor relearning.

  16. Reflex sympathetic dystrophy of the left hand and motor impairments of the unaffected right hand : impaired central motor processing?

    NARCIS (Netherlands)

    Ribbers, Gerard M.; Mulder, Theo; Geurts, Alexander C.; Den Otter, R.A.

    Objective: To test whether central motor processing can be impaired in chronic reflex sympathetic dystrophy (RSD). Design: Experimental 2-group analysis. Setting: Tertiary care center in the Netherlands. Participants: Five patients with stage 3 RSD of the left forearm, free of symptoms and

  17. Ethanol-induced oxidative stress: basic knowledge

    Science.gov (United States)

    Signorini, Cinzia; Leoncini, Silvia; Gardi, Concetta; Ciccoli, Lucia; Giardini, Anna; Vecchio, Daniela; Arezzini, Beatrice

    2009-01-01

    After a general introduction, the main pathways of ethanol metabolism (alcohol dehydrogenase, catalase, coupling of catalase with NADPH oxidase and microsomal ethanol-oxidizing system) are shortly reviewed. The cytochrome P450 isoform (CYP2E1) specifically involved in ethanol oxidation is discussed. The acetaldehyde metabolism and the shift of the NAD/NADH ratio in the cellular environment (reductive stress) are stressed. The toxic effects of acetaldehyde are mentioned. The ethanol-induced oxidative stress: the increased MDA formation by incubated liver preparations, the absorption of conjugated dienes in mitochondrial and microsomal lipids and the decrease in the most unsaturated fatty acids in liver cell membranes are discussed. The formation of carbon-centered (1-hydroxyethyl) and oxygen-centered (hydroxyl) radicals during the metabolism of ethanol is considered: the generation of hydroxyethyl radicals, which occurs likely during the process of univalent reduction of dioxygen, is highlighted and is carried out by ferric cytochrome P450 oxy-complex (P450–Fe3+O2·−) formed during the reduction of heme-oxygen. The ethanol-induced lipid peroxidation has been evaluated, and it has been shown that plasma F2-isoprostanes are increased in ethanol toxicity. PMID:20606811

  18. Ethanol-induced alterations in sup 14 C-glucose utilization: Modulation by brain adenosine in mice

    Energy Technology Data Exchange (ETDEWEB)

    Anwer, J.; Dar, M.S. (East Carolina Univ., Greenville, NC (United States))

    1992-02-26

    The possible role of brain adenosine (Ado) in acute ethanol-induced alteration in glucose utilization in the cerebellum and brain stem was investigated. The slices were incubated for 100 min in a glucose medium in Warburg flasks using {sup 14}C-glucose as a tracer. Trapped {sup 14}CO{sub 2} was counted to estimate glucose utilization. Ethanol markedly increased the glucose utilization in both areas of brain. Theophylline, an Ado antagonist, significantly reduced ethanol-induced increase in glucose utilization in both brain areas. Ado agonist CHA significantly accentuated ethanol-induced increase in glucose utilization in both motor areas. Ado agonist CHA significantly accentuated ethanol-induced increase in glucose utilization in both motor areas. Ethanol was still able to produce a smaller but significant increase in glucose utilization in both brain areas when theophylline and CHA were given together, suggesting an additional mechanism. Collectively, the data indicate that ethanol-induced glucose utilization in the cerebellum and brain stem is modulated by brain Ado receptor and by non-adenosinergic mechanism.

  19. Reversible cognitive, motor, and driving impairments in severe hypothyroidism.

    Science.gov (United States)

    Smith, Charles D; Grondin, Richard; LeMaster, William; Martin, Barbara; Gold, Brian T; Ain, Kenneth B

    2015-01-01

    Hypothyroidism has been associated with cognitive and motor impairments that are likely to constitute hazards in the operation of motor vehicles and a public safety risk. However, there is a paucity of data that would provide an evidence basis for recommendations to hypothyroid patients. The purpose of this study was to determine the specific neurological and psychological deficits consequent to hypothyroidism and whether they are of sufficient magnitude to impede the safe operation of motor vehicles. Repeated measurements were obtained in euthyroid, hypothyroid, and euthyroid hormone replaced states of thyroid cancer outpatients, at an academic medical center, who underwent thyroid hormone withdrawal preparation for radioiodine scanning. Study design used a within-subjects longitudinal "A-B-A" with each subject tested at three visits in the same sequence: euthyroid, hypothyroid, and euthyroid for a total of 32 subjects. Data on clinical status and cognitive performance were collected using standard instruments, including ThyDQoL and ThySRQ measures, National Adult Reading Test, Boston Naming Test, Mini-Mental State Exam, Wechsler Adult Intelligence Test-Revised, Letter Fluency FAS, and Beck Depression Inventory. Fine-motor function was measured with an automated assessment panel, and driving performance on a commercial driving simulator. In severe hypothyroidism (median thyrotropin 83.2 mIU/L), fine-motor performance of hands and reaction times in emergency braking tests were slowed, as well as subjective slowing reported on structured clinical scales. Depression was present, typified by vegetative and mood alterations, but lacking reported guilt and lowered self-esteem seen in other types of depression. Cognitive impairment was characterized by declines on speeded executive tests. In contrast, episodic memory performance improved over time regardless of thyroid hormone status. Braking times increased in hypothyroidism by 8.5%, equivalent to reports of effects

  20. Antiulcerogenic benefits of herbal ingredients in ethanol-induced ...

    African Journals Online (AJOL)

    Numerous studies have demonstrated that herbal medicines display preventive benefit in the development of ethanol-induced gastric ulcers in both rat and mouse models. The preventive efficacy of herbal medicines on the development of ethanol-induced gastric ulcers is comparable or superior to histamine receptor 2 ...

  1. Divided attention impairs human motor adaptation but not feedback control.

    Science.gov (United States)

    Taylor, Jordan A; Thoroughman, Kurt A

    2007-07-01

    When humans experience externally induced errors in a movement, the motor system's feedback control compensates for those errors within the movement. The motor system's predictive control then uses information about those errors to inform future movements. The role of attention in these two distinct motor processes is unclear. Previous experiments have revealed a role for attention in motor learning over the course of many movements; however, these experimental paradigms do not determine how attention influences within-movement feedback control versus across-movement adaptation. Here we develop a dual-task paradigm, consisting of movement and audio tasks, which can differentiate and expose attention's role in these two processes of motor control. Over the course of several days, subjects performed horizontal reaching movements, with and without the audio task; movements were occasionally subjected to transient force perturbations. On movements with a force perturbation, subjects compensated for the force-induced movement errors, and on movements immediately after the force perturbation subjects exhibited adaptation. On every movement trial, subjects performed a two-tone frequency-discrimination task. The temporal specificity of the frequency-discrimination task allowed us to divide attention within and across movements. We find that divided attention did not impair the within-movement feedback control of the arm, but did reduce subsequent movement adaptation. We suggest that the secondary task interfered with the encoding and transformation of errors into changes in predictive control.

  2. Are Motor Skills and Motor Inhibitions Impaired in Tourette Syndrome? A Review

    Directory of Open Access Journals (Sweden)

    Navkiran Kalsi

    2015-01-01

    Full Text Available Tourette syndrome (TS is a neurodevelopmental motor disorder described as an inability to inhibit unwanted motor movements. This article reviews research on the execution and inhibition of voluntary motor movements in TS. Over last two decades, a number of studies have addressed the structural and functional deficits associated with this syndrome. Only a limited number of studies have assessed the motor skills in these patients but have failed to reach any conclusive outcome. In the domain of response inhibition also, studies have reported arguable impairments in these patients. It is suggested that these conflicting results can be attributed to co-occurring comorbid conditions, the constraints posed by variable age groups, lack of control measures, and lack of specificity of domains addressed. This review will describe a way in which future research can be directed to increase our knowledge of this otherwise complex spectrum of disorders.

  3. Delayed motor skill acquisition in kindergarten children with language impairment.

    Science.gov (United States)

    Adi-Japha, Esther; Strulovich-Schwartz, Orli; Julius, Mona

    2011-01-01

    The acquisition and consolidation of a new grapho-motor symbol into long-term memory was studied in 5-year-old children with language impairment (LI) and peers matched for age and visual-motor integration skills. The children practiced the production of a new symbol and were tested 24h and two weeks post-practice day. Differences in performance speed emerged between the groups: children with LI showed a later onset of rapid learning in the practice phase, and only the comparison group exhibited delayed, consolidation, gains 24h post-training. At two weeks post-training, children with LI improved, closing the gap in performance speed. Speed-accuracy trade-off was characteristic of speed improvements in LI. These results indicate atypical and delayed acquisition in children with LI, and support the view that deficient skill acquisition in LI goes beyond the language system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Eye Gaze Correlates of Motor Impairment in VR Observation of Motor Actions.

    Science.gov (United States)

    Alves, J; Vourvopoulos, A; Bernardino, A; Bermúdez I Badia, S

    2016-01-01

    This article is part of the Focus Theme of Methods of Information in Medicine on "Methodologies, Models and Algorithms for Patients Rehabilitation". Identify eye gaze correlates of motor impairment in a virtual reality motor observation task in a study with healthy participants and stroke patients. Participants consisted of a group of healthy subjects (N = 20) and a group of stroke survivors (N = 10). Both groups were required to observe a simple reach-and-grab and place-and-release task in a virtual environment. Additionally, healthy subjects were required to observe the task in a normal condition and a constrained movement condition. Eye movements were recorded during the observation task for later analysis. For healthy participants, results showed differences in gaze metrics when comparing the normal and arm-constrained conditions. Differences in gaze metrics were also found when comparing dominant and non-dominant arm for saccades and smooth pursuit events. For stroke patients, results showed longer smooth pursuit segments in action observation when observing the paretic arm, thus providing evidence that the affected circuitry may be activated for eye gaze control during observation of the simulated motor action. This study suggests that neural motor circuits are involved, at multiple levels, in observation of motor actions displayed in a virtual reality environment. Thus, eye tracking combined with action observation tasks in a virtual reality display can be used to monitor motor deficits derived from stroke, and consequently can also be used for rehabilitation of stroke patients.

  5. Motor Impairment in Sibling Pairs Concordant and Discordant for Autism Spectrum Disorders

    Science.gov (United States)

    Hilton, Claudia List; Zhang, Yi; Whilte, Megan R.; Klohr, Cheryl L.; Constantino, John

    2012-01-01

    Aim: Although motor impairment is frequently observed in children with autism spectrum disorders (ASD), the manner in which these impairments aggregate in families affected by autism is unknown. We used a standardized measure of motor proficiency to objectively examine quantitative variation in motor proficiency in sibling pairs concordant and…

  6. Effects of elastic therapeutic taping on motor function in children with motor impairments: a systematic review.

    Science.gov (United States)

    Cunha, Andréa Baraldi; Lima-Alvarez, Carolina Daniel de; Rocha, Ana Carolinne Portela; Tudella, Eloisa

    2017-03-22

    The elastic therapeutic taping has been considered a promising resource for disabled children. To systematically review the evidence of the effects of elastic therapeutic taping on motor function in children with motor impairments. Three independent evaluators conducted searches in electronic databases (MEDLINE/PubMed, Scopus, LILACS, BIREME/BVS, Science Direct, SciELO, and PEDro). Clinical studies design, published until 2016, involving elastic therapeutic taping and children aged 0-12 years with motor impairments were included. The variables considered were the methodological aspects (study design, participants, outcome measurements, and experimental conditions); results presented in the studies, and also the methodological quality of studies. Final selection was composed by 12 manuscripts (five randomized controlled trials), published in the last 10 years. Among them, cerebral palsy (CP) was the most recurrent disorder (n = 7), followed by congenital muscular torticollis (n = 2) and brachial plexus palsy (n = 2). Positive results were associated with taping application: improvement in the upper limb function, gross motor skills, postural control, muscular balance, and performance in the dynamics functional and daily activities. Lower quality of the studies, clinical and population heterogeneity existed across studies. The elastic therapeutic taping has been shown to be a promising adjunct resource to the conventional rehabilitation in children with motor impairments. However, high methodological studies about its efficacy in this population are already scarce. Implications for Rehabilitation Elastic therapeutic taping has been shown to be a promising adjunct resource to the conventional rehabilitation in disabled children. Clinical trials have indicated improvement in the postural control and functional activities with both, upper and lower limbs, and increase in the functional independency resulting from the taping use. Randomized control trials and

  7. Improvement of fine motor skills in children with visual impairment: an explorative study

    NARCIS (Netherlands)

    Reimer, A.M.; Cox, R.F.; Nijhuis-Van der Sanden, M.W.G.; Boonstra, F.N.

    2011-01-01

    In this study we analysed the potential spin-off of magnifier training on the fine-motor skills of visually impaired children. The fine-motor skills of 4- and 5-year-old visually impaired children were assessed using the manual skills test for children (6-12 years) with a visual impairment (ManuVis)

  8. Improvement of fine motor skills in children with visual impairment: An explorative study

    NARCIS (Netherlands)

    Reimer, A.M.; Cox, R.F.A.; Nijhuis-Van der Sanden, M.W.G.; Boonstra, F.N.

    2011-01-01

    In this study we analysed the potential spin-off of magnifier training on the fine-motor skills of visually impaired children. The fine-motor skills of 4- and 5-year-old visually impaired children were assessed using the manual skills test for children (6-12 years) with a visual impairment (ManuVis)

  9. Improvement of Fine Motor Skills in Children with Visual Impairment: An Explorative Study

    Science.gov (United States)

    Reimer, A. M.; Cox, R. F. A.; Nijhuis-Van der Sanden, M. W. G.; Boonstra, F. N.

    2011-01-01

    In this study we analysed the potential spin-off of magnifier training on the fine-motor skills of visually impaired children. The fine-motor skills of 4- and 5-year-old visually impaired children were assessed using the manual skills test for children (6-12 years) with a visual impairment (ManuVis) and movement assessment for children (Movement…

  10. Implicit Spoken Words and Motor Sequences Learning Are Impaired in Children with Specific Language Impairment.

    Science.gov (United States)

    Desmottes, Lise; Meulemans, Thierry; Maillart, Christelle

    2016-05-01

    This study aims to compare verbal and motor implicit sequence learning abilities in children with and without specific language impairment (SLI). Forty-eight children (24 control and 24 SLI) were administered the Serial Search Task (SST), which enables the simultaneous assessment of implicit spoken words and visuomotor sequences learning. Results showed that control children implicitly learned both the spoken words as well as the motor sequences. In contrast, children with SLI showed deficits in both types of learning. Moreover, correlational analyses revealed that SST performance was linked with grammatical abilities in control children but with lexical abilities in children with SLI. Overall, this pattern of results supports the procedural deficit hypothesis and suggests that domain general implicit sequence learning is impaired in SLI.

  11. Structural Equation Modeling of Motor Impairment, Gross Motor Function, and the Functional Outcome in Children with Cerebral Palsy

    Science.gov (United States)

    Park, Eun-Young; Kim, Won-Ho

    2013-01-01

    Physical therapy intervention for children with cerebral palsy (CP) is focused on reducing neurological impairments, improving strength, and preventing the development of secondary impairments in order to improve functional outcomes. However, relationship between motor impairments and functional outcome has not been proved definitely. This study…

  12. An overview of motor skill performance and balance in hearing impaired children

    Directory of Open Access Journals (Sweden)

    Roy Finita

    2011-07-01

    Full Text Available Abstract Childhood hearing impairment is a common chronic condition that may have a major impact on acquisition of speech, social and physical development. Numerous literature states that injury to the vestibular organs may result in accompanying balance and motor development disorders. But still postural control and motor assessments are not a routine procedure in hearing impaired children. Hence, we aim to provide an overview on motor skill performance and balance in hearing impaired children.

  13. Mechanisms of Ethanol-induced Death of Cerebellar Granule Cells

    Science.gov (United States)

    Luo, Jia

    2012-01-01

    Maternal ethanol exposure during pregnancy may cause fetal alcohol spectrum disorders (FASD). FASD is the leading cause of mental retardation. The most deleterious effect of fetal alcohol exposure is inducing neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system (CNS) underlies many of the behavioral deficits observed in FASD. The cerebellum is one of the brain areas that is most susceptible to ethanol during development. Ethanol exposure causes a loss of both cerebellar Purkinje cells and granule cells. This review focuses on the toxic effect of ethanol on cerebellar granule cells (CGC) and the underlying mechanisms. Both in vitro and in vivo studies indicate that ethanol induces apoptotic death of CGC. The vulnerability of CGC to ethanol-induced death diminishes over time as neurons mature. Several mechanisms for ethanol-induced apoptosis of CGC have been suggested. These include inhibition of NMDA receptors, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, disturbance of potassium channel currents, thiamine deficiency, and disruption of translational regulation. Cultures of CGC provide an excellent system to investigate cellular/molecular mechanisms of ethanol-induced neurodegeneration and to evaluate interventional strategies. This review will also discuss the approaches leading to neuroprotection against ethanol-induced neuroapoptosis. PMID:20927663

  14. Reflex mechanisms for motor impairment in spinal cord injury.

    Science.gov (United States)

    Schmit, Brian D; Benz, Ela N; Rymer, William Z

    2002-01-01

    Spasticity is common feature of human spinal cord injury. It contributes to motor impairment and it also promotes joint deformity in patients who have sustained such injury. The classical definition of spasticity highlights the increased resistance of a joint to externally imposed motion. This resistance is attributable largely to changes in stretch reflex excitability, and it is manifested primarily in those muscles being stretched by the motion. Under this definition, there would be little activity in muscles crossing other joints. In spinal cord injury, however, muscles innervated from distal spinal segments often exhibit little hypertonia, yet patients report the occurrence of disabling spasms. These spasms appear as coordinated patterns of muscle activation throughout the limb, involving either limb flexors or extensors. These patterns are therefore quite different from those of classical spasticity. The receptor origins and neural pathways responsible for the spasms in spinal cord injury will be addressed.

  15. Distinguishing Motor Weakness From Impaired Spatial Awareness: A Helping Hand!

    Directory of Open Access Journals (Sweden)

    Suneil A Raju

    2017-05-01

    Full Text Available Our patient, aged 73 years, had background peripheral neuropathy of unknown cause, stable for several years, which caused some difficulty in walking on uneven ground. He attended for a teaching session but now staggered in, a new development. He had apparent weakness of his right arm, but there was difficulty in distinguishing motor weakness from impaired spatial awareness suggestive of parietal lobe dysfunction. With the patient seated, eyes closed, and left arm outstretched, S.A.R. lifted the patient’s right arm and asked him to indicate when both were level. This confirmed motor weakness. Urgent computed tomographic scan confirmed left subdural haematoma and its urgent evacuation rapidly resolved the patient’s symptoms. Intrigued by our patient’s case, we explored further and learnt that in rehabilitation medicine, the awareness of limb position is commonly viewed in terms of joint position sense. We present recent literature evidence indicating that the underlying mechanisms are more subtle.

  16. Corpus callosum tissue loss and development of motor and global cognitive impairment

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Garde, Ellen; Skimminge, Arnold

    2011-01-01

    To examine the impact of corpus callosum (CC) tissue loss on the development of global cognitive and motor impairment in the elderly.......To examine the impact of corpus callosum (CC) tissue loss on the development of global cognitive and motor impairment in the elderly....

  17. Motor skill performance of school-age children with visual impairments

    NARCIS (Netherlands)

    Houwen, Suzanne

    2008-01-01

    This thesis focuses on the motor skill performance of school-age children with visual impairments (VI). Children with VI are at risk of poor motor skill performance, as vision guides and controls the acquisition, differentiation, and automatization of motor skills. Yet though the presence or absence

  18. Motor Skills in Hearing Impaired Children with or without Cochlear Implant – A Systematic Review

    OpenAIRE

    Vidranski, Tihomir; Farkaš, Daria

    2015-01-01

    Hearing impairment is a major limitation in communication, and it can obstruct psychological development, development of social skills and motor development. Hearing impairment is the third most common contemporary chronic health condition, and it has become a public health problem. The effectiveness of problem solving in everyday life and in emergency situations depends greatly on the amount and quality of the motor programs. Therefore, it is evident that the normal motor develop...

  19. Gross motor skills and sports participation of children with visual impairments

    NARCIS (Netherlands)

    Houwen, S; Visscher, C.; Hartman, E.; Lemmink, K.A.P.M.

    Gross motor skill performance of children with visual impairments and its association with the degree of visual impairment and sports participation was examined. Twenty children with visual impairments (M age = 9.2 years, SD =1.5) and 100 sighted children (M age = 9.1 years, SD = 1.5) from

  20. Gross Motor Skills and Sports Participation of Children with Visual Impairments

    Science.gov (United States)

    Houwen, Suzanne; Visscher, Chris; Hartman, Esther; Lemmink, Koen A. P. M.

    2007-01-01

    Gross motor skill performance of children with visual impairments and its association with the degree of visual impairment and sports participation was examined. Twenty children with visual impairments (M age = 9.2 years, SD = 1.5) and 100 sighted children (M age = 9.1 years, SD = 1.5) from mainstream schools participated. The results showed that…

  1. Motor impairment in children with Neurofibromatosis type 1: Effect of the comorbidity with language disorders.

    Science.gov (United States)

    Iannuzzi, Stéphanie; Albaret, Jean-Michel; Chignac, Céline; Faure-Marie, Nathalie; Barry, Isabelle; Karsenty, Caroline; Chaix, Yves

    2016-02-01

    There is a body of evidence demonstrating comorbidity of motor and cognitive deficit in «idiopathic» developmental disorders. These associations are also found in developmental disorders secondary to monogenic disorders as in Neurofibromatosis type 1 for which the principal complication during childhood is learning disabilities. The comparison of motor impairment between developmental disorders either idiopathic or secondary as in NF1 could help us to better understand the cause of the combined language/motor deficit in these populations. The aim of this current study was to investigate motor impairment in children with NF1 for which oral language had been specified and then to compare the motors skills of the NF1 group to motor performance of children with Specific Language Disorder (SLD). Two groups of 49 children between 5 and 12years old were included and compared, the NF1 group and the SLD (Specific Language Disorder) group. Each child completed evaluation involving cognitive, language and motor assessment. In NF1 group, motor impairment was more frequent and more severe and concerned specifically balance rather than manual dexterity or ball skills, compared to a group of children with SLD. This motor impairment was independent of language status in the NF1 group. These results as well as other studies on the same topic could suggest that in NF1 children, fine motor skills impairment would be dependent on the existence of comorbidity with language disorders. Also, that gross motor skills impairment, and more precisely the balance deficit would be characteristic of NF1. This issue encourages studies of procedural learning that can involve the fronto-striatal or the fronto-cerebellar loops according to the type of motor tasks and the stage of learning. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  2. Differential changes in the development of motor coordination and executive functions in children with motor coordination impairments.

    Science.gov (United States)

    Michel, Eva; Molitor, Sabine; Schneider, Wolfgang

    2018-01-01

    Cognitive and motor coordination skills of children with and without motor coordination impairments were examined with a one-year follow-up investigation. Initially, children were between 4 and 6 years old. Age-appropriate tests of executive functions (updating, switching, inhibition, interference control), motor coordination (the Movement Assessment Battery for Children-2) and fitness (the Körperkoordinations-Test für Kinder) were administered in two consecutive years. Several background variables (age, socioeconomic status, medical support, clinical interventions, leisure activities) and potential moderators (nonverbal intelligence, reaction time, visual perception) were controlled. The matched sample consisted of 48 control children and 48 children with motor coordination impairments. The children's executive functions dramatically improved during the one-year period. With regard to motor coordination performance, half of the impaired children caught up to the control children's level ("remission group"), while the remaining half showed no improvement ("persisting group"). Compared to the persisting group, the children in the remission group showed markedly better interference control at both measurement points. The correlation between executive functions and motor coordination is significant in the persisting group, but not in the remission group. The results of the study are discussed in the light of the role of executive functions, especially inhibition processes, for the automatization of motor coordination tasks.

  3. Aquatic intervention in children with neuro-motor impairments

    OpenAIRE

    Getz, M.D.

    2006-01-01

    The present thesis addresses the influence of aquatic interventions on motor performance of children with neuro-motor deficiencies in a functional context. The theoretical framework is based on a functional approach in compliance to the International Classification of Function and Disability (ICF). Chapter 2 addresses the relationship between motor performance in the aquatic environment setting as measured by the Aquatic Independence Measure (AIM) to motor performance on land as measured by t...

  4. Ethanol inducible isopentenyl transferase as a high efficiency ...

    African Journals Online (AJOL)

    The isopentenyl transforase gene from Agrobacterium tumefaciens is one positive selectable marker genes for plant transformation. In this research, the ipt gene was placed under the control of ethanol-inducible system and was introduced into Nicotiana tabacum cv. Xanthi via Agrobacterium-mediated transformation.

  5. Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients

    Directory of Open Access Journals (Sweden)

    Máximo Zimerman

    2015-10-01

    Interpretations: Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as suggested in previous animal work.

  6. Nigrostriatal proteasome inhibition impairs dopamine neurotransmission and motor function in minipigs

    DEFF Research Database (Denmark)

    Lillethorup, Thea Pinholt; Glud, Andreas Nørgaard; Alstrup, Aage Kristian Olsen

    2018-01-01

    Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra leading to slowness and stiffness of limb movement with rest tremor. Using ubiquitin proteasome system inhibitors, rodent models have shown nigrostriatal degeneration and motor impairment. We...

  7. Apollo's curse: neurological causes of motor impairments in musicians.

    Science.gov (United States)

    Altenmüller, Eckart; Ioannou, Christos I; Lee, Andre

    2015-01-01

    Performing music at a professional level is probably one of the most complex human accomplishments. Extremely fast and complex, temporo-spatially predefined movement patterns have to be learned, memorized, and retrieved with high reliability in order to meet the expectations of listeners. Performing music requires not only the integration of multimodal sensory and motor information, and its precise monitoring via auditory and kinesthetic feedback, but also emotional communicative skills, which provide a "speaking" rendition of a musical masterpiece. To acquire these specialized auditory-sensory-motor and emotional skills, musicians must undergo extensive training periods over many years, which start in early childhood and continue on through stages of increasing physical and strategic complexities. Performance anxiety, linked to high societal pressures such as the fear of failure and heightened self-demands, frequently accompanies these learning processes. Motor disturbances in musicians are common and include mild forms, such as temporary motor fatigue with short-term reduction of motor skills, painful overuse injuries following prolonged practice, anxiety-related motor failures during performances (choking under pressure), as well as more persistent losses of motor control, here termed "dynamic stereotypes" (DSs). Musician's dystonia (MD), which is characterized by the permanent loss of control of highly skilled movements when playing a musical instrument, is the gravest manifestation of dysfunctional motor programs, frequently linked to a genetic susceptibility to develop such motor disturbances. In this review chapter, we focus on different types of motor failures in musicians. We argue that motor failures in musicians develop along a continuum, starting with subtle transient degradations due to fatigue, overuse, or performance stress, which transform by and by into more permanent, still fluctuating motor degradations, the DSs, until a more irreversible

  8. Motor control impairment of the contralateral wrist in patients with unilateral chronic wrist pain

    NARCIS (Netherlands)

    Smeulders, MJC; Kreulen, M; Hage, JJ; Ritt, MJPF; Mulder, T

    Objective: Assessment of the quality of fine motor control in patients with unilateral chronic wrist pain seldom focuses on the possibility that control of movements is effector independent at the cerebral level. This mechanism may be involved in an impairment of motor function in the unaffected

  9. Interaction of Language Processing and Motor Skill in Children with Specific Language Impairment

    Science.gov (United States)

    DiDonato Brumbach, Andrea C.; Goffman, Lisa

    2014-01-01

    Purpose: To examine how language production interacts with speech motor and gross and fine motor skill in children with specific language impairment (SLI). Method: Eleven children with SLI and 12 age-matched peers (4-6 years) produced structurally primed sentences containing particles and prepositions. Utterances were analyzed for errors and for…

  10. Aquatic intervention in children with neuro-motor impairments

    NARCIS (Netherlands)

    Getz, M.D.

    2006-01-01

    The present thesis addresses the influence of aquatic interventions on motor performance of children with neuro-motor deficiencies in a functional context. The theoretical framework is based on a functional approach in compliance to the International Classification of Function and Disability (ICF).

  11. Mild impairments of motor imagery skills in children with DCD

    NARCIS (Netherlands)

    Noten, M.; Wilson, P.H.; Ruddock, S.; Steenbergen, B.

    2014-01-01

    It has been hypothesized that the underlying mechanism of clumsy motor behaviour in children with Developmental Coordination Disorder (DCD) is caused by a deficit in the internal modelling for motor control. An internal modelling deficit can be shown on a behavioural level by a task that requires

  12. A Perceptual-Motor Deficit Predicts Social and Communicative Impairments in Individuals With Autism Spectrum Disorders

    NARCIS (Netherlands)

    Linkenauger, S.A.; Lerner, M.D.; Ramenzoni, V.C.; Proffitt, D.R.

    2012-01-01

    Individuals with autism spectrum disorders (ASDs) have known impairments in social and motor skills. Identifying putative underlying mechanisms of these impairments could lead to improved understanding of the etiology of core social/communicative deficits in ASDs, and identification of novel

  13. Physical Activity and Motor Skills in Children with and without Visual Impairments

    NARCIS (Netherlands)

    Houwen, Suzanne; Hartman, Esther; Visscher, Chris

    HOUWEN, S., E. HARTMAN, and C. VISSCHER. Physical Activity and Motor Skills in Children with and without Visual Impairments. Med. Sci. Sports Exerc., Vol. 41, No, 1, pp. 103-109, 2009. Purpose: To examine the physical activity levels of children with and without visual impairments(VI). We further

  14. Methods of development of fine and gross motor skills of visually impaired children.

    OpenAIRE

    Brožová, Pavla

    2009-01-01

    The theme of the bachelor's paper is ``Methods of development of fine and gross motor skills of visually impaired children{\\crqq}. The theoretical part is aimed at clarification of the terms ``vision{\\crqq}, ``development of visual perception{\\crqq}, and also ``visually impaired child{\\crqq}. I have further introduced there the terms ``gross and fine motor skills{\\crqq}, which I defined in relation to children with visual impairment in pre-school age. The practical part of the paper is dedica...

  15. Are Motor Skills and Motor Inhibitions Impaired in Tourette Syndrome? A Review

    OpenAIRE

    Navkiran Kalsi; Renata Tambelli; Paola Aceto; Carlo Lai

    2015-01-01

    Tourette syndrome (TS) is a neurodevelopmental motor disorder described as an inability to inhibit unwanted motor movements. This article reviews research on the execution and inhibition of voluntary motor movements in TS. Over last two decades, a number of studies have addressed the structural and functional deficits associated with this syndrome. Only a limited number of studies have assessed the motor skills in these patients but have failed to reach any conclusive outcome. In the domain o...

  16. Oral Motor Deficits in Speech-Impaired Children with Autism

    OpenAIRE

    Matthew K Belmonte; Tanushree eSaxena-Chandhok; Ruth eCherian; Reema eMuneer; Lisa eGeorge; Prathibha eKaranth

    2013-01-01

    Absence of communicative speech in autism has been presumed to reflect a fundamental deficit in the use of language, but at least in a subpopulation may instead stem from motor and oral motor issues. Clinical reports of disparity between receptive versus expressive speech / language abilities reinforce this hypothesis. Our early-intervention clinic develops skills prerequisite to learning and communication, including sitting, attending, and pointing or reference, in children below 6 years of ...

  17. Oral motor deficits in speech-impaired children with autism

    OpenAIRE

    Belmonte, MK; Saxena-Chandhok, T; Cherian, R.; Muneer, R; George, L; P Karanth

    2013-01-01

    Absence of communicative speech in autism has been presumed to reflect a fundamental deficit in the use of language, but at least in a subpopulation may instead stem from motor and oral motor issues. Clinical reports of disparity between receptive vs. expressive speech/language abilities reinforce this hypothesis. Our early-intervention clinic develops skills prerequisite to learning and communication, including sitting, attending, and pointing or reference, in children below 6 years of age. ...

  18. Corpus callosum tissue loss and development of motor and global cognitive impairment: the LADIS study.

    Science.gov (United States)

    Frederiksen, Kristian S; Garde, Ellen; Skimminge, Arnold; Barkhof, Frederik; Scheltens, Philip; van Straaten, Elisabeth C W; Fazekas, Franz; Baezner, Hansjörg; Verdelho, Ana; Ferro, José M; Erkinjuntti, Timo; Jokinen, Hanna; Wahlund, Lars-Olof; O'Brien, John T; Basile, Anna M; Pantoni, Leonardo; Inzitari, Domenico; Waldemar, Gunhild

    2011-01-01

    To examine the impact of corpus callosum (CC) tissue loss on the development of global cognitive and motor impairment in the elderly. This study was based on the Leukoaraiosis and Disability (LADIS) study. Assessment of cognitive and motor functions and magnetic resonance imaging (MRI) were done at baseline and at a 3-year follow-up in nondemented elderly subjects. 328 of 639 LADIS subjects had MRIs at baseline and at the 3-year follow-up, which allowed for assessment of CC. Logistic regression revealed differential tissue loss rates in posterior CC in subjects converting to dementia, compared to nonconverters (p CC tissue loss was significantly correlated with self-perceived memory impairment in nonconverters (p CC tissue loss was also significantly associated with impaired single leg stance time (p CC supports the role of callosal tissue loss in the development of global cognitive as well as motor impairment. Copyright © 2012 S. Karger AG, Basel.

  19. Stroke subtype and motor impairment influence contralesional excitability.

    Science.gov (United States)

    Thickbroom, Gary W; Cortes, Mar; Rykman, Avrielle; Volpe, Bruce T; Fregni, Felipe; Krebs, H Igo; Pascual-Leone, Alvaro; Edwards, Dylan J

    2015-08-11

    The nonlesioned motor cortex (M1NL) is thought to be hyperexcitable in patients with subacute or chronic stroke and offers a promising therapeutic target. However, whether M1NL excitability behaves the same for subcortical and cortical strokes is unknown. The aim of the present study was to determine whether cortical, or purely subcortical, strokes have a different effect on M1NL excitability. We looked for correlations between the Fugl-Meyer (FM) score and M1NL resting motor threshold (RMTNL) in 34 stroke survivors classified according to lesion location (cortico-subcortical or purely subcortical). In addition to the FM, the Wolf Motor Score and motor power were measured. FM correlated with RMTNL for subcortical (r = 0.82; p = 0.001) but not for cortical strokes (r = 0.11; p = 0.62). Likewise, Wolf Motor Score (r = -0.62; p = 0.03) and motor power (r = 0.64; p = 0.023) were correlated with RMTNL for the subcortical group, but not for the cortical group. We show that the impact on M1NL depends on lesion location and conclude that protocols aimed at reducing M1NL cortical excitability may be worth exploring for subcortical but not for cortical stroke. © 2015 American Academy of Neurology.

  20. Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.

    Science.gov (United States)

    Dar, M Saeed

    2015-08-01

    The cerebellum is an important target of ethanol toxicity given that cerebellar ataxia is the most consistent physical manifestation of acute ethanol consumption. Despite the significance of the cerebellum in ethanol-induced cerebellar ataxia (EICA), the cellular and molecular mechanisms underlying EICA are incompletely understood. However, two important findings have shed greater light on this phenomenon. First, ethanol-induced blockade of cerebellar adenosine uptake in rodent models points to a role for adenosinergic A1 modulation of EICA. Second, the consistent observation that intracerebellar administration of nicotine in mice leads to antagonism of EICA provides evidence for a critical role of cerebellar nitric oxide (NO) in EICA reversal. Based on these two important findings, this review discusses the potential molecular events at two key synaptic sites (mossy fiber-granule cell-Golgi cell (MGG synaptic site) and granule cell parallel fiber-Purkinje cell (GPP synaptic site) that lead to EICA. Specifically, ethanol-induced neuronal NOS inhibition at the MGG synaptic site acts as a critical trigger for Golgi cell activation which leads to granule cell deafferentation. Concurrently, ethanol-induced inhibition of adenosine uptake at the GPP synaptic site produces adenosine accumulation which decreases glutamate release and leads to the profound activation of Purkinje cells (PCs). These molecular events at the MGG and GPP synaptic sites are mutually reinforcing and lead to cerebellar dysfunction, decreased excitatory output of deep cerebellar nuclei, and EICA. The critical importance of PCs as the sole output of the cerebellar cortex suggests normalization of PC function could have important therapeutic implications.

  1. Recovery of Saccharomyces cerevisiae from ethanol-induced growth inhibition.

    OpenAIRE

    Walker-Caprioglio, H M; Rodriguez, R J; Parks, L W

    1985-01-01

    Ethanol caused altered mobility of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene in plasma membrane preparations of Saccharomyces cerevisiae. Because lipids had been shown to protect yeast cells against ethanol toxicity, sterols, fatty acids, proteins, and combinations of these were tested; however, protection from growth inhibition was not seen. Ethanol-induced, prolonged lag periods and diminished growth rates in S. cerevisiae were reduced by an autoconditioning of the medium by the in...

  2. Mechanisms of Ethanol-induced Death of Cerebellar Granule Cells

    OpenAIRE

    Luo, Jia

    2012-01-01

    Maternal ethanol exposure during pregnancy may cause fetal alcohol spectrum disorders (FASD). FASD is the leading cause of mental retardation. The most deleterious effect of fetal alcohol exposure is inducing neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system (CNS) underlies many of the behavioral deficits observed in FASD. The cerebellum is one of the brain areas that is most susceptible to ethanol during development. Ethanol exposure causes...

  3. Causes of visual impairment among commercial motor vehicle ...

    African Journals Online (AJOL)

    Human factor contributed 27.7% to the cause of accidents. Causes of visual impairment included refractive error, glaucoma and cataract. Conclusion: There was no statistically significant association between RTA and visual impairment but there was statistically significant association between RTA and visual field defect ...

  4. Recovery-related indicators of motor network plasticity according to impairment severity after stroke.

    Science.gov (United States)

    Lee, J; Park, E; Lee, A; Chang, W H; Kim, D-S; Kim, Y-H

    2017-10-01

    Brain connectivity analysis has been widely used to investigate brain plasticity and recovery-related indicators of patients with stroke. However, results remain controversial because of interindividual variability of initial impairment and subsequent recovery of function. In this study, we aimed to investigate the differences in network plasticity and motor recovery-related indicators according to initial severity. We divided participants (16 males and 14 females, aged 54.2 ± 12.0 years) into groups of different severity by Fugl-Mayer Assessment score, i.e. moderate (50-84), severe (20-49) and extremely severe (impairment groups. Longitudinal resting-state functional magnetic resonance imaging data were acquired at 2 weeks and 3 months after onset. The differences in network plasticity and recovery-related indicators between groups were investigated using network distance and graph measurements. As the level of impairment increased, the network balance was more disrupted. Network balance, interhemispheric connectivity and network efficiency were recovered at 3 months only in the moderate impairment group. However, this was not the case in the extremely severe impairment group. A single connection strength between the ipsilesional primary motor cortex and ventral premotor cortex was implicated in the recovery of motor function for the extremely severe impairment group. The connections of the ipsilesional primary motor cortex-ventral premotor cortex were positively associated with motor recovery as the patients were more severely impaired. Differences in plasticity and recovery-related indicators of motor networks were noted according to impairment severity. Our results may suggest meaningful implications for recovery prediction and treatment strategies in future stroke research. © 2017 EAN.

  5. Resection of Navigated Transcranial Magnetic Stimulation-Positive Prerolandic Motor Areas Causes Permanent Impairment of Motor Function.

    Science.gov (United States)

    Moser, Tobias; Bulubas, Lucia; Sabih, Jamil; Conway, Neal; Wildschutz, Noémie; Sollmann, Nico; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

    2017-07-01

    Navigated transcranial magnetic stimulation (nTMS) helps to determine the distribution of motor eloquent areas prior to brain surgery. Yet, the eloquence of primary motor areas frontal to the precentral gyrus identified via nTMS is unclear. To investigate the resection of nTMS-positive prerolandic motor areas and its correlation with postsurgical impairment of motor function. Forty-three patients with rolandic or prerolandic gliomas (WHO grade I-IV) underwent nTMS prior to surgery. Only patients without ischemia within the motor system in postoperative MRI diffusion sequences were enrolled. Based on the 3-dimensional fusion of preoperative nTMS motor mapping data with postsurgical MRI scans, we identified nTMS points that were resected in the infiltration zone of the tumor. We then classified the resected points according to the localization and latency of their motor evoked potentials. Surgery-related paresis was graded as transient (≤6 weeks) or permanent (>6 weeks). Out of 43, 31 patients (72%) showed nTMS-positive motor points in the prerolandic gyri. In general, 13 out of 43 patients (30%) underwent resection of nTMS points. Ten out of these patients showed postoperative paresis. There were 2 (15%) patients with a transient and 8 (62%) with a permanent surgery-related paresis. In 3 cases (23%), motor function remained unimpaired. After resection of nTMS-positive motor points, 62% of patients suffered from a new permanent paresis. Thus, even though they are located in the superior or middle frontal gyrus, these cortical areas must undergo intraoperative mapping.

  6. Deficits in motor performance after pedunculopontine lesions in rats--impairment depends on demands of task.

    Science.gov (United States)

    MacLaren, Duncan A A; Santini, Joseph A; Russell, Ashley L; Markovic, Tamara; Clark, Stewart D

    2014-10-01

    Anatomically and functionally located between basal ganglia and brainstem circuitry, the pedunculopontine tegmental nucleus (PPTg) is in a pivotal position to contribute to motor behavior. Studies in primates have reported akinesia and postural instability following destruction of the PPTg. In humans, the PPTg partially degenerates in Parkinson's disease and stimulation of this region is under investigation as a possible therapeutic. Studies in rats report no crude motor impairment following PPTg lesion, although a detailed assessment of the role of the PPTg in rat motor function has not been reported. Our studies applied motor tests generally used in rodent models of Parkinson's disease to rats bearing either excitotoxic damage to all neuronal populations within PPTg, or selective destruction of the cholinergic subpopulation created with the toxin Dtx-UII. Neither lesion type altered baseline locomotion. On the rotarod, excitotoxic lesions produced a persistent impairment on the accelerating, but not fixed speed, conditions. In the vermicelli handling task (a quantitative measure of fine motor control and effective behavioral sequencing) excitotoxic lesions produced no single impairment, but globally increased the number of normal and abnormal behaviors. In contrast, depletion of cholinergic PPTg neurons produced impairment on the accelerating rotarod but no changes in vermicelli handling. Together, these results show that while PPTg lesions produce no impairment in the execution of individual motor actions, impairments emerge when the demands of the task increase. Results are discussed in terms of PPTg acting as part of a rapid action selection system, which integrates sensory information into motor output. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. Rosmarinic acid protects against chronic ethanol-induced learning and memory deficits in rats.

    Science.gov (United States)

    Hasanein, Parisa; Seifi, Rosa; Hajinezhad, Mohammad Reza; Emamjomeh, Abbasali

    2017-11-01

    Ethanol consumption induces neurological disorders including cognitive dysfunction. Oxidative damage is considered a likely cause of cognitive deficits. We aimed to investigate the effects of rosmarinic acid (RA) in different doses for 30 days on chronic ethanol-induced cognitive dysfunction using the passive avoidance learning (PAL) and memory task in comparison with donepezil, a reference drug. We also evaluated the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation in hippocampus as possible mechanisms. Memory impairment was induced by 15% w/v ethanol (2 g/kg, i.g.) administration for 30 days. RA (8, 16, and 32 mg/kg, i.g.) or donepezil (2 mg/kg, i.g.) was administered 30 minutes before ethanol. The acquisition trial was done 1 hour after the last administration of RA and donepezil. At the end, animals were weighed and hippocami were isolated for analyzing of oxidant/antioxidant markers. Ethanol caused cognition deficits in the PAL and memory task. While RA 16 and 32 mg/kg improved cognition in control rats, it prevented learning and memory deficits of alcoholic groups. RA 8 mg/kg did not influence cognitive function in both control and alcoholic rats. RA 32 mg/kg had comparable effects with donepezil in prevention of acquisition and retention memory impairment. The higher doses of RA not only prevented increased lipid peroxidation and nitrite content but also decreased SOD, CAT, GSH, and FRAP levels in alcoholic groups and exerted antioxidant effects in non-alcoholic rats. We showed that RA administration dose-dependently prevented cognitive impairment induced by chronic ethanol in PAL and memory and disturbed oxidant/antioxidant status as a possible mechanism. The antioxidant, anticholinesterase, and neuroprotective properties of RA may be involved in the observed effects. Therefore, RA represents a potential therapeutic option against chronic ethanol-induced amnesia which deserves consideration and further examination.

  8. Protective effect of berberine, an isoquinoline alkaloid ameliorates ethanol-induced oxidative stress and memory dysfunction in rats.

    Science.gov (United States)

    Patil, Shaktipal; Tawari, Santosh; Mundhada, Dharmendra; Nadeem, Sayyed

    2015-09-01

    Memory impairment induced by ethanol in rats is a consequence of changes in the CNS that are secondary to impaired oxidative stress and cholinergic dysfunction. Treatment with antioxidants and cholinergic agonists are reported to produce beneficial effects in this model. Berberine, an isoquinoline alkaloid is reported to exhibit antioxidant effect and cholinesterase (ChE) inhibitor activity. However, no report is available on the influence of berberine on ethanol-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in ethanol-induced rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameter of oxidative stress and cholinesterase (ChE) activity as a marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Forty five days after ethanol treated rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100mg/kg, p.o., once a day for 45days) improved cognitive performance, and lowered oxidative stress and ChE activity in ethanol treated rats. In another set of experiments, berberine (100mg/kg) treatment during training trials also improved learning and memory, and lowered oxidative stress and ChE activity. Chronic treatment (45days) with vitamin C, and donepezil during training trials also improved ethanol-induced memory impairment and reduced oxidative stress and/or cholinesterase activity. In conclusion, the present study demonstrates that treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in ethanol treated rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Motor Impairments in Transient Ischemic Attack Increase the Odds of a Subsequent Stroke: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Neha Lodha

    2017-06-01

    Full Text Available Background and purposeTransient ischemic attack (TIA increases the risk for a subsequent stroke. Typical symptoms include motor weakness, gait disturbance, and loss of coordination. The association between the presence of motor impairments during a TIA and the chances of a subsequent stroke has not been examined. In the current meta-analysis, we examine whether the odds of a stroke are greater in TIA individuals who experience motor impairments as compared with those who do not experience motor impairments.MethodsWe conducted a systematic search of electronic databases as well as manual searches of the reference lists of retrieved articles. The meta-analysis included studies that reported an odds ratio relating motor impairments to a subsequent stroke, or the number of individuals with or without motor impairments who experienced a subsequent stroke. We examined these studies using rigorous meta-analysis techniques including random effects model, forest and funnel plots, I2, publication bias, and fail-safe analysis.ResultsTwenty-four studies with 15,129 participants from North America, Australia, Asia, and Europe qualified for inclusion. An odds ratio of 2.11 (95% CI, 1.67–2.65, p = 0.000 suggested that the chances of a subsequent stroke are increased by twofolds in individuals who experience motor impairments during a TIA compared with those individuals who have no motor impairments.ConclusionThe presence of motor impairments during TIA is a significantly high-risk clinical characteristic for a subsequent stroke. The current evidence for motor impairments following TIA relies exclusively on the clinical reports of unilateral motor weakness. A comprehensive examination of motor impairments in TIA will enhance TIA prognosis and restoration of residual motor impairments.

  10. Impaired motor imagery in right hemiparetic cerebral palsy

    NARCIS (Netherlands)

    Mutsaarts, M.J.H.; Steenbergen, B.; Bekkering, H.

    2007-01-01

    It is generally assumed that movements of a part of the body (e.g., hands) are simulated in motor imagery (MI) tasks. This is evidenced by a linear increase in reaction time as a function of the angular rotation of the stimulus. Under the assumption that MI plays a critical role for anticipatory

  11. Potential predictors of lower extremity impairments in motor coordination of stroke survivors.

    Science.gov (United States)

    Menezes, Kenia K; Scianni, Aline A; Faria-Fortini, Iza; Avelino, Patrick R; Carvalho, Augusto C; Faria, Christina D; Teixeira-Salmela, Luci F

    2016-06-01

    It is well recognized that the negative motor impairments following upper motor neuron damage, e.g., loss of strength and dexterity (motor coordination), mostly contribute to disability. Many factors may predict impairments in motor coordination (MC) and the identifications of these factors could help rehabilitation professionals to select variables to be considered in the evaluation and interventions aimed at improving MC of the lower limbs after stroke. To investigate the potential predictors of motor coordination (MC) of the paretic lower limb with stroke subjects, as assessed by the Lower Limb Motor Coordination Test (LEMOCOT). Cross-sectional, observational study. University laboratory. One hundred and six stroke subjects. The selected potential predictors of the LEMOCOT scores were age, gender, motor recovery and sensation of the lower limb, tonus of the knee extensor and plantar flexor muscles, and strength of the hip flexor and knee flexor/extensor muscles. Step-wise multiple regression was employed for analysis. Only motor recovery, tonus of the plantar flexor muscles, and age reached significance (Pmuscles and age were included in the model, the explained variance increased to 54% (F=42.0, PLower limb motor recovery was positively associated with the LEMOCOT scores, whereas the tonus of the plantar flexor muscles and age were negatively correlated. Motor recovery of the lower limb, tonus of the plantar flexor muscles, and age were significant predictors of MC of the paretic lower limb. These findings could help rehabilitation professionals to evaluate MC deficits and plan interventions aimed at improving MC of the lower limbs for stroke subjects, based upon the knowledge of the possible factors that could contribute to MC impairments.

  12. The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.

    Directory of Open Access Journals (Sweden)

    Anna Sommansson

    Full Text Available Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v. did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v. but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

  13. Low Motor Assessment : A Comparative Pilot Study with Young Children With and Without Motor Impairment

    NARCIS (Netherlands)

    Ruiter, S.A.J.; Nakken, H.; Van der Meulen, B.F.; Lunenborg, C.B.

    Most of the developmental instruments that measure cognitive development in children rely heavily on fine motor skills, especially for young children whose language skills are not yet well developed. This is problematic when evaluating the cognitive development of young children with motor

  14. Actigraphic Motor Activity in Mild Cognitive Impairment Patients Carrying Out Short Functional Activity Tasks: Comparison between Mild Cognitive Impairment with and without Depressive Symptoms

    NARCIS (Netherlands)

    Yakhia, M.; Konig, A.; van der Flier, W.M.; Friedman, L.; Robert, P.H.; David, R.

    2014-01-01

    Background: Individuals with mild cognitive impairment (MCI) may exhibit changes in motor activity in conducting their activities of daily living. Depression, one of the most frequent neuropsychiatric symptoms, might affect motor activity in MCI. Objective: To assess motor activity in MCI subjects

  15. Impaired Motor Learning in a Disorder of the Inferior Olive: Is the Cerebellum Confused?

    Science.gov (United States)

    Shaikh, Aasef G; Wong, Aaron L; Optican, Lance M; Zee, David S

    2017-02-01

    An attractive hypothesis about how the brain learns to keep its motor commands accurate is centered on the idea that the cerebellar cortex associates error signals carried by climbing fibers with simultaneous activity in parallel fibers. Motor learning can be impaired if the error signals are not transmitted, are incorrect, or are misinterpreted by the cerebellar cortex. Learning might also be impaired if the brain is overwhelmed with a sustained barrage of meaningless information unrelated to simultaneously appearing error signals about incorrect performance. We test this concept in subjects with syndrome of oculopalatal tremor (OPT), a rare disease with spontaneous, irregular, roughly pendular oscillations of the eyes thought to reflect an abnormal, synchronous, spontaneous discharge to the cerebellum from the degenerating neurons in the inferior olive. We examined motor learning during a short-term, saccade adaptation paradigm in patients with OPT and found a unique pattern of disturbed adaptation, quite different from the abnormal adaption when the cerebellum is involved directly. Both fast (seconds) and slow (minutes) timescales of learning were impaired. We suggest that the spontaneous, continuous, synchronous output from the inferior olive prevents the cerebellum from receiving the error signals it needs for appropriate motor learning. The important message from this study is that impaired motor adaptation and resultant dysmetria is not the exclusive feature of cerebellar disorders, but it also highlights disorders of the inferior olive and its connections to the cerebellum.

  16. "Motor" impairment in Asperger syndrome: evidence for a deficit in proprioception.

    Science.gov (United States)

    Weimer, A K; Schatz, A M; Lincoln, A; Ballantyne, A O; Trauner, D A

    2001-04-01

    Motor impairment has frequently been described in Asperger syndrome (AS), a pervasive developmental disorder included in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Previous research focusing on this motor dysfunction has yielded inconsistent results, and the "clumsiness" observed clinically remains poorly defined. To clarify further the issue of motor impairment, we compared a group of 10 children and young adults who met DSM-IV criteria for AS with a control group with no neurological impairment. Subjects were matched on age, sex, socioeconomic status, and Verbal IQ. A broad battery of motoric tests was administered. Subjects with AS were found to perform more poorly than controls on tests of apraxia, one-leg balance with eyes closed, tandem gait, and repetitive finger-thumb apposition. No significant differences were found on tests of finger tapping, grooved pegboard, trail making, or visual-motor integration. The pattern of impairments suggests that a proprioceptive deficit may underlie the incoordination observed in AS and that these individuals may be overreliant on visual input to maintain balance and position in space.

  17. Transcriptomics of aged Drosophila motor neurons reveals a matrix metalloproteinase that impairs motor function.

    Science.gov (United States)

    Azpurua, Jorge; Mahoney, Rebekah E; Eaton, Benjamin A

    2018-02-07

    The neuromuscular junction (NMJ) is responsible for transforming nervous system signals into motor behavior and locomotion. In the fruit fly Drosophila melanogaster, an age-dependent decline in motor function occurs, analogous to the decline experienced in mice, humans, and other mammals. The molecular and cellular underpinnings of this decline are still poorly understood. By specifically profiling the transcriptome of Drosophila motor neurons across age using custom microarrays, we found that the expression of the matrix metalloproteinase 1 (dMMP1) gene reproducibly increased in motor neurons in an age-dependent manner. Modulation of physiological aging also altered the rate of dMMP1 expression, validating dMMP1 expression as a bona fide aging biomarker for motor neurons. Temporally controlled overexpression of dMMP1 specifically in motor neurons was sufficient to induce deficits in climbing behavior and cause a decrease in neurotransmitter release at neuromuscular synapses. These deficits were reversible if the dMMP1 expression was shut off again immediately after the onset of motor dysfunction. Additionally, repression of dMMP1 enzymatic activity via overexpression of a tissue inhibitor of metalloproteinases delayed the onset of age-dependent motor dysfunction. MMPs are required for proper tissue architecture during development. Our results support the idea that matrix metalloproteinase 1 is acting as a downstream effector of antagonistic pleiotropy in motor neurons and is necessary for proper development, but deleterious when reactivated at an advanced age. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  18. CONTRIBUTION OF AXIAL MOTOR IMPAIRMENT TO PHYSICAL INACTIVITY IN PARKINSON'S DISEASE

    Science.gov (United States)

    Bryant, Mon S; Hou, Jyhgong Gabriel; Collins, Robert L; Protas, Elizabeth J

    2015-01-01

    Objective To investigate the relationships between motor symptoms of Parkinson’s disease (PD) and activity limitations in persons with PD. Design/Methods Cross-sectional study of persons with mild to moderate PD (N=90). Associations among axial motor features, limb motor signs, the Physical Activity Scale for Elders (PASE), the ability to perform Activities of Daily Living (ADL) and level of ADL dependency were studied. A composite score of axial motor features included the following UPDRS items: speech, rigidity of the neck, arising from chair, posture, gait and postural stability. A composite score of limb motor signs included the following UPDRS items: tremor at rest of all extremities, action tremor, rigidity of all extremities, finger taps, hand movement, rapid alternating hand movements and foot tapping. Results Axial motor features of PD were significantly correlated with physical inactivity (pphysical inactivity. After controlling for age, gender, disease duration and comorbidity, axial motor features contributed significantly to physical inactivity, decreased ADL and increase in ADL dependency, whereas the limb motor signs did not. Conclusions Axial motor impairment contributed to physical inactivity and decreased ability to perform ADLs in persons with PD. PMID:26368837

  19. Parkinson’s disease progression: implicit acquisition, cognitive and motor impairments, and medication effects

    Directory of Open Access Journals (Sweden)

    Rodrigo ePavão

    2012-08-01

    Full Text Available Parkinson’s disease (PD symptoms have been collectively ascribed to malfunctioning of dopamine-related nigro-striatal and cortico-striatal loops. However, some doubts about this proposition are raised by controversies about the temporal progression of the impairments, and whether they are concomitant or not. The present study consists of a systematic revision of literature data on both functional PD impairments and dopaminergic medication effects in order to draw a coherent picture about the disease progression. It was done in terms of an explanatory model for the disruption of implicit knowledge acquisition, motor and cognitive impairments, and the effects of dopaminergic medication on these functions. Cognitive impairments arise at early stages of PD and stabilizes while disruption of acquisition of implicit knowledge and motor impairments are still in progression; additionally, dopaminergic medication reduces motor impairments and increases disruption of acquisition of implicit knowledge. Since this model revealed consistency and plausibility when confronted with data of others studies not included in model's formulation, it may turn out to be a useful tool for understanding the multifaceted characteristics of PD.

  20. Treatment of language, motor speech impairments, and Dysphagia.

    Science.gov (United States)

    Anderson, Maria; Anzalone, Jessie; Holland, Lauren; Tracey, Elvira

    2011-06-01

    Language, speech, cognitive-associated communication deficits, and dysphagia are common following acquired brain injury (stroke, traumatic brain injury, and others). Treatment of these disorders can be divided into restorative, compensatory, and supportive approaches. Although therapy must be individualized for each person, components of all three approaches are necessary to maximize an individual's recovery. This article provides a general overview of traditional as well as state-of-the-art treatment for aphasia, cognitive-linguistic impairments, dysarthria, apraxia, and dysphagia.

  1. Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study.

    Science.gov (United States)

    Martinuzzi, Andrea; Montanaro, Domenico; Vavla, Marinela; Paparella, Gabriella; Bonanni, Paolo; Musumeci, Olimpia; Brighina, Erika; Hlavata, Hana; Rossi, Giuseppe; Aghakhanyan, Gayane; Martino, Nicola; Baratto, Alessandra; D'Angelo, Maria Grazia; Peruch, Francesca; Fantin, Marianna; Arnoldi, Alessia; Citterio, Andrea; Vantaggiato, Chiara; Rizzo, Vincenzo; Toscano, Antonio; Bresolin, Nereo; Bassi, Maria Teresa

    2016-01-01

    Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system ("pure" forms). The involvement of other components of the central nervous system or of other systems is described in the "complicate" forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis. We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology. Clinically increased deep tendon reflexes and lower limb (LL) weakness are constant findings in all patients. The "complicated" forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI) highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST) DTI consistently discriminated patients from controls. We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel DTI approach may add significant elements in

  2. Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Andrea Martinuzzi

    Full Text Available Hereditary spastic paraplegias (HSP are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system ("pure" forms. The involvement of other components of the central nervous system or of other systems is described in the "complicate" forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis.We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology.Clinically increased deep tendon reflexes and lower limb (LL weakness are constant findings in all patients. The "complicated" forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST DTI consistently discriminated patients from controls.We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel DTI approach may add significant

  3. Unbiased and Mobile Gait Analysis Detects Motor Impairment in Parkinson's Disease

    Science.gov (United States)

    Klucken, Jochen; Barth, Jens; Kugler, Patrick; Schlachetzki, Johannes; Henze, Thore; Marxreiter, Franz; Kohl, Zacharias; Steidl, Ralph; Hornegger, Joachim; Eskofier, Bjoern; Winkler, Juergen

    2013-01-01

    Motor impairments are the prerequisite for the diagnosis in Parkinson's disease (PD). The cardinal symptoms (bradykinesia, rigor, tremor, and postural instability) are used for disease staging and assessment of progression. They serve as primary outcome measures for clinical studies aiming at symptomatic and disease modifying interventions. One major caveat of clinical scores such as the Unified Parkinson Disease Rating Scale (UPDRS) or Hoehn&Yahr (H&Y) staging is its rater and time-of-assessment dependency. Thus, we aimed to objectively and automatically classify specific stages and motor signs in PD using a mobile, biosensor based Embedded Gait Analysis using Intelligent Technology (eGaIT). eGaIT consist of accelerometers and gyroscopes attached to shoes that record motion signals during standardized gait and leg function. From sensor signals 694 features were calculated and pattern recognition algorithms were applied to classify PD, H&Y stages, and motor signs correlating to the UPDRS-III motor score in a training cohort of 50 PD patients and 42 age matched controls. Classification results were confirmed in a second independent validation cohort (42 patients, 39 controls). eGaIT was able to successfully distinguish PD patients from controls with an overall classification rate of 81%. Classification accuracy increased with higher levels of motor impairment (91% for more severely affected patients) or more advanced stages of PD (91% for H&Y III patients compared to controls), supporting the PD-specific type of analysis by eGaIT. In addition, eGaIT was able to classify different H&Y stages, or different levels of motor impairment (UPDRS-III). In conclusion, eGaIT as an unbiased, mobile, and automated assessment tool is able to identify PD patients and characterize their motor impairment. It may serve as a complementary mean for the daily clinical workup and support therapeutic decisions throughout the course of the disease. PMID:23431395

  4. Red sorrel (Hibiscus Sabdariffa) prevents the ethanol-induced deficits of Purkinje cells in the cerebellum.

    Science.gov (United States)

    Suryanti, S; Partadiredja, G; Atthobari, J

    2015-01-01

    The present study is aimed at investigating the possible protective effects of H. sabdariffa on ethanol-elicited deficits of motor coordination and estimated total number of the Purkinje cells of the cerebellums of adolescent male Wistar rats. Forty male Wistar rats aged 21 days were divided into five groups. Na/wtr group was given water orally and injected with normal saline intra peritoneally (ip). Eth/wtr group was given water orally and ethanol (ip). Another three experimental groups (Eth/Hsab) were given different dosages of H. sabdariffa and ethanol (ip). All groups were treated intermittently for the total period of treatment of two weeks. The motor coordination of rats was tested prior and subsequent to the treatments. The rats were euthanized, and their cerebellums were examined. The total number of Purkinje cells was estimated using physical fractionator method. Upon revolving drum test, the number of falls of rats increased following ethanol treatment. There was no significant difference between the total number of falls prior and subsequent to treatment in all Eth/Hsab groups. The estimated total number of Purkinje cells in Eth/Hsab groups was higher than in Eth/wtr group. H. sabdariffa may prevent the ethanol-induced deficits of motor coordination and estimated total number of Purkinje cells of the cerebellums in adolescent rats (Tab. 3, Fig. 1, Ref. 42).

  5. Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease

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    Troakes Claire

    2011-03-01

    Full Text Available Abstract Background The cause of sporadic amyotrophic lateral sclerosis (ALS is largely unknown but hypotheses about disease mechanisms include oxidative stress, defective axonal transport, mitochondrial dysfunction and disrupted RNA processing. Whereas familial ALS is well represented by transgenic mutant SOD1 mouse models, the mouse mutant wobbler (WR develops progressive motor neuron degeneration due to a point mutation in the Vps54 gene, and provides an animal model for sporadic ALS. VPS54 protein as a component of a protein complex is involved in vesicular Golgi trafficking; impaired vesicle trafficking might also be mechanistic in the pathogenesis of human ALS. Results In motor neurons of homozygous symptomatic WR mice, a massive number of endosomal vesicles significantly enlarged (up to 3 μm in diameter were subjected to ultrastructural analysis and immunohistochemistry for the endosome-specific small GTPase protein Rab7 and for amyloid precursor protein (APP. Enlarged vesicles were neither detected in heterozygous WR nor in transgenic SOD1(G93A mice; in WR motor neurons, numerous APP/Rab7-positive vesicles were observed which were mostly LC3-negative, suggesting they are not autophagosomes. Conclusions We conclude that endosomal APP/Rab7 staining reflects impaired vesicle trafficking in WR mouse motor neurons. Based on these findings human ALS tissues were analysed for APP in enlarged vesicles and were detected in spinal cord motor neurons in six out of fourteen sporadic ALS cases. These enlarged vesicles were not detected in any of the familial ALS cases. Thus our study provides the first evidence for wobbler-like aetiologies in human ALS and suggests that the genes encoding proteins involved in vesicle trafficking should be screened for pathogenic mutations.

  6. Prognostic factors of motor impairment, disability, and quality of life in newly diagnosed PD.

    Science.gov (United States)

    Velseboer, Daan C; Broeders, Mark; Post, Bart; van Geloven, Nan; Speelman, Johannes D; Schmand, Ben; de Haan, Rob J; de Bie, Rob M A

    2013-02-12

    In Parkinson disease (PD), the rate of clinical progression is highly variable. To date, there are conflicting findings concerning the prognostic factors influencing the rate of progression. Methodologic issues such as the use of selected patients from therapeutic trials, and short durations of follow-up probably underlie this problem. We therefore designed a prospective follow-up study of a cohort of newly diagnosed patients with PD. A cohort of 129 patients with newly diagnosed PD was assessed at baseline, and 1, 2, 3, and 5 years later. The rate of progression and its prognostic factors on the level of motor impairments, disability, and quality of life were investigated using linear mixed-model analysis. Annual increase of motor impairments measured with the Unified Parkinson's Disease Rating Scale-Motor Examination was estimated to be 2.46 points (95% confidence interval: 2.05-2.88). The main determinants of faster increase of motor impairments were male sex and cognitive dysfunction at the time of diagnosis. The main determinants of faster increase of disability were higher age at onset, cognitive dysfunction, and the presence of levodopa-nonresponsive motor symptoms at the time of diagnosis. No clinically relevant determinants were found for the decrease in quality of life. This study shows the importance of nondopaminergic symptoms at the time of diagnosis, because these symptoms are the main determinants of increased disability in the first 5 years of the disease.

  7. Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

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    Brigitte Gonthier

    2012-01-01

    Full Text Available Aims. 3,5,4′-Trihydroxy-trans-stilbene, a natural polyphenolic compound present in wine and grapes and better known as resveratrol, has free radical scavenging properties and is a potent protector against oxidative stress induced by alcohol metabolism. Today, the mechanism by which ethanol exerts its toxicity is still not well understood, but it is generally considered that free radical generation plays an important role in the appearance of structural and functional alterations in cells. The aim of this study was to evaluate the protective action of resveratrol against ethanol-induced brain cell injury. Methods. Primary cultures of rat astrocytes were exposed to ethanol, with or without a pretreatment with resveratrol. We examined the dose-dependent effects of this resveratrol pretreatment on cytotoxicity and genotoxicity induced by ethanol. Cytotoxicity was assessed using the MTT reduction test. Genotoxicity was evidenced using single cell gel electrophoresis. In addition, DNA staining with fluorescent dyes allowed visualization of nuclear damage using confocal microscopy. Results. Cell pretreatment with low concentrations of trans-resveratrol (0.1–10 μM slowed down cell death and DNA damage induced by ethanol exposure, while higher concentrations (50–100 μM enhanced these same effects. No protection by cis-resveratrol was observed. Conclusion. Protection offered by trans-resveratrol against ethanol-induced neurotoxicity was only effective for low concentrations of this polyphenol.

  8. Predicting severe motor impairment in preterm children at age 5 years

    NARCIS (Netherlands)

    Synnes, Anne; Anderson, Peter J.; Grunau, Ruth E.; Dewey, Deborah; Moddemann, Diane; Tin, Win; Davis, Peter G.; Doyle, Lex W.; Foster, Gary; Khairy, May; Nwaesei, Chukwuma; Schmidt, Barbara; D'Ilario, Judy; Cairnie, Janice; Dix, Joanne; Adams, Beth Anne; Warriner, Erin; Kim, Mee-Hai Marie; Argus, Brenda; Callanan, Catherine; Davis, Noni; Duff, Julianne; McDonald, Marion; Asztalos, Elizabeth; Hohn, Denise; Lacy, Maralyn; Haslam, Ross; Barnett, Christopher; Goodchild, Louise; Lontis, Rosslyn Marie; Fraser, Simon; Keng, Julie; Saunders, Kerryn; Opie, Gillian; Kelly, Elaine; Woods, Heather; Marchant, Emma; Turner, Anne-Marie; Magrath, Emma; Williamson, Amanda; Bairam, Aida; Bélanger, Sylvie; Fraser, Annie; Blayney, Marc; Lemyre, Brigitte; Frank, Jane; Solimano, Alfonso; Hubber-Richard, Philippa; Rogers, Marilyn; Mackay, Margot; Petrie-Thomas, Julianne; Butt, Arsalan; van Wassenaer, Aleid; Nuytemans, Debbie; Houtzager, Bregje; van Sonderen, Loekie; Regev, Rivka; Itzchack, Netter; Arnon, Shmuel; Chalaf, Adiba; Ohlsson, Arne; O'Brien, Karel; Hamilton, Anne-Marie; Chan, May Lee; Sankaran, Koravangattu; Proctor, Pat; Golan, Agneta; Goldsch-Lerman, Esther; Reynolds, Graham; Dromgool, Barbara; Meskell, Andra; Parr, Vanessa; Maher, Catherine; Broom, Margaret; Kecskes, Zsuzsoka; Ringland, Cathy; McMillan, Douglas; Spellen, Elizabeth; Sauve, Reginald S.; Christianson, Heather; Anseeuw-Deeks, Deborah; Creighton, Dianne; Heath, Jennifer; Alvaro, Ruben; Chiu, Aaron; Porter, Ceceile; Turner, Gloria; Granke, Naomi; Penner, Karen; Bow, Jane; Mulder, Antonius; Wassenberg, Renske; van der Hoeven, Markus; Clarke, Maxine; Parfitt, Judy; Parker, Kevin; Ryan, Heather; Saunders, Cory; Schulze, Andreas; Wermuth, Inga; Hilgendorff, Anne; Flemmer, Andreas W.; Herlenius, Eric; Legnevall, Lena; Lagercrantz, Hugo; Matthew, Derek; Amos, Wendy; Tulsiani, Suresh; Tan-Dy, Cherrie; Turner, Marilyn; Phelan, Constance; Shinwell, Eric S.; Levine, Michael; Juster-Reicher, Ada; Grier, Patricia; Vachon, Julie; Perepolkin, Larissa; Barrington, Keith J.; Sinha, Sunil Kumar; Fritz, Susan; Walti, Herve; Royer, Diane; Halliday, Henry; Millar, David; Mayes, Clifford; McCusker, Christopher; McLaughlin, Olivia; Fahnenstich, Hubert; Tillmann, Bettina; Weber, Peter; Wariyar, Unni; Embleton, Nicholas; Swamy, Ravi; Bucher, Hans U.; Fauchere, Jean-Claude; Dietz, Vera; Harikumar, Chidambara; Asztalos, Elizabeth V.; Gent, Michael; Fraser, William; Hey, Edmund; Thorpe, Kevin; Gray, Shari; Roberts, Robin S.; Chambers, Carole; Costantini, Lorrie; Yacura, Wendy; McGean, Erin; Scapinello, Lori

    2015-01-01

    Objective To determine whether the ability to predict severe motor impairment at age 5 years improves between birth and 18 months. Design Ancillary study of the Caffeine for Apnea of Prematurity Trial. Setting and Patients International cohort of very low birth weight children who were assessed

  9. Motor Skill Performance of Children and Adolescents With Visual Impairments : A Review

    NARCIS (Netherlands)

    Houwen, Suzanne; Visscher, Chris; Lemmink, Koen A. P. M.; Hartman, Esther

    2009-01-01

    This article reviews studies on variables that are related to the motor skill performance of children and adolescents with visual impairments (W). Three major groups of variables are considered (child, environmental, and task). Thirty-nine studies are included in this review, 26 of which examined

  10. Postural Care for People with Intellectual Disabilities and Severely Impaired Motor Function: A Scoping Review

    Science.gov (United States)

    Robertson, Janet; Baines, Susannah; Emerson, Eric; Hatton, Chris

    2018-01-01

    Background: Poor postural care can have severe and life-threatening complications. This scoping review aims to map and summarize existing evidence regarding postural care for people with intellectual disabilities and severely impaired motor function. Method: Studies were identified via electronic database searches (MEDLINE, CINAHL, PsycINFO and…

  11. Neonatal White Matter Abnormality Predicts Childhood Motor Impairment in Very Preterm Children

    Science.gov (United States)

    Spittle, Alicia J.; Cheong, Jeanie; Doyle, Lex W.; Roberts, Gehan; Lee, Katherine J.; Lim, Jeremy; Hunt, Rod W.; Inder, Terrie E.; Anderson, Peter J.

    2011-01-01

    Aim: Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor…

  12. Grasping Motor Impairments in Autism: Not Action Planning but Movement Execution Is Deficient

    Science.gov (United States)

    Stoit, Astrid M. B.; van Schie, Hein T.; Slaats-Willemse, Dorine I. E.; Buitelaar, Jan K.

    2013-01-01

    Different views on the origin of deficits in action chaining in autism spectrum disorders (ASD) have been posited, ranging from functional impairments in action planning to internal models supporting motor control. Thirty-one children and adolescents with ASD and twenty-nine matched controls participated in a two-choice reach-to-grasp paradigm…

  13. Motor Control and Nonword Repetition in Specific Working Memory Impairment and SLI

    Science.gov (United States)

    Archibald, Lisa M. D.; Joanisse, Marc F.; Munson, Benjamin

    2013-01-01

    Purpose: Debate around the underlying cognitive factors leading to poor performance in the repetition of nonwords by children with developmental impairments in language has centered around phonological short-term memory, lexical knowledge, and other factors. This study examines the impact of motor control demands on nonword repetition in groups of…

  14. Motor sequence chunking is impaired by basal ganglia stroke.

    Science.gov (United States)

    Boyd, L A; Edwards, J D; Siengsukon, C S; Vidoni, E D; Wessel, B D; Linsdell, M A

    2009-07-01

    Our main aim was to determine whether individuals with stroke that affected the basal ganglia, organized movement sequences into chunks in the same fashion as neurologically intact individuals. To address this question, we compared motor response times during the performance of repeated sequences that were learned, and thus may be planned in advance, with random sequences where there is minimal if any advance preparation or organization of responses. The pattern of responses illustrated that, after basal ganglia stroke, individuals do not chunk elements of the repeated sequence into functional sub-sequences of movement to the same extent as neurologically intact age-matched people. Limited chunking of learned movements after stroke may explain past findings that show overall slower responses even when sequences of action are learned by this population. Further, our data in combination with other work, suggest that chunking may be a function of the basal ganglia.

  15. Interaction of language processing and motor skill in children with specific language impairment.

    Science.gov (United States)

    DiDonato Brumbach, Andrea C; Goffman, Lisa

    2014-02-01

    To examine how language production interacts with speech motor and gross and fine motor skill in children with specific language impairment (SLI). Eleven children with SLI and 12 age-matched peers (4-6 years) produced structurally primed sentences containing particles and prepositions. Utterances were analyzed for errors and for articulatory duration and variability. Standard measures of motor, language, and articulation skill were also obtained. Sentences containing particles, as compared with prepositions, were less likely to be produced in a priming task and were longer in duration, suggesting increased difficulty with this syntactic structure. Children with SLI demonstrated higher articulatory variability and poorer gross and fine motor skills compared with aged-matched controls. Articulatory variability was correlated with generalized gross and fine motor performance. Children with SLI show co-occurring speech motor and generalized motor deficits. Current theories do not fully account for the present findings, though the procedural deficit hypothesis provides a framework for interpreting overlap among language and motor domains.

  16. Electrophysiological Evidence for Impaired Control of Motor Output in Schizophrenia.

    Science.gov (United States)

    Kappenman, Emily S; Luck, Steven J; Kring, Ann M; Lesh, Tyler A; Mangun, George R; Niendam, Tara; Ragland, J Daniel; Ranganath, Charan; Solomon, Marjorie; Swaab, Tamara Y; Carter, Cameron S

    2016-05-01

    Previous research has demonstrated pervasive deficits in response-related processing in people with schizophrenia (PSZ). The present study used behavioral measures and event-related potentials (ERPs) to test the hypothesis that schizophrenia involves specific impairment in the ability to exert control over response-related processing. Twenty-two PSZ and 22 matched control participants completed a choice response task in counterbalanced testing sessions that emphasized only accuracy (the unspeeded condition) or emphasized speed and accuracy equally (the speeded condition). Control participants successfully modulated behavioral and ERP indices of response-related processing under speed pressure, as evidenced by faster and less variable reaction times (RTs) and an earlier onset and increased amplitude lateralized readiness potential (LRP). By contrast, PSZ were unable to improve RT speed or variability or to modulate the LRP under speed pressure, despite showing a decrease in accuracy. Notably, response-related deficits in PSZ emerged only in the speeded condition; behavioral and ERP measures did not differ between groups in the unspeeded condition. Together, these results indicate that impairment in the ability to exert control over response-related processing may underlie response-related deficits in schizophrenia. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Distinct motor impairments of dopamine D1 and D2 receptor knockout mice revealed by three types of motor behavior

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    Toru eNakamura

    2014-07-01

    Full Text Available Both D1R and D2R knock out (KO mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT mice. First, we examined spontaneous motor activity in the home cage environment for consecutive five days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h activities, respectively, than WT mice. In the rota-rod tasks, at a low speed, D1R KO mice showed poor performance but later improved, whereas D2R KO mice showed a good performance at early days without further improvement. When first subjected to a high speed task, the D2R KO mice showed poorer rota-rod performance at a low speed than the D1R KO mice. In the Step-Wheel task, across daily sessions, D2R KO mice increased the duration that mice run sufficiently close to the spout to drink water, and decreased time to touch the floor due to missing the peg steps and number of times the wheel was stopped, which performance was much better than that of D1R KO mice. These incongruent results between the two tasks for D1R and D2R KO mice may be due to the differences in the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward-driven, respectively. The Step-Wheel system may become a useful tool for assessing the motor ability of WT

  18. Selective impairments of motor sequence learning in multiple sclerosis patients with minimal disability.

    Science.gov (United States)

    Tacchino, Andrea; Bove, Marco; Roccatagliata, Luca; Luigi Mancardi, Giovanni; Uccelli, Antonio; Bonzano, Laura

    2014-10-17

    Patients with Multiple Sclerosis (PwMS) with severe sensorimotor and cognitive deficits show reduced ability in motor sequence learning. Conversely, in PwMS with minimal disability (EDSS≤2), showing only subtle neurological impairments and no particular deficits in everyday life activities, motor sequence learning has been poorly addressed. Here, we investigated whether PwMS with minimal disability already show a specific impairment in motor sequence learning and which component of this process can be first affected in MS. We implemented a serial reaction time task based on thumb-to-finger opposition movements in response to visual stimuli. Each session included 14 blocks of 120 stimuli presented randomly or in ten repetitions of a 12-item sequence. Random (R) and sequence (S) blocks were temporally alternated (R1, R2, S1/S5, R3, S6/S10, R4). Random blocks were designed to evaluate the motor component; sequence blocks, beside the motor component, allowed to discriminate the procedural performance. Twenty-two PwMS and 22 control healthy subjects were asked to perform the task under implicit or explicit instructions (11 subjects for each experimental condition). PwMS with minimal disability improved motor performance in random blocks reducing response time with practice with a trend similar to control subjects, suggesting that short-term learning of simple motor tasks is nearly preserved at this disease stage. Conversely, they found difficulties in sequence-specific learning in implicit and explicit condition, with more pronounced impairment in the implicit condition. These findings could suggest an involvement of different circuits in implicit and explicit sequence learning that could deteriorate at different disease stages. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Disruption of M1 Activity during Performance Plateau Impairs Consolidation of Motor Memories.

    Science.gov (United States)

    Hamel, Raphaël; Trempe, Maxime; Bernier, Pierre-Michel

    2017-09-20

    Upon exposure to a new sensorimotor relationship, motor behaviors iteratively change early in adaptation but eventually stabilize as adaptation proceeds. Behavioral work suggests that motor memory consolidation is initiated upon the attainment of asymptotic levels of performance. Separate lines of evidence point to a critical role of the primary motor cortex (M1) in consolidation. However, a causal relationship between M1 activity during asymptote and consolidation has yet to be demonstrated. The present study investigated this issue in male and female participants using single-pulse transcranial magnetic stimulation (TMS) to interfere with postmovement activity in M1 in two behavioral phases of a ramp-and-hold visuomotor adaptation paradigm. TMS was either provided after each trial of the ramp phase of adaptation when a gradual increase in the visuomotor rotation caused movements to be changing, or after each trial of the hold phase of adaptation when the rotation was held constant and movements tended to stabilize. Consolidation was assessed by measuring performance on the same task 24 h later. Results revealed that TMS did not influence adaptation to the new visuomotor relationship in either condition. Critically, however, TMS disruption of M1 activity selectively impaired consolidation of motor memories when it was provided during the hold phase of adaptation. This effect did not take place when TMS was delivered over adjacent dorsal premotor cortex or when motor behaviors in late adaptation were prevented from plateauing. Together, these data suggest that the impaired consolidation stemmed from interference with mechanisms of repetition-dependent plasticity in M1.SIGNIFICANCE STATEMENT The present work demonstrates that TMS disruption of M1 activity impairs the consolidation of motor memories selectively when performance reaches asymptotic levels during sensorimotor adaptation. These findings provide evidence for a causal contribution of M1 to motor memory

  20. Alcohol oxidizing enzymes and ethanol-induced cytotoxicity in rat pancreatic acinar AR42J cells.

    Science.gov (United States)

    Bhopale, Kamlesh K; Falzon, Miriam; Ansari, G A S; Kaphalia, Bhupendra S

    2014-04-01

    Alcoholic chronic pancreatitis (ACP) is a serious inflammatory disease causing significant morbidity and mortality. Due to lack of a suitable animal model, the underlying mechanism of ACP is poorly understood. Chronic alcohol abuse inhibits alcohol dehydrogenase (ADH) and facilitates nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs) in the pancreas frequently damaged during chronic ethanol abuse. Earlier, we reported a concentration-dependent formation of FAEEs and cytotoxicity in ethanol-treated rat pancreatic tumor (AR42J) cells, which express high FAEE synthase activity as compared to ADH and cytochrome P450 2E1. Therefore, the present study was undertaken to investigate the role of various ethanol oxidizing enzymes in ethanol-induced pancreatic acinar cell injury. Confluent AR42J cells were pre-treated with inhibitors of ADH class I and II [4-methylpyrazole (MP)] or class I, II, and III [1,10-phenanthroline (PT)], cytochrome P450 2E1 (trans-1,2-dichloroethylene) or catalase (sodium azide) followed by incubation with 800 mg% ethanol at 37°C for 6 h. Ethanol metabolism, cell viability, cytotoxicity (apoptosis and necrosis), cell proliferation status, and formation of FAEEs in AR42J cells were measured. The cell viability and cell proliferation rate were significantly reduced in cells pretreated with 1,10-PT + ethanol followed by those with 4-MP + ethanol. In situ formation of FAEEs was twofold greater in cells incubated with 1,10-PT + ethanol and ∼1.5-fold in those treated with 4-MP + ethanol vs. respective controls. However, cells treated with inhibitors of cytochrome P450 2E1 or catalase in combination of ethanol showed no significant changes either for FAEE formation, cell death or proliferation rate. Therefore, an impaired ADH class I-III catalyzed oxidation of ethanol appears to be a key contributing factor in ethanol-induced pancreatic injury via formation of nonoxidative metabolites of ethanol.

  1. Motoric impairment following manganese exposure in asteroid echinoderms.

    Science.gov (United States)

    Sköld, Helen Nilsson; Baden, Susanne P; Looström, Jakob; Eriksson, Susanne P; Hernroth, Bodil E

    2015-10-01

    In the oceans, naturally occurring manganese (Mn) is released from the sediments during events of hypoxia. While neuro- and immuno-toxic effects of bioavailable manganese are well documented for crustaceans, studies of similar effects of manganese on other marine invertebrates are comparatively few. Here, we developed a new functional test "the repeated turning assay" to investigate if manganese exposure at ∼12 mg L(-1) affected motoric behaviour of two asteroid echinoderms, the Common sea star, Asterias rubens, and the Black brittle star, Ophiocomina nigra. By measuring of the turning-over capacity, from dorsal to ventral position, after one and two weeks of manganese exposure, we showed that for both species Mn exposure significantly delayed the ability to turn. After a recovery period of two weeks, the capacity of turning-over was not restored to that of unexposed animals neither for A. rubens nor for O. nigra. Further investigation of sea stars showed that Mn accumulated ∼5 fold in the tube feet, organs involved in their turning-over activity, and the high concentration remained after the recovery period. In the tube feet we also recorded an increased activity of acetylcholinesterase (AChE), here used as a proxy for neuromuscular disturbances. The results indicated that Mn induces neuromuscular disturbance in echinoderms which is important news, given that previous studies have concluded that adult echinoderms are relatively tolerant to Mn. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Hemispheric asymmetry in myelin after stroke is related to motor impairment and function.

    Science.gov (United States)

    Lakhani, Bimal; Hayward, Kathryn S; Boyd, Lara A

    2017-01-01

    The relationships between impairment, function, arm use and underlying brain structure following stroke remain unclear. Although diffusion weighted imaging is useful in broadly assessing white matter structure, it has limited utility in identifying specific underlying neurobiological components, such as myelin. The purpose of the present study was to explore relationships between myelination and impairment, function and activity in individuals with chronic stroke. Assessments of paretic upper-extremity impairment and function were administered, and 72-hour accelerometer based activity monitoring was conducted on 19 individuals with chronic stroke. Participants completed a magnetic resonance imaging protocol that included a high resolution T1 anatomical scan and a multi-component T2 relaxation imaging scan to quantify myelin water fraction (MWF). MWF was automatically parcellated from pre- and post-central subcortical regions of interest and quantified as an asymmetry ratio (contralesional/ipsilesional). Cluster analysis was used to group more and less impaired individuals based on Fugl-Meyer upper extremity scores. A significantly higher precentral MWF asymmetry ratio was found in the more impaired group compared to the less impaired group (p < 0.001). There were no relationships between MWF asymmetry ratio and upper-limb use. Stepwise multiple linear regression identified precentral MWF asymmetry as the only variable to significantly predict impairment and motor function in the upper extremity (UE). These results suggest that asymmetric myelination in a motor specific brain area is a significant predictor of upper-extremity impairment and function in individuals with chronic stroke. As such, myelination may be utilized as a more specific marker of the neurobiological changes that predict long term impairment and recovery from stroke.

  3. AAV-BDNF mediated attenuation of quinolinic acid-induced neuropathology and motor function impairment.

    Science.gov (United States)

    Kells, A P; Henry, R A; Connor, B

    2008-07-01

    Maintenance and plasticity of striatal neurons is dependent on brain-derived neurotrophic factor (BDNF), which is depleted in the Huntington's disease striatum due to reduced expression and disrupted corticostriatal transportation. In this study we demonstrate that overexpression of BDNF in the striatum attenuates motor impairment and reduces the extent of striatal damage following quinolinic acid lesioning. Transfer of the BDNF gene to striatal neurons using serotype 1/2 adeno-associated viral vectors enhanced BDNF protein levels in the striatum, but induced weight loss and seizure activity following long-term high-level expression. Lower concentration BDNF expression supported striatal neurons against excitotoxic insult, as demonstrated by enhanced krox-24 immunopositive neuron survival, reduction of striatal atrophy and maintenance of the patch/matrix organization. Additionally, BDNF expression attenuated motor impairment in the forelimb use cylinder test, sensorimotor neglect in the corridor food selection task and reversed apomorphine-induced rotational behaviour. Direct correlations were shown for the first time between BDNF-mediated attenuation of behavioural impairment and the integrity of the globus pallidus, seemingly independent from the severity of striatal lesioning. These results demonstrate that BDNF holds considerable therapeutic potential for alleviating both neuropathological and motor function deficits in the Huntington's disease brain, and the critical role of pallidal neurons in facilitating motor performance.

  4. Stimulation over primary motor cortex during action observation impairs effector recognition.

    Science.gov (United States)

    Naish, Katherine R; Barnes, Brittany; Obhi, Sukhvinder S

    2016-04-01

    Recent work suggests that motor cortical processing during action observation plays a role in later recognition of the object involved in the action. Here, we investigated whether recognition of the effector making an action is also impaired when transcranial magnetic stimulation (TMS) - thought to interfere with normal cortical activity - is applied over the primary motor cortex (M1) during action observation. In two experiments, single-pulse TMS was delivered over the hand area of M1 while participants watched short clips of hand actions. Participants were then asked whether an image (experiment 1) or a video (experiment 2) of a hand presented later in the trial was the same or different to the hand in the preceding video. In Experiment 1, we found that participants' ability to recognise static images of hands was significantly impaired when TMS was delivered over M1 during action observation, compared to when no TMS was delivered, or when stimulation was applied over the vertex. Conversely, stimulation over M1 did not affect recognition of dot configurations, or recognition of hands that were previously presented as static images (rather than action movie clips) with no object. In Experiment 2, we found that effector recognition was impaired when stimulation was applied part way through (300ms) and at the end (500ms) of the action observation period, indicating that 200ms of action-viewing following stimulation was not long enough to form a new representation that could be used for later recognition. The findings of both experiments suggest that interfering with cortical motor activity during action observation impairs subsequent recognition of the effector involved in the action, which complements previous findings of motor system involvement in object memory. This work provides some of the first evidence that motor processing during action observation is involved in forming representations of the effector that are useful beyond the action observation period

  5. Gesture and motor skill in relation to language in children with language impairment.

    Science.gov (United States)

    Iverson, Jana M; Braddock, Barbara A

    2011-02-01

    To examine gesture and motor abilities in relation to language in children with language impairment (LI). Eleven children with LI (aged 2;7 to 6;1 [years;months]) and 16 typically developing (TD) children of similar chronological ages completed 2 picture narration tasks, and their language (rate of verbal utterances, mean length of utterance, and number of different words) and gestures (coded for type, co-occurrence with language, and informational relationship to language) were examined. Fine and gross motor items from the Battelle Developmental Screening Inventory (J. Newborg, J. R. Stock, L. Wneck, J. Guidubaldi, & J. Suinick, 1994) and the Child Development Inventory (H. R. Ireton, 1992) were administered. Relative to TD peers, children with LI used gestures at a higher rate and produced greater proportions of gesture-only communications, conventional gestures, and gestures that added unique information to co-occurring language. However, they performed more poorly on measures of fine and gross motor abilities. Regression analyses indicated that within the LI but not the TD group, poorer expressive language was related to more frequent gesture production. When language is impaired, difficulties are also apparent in motor abilities, but gesture assumes a compensatory role. These findings underscore the utility of including spontaneous gesture and motor abilities in clinical assessment of and intervention for preschool children with language concerns.

  6. Learning trajectories for speech motor performance in children with specific language impairment.

    Science.gov (United States)

    Richtsmeier, Peter T; Goffman, Lisa

    2015-01-01

    Children with specific language impairment (SLI) often perform below expected levels, including on tests of motor skill and in learning tasks, particularly procedural learning. In this experiment we examined the possibility that children with SLI might also have a motor learning deficit. Twelve children with SLI and thirteen children with typical development (TD) produced complex nonwords in an imitation task. Productions were collected across three blocks, with the first and second blocks on the same day and the third block one week later. Children's lip movements while producing the nonwords were recorded using an Optotrak camera system. Movements were then analyzed for production duration and stability. Movement analyses indicated that both groups of children produced shorter productions in later blocks (corroborated by an acoustic analysis), and the rate of change was comparable for the TD and SLI groups. A nonsignificant trend for more stable productions was also observed in both groups. SLI is regularly accompanied by a motor deficit, and this study does not dispute that. However, children with SLI learned to make more efficient productions at a rate similar to their peers with TD, revealing some modification of the motor deficit associated with SLI. The reader will learn about deficits commonly associated with specific language impairment (SLI) that often occur alongside the hallmark language deficit. The authors present an experiment showing that children with SLI improved speech motor performance at a similar rate compared to typically developing children. The implication is that speech motor learning is not impaired in children with SLI. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Central Processing Energetic Factors Mediate Impaired Motor Control in ADHD Combined Subtype but Not in ADHD Inattentive Subtype

    Science.gov (United States)

    Egeland, Jens; Ueland, Torill; Johansen, Susanne

    2012-01-01

    Participants with attention-deficit/hyperactivity disorder (ADHD) are often impaired in visuomotor tasks. However, little is known about the contribution of modal impairment in motor function relative to central processing deficits or whether different processes underlie the impairment in ADHD combined (ADHD-C) versus ADHD inattentive (ADHD-I)…

  8. Ethanol-induced hypothermia and hyperglycemia in genetically obese mice

    Energy Technology Data Exchange (ETDEWEB)

    Haller, E.W.; Wittmers, L.E. Jr.

    1989-01-01

    Blood glucose and rectal temperatures were monitored in two strains of genetically obese mice (C57 BL/6J ob/ob) prior to and following intragastric ethanol administration in an attempt to relate the hypothermic response to ethanol to extracellular glucose concentration. In contrast to expectation, ethanol administration was typically associated with a hyperglycemia and a hypothermic response. In the ob/ob genotype, the hypothermic response was associated with pronounced hyperglycemia which was more emphatic in older animals. The data support the conclusion that ethanol-induced hypothermia is independent of blood glucose levels. In light of the known sensitivity of ob/ob mice to insulin, it is suggested further that the observed hypothermic response was not a function of the animals' ability to transport glucose into peripheral cells. The observed hyperglycemia of the obese animals was most likely stress-related

  9. Altered Rolandic gamma-band activation associated with motor impairment and ictal network desynchronization in childhood epilepsy.

    Directory of Open Access Journals (Sweden)

    Sam M Doesburg

    Full Text Available Epilepsy is associated with an abnormal expression of neural oscillations and their synchronization across brain regions. Oscillatory brain activation and synchronization also play an important role in cognition, perception and motor control. Childhood epilepsy is associated with a variety of cognitive and motor deficits, but the relationship between altered functional brain responses in various frequency ranges and functional impairment in these children remains poorly understood. We investigated functional magnetoencephalographic (MEG responses from motor cortex in multiple functionally relevant frequency bands following median nerve stimulation in twelve children with epilepsy, including four children with motor impairments. We demonstrated that children with motor impairments exhibit an excessive gamma-band response from Rolandic cortex, and that the magnitude of this Rolandic gamma response is negatively associated with motor function. Abnormal responses from motor cortex were also associated with ictal desynchronization of oscillations within Rolandic cortex measured using intracranial EEG (iEEG. These results provide the evidence that ictal disruption of motor networks is associated with an altered functional response from motor cortex, which is in turn associated with motor impairment.

  10. Altered Rolandic gamma-band activation associated with motor impairment and ictal network desynchronization in childhood epilepsy.

    Science.gov (United States)

    Doesburg, Sam M; Ibrahim, George M; Smith, Mary Lou; Sharma, Rohit; Viljoen, Amrita; Chu, Bill; Rutka, James T; Snead, O Carter; Pang, Elizabeth W

    2013-01-01

    Epilepsy is associated with an abnormal expression of neural oscillations and their synchronization across brain regions. Oscillatory brain activation and synchronization also play an important role in cognition, perception and motor control. Childhood epilepsy is associated with a variety of cognitive and motor deficits, but the relationship between altered functional brain responses in various frequency ranges and functional impairment in these children remains poorly understood. We investigated functional magnetoencephalographic (MEG) responses from motor cortex in multiple functionally relevant frequency bands following median nerve stimulation in twelve children with epilepsy, including four children with motor impairments. We demonstrated that children with motor impairments exhibit an excessive gamma-band response from Rolandic cortex, and that the magnitude of this Rolandic gamma response is negatively associated with motor function. Abnormal responses from motor cortex were also associated with ictal desynchronization of oscillations within Rolandic cortex measured using intracranial EEG (iEEG). These results provide the evidence that ictal disruption of motor networks is associated with an altered functional response from motor cortex, which is in turn associated with motor impairment.

  11. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    Science.gov (United States)

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  12. Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats.

    Science.gov (United States)

    Goodfellow, Molly J; Shin, Youn Ju; Lindquist, Derick H

    2018-02-15

    Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Motor Skills and Social Impairments in Children With Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Shogo Hirata

    2015-08-01

    Full Text Available The purpose of this study was to examine the relationship between the Japanese version of the Developmental Coordination Disorder Questionnaire (DCDQ-J and the Social Responsiveness Scale (SRS in Japanese children with autism spectrum disorders (ASD. The participants were 19 children with ASD. The DCDQ-J is a parent questionnaire that can assess the degree of motor skill impairments, and the SRS assesses the severity of social impairments. To check the criterion-related validity of the DCDQ-J in children with ASD, the Japanese version of the Movement Assessment Battery for Children-2 (MABC2-J was also conducted. The total score of the DCDQ-J was significantly negatively correlated with the SRS score in the same way as the MABC2-J total score. These results indicate that the severity of social impairments in children with ASD is related not only to the child’s fundamental motor abilities but also to practical motor skills in everyday life.

  14. Cannabidiol prevents motor and cognitive impairments induced by reserpine in rats

    Directory of Open Access Journals (Sweden)

    Fernanda Fiel Peres

    2016-09-01

    Full Text Available Cannabidiol (CBD is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory and neuroprotective effects. In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg or vehicle (days 2-5. On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals’ performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg attenuated the increase in catalepsy behavior and in oral movements – but not the decrease in locomotion – induced by reserpine. CBD (0.5 mg/kg also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson’s disease and tardive dyskinesia.

  15. Neurotoxicity induced by alkyl nitrites: Impairment in learning/memory and motor coordination.

    Science.gov (United States)

    Cha, Hye Jin; Kim, Yun Ji; Jeon, Seo Young; Kim, Young-Hoon; Shin, Jisoon; Yun, Jaesuk; Han, Kyoungmoon; Park, Hye-Kyung; Kim, Hyung Soo

    2016-04-21

    Although alkyl nitrites are used as recreational drugs, there is only little research data regarding their effects on the central nervous system including their neurotoxicity. This study investigated the neurotoxicity of three representative alkyl nitrites (isobutyl nitrite, isoamyl nitrite, and butyl nitrite), and whether it affected learning/memory function and motor coordination in rodents. Morris water maze test was performed in mice after administrating the mice with varying doses of the substances in two different injection schedules of memory acquisition and memory retention. A rota-rod test was then performed in rats. All tested alkyl nitrites lowered the rodents' capacity for learning and memory, as assessed by both the acquisition and retention tests. The results of the rota-rod test showed that isobutyl nitrite in particular impaired motor coordination in chronically treated rats. The mice chronically injected with isoamyl nitrite also showed impaired function, while butyl nitrite had no significant effect. The results of the water maze test suggest that alkyl nitrites may impair learning and memory. Additionally, isoamyl nitrite affected the rodents' motor coordination ability. Collectively, our findings suggest that alkyl nitrites may induce neurotoxicity, especially on the aspect of learning and memory function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. The influence of a vestibular dysfunction on the motor development of hearing-impaired children.

    Science.gov (United States)

    De Kegel, Alexandra; Maes, Leen; Baetens, Tina; Dhooge, Ingeborg; Van Waelvelde, Hilde

    2012-12-01

    To identify the predictive ability of vestibular function test results on motor performance among hearing-impaired children. Cross-sectional study. Fifty-one typically developing children and 48 children with a unilateral (n = 9) or bilateral hearing impairment (n = 39) of more than 40 dB HL between 3 and 12 years were tested by the Movement Assessment Battery for Children-Second Edition (M ABC-2), clinical balance tests, posturography, rotatory chair testing, and vestibular evoked myogenic potential (VEMP). From the group of hearing-impaired children, 23 had cochlear implants. Balance performance on M ABC-2, clinical balance tests, as well as the sway velocity assessed by posturography in bipedal stance on a cushion with eyes closed and in unilateral stance differed significantly between both groups. Presence of a VEMP response is an important clinical parameter because comparison of the motor performance among hearing-impaired children between those with present and absent VEMPs showed significant differences in balance performance. The three most important predictor variables on motor performance by bivariate regression analyses are the vestibular-ocular reflex (VOR) gain value of the rotatory chair test at 0.01 and 0.05 Hz frequency, as well as the VEMP asymmetry ratio. Multivariate regression analyses suggest that the VOR asymmetry value of the rotatory chair test at 0.05 Hz and the etiology of the hearing loss seem to have additional predictive value. Hearing-impaired children are at risk for balance deficits. A combination of rotatory chair testing and VEMP testing can predict the balance performance. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  17. Vision of the active limb impairs bimanual motor tracking in young and older adults

    Directory of Open Access Journals (Sweden)

    Matthieu P. Boisgontier

    2014-11-01

    Full Text Available Despite the intensive investigation of bimanual coordination, it remains unclear how directing vision toward either limb influences performance, and whether this influence is affected by age. To examine these questions, we assessed the performance of young and older adults on a bimanual tracking task in which they matched motor-driven movements of their right hand (passive limb with their left hand (active limb according to in-phase and anti-phase patterns. Performance in six visual conditions involving central vision, and/or peripheral vision of the active and/or passive limb was compared to performance in a no vision condition. Results indicated that directing central vision to the active limb consistently impaired performance, with higher impairment in older than young adults. Conversely, directing central vision to the passive limb improved performance in young adults, but less consistently in older adults. In conditions involving central vision of one limb and peripheral vision of the other limb, similar effects were found to those for conditions involving central vision of one limb only. Peripheral vision alone resulted in similar or impaired performance compared to the no vision condition. These results indicate that the locus of visual attention is critical for bimanual motor control in young and older adults, with older adults being either more impaired or less able to benefit from a given visual condition.

  18. Erythropoietin ameliorates the motor and cognitive function impairments in a rat model of hepatic cirrhosis.

    Science.gov (United States)

    Aghaei, Iraj; Nazeri, Masoud; Shabani, Mohammad; Mossavinasab, Marziehsadat; Mirhosseini, Fatemeh Khaleghi; Nayebpour, Mohsen; Dalili, Afshin

    2015-02-01

    Hepatic encephalopathy (HE) is a serious consequence of hepatic cirrhosis (HC). Previous studies have demonstrated cognitive impairments in both clinical and animal experiments of HC. Some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of HC. In the current study, the possible effect of erythropoietin (ERY) as a potent neuroprotective agent on motor and cognitive impairments induced by HC has been studied. Male Wistar rats (180-200 g) underwent bile duct ligation (BDL) or sham surgery. Administration of ERY (5,000 IU/kg, i.p., daily for three days) was initiated 2 weeks after surgery and lasted for the next 28 days. Open field, rotarod, Morris water maze and passive avoidance learning was used to evaluate the motor and cognitive function of the animals. ANOVA and repeated measures ANOVA were used to analyze the data. p balance function by BDL was reversed by ERY. Spatial and passive avoidance learning impairments observed in BDL rats were also reversed by chronic administration of ERY. ERY can be offered as a potential neuroprotective agent in the treatment of patients with HC that manifest mental dysfunctions. Though further studies are needed to clarify the exact mechanisms, the neuroprotective properties of ERY against BDL impairments were demonstrated in the current study.

  19. Disturbances of grip force behaviour in focal hand dystonia: evidence for a generalised impairment of sensory-motor integration?

    OpenAIRE

    Nowak, D.; Rosenkranz, K; Topka, H.; Rothwell, J

    2005-01-01

    Background: Focal task specific dystonia occurs preferentially during performance of a specific task. There may be an inefficiently high grip force when doing manipulative tasks other than the trigger task, possibly reflecting a generalised impairment of sensory-motor integration.

  20. Alcohol hangover: type and time-extension of motor function impairments.

    Science.gov (United States)

    Karadayian, Analía G; Cutrera, Rodolfo A

    2013-06-15

    Alcohol hangover is defined as the unpleasant next-day state following an evening of excessive alcohol consumption. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. During hangover cognitive functions and subjective capacities are affected along with inefficiency, reduced productivity, absenteeism, driving impairments, poor academic achievement and reductions in motor coordination. The aim of this work was to study the type and length of motor and exploratory functions from the beginning to the end of the alcohol hangover. Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Motor performance, walking deficiency, motor strength, locomotion and exploratory activity were evaluated at a basal point (ZT0) and every 2 h up to 20 h after blood alcohol levels were close to zero (hangover onset). Motor performance was 80% decreased at the onset of hangover (pperformance during the next 16 h (peffects of alcohol hangover. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Progressive solitary sclerosis: Gradual motor impairment from a single CNS demyelinating lesion.

    Science.gov (United States)

    Keegan, B Mark; Kaufmann, Timothy J; Weinshenker, Brian G; Kantarci, Orhun H; Schmalstieg, William F; Paz Soldan, M Mateo; Flanagan, Eoin P

    2016-10-18

    To report patients with progressive motor impairment resulting from an isolated CNS demyelinating lesion in cerebral, brainstem, or spinal cord white matter that we call progressive solitary sclerosis. Thirty patients were identified with (1) progressive motor impairment for over 1 year with a single radiologically identified CNS demyelinating lesion along corticospinal tracts, (2) absence of other demyelinating CNS lesions, and (3) no history of relapses affecting other CNS pathways. Twenty-five were followed prospectively in our multiple sclerosis (MS) clinic and 5 were identified retrospectively from our progressive MS database. Patients were excluded if an alternative etiology for progressive motor impairment was found. Multiple brain and spinal cord MRI were reviewed by a neuroradiologist blinded to the clinical details. The patients' median age was 48.5 years (range 23-71) and 15 (50%) were women. The median follow-up from symptom onset was 100 months (range 15-343 months). All had insidiously progressive upper motor neuron weakness attributable to the solitary demyelinating lesion found on MRI. Clinical presentations were hemiparesis/monoparesis (n = 24), quadriparesis (n = 5), and paraparesis (n = 1). Solitary MRI lesions involved cervical spinal cord (n = 18), cervico-medullary/brainstem region (n = 6), thoracic spinal cord (n = 4), and subcortical white matter (n = 2). CSF abnormalities consistent with MS were found in 13 of 26 (50%). Demyelinating disease was confirmed pathologically in 2 (biopsy, 1; autopsy, 1). Progressive solitary sclerosis results from an isolated CNS demyelinating lesion. Future revisions to MS diagnostic criteria could incorporate this presentation of demyelinating disease. © 2016 American Academy of Neurology.

  2. Stereopsis impairment is associated with decreased color perception and worse motor performance in Parkinson's disease.

    Science.gov (United States)

    Sun, Liang; Zhang, Hui; Gu, Zhuqin; Cao, Ming; Li, Dawei; Chan, Piu

    2014-05-24

    We conducted this study is to investigate the correlation between stereopsis dysfunction and color perception, as well as whether stereopsis impairment is associated with motor dysfunction in patients with Parkinson's disease (PD). Our present study included 45 PD patients and 50 non-PD control patients attending the Movement Disorder Center at Xuanwu Hospital Capital Medical University in Beijing from July 2011 to November 2011. Neurologic evaluations and visual function assessments were conducted, and the results between two groups of patients were compared. We found that the total error scores (TESs) and partial error scores (PESs) for red, green, blue and purple were all significantly higher in PD patients than in control patients. The limited grade on the FLY Stereo Acuity Test with LEA Symbols was significantly lower in PD patients than in control patients (P = 0.0001), whereas the percentage of abnormal stereopsis in PD patients was significantly higher than in control patients (42.2% vs. 12%; P = 0.001). Multiple linear regression analysis showed that PD patients with higher Hoehn and Yahr Scale stage, and those with decreased stereopsis had higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and worse motor function. Furthermore, our study demonstrates that the UPDRS motor scores and total average number of the Purdue Pegboard Test scores of PD patients were significantly improved when they had taken their medications, and the TESs and PESs for green were lower in when they were off their medications. Our results provide more information on the underlying mechanisms of vision, motor and stereopsis impairments in PD patients.

  3. A descriptive study on wrist and hand sensori-motor impairment and function following distal radius fracture intervention.

    Science.gov (United States)

    Karagiannopoulos, Christos; Sitler, Michael; Michlovitz, Susan; Tierney, Ryan

    2013-01-01

    Descriptive cross-sectional design. Wrist and hand sensori-motor impairment have been observed after distal radius fracture (DRF) treatment. This impairment and its relationship to function lack research. The primary aim of this exploratory study was to determine the magnitude of wrist and hand sensori-motor impairment following surgical and non-surgical treatment among older patients following DRF. Secondary aims were to determine the relationship between wrist and hand sensori-motor impairment with function and pain as well as the relationships among wrist and hand sensori-motor impairment and function and age following DRF. Ten Test (TT), active joint position sense (JPS), electromyography (EMG), computerized hand-grip dynamometer (CHD), and the Patient-Rated Wrist Evaluation (PRWE) were used to assess twenty-four female participants 8 weeks following DRF treatment and their 24 matched-control healthy counterparts on wrist and hand sensibility, proprioception, muscle recruitment, grip force, muscle fatigue, and functional status. Participants following DRF demonstrated significantly (p wrist and hand sensori-motor impairment and functional deficits among older females 8 weeks following DRF surgical and non-surgical interventions were revealed. JPS and total grip force were the most clinically meaningful tests for assessing the sensori-motor status as well as explaining functional disability and pain levels for these patients. 2c. Copyright © 2013 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  4. Sphingosine-1 phosphate prevents ethanol-induced corneal epithelial apoptosis

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    Pierre Fournie

    2012-01-01

    Full Text Available Background: Apoptosis is a programmed cell death in multicellular organisms, found in a wide variety of conditions, including inflammatory process, everywhere in the body, including the cornea and conjunctiva. Aim: To evaluate the effect of a new topical formulation of sphingosine-1 phosphate on preventing apoptosis of the corneal epithelium. Setting: Medical University. Materials and Methods: We tested several formulations suitable for topical application. Twenty-five rabbits were distributed among five groups. Group 1 comprised the controls. In Group 2, 20% ethanol was applied topically for 20 seconds; in Group 3, 50 μM topical sphingosine-1 phosphate was applied 2 hours prior to 20% ethanol application. In Group 4, 200 μM topical sphingosine-1 phosphate was applied 2 hours before the 20% ethanol application. In Group 5, only 200 μM topical sphingosine-1 phosphate was applied. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (TUNEL assay. Pairwise comparisons were performed using t-tests with Scheffe′s correction. Data were analyzed using STATA 9.0 statistical software. Results: A suspension of sphingosine-1 phosphate in the presence of Montanox 80 was stable and could be formulated without sonication. Epithelial apoptosis was detected only in Groups 2 and 3. Conclusion: Sphingosine-1 phosphate can prevent ethanol-induced apoptosis in the corneal epithelium of rabbits.

  5. Mental rotation as an indicator of motor representation in patients with mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Julien eBourrelier

    2015-12-01

    Full Text Available This internal representation of movement of part(s of the body is involved during Implicit Motor Imagery tasks (IMI; the same representations are employed in the laterality judgment task. Few studies have looked at the consequences of aging, Alzheimer’s disease (AD and mild cognitive impairment (MCI on the processes of motor preparation but none showed evidence of an alteration of action representation in patient with amnestic MCI. In the present study, the IMI task was used to assess the action representation abilities in MCI patients and healthy counterparts. A total of 24 elderly participants aged between 65 and 90 years old (12 women, 73.4 ± 6 years, mean ± S.D. were recruited: 12 patients with MCI (MCI group and 12 healthy aged adults (HAA group. The results showed that MCI patients have significantly a greater response time (RT than HAA subjects only in IMI task and more precisely when performing their mental rotation at the challenging conditions. Furthermore, the IMI task related to the non-dominant hand induced a significant increase of RT only in MCI subjects. At the light of these results, we assume that MCI patients are able to engage themselves in implicit motor imagery processes, still showing a compelling impairment of this mental ability across its complexity.

  6. fMRI and sleep correlates of the age-related impairment in motor memory consolidation.

    Science.gov (United States)

    Fogel, Stuart M; Albouy, Genevieve; Vien, Catherine; Popovicci, Romana; King, Bradley R; Hoge, Rick; Jbabdi, Saad; Benali, Habib; Karni, Avi; Maquet, Pierre; Carrier, Julie; Doyon, Julien

    2014-08-01

    Behavioral studies indicate that older adults exhibit normal motor sequence learning (MSL), but paradoxically, show impaired consolidation of the new memory trace. However, the neural and physiological mechanisms underlying this impairment are entirely unknown. Here, we sought to identify, through functional magnetic resonance imaging during MSL and electroencephalographic (EEG) recordings during daytime sleep, the functional correlates and physiological characteristics of this age-related motor memory deficit. As predicted, older subjects did not exhibit sleep-dependent gains in performance (i.e., behavioral changes that reflect consolidation) and had reduced sleep spindles compared with young subjects. Brain imaging analyses also revealed that changes in activity across the retention interval in the putamen and related brain regions were associated with sleep spindles. This change in striatal activity was increased in young subjects, but reduced by comparison in older subjects. These findings suggest that the deficit in sleep-dependent motor memory consolidation in elderly individuals is related to a reduction in sleep spindle oscillations and to an associated decrease of activity in the cortico-striatal network. Copyright © 2013 Wiley Periodicals, Inc.

  7. Comparative analysis of speech impairment and upper limb motor dysfunction in Parkinson's disease.

    Science.gov (United States)

    Rusz, Jan; Tykalová, Tereza; Krupička, Radim; Zárubová, Kateřina; Novotný, Michal; Jech, Robert; Szabó, Zoltán; Růžička, Evžen

    2017-04-01

    It is currently unknown whether speech and limb motor effectors in Parkinson's disease (PD) are controlled by similar underlying brain processes. Based on computerized objective analysis, the aim of this study was to evaluate potential correlation between speech and mechanical tests of upper limb motor function. Speech and upper limb motor tests were performed in 22 PD patients and 22 healthy controls. Quantitative acoustic analyses of eight key speech dimensions of hypokinetic dysarthria, including quality of voice, sequential motion rates, consonant articulation, vowel articulation, average loudness, loudness variability, pitch variability, and number of pauses, were performed. Upper limb movements were assessed using the motor part of the Unified Parkinson's Disease Rating Scale, contactless three-dimensional motion capture system, blinded expert evaluation, and the Purdue Pegboard Test. Significant relationships were observed between the quality of voice assessed by jitter and amplitude decrement of finger tapping (r = 0.61, p = 0.003), consonant articulation evaluated using voice onset time and expert rating of finger tapping (r = 0.60, p = 0.003), and number of pauses and Purdue Pegboard Test score (r = 0.60, p = 0.004). The current study supports the hypothesis that speech impairment in PD shares, at least partially, similar pathophysiological processes with limb motor dysfunction. Vocal fold vibration irregularities appeared to be influenced by mechanisms similar to amplitude decrement during repetitive limb movements. Consonant articulation deficits were associated with decreased manual dexterity and movement speed, likely reflecting fine motor control involvement in PD.

  8. Glutathione prevents ethanol induced gastric mucosal damage and depletion of sulfhydryl compounds in humans.

    Science.gov (United States)

    Loguercio, C; Taranto, D; Beneduce, F; del Vecchio Blanco, C; de Vincentiis, A; Nardi, G; Romano, M

    1993-01-01

    Whether parenteral administration of reduced glutathione prevented ethanol induced damage to and depletion of sulfhydryl compounds in the human gastric mucosa was investigated. Ten healthy volunteers underwent endoscopy on three separate occasions. Gastric mucosal damage was induced by spraying 80% ethanol on to the gastric mucosa through the biopsy channel of the endoscope. The gastric mucosal score, total sulfhydryls, glutathione, and cysteine were evaluated in basal conditions and after ethanol administration with and without pretreatment with parenteral glutathione. Glutathione significantly decreased the extent of ethanol induced macroscopic injury to the mucosa of the gastric body and antrum. Glutathione's protective effect is associated with appreciable inhibition of ethanol induced depletion of gastric sulfhydryl compounds. This is the first report of protection against ethanol induced gastric mucosal damage by a sulfhydryl containing agent in humans. PMID:8432465

  9. Actigraphic motor activity in mild cognitive impairment patients carrying out short functional activity tasks: comparison between mild cognitive impairment with and without depressive symptoms.

    Science.gov (United States)

    Yakhia, Maja; König, Alexandra; van der Flier, Wiesje M; Friedman, Leah; Robert, Philippe H; David, Renaud

    2014-01-01

    Individuals with mild cognitive impairment (MCI) may exhibit changes in motor activity in conducting their activities of daily living. Depression, one of the most frequent neuropsychiatric symptoms, might affect motor activity in MCI. To assess motor activity in MCI subjects carrying out short functional activity tasks using ambulatory actigraphy. Secondly, we sought to investigate the influence of depressive symptoms on motor activity. 20 MCI and 14 healthy subjects carried out a 30-minute standardized scenario while wearing a chest actigraph. The protocol consisted of directed activities (execution of motor tasks), semi-directed activities (execution of Instrumental Activities of Daily Living, IADL), and undirected 'free' activities. Several common assessment scales (GDS, MADRS, and NPI) were used to diagnose depression. MCI subjects had significantly reduced mean motor activity while carrying out directed and semi-directed activities, compared to healthy control subjects. No difference was found in motor activity between MCI subjects with or without depression. Actigraphic measurement of motor activity during the evaluation of IADLs and motor tasks is a potential objective tool in detecting early changes in MCI. Depressive symptoms seem not to be associated with motor activity in MCI subjects.

  10. Gastroprotective Effect of Selenium on Ethanol-Induced Gastric Damage in Rats

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    Jeong-Hwan Kim

    2012-05-01

    Full Text Available In the present study, we examined the gastroprotective effect of selenium against ethanol-induced gastric mucosal lesions in rats. The gastric mucosal lesions were produced by oral administration with various concentrations of ethanol for three days, and 80% ethanol treatment was determined to be the optimal condition for induction of gastric damage. To identify the protective effect of selenium on ethanol-induced gastric damage, various doses of selenium were given as pretreatment for three days, and then gastric damage was induced by 80% ethanol treatment. Selenium showed a protective effect against ethanol-induced gastric mucosal lesions in a dose dependent manner. Specifically, 100 μg/kg selenium showed the highest level of gastroprotection. In addition, selenium markedly attenuated ethanol-induced lipid peroxidation in gastric mucosa and increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD, catalase, and glutathione peroxidase in a dose-dependent manner. Histological data showed that 100 μg/kg selenium distinctly reduced the depth and severity of the ethanol induced gastric lesion. These results clearly demonstrate that selenium inhibits the formation of ethanol-induced gastric mucosal lesions through prevention of lipid peroxidation and activation of enzymatic radical scavenging.

  11. Gastroprotective effect of selenium on ethanol-induced gastric damage in rats.

    Science.gov (United States)

    Kim, Jeong-Hwan; Park, Shin-Hyung; Nam, Soo-Wan; Choi, Yung-Hyun

    2012-01-01

    In the present study, we examined the gastroprotective effect of selenium against ethanol-induced gastric mucosal lesions in rats. The gastric mucosal lesions were produced by oral administration with various concentrations of ethanol for three days, and 80% ethanol treatment was determined to be the optimal condition for induction of gastric damage. To identify the protective effect of selenium on ethanol-induced gastric damage, various doses of selenium were given as pretreatment for three days, and then gastric damage was induced by 80% ethanol treatment. Selenium showed a protective effect against ethanol-induced gastric mucosal lesions in a dose dependent manner. Specifically, 100 μg/kg selenium showed the highest level of gastroprotection. In addition, selenium markedly attenuated ethanol-induced lipid peroxidation in gastric mucosa and increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Histological data showed that 100 μg/kg selenium distinctly reduced the depth and severity of the ethanol induced gastric lesion. These results clearly demonstrate that selenium inhibits the formation of ethanol-induced gastric mucosal lesions through prevention of lipid peroxidation and activation of enzymatic radical scavenging.

  12. Cortical disconnection of the ipsilesional primary motor cortex is associated with gait speed and upper extremity motor impairment in chronic left hemispheric stroke.

    Science.gov (United States)

    Peters, Denise M; Fridriksson, Julius; Stewart, Jill C; Richardson, Jessica D; Rorden, Chris; Bonilha, Leonardo; Middleton, Addie; Gleichgerrcht, Ezequiel; Fritz, Stacy L

    2018-01-01

    Advances in neuroimaging have enabled the mapping of white matter connections across the entire brain, allowing for a more thorough examination of the extent of white matter disconnection after stroke. To assess how cortical disconnection contributes to motor impairments, we examined the relationship between structural brain connectivity and upper and lower extremity motor function in individuals with chronic stroke. Forty-three participants [mean age: 59.7 (±11.2) years; time poststroke: 64.4 (±58.8) months] underwent clinical motor assessments and MRI scanning. Nonparametric correlation analyses were performed to examine the relationship between structural connectivity amid a subsection of the motor network and upper/lower extremity motor function. Standard multiple linear regression analyses were performed to examine the relationship between cortical necrosis and disconnection of three main cortical areas of motor control [primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA)] and motor function. Anatomical connectivity between ipsilesional M1/SMA and the (1) cerebral peduncle, (2) thalamus, and (3) red nucleus were significantly correlated with upper and lower extremity motor performance (P ≤ 0.003). M1-M1 interhemispheric connectivity was also significantly correlated with gross manual dexterity of the affected upper extremity (P = 0.001). Regression models with M1 lesion load and M1 disconnection (adjusted for time poststroke) explained a significant amount of variance in upper extremity motor performance (R 2  = 0.36-0.46) and gait speed (R 2  = 0.46), with M1 disconnection an independent predictor of motor performance. Cortical disconnection, especially of ipsilesional M1, could significantly contribute to variability seen in locomotor and upper extremity motor function and recovery in chronic stroke. Hum Brain Mapp 39:120-132, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Implicit perceptual-motor skill learning in mild cognitive impairment and Parkinson's disease.

    Science.gov (United States)

    Gobel, Eric W; Blomeke, Kelsey; Zadikoff, Cindy; Simuni, Tanya; Weintraub, Sandra; Reber, Paul J

    2013-05-01

    Implicit skill learning is hypothesized to depend on nondeclarative memory that operates independent of the medial temporal lobe (MTL) memory system and instead depends on cortico striatal circuits between the basal ganglia and cortical areas supporting motor function and planning. Research with the Serial Reaction Time (SRT) task suggests that patients with memory disorders due to MTL damage exhibit normal implicit sequence learning. However, reports of intact learning rely on observations of no group differences, leading to speculation as to whether implicit sequence learning is fully intact in these patients. Patients with Parkinson's disease (PD) often exhibit impaired sequence learning, but this impairment is not universally observed. Implicit perceptual-motor sequence learning was examined using the Serial Interception Sequence Learning (SISL) task in patients with amnestic Mild Cognitive Impairment (MCI; n = 11) and patients with PD (n = 15). Sequence learning in SISL is resistant to explicit learning and individually adapted task difficulty controls for baseline performance differences. Patients with MCI exhibited robust sequence learning, equivalent to healthy older adults (n = 20), supporting the hypothesis that the MTL does not contribute to learning in this task. In contrast, the majority of patients with PD exhibited no sequence-specific learning in spite of matched overall task performance. Two patients with PD exhibited performance indicative of an explicit compensatory strategy suggesting that impaired implicit learning may lead to greater reliance on explicit memory in some individuals. The differences in learning between patient groups provides strong evidence in favor of implicit sequence learning depending solely on intact basal ganglia function with no contribution from the MTL memory system.

  14. Visual-motor integration performance in children with severe specific language impairment.

    Science.gov (United States)

    Nicola, K; Watter, P

    2016-09-01

    This study investigated (1) the visual-motor integration (VMI) performance of children with severe specific language impairment (SLI), and any effect of age, gender, socio-economic status and concomitant speech impairment; and (2) the relationship between language and VMI performance. It is hypothesized that children with severe SLI would present with VMI problems irrespective of gender and socio-economic status; however, VMI deficits will be more pronounced in younger children and those with concomitant speech impairment. Furthermore, it is hypothesized that there will be a relationship between VMI and language performance, particularly in receptive scores. Children enrolled between 2000 and 2008 in a school dedicated to children with severe speech-language impairments were included, if they met the criteria for severe SLI with or without concomitant speech impairment which was verified by a government organization. Results from all initial standardized language and VMI assessments found during a retrospective review of chart files were included. The final study group included 100 children (males = 76), from 4 to 14 years of age with mean language scores at least 2SD below the mean. For VMI performance, 52% of the children scored below -1SD, with 25% of the total group scoring more than 1.5SD below the mean. Age, gender and the addition of a speech impairment did not impact on VMI performance; however, children living in disadvantaged suburbs scored significantly better than children residing in advantaged suburbs. Receptive language scores of the Clinical Evaluation of Language Fundamentals was the only score associated with and able to predict VMI performance. A small subgroup of children with severe SLI will also have poor VMI skills. The best predictor of poor VMI is receptive language scores on the Clinical Evaluation of Language Fundamentals. Children with poor receptive language performance may benefit from VMI assessment and multidisciplinary

  15. Kinetic measurements of hand motor impairments after mild to moderate stroke using grip control tasks.

    Science.gov (United States)

    Ye, Yu; Ma, Le; Yan, Tiebin; Liu, Huihua; Wei, Xijun; Song, Rong

    2014-05-11

    The aim of this study is to investigate quantitative outcome measurements of hand motor performance for subjects after mild to moderate stroke using grip control tasks and characterize abnormal flexion synergy of upper extremities after stroke. A customized dynamometer with force sensors was used to measure grip force and calculate rotation torque during the sub-maximal grip control tasks. The paretic and nonpartic sides of eleven subjects after stroke and the dominant sides of ten healthy persons were tested. Their maximal voluntary grip force was measured and used to set sub-maximal grip control tasks at three different target force levels. Force control ability was characterized by the maximal grip force, mean force percentage, coefficient of variation (CV), target deviation ratio (TDR), and rotation torque ratio (RTR). The motor impairments of subjects after stroke were also evaluated using the Fugl-Meyer assessment for upper extremity (FMA-UE) and Wolf Motor Function Test (WMFT). Maximal grip force of the paretic side was significantly reduced as compared to the nonparetic side and the healthy group, while the difference of maximal grip force between the nonparetic side and the healthy group was not significant. TDR and RTR increased for all three groups with increasing target force level. There were significant differences of CV, TDR and RTR between the paretic side and the healthy group at all the force levels. CV, TDR and RTR showed significant negative correlations with FMA-UE and WMFT at 50% of maximum grip force. This study designed a customized dynamometer together with an innovative measurement, RTR, to investigate the hand motor performance of subjects after mild to moderate stroke during force control tasks. And stroke-induced abnormal flexion synergy of wrist and finger muscles could be characterized by RTR. This study also identified a set of kinetic parameters which can be applied to quantitatively assess the hand motor function of subjects after

  16. The Rett syndrome: gross motor disability and neural impairment in adults.

    Science.gov (United States)

    Witt-Engerström, I; Hagberg, B

    1990-01-01

    Profile and variation of gross motor disability and neural impairments were studied in a series of 30 women, aged 22-44 years, fulfilling the diagnostic criteria for the Rett syndrome (RS). The sequential development of neurological signs and a movement disorder causing immobility in 80% were found. On the basis of acquired and sustained walking ability, the women could be divided into three groups: one comprising those 20% still walking (group III), one those 60% previously walking (group IVA) and the third those 20% who had never developed walking ability (group IVB). Spastic signs, seldom prominent, were found in all the three groups, while dystonic signs were most common in those previously walking, and weakness and wasting in the group that never acquired that skill. Early progressive scoliosis, peroneal weakness and excavated feet, interpreted as lower motor neuron signs mainly due to spinal tract impairment, were most extensive among those never able to walk. Loss of walking was considered a consequence of deranging combinations of weakness and dystonia. The patterns of neuromotor disturbances are discussed in relation to other manifestations of RS.

  17. Postural control, motor skills, and health-related quality of life in children with hearing impairment: a systematic review.

    Science.gov (United States)

    Rajendran, Venkadesan; Roy, Finita Glory; Jeevanantham, Deepa

    2012-04-01

    Children with hearing impairment have balance and motor deficits primarily due to concomitant damage to the vestibular structures. Psycho-intellectual and social developmental disorders, as well as elimination of social activities and participation may diminish health-related quality of life in these children. Despite the documentation, assessment of balance, motor deficits, and health-related quality of life of these children are not included in the educational program, unless obvious neurological or orthopedic disorders are diagnosed. The objective of this review was to systematically analyze the available information in the literatures regarding the postural control, motor skills, and health-related quality of life in children with hearing impairment. Searches of data sources PubMed, MEDLINE, CINHAL, EMBASE, SCOPUS, ISI of web science, Cochrane Library, and AMED database were performed from the earliest to 7 February 2011. Study eligibility criteria included non-interventional studies that addressed postural control, motor skills, and health-related quality of life in children with hearing impairment. For each eligible article, data were extracted using custom-designed forms by a single investigator. Collected data included study demographics, study design, study population, sample size, outcome measures, and results. A total of 11,872 articles were retrieved, and 17 articles were found to be eligible for inclusion. Of the 17 articles included, five articles analyzed health-related quality of life alone, two articles analyzed balance alone, two articles analyzed motor performance alone, two articles analyzed vestibular dysfunction alone, two articles included both vestibular dysfunction and balance, two articles included both motor performance and balance, and two articles investigated vestibular, balance as well as motor impairments. Heterogeneity of the studies prevented us from performing methodological quality assessment and meta-analysis. The results of

  18. Interhemispheric Pathways Are Important for Motor Outcome in Individuals with Chronic and Severe Upper Limb Impairment Post Stroke

    Directory of Open Access Journals (Sweden)

    Kathryn S. Hayward

    2017-01-01

    Full Text Available Background. Severity of arm impairment alone does not explain motor outcomes in people with severe impairment post stroke. Objective. Define the contribution of brain biomarkers to upper limb motor outcomes in people with severe arm impairment post stroke. Methods. Paretic arm impairment (Fugl-Meyer upper limb, FM-UL and function (Wolf Motor Function Test rate, WMFT-rate were measured in 15 individuals with severe (FM-UL ≤ 30/66 and 14 with mild–moderate (FM-UL > 40/66 impairment. Transcranial magnetic stimulation and diffusion weight imaging indexed structure and function of the corticospinal tract and corpus callosum. Separate models of the relationship between possible biomarkers and motor outcomes at a single chronic (≥6 months time point post stroke were performed. Results. Age (ΔR20.365, p=0.017 and ipsilesional-transcallosal inhibition (ΔR20.182, p=0.048 explained a 54.7% (p=0.009 variance in paretic WMFT-rate. Prefrontal corpus callous fractional anisotropy (PF-CC FA alone explained 49.3% (p=0.007 variance in FM-UL outcome. The same models did not explain significant variance in mild–moderate stroke. In the severe group, k-means cluster analysis of PF-CC FA distinguished two subgroups, separated by a clinically meaningful and significant difference in motor impairment (p=0.049 and function (p=0.006 outcomes. Conclusion. Corpus callosum function and structure were identified as possible biomarkers of motor outcome in people with chronic and severe arm impairment.

  19. Fatigue versus activity-dependent fatigability in patients with central or peripheral motor impairments.

    Science.gov (United States)

    Dobkin, Bruce H

    2008-01-01

    In the rehabilitation literature, fatigue is a common symptom of patients with any neurological impairment when defined as a subjective lack of physical and mental energy that interferes with usual activities. Some complaints may, however, arise from fatigability , an objective decline in strength as routine use of muscle groups proceeds. By this refined definition of fatigue, exercise or sustained use reduces the ability of muscles to produce force or power, regardless of whether the task can be sustained. Fatigability may be masked clinically because (1) the degree of weakening is not profound, (2) activity-induced weakness rapidly lessens with cessation of exertion, and (3) clinicians rarely test for changes in strength after repetitive movements to objectively entertain the diagnosis. The repetitive movements that induce fatigability during daily activities are an iterative physiological process that depends on changing states induced by activation of spared central and peripheral neurons and axons and compromised muscle. Fatigability may be especially difficult to localize in patients undergoing neurorehabilitation, in part because no finite boundary exists between the central and peripheral components of motor reserve and endurance. At the bedside, however, manual muscle testing before and after repetitive movements could at least put some focus on the presence of fatigability in any patient with motor impairments and related disabilities. Reliable measures of fatigability beyond a careful clinical examination, such as physiological changes monitored by cerebral functional neuroimaging techniques and more standardized central and peripheral electrical and magnetic stimulation paradigms, may help determine the mechanisms of activity-dependent weakening and lead to specific therapies. Testable interventions to increase motor reserve include muscle strengthening and endurance exercises, varying the biomechanical requirements of repetitive muscle contractions

  20. 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

  1. Impairment of fine motor dexterity in mild cognitive impairment and Alzheimer’s disease dementia: association with activities of daily living

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    Jonas J. de Paula

    Full Text Available Objective: Cognitive impairment is a hallmark of mild cognitive impairment (MCI and Alzheimer’s disease dementia (AD. Although the cognitive profile of these patients and its association with activities of daily living (ADLs is well documented, few studies have assessed deficits in fine motor dexterity and their association with ADL performance. The objective of this research paper is to evaluate fine motor dexterity performance among MCI and AD patients and to investigate its association with different aspects of ADLs. Methods: We assessed normal aging controls, patients with multiple- and single-domain amnestic MCI (aMCI, and patients with mild AD. Fine motor dexterity was measured with the Nine-Hole Peg Test and cognitive functioning by the Mattis Dementia Rating Scale. We analyzed the data using general linear models. Results: Patients with AD or multiple-domain aMCI had slower motor responses when compared to controls. AD patients were slower than those with single-domain aMCI. We found associations between cognition and instrumental ADLs, and between fine motor dexterity and self-care ADLs. Conclusion: We observed progressive slowing of fine motor dexterity along the normal aging-MCI-AD spectrum, which was associated with autonomy in self-care ADLs.

  2. Neonatal Magnesium Levels Between 24 and 48 Hours of Life and Outcomes for Epilepsy and Motor Impairment in Premature Infants.

    Science.gov (United States)

    Ostrander, Betsy; Bardsley, Tyler; Korgenski, Ernest Kent; Greene, Tom; Bonkowsky, Joshua L

    2016-06-01

    Elevated rates of epilepsy and motor impairments including cerebral palsy are observed in children who were born prematurely. Maternal antenatal magnesium supplementation has been associated with decreased rates of cerebral palsy in infants born prematurely. Our objective was to determine whether the neonatal serum magnesium level between 24 and 48 hours after birth is associated with better long-term neurodevelopmental outcomes (epilepsy, motor impairment) in premature infants. We performed a retrospective cohort analysis in infants born less than 37-weeks gestation over a ten-year period. Prenatal, perinatal, and postnatal clinical and demographic information was collected. Crude and adjusted odds ratios were estimated under generalized linear models with generalized estimating equations to examine the association of the neonatal serum magnesium level between 24 and 48 hours after birth with the risk of epilepsy and/or motor impairment (spasticity; hypotonia; cerebral palsy). The final cohort included 5461 infants born less than 37-weeks gestation from 2002 to 2011. The adjusted relative risk ratio for the combined outcomes of epilepsy and/or motor impairment, controlling for gestational age, current age, maternal magnesium supplementation, maternal steroid administration, five-minute Apgar score, neonatal infection, need for vasopressor use, and birth weight and with serum magnesium level as the main independent variable, was 0.85 (P = 0.24). Stratified analyses by gestational age less than 32 or greater than 32 weeks were not significantly associated with adverse neurodevelopmental outcome (risk ratio = 0.79 and 1.2, P = 0.12 and 0.49, respectively). A multivariate analysis for the risk of motor impairment alone had a risk ratio of 0.94 (P = 0.72). This study demostrates that the neonatal magnesium level between 24 and 48 hours of life in premature infants is not significantly associated with the risk for developing epilepsy or motor impairment

  3. Altered Rolandic Gamma-Band Activation Associated with Motor Impairment and Ictal Network Desynchronization in Childhood Epilepsy

    OpenAIRE

    Sam M Doesburg; George M Ibrahim; Mary Lou Smith; Rohit Sharma; Amrita Viljoen; Bill Chu; Rutka, James T.; O. Carter Snead; Pang, Elizabeth W.

    2013-01-01

    Epilepsy is associated with an abnormal expression of neural oscillations and their synchronization across brain regions. Oscillatory brain activation and synchronization also play an important role in cognition, perception and motor control. Childhood epilepsy is associated with a variety of cognitive and motor deficits, but the relationship between altered functional brain responses in various frequency ranges and functional impairment in these children remains poorly understood. We investi...

  4. Neuroprotective effect of osmotin against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

    Science.gov (United States)

    Naseer, M I; Ullah, I; Narasimhan, M L; Lee, H Y; Bressan, R A; Yoon, G H; Yun, D J; Kim, M O

    2014-03-27

    Fetal alcohol syndrome is a neurological and developmental disorder caused by exposure of developing brain to ethanol. Administration of osmotin to rat pups reduced ethanol-induced apoptosis in cortical and hippocampal neurons. Osmotin, a plant protein, mitigated the ethanol-induced increases in cytochrome c, cleaved caspase-3, and PARP-1. Osmotin and ethanol reduced ethanol neurotoxicity both in vivo and in vitro by reducing the protein levels of cleaved caspase-3, intracellular [Ca(2+)]cyt, and mitochondrial transmembrane potential collapse, and also upregulated antiapoptotic Bcl-2 protein. Osmotin is a homolog of adiponectin, and it controls energy metabolism via phosphorylation. Adiponectin can protect hippocampal neurons against ethanol-induced apoptosis. Abrogation of signaling via receptors AdipoR1 or AdipoR2, by transfection with siRNAs, reduced the ability of osmotin and adiponectin to protect neurons against ethanol-induced neurodegeneration. Metformin, an activator of AMPK (adenosine monophosphate-activated protein kinase), increased whereas Compound C, an inhibitor of AMPK pathway, reduced the ability of osmotin and adiponectin to protect against ethanol-induced apoptosis. Osmotin exerted its neuroprotection via Bcl-2 family proteins and activation of AMPK signaling pathway. Modulation of AMPK pathways by osmotin, adiponectin, and metformin hold promise as a preventive therapy for fetal alcohol syndrome.

  5. Cognitive-Motor Interference during Walking in Older Adults with Probable Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Thomas J. Klotzbier

    2017-12-01

    Full Text Available Although several studies have shown that dual-tasking (DT mobility is impaired in Alzheimer's disease, studies on the effects of DT conditions in probable Mild Cognitive Impairment (pMCI have not yielded unequivocal results. The objectives of the study were to (1 examine the effect of a concurrent task on a complex walking task in adults with cognitive impairment; and (2 determine whether the effect varied with different difficulty levels of the concurrent task. Furthermore, the study was designed to evaluate the Trail-Walking Test (TWT as a potential detection tool for MCI. We examined DT performance in 42 young adults (mean age 23.9 ± 1.98, and 43 older adults (mean age 68.2 ± 6.42. The MoCA was used to stratify the subjects into those with and without pMCI. DT was assessed using the TWT: participants completed 5 trials each of walking along a fixed pathway, stepping on targets with increasing sequential numbers (i.e., 1-2-…-15, and increasing sequential numbers and letters (i.e., 1-A-2-B-3-…-8. Motor and cognitive DT effects (DTE were calculated for each task. ROC curves were used to distinguish younger and healthy older adults from older adults with pMCI. The TWT showed excellent test-retest reliability across all conditions and groups (ICC : 0.83–0.97. SEM% was also low (<11% as was the MDC95% (<30%. Within the DT conditions, the pMCI group showed significantly longer durations for all tasks regardless of the cognitive load compared to the younger and the healthy older adults. The motor DTEs were greatest for the complex condition in older adults with pMCI more so than in comparison with younger and healthy older adults. ROC analyses confirmed that only the tasks with higher cognitive load could differentiate older adults with pMCI from controls (area under the curve >0.7, p < 0.05. The TWT is a reliable DT mobility measure in people with pMCI. However, the condition with high cognitive load is more sensitive than the condition with

  6. Impairment of motor skills in children with fetal alcohol spectrum disorders in remote Australia: The Lililwan Project.

    Science.gov (United States)

    Lucas, Barbara R; Doney, Robyn; Latimer, Jane; Watkins, Rochelle E; Tsang, Tracey W; Hawkes, Genevieve; Fitzpatrick, James P; Oscar, June; Carter, Maureen; Elliott, Elizabeth J

    2016-11-01

    We aimed to characterise motor performance in predominantly Aboriginal children living in very remote Australia, where rates of prenatal alcohol exposure (PAE) are high. Motor performance was assessed, and the relationship between motor skills, fetal alcohol spectrum disorders (FASD) and PAE was explored. Motor performance was assessed using the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition Complete Form, in a population-based study of children born in 2002 or 2003 living in the Fitzroy Valley, Western Australia. Composite scores ≥2SD (2nd percentile) and ≥1SD (16th percentile) below the mean were used respectively for FASD diagnosis and referral for treatment. FASD diagnoses were assigned using modified Canadian Guidelines. A total of 108 children (Aboriginal: 98.1%; male: 53%) with a mean age of 8.7 years was assessed. The cohort's mean total motor composite score (mean ± SD 47.2 ± 7.6) approached the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition normative mean (50 ± 10). Motor performance was lower in children with FASD diagnosis than without (mean difference (MD) ± SD: -5.0 ± 1.8; confidence interval: -8.6 to -1.5). There was no difference between children with PAE than without (MD ± SE: -2.2 ± 1.5; confidence interval: -5.1 to 0.80). The prevalence of motor impairment (≥-2SD) was 1.9% in the entire cohort, 9.5% in children with FASD, 3.3% in children with PAE and 0.0% both in children without PAE or FASD. Almost of 10% of children with FASD has significant motor impairment. Evaluation of motor function should routinely be included in assessments for FASD, to document impairment and enable targeted early intervention.[Lucas BR, Doney R, Latimer J, Watkins RE, Tsang TW, Hawkes G, Fitzpatrick JP, Oscar J, Carter M, Elliott EJ. Impairment of motor skills in children with fetal alcohol spectrum disorders in remote Australia: The Lililwan Project. Drug Alcohol Rev 2016;35:719-727]. © 2016

  7. Motor impairment after severe traumatic brain injury: A longitudinal multicenter study.

    Science.gov (United States)

    Walker, William C; Pickett, Treven C

    2007-01-01

    Neuromotor impairment is a common sequela of severe traumatic brain injury (TBI) but has been understudied relative to neurocognitive outcomes. This multicenter cohort study describes the longitudinal course of neurological examination-based motor abnormalities after severe TBI. Subjects were enrolled from the four lead Department of Veterans Affairs and Defense and Veterans Brain Injury Center sites. The study cohort consisted of 102 consecutive patients (active duty, veteran, or military dependent) with severe TBI who consented during acute rehabilitation for data collection and completed all follow-up evaluations. Paresis, ataxia, and postural instability measures showed a pattern of improvement over time, with the greatest improvement occurring between the inpatient (baseline) and 6-month follow-up assessments. Involuntary movement disorders were rare at all time points. Two years following acute rehabilitation, more than one-third of subjects continued to display a neuromotor abnormality on basic neurological examination. Persistence of tandem gait abnormality was particularly common.

  8. Disruption of rolandic gamma-band functional connectivity by seizures is associated with motor impairments in children with epilepsy.

    Directory of Open Access Journals (Sweden)

    George M Ibrahim

    Full Text Available Although children with epilepsy exhibit numerous neurological and cognitive deficits, the mechanisms underlying these impairments remain unclear. Synchronization of oscillatory neural activity in the gamma frequency range (>30 Hz is purported to be a mechanism mediating functional integration within neuronal networks supporting cognition, perception and action. Here, we tested the hypothesis that seizure-induced alterations in gamma synchronization are associated with functional deficits. By calculating synchrony among electrodes and performing graph theoretical analysis, we assessed functional connectivity and local network structure of the hand motor area of children with focal epilepsy from intracranial electroencephalographic recordings. A local decrease in inter-electrode phase synchrony in the gamma bands during ictal periods, relative to interictal periods, within the motor cortex was strongly associated with clinical motor weakness. Gamma-band ictal desychronization was a stronger predictor of deficits than the presence of the seizure-onset zone or lesion within the motor cortex. There was a positive correlation between the magnitude of ictal desychronization and impairment of motor dexterity in the contralateral, but not ipsilateral hand. There was no association between ictal desynchronization within the hand motor area and non-motor deficits. This study uniquely demonstrates that seizure-induced disturbances in cortical functional connectivity are associated with network-specific neurological deficits.

  9. Impaired motor inhibition in adults who stutter - evidence from speech-free stop-signal reaction time tasks.

    Science.gov (United States)

    Markett, Sebastian; Bleek, Benjamin; Reuter, Martin; Prüss, Holger; Richardt, Kirsten; Müller, Thilo; Yaruss, J Scott; Montag, Christian

    2016-10-01

    Idiopathic stuttering is a fluency disorder characterized by impairments during speech production. Deficits in the motor control circuits of the basal ganglia have been implicated in idiopathic stuttering but it is unclear how these impairments relate to the disorder. Previous work has indicated a possible deficiency in motor inhibition in children who stutter. To extend these findings to adults, we designed two experiments to probe executive motor control in people who stutter using manual reaction time tasks that do not rely on speech production. We used two versions of the stop-signal reaction time task, a measure for inhibitory motor control that has been shown to rely on the basal ganglia circuits. We show increased stop-signal reaction times in two independent samples of adults who stutter compared to age- and sex-matched control groups. Additional measures involved simple reaction time measurements and a task-switching task where no group difference was detected. Results indicate a deficiency in inhibitory motor control in people who stutter in a task that does not rely on overt speech production and cannot be explained by general deficits in executive control or speeded motor execution. This finding establishes the stop-signal reaction time as a possible target for future experimental and neuroimaging studies on fluency disorders and is a further step towards unraveling the contribution of motor control deficits to idiopathic stuttering. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Irisolidone attenuates ethanol-induced gastric injury in mice by inhibiting the infiltration of neutrophils.

    Science.gov (United States)

    Kang, Geum-Dan; Lee, Sang-Yoon; Jang, Se-Eun; Han, Myung Joo; Kim, Dong-Hyun

    2017-02-01

    This study was designed to determine whether irisolidone and its glycoside kakkalide, which are the major constituents of the flower of Pueraria lobata (Kudzu) can attenuate ethanol-induced gastritic injury in mice. Irisolidone and kakkalide inhibited IL-8 secretion and NF-κB activation in lipopolysaccharide-stimulated KATO III cells. Therefore, we investigated their protective effects against ethanol-induced gastric injury in mice. Pretreatment with kakkalide or irisolidone decreased the area of hemorrhagic ulcerative lesions caused by ethanol and suppressed stomach myeloperoxidase activity, CXCL4 secretion, and NF-κB activation. The ameliorating effect of irisolidone was more potent than that of kakkalide. Irisolidone may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, particularly neutrophils, through the regulation of CXCL-4 or IL-8 secretion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Impairments of motor-cortex responses to unilateral and bilateral direct current stimulation in schizophrenia

    Directory of Open Access Journals (Sweden)

    Alkomiet eHasan

    2013-10-01

    Full Text Available Transcranial direct current stimulation (tDCS is a non-invasive stimulation technique that can be applied to modulate cortical activity through induction of cortical plasticity. Since various neuropsychiatric disorders are characterised by fluctuations in cortical activity levels (e.g. schizophrenia, tDCS is increasingly investigated as a treatment tool. Several studies have shown that the induction of cortical plasticity following classical, unilateral tDCS is reduced or impaired in the stimulated and non-stimulated primary motor cortices (M1 of schizophrenia patients. Moreover, an alternative, bilateral tDCS setup has recently been shown to modulate cortical plasticity in both hemispheres in healthy subjects, highlighting another potential treatment approach. Here we present the first study comparing the efficacy of unilateral tDCS (cathode left M1, anode right supraorbital with simultaneous bilateral tDCS (cathode left M1, anode right M1 in schizophrenia patients. tDCS-induced cortical plasticity was monitored by investigating motor-evoked potentials induced by single-pulse transcranial magnetic stimulation applied to both hemispheres. Healthy subjects showed a reduction of left M1 excitability following unilateral tDCS on the stimulated left hemisphere and an increase in right M1 excitability following bilateral tDCS. In schizophrenia, no plasticity was induced following both stimulation paradigms. The pattern of these results indicates a complex interplay between plasticity and connectivity that is impaired in schizophrenia patients. Further studies are needed to clarify the biological underpinnings and clinical impact of these findings.

  12. Impaired body balance, fine motor function and hearing in women with Turner syndrome.

    Science.gov (United States)

    El-Mansoury, Mostafa; Barrenäs, Marie-Louise; Bryman, Inger; Hanson, Charles; Landin-Wilhelmsen, Kerstin

    2009-08-01

    Fractures are related to falling. Turner syndrome (TS) is associated with hypogonadism, osteoporosis and fractures and has been considered as a syndrome of early ageing. The aim was to study whether fine motor function (FM) and body balance (BB) were impaired and related to genotype, fractures, metabolic variables and hearing. Cross-sectional study. TS women, n = 75, mean age 30 years (range 16-59) and treated with oestrogen hormone replacement therapy (HRT) at the out-patient clinic, Sahlgrenska University Hospital, Göteborg, Sweden, and 31 healthy controls, mean age 37 years (range 24-63). Six FM and eight BB tests with open and closed eyes, respectively, were done. Bone mineral density was estimated with Dual energy X-ray Absorptiometry. Presence/absence of fractures was noted, blood samples were taken and audiometry was done in the TS women. TS women had poorer FM (27.4 +/- 6.0 vs. 32.8 +/- 2.2; P < 0.0001) and BB (28.0 +/- 8.1 vs. 34.7 +/- 2.4; P < 0.0001) than controls. FM was poorer in TS women with hearing aids compared to those without (P < 0.05). FM and BB were negatively correlated with age, waist : hip ratio and positively correlated with hearing, and bone mineral density, and BB was negatively correlated with physical activity in TS women. BB correlated negatively with age in controls. FM, BB and hearing function were poorer in 45,X, nonmosaics, than in 45,X/46,XX, mosaics. FM and BB were poorer in adult TS women on HRT than in controls. Higher age, hearing impairment, osteoporosis, abdominal obesity, a sedentary lifestyle and the TS per se were strong determinants, and mosaicism mitigated both fine motor function and BB in TS.

  13. Protective role of licochalcone B against ethanol-induced hepatotoxicity through regulation of Erk signaling

    Directory of Open Access Journals (Sweden)

    Xiao-peng Gao

    2017-02-01

    Full Text Available Objective(s: Oxidative stress has been established as a key cause of alcohol-induced hepatotoxicity. Licochalcone B, an extract of licorice root, has shown antioxidative properties. This study was to investigate the effects and mechanisms of licochalcone B in ethanol-induced hepatic injury in an in vitro study. Materials and Methods: An in vitro model of Ethanol-induced cytotoxicity in BRL cells was used in this study. Cell injury was assessed using WST-1 assay and lactate dehydrogenase, alanine transaminase, and aspartate aminotransferase release assay. Cell apoptosis were quantified by flow cytometric analysis. The intracellular oxidative level was evaluated by reactive oxidative species, malondialdehyde and glutathione detection. Furthermore, the expression level of Erk, p-Erk, Nrf-2 were assessed using Western blot. Results: Treatment with ethanol induced marked cell injury and cell apoptosis in BRL cells. Licochalcone B significantly attenuated ethanol-induced cell injury, and inhibited cell apoptosis. Furthermore, licochalcone B significantly inhibited ethanol-induced intracellular oxidative level, upregulated the expression of p-Erk, and promoted nuclear localization of Nrf2. Additionally, this hepatoprotective role was significantly abolished by inhibition of Erk signaling. However, no apparent effects of Erk inhibition were observed on ethanol-induced hepatotoxicity. Conclusion: This study demonstrates that licochalcone B protects hepatocyte from alcohol-induced cell injury, and this hepatoprotective role might be attributable to apoptosis reduction, inhibition of oxidative stress, and upregulation of Erk–Nrf2. Therefore, licochalcone B might possess potential as a novel therapeutic drug candidate for alcohol-related liver disorders.

  14. Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

    Science.gov (United States)

    Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

    2013-01-01

    Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

  15. Training leads to increased auditory brain-computer interface performance of end-users with motor impairments.

    Science.gov (United States)

    Halder, S; Käthner, I; Kübler, A

    2016-02-01

    Auditory brain-computer interfaces are an assistive technology that can restore communication for motor impaired end-users. Such non-visual brain-computer interface paradigms are of particular importance for end-users that may lose or have lost gaze control. We attempted to show that motor impaired end-users can learn to control an auditory speller on the basis of event-related potentials. Five end-users with motor impairments, two of whom with additional visual impairments, participated in five sessions. We applied a newly developed auditory brain-computer interface paradigm with natural sounds and directional cues. Three of five end-users learned to select symbols using this method. Averaged over all five end-users the information transfer rate increased by more than 1800% from the first session (0.17 bits/min) to the last session (3.08 bits/min). The two best end-users achieved information transfer rates of 5.78 bits/min and accuracies of 92%. Our results show that an auditory BCI with a combination of natural sounds and directional cues, can be controlled by end-users with motor impairment. Training improves the performance of end-users to the level of healthy controls. To our knowledge, this is the first time end-users with motor impairments controlled an auditory brain-computer interface speller with such high accuracy and information transfer rates. Further, our results demonstrate that operating a BCI with event-related potentials benefits from training and specifically end-users may require more than one session to develop their full potential. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Investigation of language and motor skills in Serbian speaking children with specific language impairment and in typically developing children.

    Science.gov (United States)

    Vukovic, Mile; Vukovic, Irena; Stojanovik, Vesna

    2010-01-01

    Specific language impairment (SLI) is usually defined as a developmental language disorder which does not result from a hearing loss, autism, neurological and emotional difficulties, severe social deprivation, low non-verbal abilities. Children affected with SLI typically have difficulties with the acquisition of different aspects of language and by definition, their impairment is specific to language and no other skills are affected. However, there has been a growing body of literature to suggest that children with SLI also have non-linguistic deficits, including impaired motor abilities. The aim of the current study is to investigate language and motor abilities of a group of thirty children with SLI (aged between 4 and 7) in comparison to a group of 30 typically developing children matched for chronological age. The results showed that the group of children with SLI had significantly more difficulties on the language and motor assessments compared to the control group. The SLI group also showed delayed onset in the development of all motor skills under investigation in comparison to the typically developing group. More interestingly, the two groups differed with respect to which language abilities were correlated with motor abilities, however Imitation of Complex Movements was the unique skill which reliably predicted expressive vocabulary in both typically developing children and in children with SLI. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Impaired transcallosally mediated motor inhibition in adults with attention-deficit/hyperactivity disorder is modulated by methylphenidate.

    Science.gov (United States)

    Hoeppner, Jacqueline; Wandschneider, Roland; Neumeyer, Martin; Gierow, Wolfgang; Haessler, Frank; Herpertz, Sabine C; Buchmann, Johannes

    2008-05-01

    Using transcranial magnetic stimulation (TMS) in children with ADHD, an impaired transcallosally mediated motor inhibition (ipsilateral silent period, iSP) was found, and its restoration was correlated with improvement of hyperactivity under medication with methylphenidate (MPH). Hyperactivity has been reported to decrease during transition into adulthood, although some motor dysfunction might persist. As one underlying neurophysiological process, a development-dependent normalization of motor cortical excitability might be postulated. In order to test this hypothesis, we measured the iSP in 21 adult ADHD patients and twenty-one sex- and age-matched healthy controls. In 16 of these patients, a second TMS was performed under treatment with MPH. Our results indicate a persistence of impaired transcallosally mediated motor cortical inhibition (shortened duration) in ADHD adults, which was correlated with clinical characteristics of hyperactivity and restlessness, and was restored by MPH. In contrast to ADHD in childhood, the iSP latency was not impaired, suggesting a partial development-dependent normalization of motor cortical excitability in ADHD adults. ISP duration appears to be a sensitive parameter for the assessment of disturbed intercortical inhibition in adults with ADHD.

  18. Progression and Prognostic Factors of Motor Impairment, Disability and Quality of Life in Newly Diagnosed Parkinson's Disease

    NARCIS (Netherlands)

    Post, Bart; Muslimovic, Dino; van Geloven, Nan; Speelman, Johannes D.; Schmand, Ben; de Haan, Rob J.

    2011-01-01

    Objective: To determine progression and prognostic factors of progression rate of motor impairment, disability, and quality of life (QoL) in patients with newly diagnosed Parkinson's disease. Methods: A group of 126 patients with newly diagnosed PD recruited from outpatient clinics participated in

  19. Progression and prognostic factors of motor impairment, disability and quality of life in newly diagnosed Parkinson's disease

    NARCIS (Netherlands)

    Post, B.; Muslimovic, D.; van Geloven, N.; Speelman, J.D.; Schmand, B.; de Haan, R.J.

    2011-01-01

    Objective: To determine progression and prognostic factors of progression rate of motor impairment, disability, and quality of life (QoL) in patients with newly diagnosed Parkinson's disease. Methods: A group of 126 patients with newly diagnosed PD recruited from outpatient clinics participated in

  20. Combined transcranial direct current stimulation and home-based occupational therapy for upper limb motor impairment following intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Mortensen, Jesper; Figlewski, Krystian; Andersen, Henning

    2016-01-01

    PURPOSE: To investigate the combined effect of transcranial direct current stimulation (tDCS) and home-based occupational therapy on activities of daily living (ADL) and grip strength, in patients with upper limb motor impairment following intracerebral hemorrhage (ICH). METHODS: A double...

  1. The Effects of Home-Based Literacy Activities on the Communication of Students with Severe Speech and Motor Impairments

    Science.gov (United States)

    Cox, Amy Swartz; Clark, Denise M.; Skoning, Stacey N.; Wegner, Theresa M.; Muwana, Florence C.

    2015-01-01

    This study examined the effects of using sensory, augmentative, and alternative communication (AAC), and supportive communication strategies on the rate and type of communication used by three students with severe speech and motor impairments (SSMI). Using a multiple baseline across behaviour design with sensory and AAC intervention phases,…

  2. Progression and prognostic factors of motor impairment, disability and quality of life in newly diagnosed Parkinson's disease

    NARCIS (Netherlands)

    Post, B.; Muslimovic, D.; Geloven, N. van; Speelman, J.D.; Schmand, B.; Haan, R.J. de

    2011-01-01

    OBJECTIVE: To determine progression and prognostic factors of progression rate of motor impairment, disability, and quality of life (QoL) in patients with newly diagnosed Parkinson's disease. METHODS: A group of 126 patients with newly diagnosed PD recruited from outpatient clinics participated in

  3. Factors associated with the severity of motor impairment in children with cerebral palsy seen in Enugu, Nigeria

    Directory of Open Access Journals (Sweden)

    S O Iloeje

    2017-10-01

    Full Text Available Background. Cerebral palsy (CP is a heterogeneous condition that is well known to cause impairments with varying degrees of severity. The gross motor function classification system (GMFCS is widely used to assess ambulatory function in CP, but little is known about the factors that account for the variations in gross motor function in children. The purpose of this study was to assess the relation between the severity of gross motor dysfunction (GMD and certain factors such as the type of CP, aetiology of CP, nutrition, socioeconomic class (SEC, and the frequency of these accompanying impairments like visual, auditory, cognitive and speech impairments. Methods. This was a cross-sectional observational study of 100 consecutively recruited CP patients aged 9 - 96 months, who attended the paediatric neurology clinics (PNCs in Enugu between April and October 2010. Each patient’s clinical history was recorded, a neurological examination conducted and GMFCS level ascertained. Statistical analyses were done to determine the association between the categorical variables. Results. The type of CP (p=0.000, aetiological factors (p=0.016, the presence of malnutrition (p=0.004 and the frequency of accompanying impairments (p=0.001 were significantly associated with the severity of GMD, while SEC (p=0.649 had no significant association. Conclusion. The type of CP, aetiological factors, the presence of malnutrition and the number of accompanying physical, mental or physiological impairments, were positively associated with the severity of GMD and walking ability in children with CP.

  4. Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials.

    Science.gov (United States)

    Harila-Saari, A H; Huuskonen, U E; Tolonen, U; Vainionpää, L K; Lanning, B M

    2001-03-01

    The objective was to evaluate whether motor nervous pathways are affected when patients are treated for childhood acute lymphoblastic leukemia (ALL). Thirty-two children with ALL were studied at the end of treatment by means of motor evoked potentials (MEPs) elicited by magnetic stimulation (MS) transcranially and peripherally and underwent a detailed neurological examination. Thirty-two healthy children matched with them for age, sex, and height served as a control group. The latencies of the MEPs were significantly prolonged along the entire motor nervous pathway in the patients with ALL compared with the healthy controls, indicating demyelination in the thick motor fibres. The MEP amplitudes of the distal extremities elicited by stimulation at the brachial plexus and LV spinal level were significantly lowered in the patients treated for ALL, also indicating anatomical or functional loss of descending motor fibres and/or muscle fibres. The MEP amplitudes elicited by cortical MS showed wider variation and no clear abnormalities were found. Neurological signs and symptoms were common after treatment: 41% of the patients had depressed deep tendon reflexes, 31% had fine motor difficulties and 63% gross motor difficulties, and 34% had dysdiadochokinesia. The conduction delay within the peripheral nerve was related to the post-therapeutic interval after administration of vincristine and the lesions within the CNS to the number of injections of intrathecal methotrexate. The present results show adverse effects of the ALL treatment on the entire motor nervous pathways. In our experience, the measurement of MEPs by MS provides an objective, painless, and practical tool for assessing the treatment-related neurotoxicity in both the CNS and the peripheral nerves. These disturbances in the motor nervous pathways at the end of treatment raise the question of the long-term effects of ALL treatment on the motor nerve tracts, and have led us to employ MEPs to study these effects

  5. Brief Report: Children with ADHD without Co-Morbid Autism Do Not Have Impaired Motor Proficiency on the Movement Assessment Battery for Children

    Science.gov (United States)

    Papadopoulos, Nicole; Rinehart, Nicole; Bradshaw, John L.; McGinley, Jennifer L.

    2013-01-01

    Motor proficiency was investigated in a sample of children with Attention Deficit Hyperactivity Disorder-Combined type (ADHD-CT) without autism. Accounting for the influence of co-morbid autistic symptoms in ADHD motor studies is vital given that motor impairment has been linked to social-communication symptoms in children who have co-morbid ADHD…

  6. Reversal of Ethanol-induced Intoxication by a Novel Modulator of Gβγ Protein Potentiation of the Glycine Receptor.

    Science.gov (United States)

    San Martin, Loreto; Cerda, Fabian; Jin, Chunyang; Jimenez, Veronica; Yevenes, Gonzalo E; Hernandez, Tania; Nova, Daniela; Fuentealba, Jorge; Aguayo, Luis G; Guzman, Leonardo

    2016-09-02

    The acute intoxicating effects of ethanol in the central nervous system result from the modulation of several molecular targets. It is widely accepted that ethanol enhances the activity of the glycine receptor (GlyR), thus enhancing inhibitory neurotransmission, leading to motor effects, sedation, and respiratory depression. We previously reported that small peptides interfered with the binding of Gβγ to the GlyR and consequently inhibited the ethanol-induced potentiation of the receptor. Now, using virtual screening, we identified a subset of small molecules capable of interacting with the binding site of Gβγ. One of these compounds, M554, inhibited the ethanol potentiation of the GlyR in both evoked currents and synaptic transmission in vitro When this compound was tested in vivo in mice treated with ethanol (1-3.5 g/kg), it was found to induce a faster recovery of motor incoordination in rotarod experiments and a shorter sedative effect in loss of righting reflex assays. This study describes a novel molecule that might be relevant for the design of useful therapeutic compounds in the treatment of acute alcohol intoxication. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Minocycline mitigates motor impairments and cortical neuronal loss induced by focal ischemia in rats chronically exposed to ethanol during adolescence.

    Science.gov (United States)

    Oliveira, Gedeão Batista; Fontes, Enéas de Andrade; de Carvalho, Sabrina; da Silva, Josiane Batista; Fernandes, Luanna Melo Pereira; Oliveira, Maria Cristina Souza Pereira; Prediger, Rui Daniel; Gomes-Leal, Walace; Lima, Rafael Rodrigues; Maia, Cristiane Socorro Ferraz

    2014-05-02

    Ethanol is an important risk factor for the occurrence of cerebral ischemia contributing to poor prognosis and inefficacy of drug treatments for stroke-related symptoms. Females have a higher lifetime risk for stroke than males. Moreover, female gender has been associated with increased ethanol consumption during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence may potentiate the motor impairments and cortical damage induced by focal ischemia in female rats. We also addressed whether these effects can be mitigated by minocycline, which has been shown to be neuroprotective against different insults in the CNS. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) for 55 days by gavage. Focal ischemia was induced by microinjections of endothelin-1 (ET-1) into the motor cortex. Animals of both groups were treated daily with minocycline (25-50 mg/kg, i.p.) or sterile saline (i.p.) for 5 days, and motor function was assessed using open field, inclined plane and rotarod tests. Chronic ethanol exposure exacerbated locomotor activity and motor coordination impairments induced by focal ischemia in rats. Moreover, histological analysis revealed that microinjections of ET-1 induced pyramidal neuron loss and microglial activation in the motor cortex. Minocycline reversed the observed motor impairments, microglial activation and pyramidal neuron loss in the motor cortex of ischemic rats even in those exposed to ethanol. These results suggest that minocycline induces neuroprotection and functional recovery in ischemic female rats intoxicated with ethanol during adolescence. Furthermore, the mechanism underlying this protective effect may be related to the modulation of neuroinflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. A causal test of the motor theory of speech perception: a case of impaired speech production and spared speech perception.

    Science.gov (United States)

    Stasenko, Alena; Bonn, Cory; Teghipco, Alex; Garcea, Frank E; Sweet, Catherine; Dombovy, Mary; McDonough, Joyce; Mahon, Bradford Z

    2015-01-01

    The debate about the causal role of the motor system in speech perception has been reignited by demonstrations that motor processes are engaged during the processing of speech sounds. Here, we evaluate which aspects of auditory speech processing are affected, and which are not, in a stroke patient with dysfunction of the speech motor system. We found that the patient showed a normal phonemic categorical boundary when discriminating two non-words that differ by a minimal pair (e.g., ADA-AGA). However, using the same stimuli, the patient was unable to identify or label the non-word stimuli (using a button-press response). A control task showed that he could identify speech sounds by speaker gender, ruling out a general labelling impairment. These data suggest that while the motor system is not causally involved in perception of the speech signal, it may be used when other cues (e.g., meaning, context) are not available.

  9. Hepatoprotective and antioxidant activities of grapeseeds against ethanol-induced oxidative stress in rats.

    Science.gov (United States)

    Dogan, Abdulahad; Celik, Ismail

    2012-01-01

    The present study was carried out to evaluate the hepatoprotective effect and antioxidant role of grape (Vitis vinifera L.) seeds (GS) against ethanol-induced oxidative stress. The hepatoprotective and antioxidant roles of the GS supplementation feed against ethanol-induced oxidative stress were evaluated by measuring liver damage serum marker enzymes, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase and lactate dehydrogenase, antioxidant defence system such as GSH, glutathione reductase, superoxide dismutase, glutathione S-transferase and glutathione peroxidase and malondialdehyde (MDA) content in various tissues of rats. Rats were divided into four experimental groups: I (control), II (20 % ethanol), III (15 % GS) and IV (20 % ethanol+15 % GS). According to the results, the level of serum marker enzymes was significantly increased in group II as compared to that of group I, but decreased in group IV as compared to that of group II. Also, administration of GS-supplemented food restored the ethanol-induced MDA, which was increased near the control level. The results indicated that GS could be as important as diet-derived antioxidants in preventing oxidative damage in the tissues by reducing the lipid oxidation or inhibiting the production of ethanol-induced free radicals in rats.

  10. Ecklonia cava polyphenol protects the liver against ethanol-induced injury in rats.

    Science.gov (United States)

    Takahashi, Mai; Satake, Naoko; Yamashita, Haruka; Tamura, Akiko; Sasaki, Mio; Matsui-Yuasa, Isao; Tabuchi, Masaki; Akahoshi, Yasumitsu; Terada, Masaki; Kojima-Yuasa, Akiko

    2012-07-01

    The development of alcoholic liver disease is a complex process that involves both the parenchymal and non-parenchymal cells of the liver. We examined the effect of an Ecklonia cava extract on ethanol-induced liver injury. Isolated hepatocytes and hepatic stellate cells (HSCs) were incubated with ethanol. Ecklonia cava polyphenol (ECP) was added to the cultures that had been incubated with ethanol. Male Wistar rats were fed a diet that included 0.02% or 0.2% ECP or no ECP. For a period of 3 weeks, the animals were given drinking water containing 5% ethanol and were also treated with carbon tetrachloride (CCl4) (0.1 ml/kg of body weight). In the cultured hepatocytes, the ECP treatment suppressed the ethanol-induced increase in cell death by maintaining intracellular glutathione (GSH) levels. In HSCs, ECP treatment suppressed the ethanol-induced increases in type I collagen and α-smooth muscle actin expression by maintaining intracellular levels of reactive oxygen species and GSH. We examined the effects of ECP on serum AST and ALT activity, as well as the progression of liver fibrosis in rats treated with ethanol and CCl4. ECP treatment suppressed plasma AST and ALT activities in the ethanol- and CCl4-treated rats. ECP treatment fully protected the rats against ethanol- and CCl4-induced liver injury. ECP may be a candidate for preventing ethanol-induced liver injury. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Curcuma aromatica Water Extract Attenuates Ethanol-Induced Gastritis via Enhancement of Antioxidant Status

    Directory of Open Access Journals (Sweden)

    Woo-Young Jeon

    2015-01-01

    Full Text Available Curcuma aromatica is an herbal medicine and traditionally used for the treatment of various diseases in Asia. We investigated the effects of C. aromatica water extract (CAW in the stomach of rats with ethanol-induced gastritis. Gastritis was induced in rats by intragastric administration of 5 mL/kg body weight of absolute ethanol. The CAW groups were given 250 or 500 mg of extract/kg 2 h before administration of ethanol, respectively. To determine the antioxidant effects of CAW, we determined the level of lipid peroxidation, the level of reduced glutathione (GSH, the activities of catalase, degree of inflammation, and mucus production in the stomach. CAW reduced ethanol-induced inflammation and loss of epithelial cells and increased the mucus production in the stomach. CAW reduced the increase in lipid peroxidation associated with ethanol-induced gastritis (250 and 500 mg/kg, p<0.01, resp. and increased mucosal GSH content (500 mg/kg, p<0.01 and the activity of catalase (250 and 500 mg/kg, p<0.01, resp.. CAW increased the production of prostaglandin E2. These findings suggest that CAW protects against ethanol-induced gastric mucosa injury by increasing antioxidant status. We suggest that CAW could be developed for the treatment of gastritis induced by alcohol.

  12. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

    2013-10-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.

  13. Bimanual coupling paradigm as an effective tool to investigate productive behaviors in motor and body awareness impairments

    Directory of Open Access Journals (Sweden)

    Francesca eGarbarini

    2013-11-01

    Full Text Available When humans move simultaneously both hands strong coupling effects arise and neither of the two hands is able to perform independent actions. It has been suggested that such motor constraints are tightly linked to action representation rather than to movement execution. Hence, bimanual tasks can represent an ideal experimental tool to investigate internal motor representations in those neurological conditions in which the movement of one hand is impaired. Indeed, any effect on the ‘moving’ (healthy hand would be caused by the constraints imposed by the ongoing motor program of the ‘impaired’ hand. Here, we review recent studies that successfully utilized the above-mentioned paradigms to investigate some types of productive motor behaviors in stroke patients. Specifically, bimanual tasks have been employed in left hemiplegic patients who report illusory movements of their contralesional limbs (anosognosia for hemiplegia. They have also been administered to patients affected by a specific monothematic delusion of body ownership, namely the belief that another person’s arm and his/her voluntary action belong to them. In summary, the reviewed studies show that bimanual tasks are a simple and valuable experimental method apt to reveal information about the motor programs of a paralyzed limb. Therefore, it can be used to objectively examine the cognitive processes underpinning motor programming in patients with different delusions of motor behavior. Additionally, it also sheds light on the mechanisms subserving bimanual coordination in the intact brain suggesting that action representation might be sufficient to produce these effects.

  14. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    Science.gov (United States)

    Chan, Ming-Huan; Chung, Shiang-Sheng; Stoker, Astrid K; Markou, Athina; Chen, Hwei-Hsien

    2012-01-01

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-d-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. PMID:23067721

  15. Function of Thymosin Beta-4 in Ethanol-Induced Microglial Activation

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    2016-05-01

    Full Text Available Background/Aims: Neuroinflammation mediated by activated microglia may play a pivotal role in a variety of central nervous system (CNS pathologic conditions, including ethanol-induced neurotoxicity. The purpose of this study was to investigate the function of Tβ4 in ethanol-induced microglia activation. Methods: Quantitative real-time PCR was conducted to assess the expression of Tβ4 and miR-339-5p. Western blot analysis was used to measure the expression of Tβ4, phosphorylated p38, ERK, JNK, Akt, and NF-κB p65. The concentration of TNF-α and IL-1β was determined using ELISA. NO concentration was measured using a nitric oxide colorimetric BioAssay Kit. Double immunofluorescence was performed to determine Tβ4 expression, in order to assess microglial activation in neonatal mouse FASD model. Results: Increased Tβ4 expression was observed in ethanol treated microglia. Knockdown of Tβ4 enhanced ethanol-induced inflammatory mediators tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β and nitric oxide (NO in BV-2 cells was performed. Exogenous Tβ4 treatment significantly inhibited expression and secretion of these inflammatory mediators. Tβ4 treatment attenuated p38, ERK MAPKs, and nuclear factor-kappa B (NF-κB pathway activation, and enhanced miR-339-5p expression induced by ethanol exposure in microglia. A neonatal mouse fetal alcohol spectrum disorders (FASD model showed that Tβ4 expression in the microglia of the hippocampus was markedly enhanced, while Tβ4 treatment effectively blocked the ethanol-induced increase in inflammatory mediators, to the level expressed in vehicle-treated control animals. Conclusion: This study is the first to demonstrate the function of Tβ4 in ethanol-induced microglia activation, thus contributing to a more robust understanding of the role of Tβ4 treatment in CNS disease.

  16. Legal consequences for alcohol-impaired drivers injured in motor vehicle collisions: A systematic review.

    Science.gov (United States)

    Green, Robert S; Kureshi, Nelofar; Erdogan, Mete

    2015-07-01

    The treatment of alcohol-impaired drivers injured in a motor vehicle collision (MVC) is a complex public health issue. We conducted a systematic review to describe the legal consequences for alcohol-impaired drivers injured in a MVC and taken to a hospital or trauma center. Methods We searched MEDLINE, Embase, and CINAHL databases from inception until August 2014. We included studies that reported legal consequences including charges or convictions of injured drivers taken to a hospital or trauma center after a MVC with a blood alcohol concentration (BAC) exceeding the legal limit.Results Twenty-six studies met inclusion criteria; twenty studies were conducted in the USA, five in Canada, and one in Sweden. All were cohort studies (23 retrospective, 3 prospective) and included 11,409 patients overall. A total of 5,127 drivers had a BAC exceeding the legal limit, with legal consequences reported in 4937 cases. The median overall DUI/DWI conviction rate was 13% (range 0-85%). The median percentage of drivers with a previous conviction on their record for driving under the influence (DUI) or driving while intoxicated (DWI) was 15.5% (range 6-40%). The median percentage of drivers convicted again for DUI/DWI during the study period was 3.5% (range 2-10%). Heterogeneity between study designs, legal jurisdictions, institutional procedures and policies for obtaining a legally admissible BAC measurement precluded a meta-analysis. Conclusions The majority of intoxicated drivers injured in MVCs and seen in the emergency department are never charged or convicted. A substantial proportion of injured intoxicated drivers had more than one conviction for DUI/DWI on their police record. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Ming-Huan [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Institute of Neuroscience, National Changchi University, Taipei, Taiwan (China); Chung, Shiang-Sheng [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacy, Yuli Veterans Hospital, Hualien, Taiwan (China); Stoker, Astrid K.; Markou, Athina [Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (United States); Chen, Hwei-Hsien, E-mail: hwei@nhri.org.tw [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China)

    2012-12-01

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene

  18. Impaired motor memory for a pursuit rotor task following Stage 2 sleep loss in college students.

    Science.gov (United States)

    Smith; MacNeill

    1994-12-01

    It has recently been reported that selective REM sleep deprivation (REMD) in college students results in memory impairment of the application of a set of rules in a logic task, but not recall of a paired associate task. The present experiments were designed to examine the effects of Total Sleep Deprivation (TSD) and (REMD) following acquisition of a pure motor task, the pursuit rotor. In Experiment 1, subjects (N = 90) were exposed to TSD for one of several nights following training. Results showed that TSD on the same night as training resulted in poorer performance on retest one week later. In Experiment 2, subjects (N = 42) were exposed to various kinds of sleep deprivation on the night of task acquisition. One group was subjected to REMD. Other groups included a non-REM awakening control group (NREMA), a TSD group, a normally rested Control group and a group allowed the first 4 h of sleep in the night before being subjected to TSD (LH - TSD) for the rest of the night. Results showed the REMD and Control groups to have excellent memory for this task while the TSD and LH - TSD subjects had significantly poorer memory for the task. The NREMA group showed a slight, but not significant deficit. It was concluded that Stage 2 sleep, rather than REM sleep was the important stage of sleep for efficient memory processing of the pursuit rotor task.

  19. Community-based rehabilitation and orthopaedic surgery for children with motor impairment in an African context.

    Science.gov (United States)

    Penny, Norgrove; Zulianello, Regina; Dreise, Marieke; Steenbeek, Michiel

    To report on the development of a program to treat and rehabilitate children with chronic orthopaedic disabilities in the sub-Saharan African context incorporating orthopaedic reconstructive surgery within community-based rehabilitation (CBR) programs. Practice of rehabilitation descriptive report. In a six-year period between 1996 and 2002, a comprehensive project addressing the rehabilitative and orthopaedic surgery needs of children with motor impairments was established in Uganda. Using the principles of CBR, more than 5000 children annually were assisted with 875 receiving orthopaedic reconstructive surgery. CBR proved a powerful tool in creating awareness and facilitating access to care amongst rural populations living in the circumstances of extreme poverty. By networking the services of several non-governmental development organizations, government agencies, service providers and community groups, a large number of children could be reached in an integrated way. The 'recipe for success' of rehabilitation required access to and integration of all of the following ingredients: CBR, a transportation system, rehabilitation hostels, physiotherapy, orthopaedic surgery, and orthopaedic appliance technology. CBR played a vital role in ensuring access to rehabilitative care and the success of orthopaedic reconstructive surgery.

  20. Overexpression of SIRT1 in mouse forebrain impairs lipid/glucose metabolism and motor function.

    Directory of Open Access Journals (Sweden)

    Dongmei Wu

    Full Text Available SIRT1 plays crucial roles in glucose and lipid metabolism, and has various functions in different tissues including brain. The brain-specific SIRT1 knockout mice display defects in somatotropic signaling, memory and synaptic plasticity. And the female mice without SIRT1 in POMC neuron are more sensitive to diet-induced obesity. Here we created transgenic mice overexpressing SIRT1 in striatum and hippocampus under the control of CaMKIIα promoter. These mice, especially females, exhibited increased fat accumulation accompanied by significant upregulation of adipogenic genes in white adipose tissue. Glucose tolerance of the mice was also impaired with decreased Glut4 mRNA levels in muscle. Moreover, the SIRT1 overexpressing mice showed decreased energy expenditure, and concomitantly mitochondria-related genes were decreased in muscle. In addition, these mice showed unusual spontaneous physical activity pattern, decreased activity in open field and rotarod performance. Further studies demonstrated that SIRT1 deacetylated IRS-2, and upregulated phosphorylation level of IRS-2 and ERK1/2 in striatum. Meanwhile, the neurotransmitter signaling in striatum and the expression of endocrine hormones in hypothalamus and serum T3, T4 levels were altered. Taken together, our findings demonstrate that SIRT1 in forebrain regulates lipid/glucose metabolism and motor function.

  1. Overexpression of SIRT1 in mouse forebrain impairs lipid/glucose metabolism and motor function.

    Science.gov (United States)

    Wu, Dongmei; Qiu, Yifu; Gao, Xiang; Yuan, Xiao-Bing; Zhai, Qiwei

    2011-01-01

    SIRT1 plays crucial roles in glucose and lipid metabolism, and has various functions in different tissues including brain. The brain-specific SIRT1 knockout mice display defects in somatotropic signaling, memory and synaptic plasticity. And the female mice without SIRT1 in POMC neuron are more sensitive to diet-induced obesity. Here we created transgenic mice overexpressing SIRT1 in striatum and hippocampus under the control of CaMKIIα promoter. These mice, especially females, exhibited increased fat accumulation accompanied by significant upregulation of adipogenic genes in white adipose tissue. Glucose tolerance of the mice was also impaired with decreased Glut4 mRNA levels in muscle. Moreover, the SIRT1 overexpressing mice showed decreased energy expenditure, and concomitantly mitochondria-related genes were decreased in muscle. In addition, these mice showed unusual spontaneous physical activity pattern, decreased activity in open field and rotarod performance. Further studies demonstrated that SIRT1 deacetylated IRS-2, and upregulated phosphorylation level of IRS-2 and ERK1/2 in striatum. Meanwhile, the neurotransmitter signaling in striatum and the expression of endocrine hormones in hypothalamus and serum T3, T4 levels were altered. Taken together, our findings demonstrate that SIRT1 in forebrain regulates lipid/glucose metabolism and motor function.

  2. Impairments in Motor Neurons, Interneurons and Astrocytes Contribute to Hyperexcitability in ALS: Underlying Mechanisms and Paths to Therapy.

    Science.gov (United States)

    Do-Ha, Dzung; Buskila, Yossi; Ooi, Lezanne

    2017-02-03

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of motor neurons leading to progressive paralysis and death. Using transcranial magnetic stimulation (TMS) and nerve excitability tests, several clinical studies have identified that cortical and peripheral hyperexcitability are among the earliest pathologies observed in ALS patients. The changes in the electrophysiological properties of motor neurons have been identified in both sporadic and familial ALS patients, despite the diverse etiology of the disease. The mechanisms behind the change in neuronal signalling are not well understood, though current findings implicate intrinsic changes in motor neurons and dysfunction of cells critical in regulating motor neuronal excitability, such as astrocytes and interneurons. Alterations in ion channel expression and/or function in motor neurons has been associated with changes in cortical and peripheral nerve excitability. In addition to these intrinsic changes in motor neurons, inhibitory signalling through GABAergic interneurons is also impaired in ALS, likely contributing to increased neuronal excitability. Astrocytes have also recently been implicated in increasing neuronal excitability in ALS by failing to adequately regulate glutamate levels and extracellular K(+) concentration at the synaptic cleft. As hyperexcitability is a common and early feature of ALS, it offers a therapeutic and diagnostic target. Thus, understanding the underlying pathways and mechanisms leading to hyperexcitability in ALS offers crucial insight for future development of ALS treatments.

  3. Impaired inhibition of prepotent motor actions in patients with Tourette syndrome

    NARCIS (Netherlands)

    Wylie, S.A.; Claassen, D.O.; Kanoff, K.E.; Ridderinkhof, K.R.; van den Wildenberg, W.P.M.

    2013-01-01

    Background: Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses

  4. Gross Motor Development of Malaysian Hearing Impaired Male Pre- and Early School Children

    Science.gov (United States)

    Zawi, Khairi; Lian, Denise Koh Choon; Abdullah, Rozlina Tan

    2014-01-01

    Acquisition of gross motor skill is a natural developmental process for children. This aspect of human development increases with one's chronological age, irrespective of any developmental conditions. The purpose of this study was to assess the level of gross motor skill development among pre- and early school-aged children with motor disability.…

  5. Neural Underpinnings of Impaired Predictive Motor Timing in Children with Developmental Coordination Disorder

    Science.gov (United States)

    Debrabant, Julie; Gheysen, Freja; Caeyenberghs, Karen; Van Waelvelde, Hilde; Vingerhoets, Guy

    2013-01-01

    A dysfunction in predictive motor timing is put forward to underlie DCD-related motor problems. Predictive timing allows for the pre-selection of motor programmes (except "program" in computers) in order to decrease processing load and facilitate reactions. Using functional magnetic resonance imaging (fMRI), this study investigated the neural…

  6. Motor abnormalities and cognitive impairment in first-episode psychosis patients, their unaffected siblings and healthy controls.

    Science.gov (United States)

    Cuesta, Manuel J; Moreno-Izco, Lucia; Ribeiro, María; López-Ilundain, Jose M; Lecumberri, Pablo; Cabada, Teresa; Lorente-Omeñaca, Ruth; Sánchez-Torres, Ana M; Gómez, M Sol; Peralta, Victor

    2017-10-31

    Motor abnormalities (MAs) may be already evidenced long before the beginning of illness and are highly prevalent in psychosis. However, the extent to which the whole range of MAs are related to cognitive impairment in psychosis remains understudied. This study aimed to examine comparatively the relationships between the whole range of motor abnormalities and cognitive impairments in the first-episode of psychosis (FEP), their unaffected siblings and healthy control subjects. Fifty FEP patients, 21 of their healthy siblings and 24 age- and sex matched healthy controls were included. Motor assessment included catatonic, extrapyramidal and neurological soft signs (NSS) by means of standardized instruments. An exhaustive neuropsychological battery was also performed to extract the 7 cognitive dimensions of MATRICS initiative. Higher scores on NSS but not on extrapyramidal and catatonic signs showed significant associations with worse cognitive performance in the three study groups. However, the pattern of associations regarding specific cognitive functions was different among the three groups. Moreover, extrapyramidal signs showed significant associations with cognitive impairment only in FEP patients but not in their unaffected siblings and healthy controls. Catatonic signs did not show any significant association with cognitive functioning in the three study groups. These findings add evidence to the associations between motor abnormalities, particularly NSS and extrapyramidal signs, and cognitive impairment in first-episode psychosis patients. In addition, our results suggest that the specific pattern of associations between MAs and cognitive functioning is different in FEP patients from those of the unaffected siblings and healthy subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Augmentative And Alternative Communication Systems For Post-Stroke Patients With Severe Communication And Motor Impairment

    Directory of Open Access Journals (Sweden)

    Talieh Zarifian

    2017-02-01

    ; AAC use patterns; AAC limitations are main issues, an AAC technology for post-stroke patients will be presented which developed by a knowledgebase company in Iran. The system allows patients with communication and motor impairment to state their intentions and feelings by a minimum movement in their body, or just by moving their eyes. Different sensors and switches are available to adopt based on the limited ability of the patients. For detecting eye movements, a novel wearable miniaturized system has been developed that is worn as a headband and detects eye movements based on processing electro-oculogram. A high performance graphical user interface has been developed to type letters and numbers in Persian language. The system also provides words prediction, text to speech conversion with natural voice, and sending/receiving messages in the mobile networks for a convenient communication experience. The developed system has been tested successfully by more than 20 patients with different disabilities, and is now commercially available. The proposed system can also help the severely disabled people with amyotrophic lateral sclerosis, quadriplegia, muscular dystrophy or cerebral palsy to communicate with others and mention their intentions, needs and feelings. This low-cost wearable device assures high level of comfort for the user without fatigue and do not need long time training. The system can also be adapted for the patients who can speak, but could not move their hands, to work with the computer and enjoy using the internet.

  8. Arbitrary visuo-motor mapping during object manipulation in mild cognitive impairment and Alzheimer's disease: a pilot study.

    Science.gov (United States)

    Ameli, Mitra; Kemper, Friederike; Sarfeld, Anna-Sophia; Kessler, Josef; Fink, Gereon R; Nowak, Dennis A

    2011-07-01

    Empirical evidence for an essential role of the hippocampal system in arbitrary visuo-motor mapping suggests that acquisition and retrieval of arbitrary visuo-motor mapping might be impaired in mild cognitive impairment (MCI) and Alzheimer's disease (AD). The present pilot study investigated whether MCI of amnestic type or AD impact upon the capacity to scale grip force in a predictive manner to the mass of an object to be lifted based on learned associations between arbitrary colour cues and mass. Patients with MCI (n=8) and AD (n=8) grasped and lifted two different masses (400g and 600g) in random order using a precision grip between index finger and thumb. In a "no cue" experiment, a non-informative neutral visual stimulus was presented prior to each lift, thereby disallowing any prediction about which of the two masses was going to be lifted in the next trial. In a "cue" experiment an arbitrary colour cue provided advance information about which of the two masses to be lifted. In the "no cue" condition patients scaled their grip force according to the mass of the preceding lift. In the "cue" experiment neither patients with amnestic MCI nor those with AD were able to adjust their grip force based on visuo-motor mappings with arbitrary colour cues. These preliminary data suggest that the hippocampal system plays an essential role for arbitrary visuo-motor mapping in the grip-lift task. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia.

    Science.gov (United States)

    Molina, Juan L; Calvó, María; Padilla, Eduardo; Balda, Mara; Alemán, Gabriela González; Florenzano, Néstor V; Guerrero, Gonzalo; Kamis, Danielle; Rangeon, Beatriz Molina; Bourdieu, Mercedes; Strejilevich, Sergio A; Conesa, Horacio A; Escobar, Javier I; Zwir, Igor; Cloninger, C Robert; de Erausquin, Gabriel A

    2017-01-01

    Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson's Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, 'explosive/borderline', 'methodical/obsessive', and 'disorganized/schizotypal' personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome.

  10. Exercise training with ageing protects against ethanol induced myocardial glutathione homeostasis.

    Science.gov (United States)

    Kakarla, Pushpalatha; Kesireddy, Sathyavelureddy; Christiaan, Leeuwenburgh

    2008-05-01

    Glutathione plays a central role in the maintenance of cellular antioxidant defense. The alterations in the glutathione and associated recyclic enzymes caused by both exercise training and ethanol are well documented; however, their interactive effects with age are not well understood. Therefore, the influence of ageing and the interactive effects of exercise training and ethanol on the myocardial glutathione system in 3 months and 18 months old rats were examined. The results showed a significant (pEthanol consumption significantly (pethanol consumption significantly (pethanol significantly (pethanol treated rats in both age groups, indicating the suppression of ethanol-induced oxidative stress by exercise training. In conclusion, there was a compensatory myocardial response lessening ethanol-induced oxidative stress by exercise training, which seemed to result from the higher activity of glutathione recycling and utilizing enzymes, which may be critical for preventing chronic oxidative damage to the myocardium during ageing and even due to ethanol consumption.

  11. Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease

    OpenAIRE

    Troakes Claire; Shaw Christopher; Heimann Peter; Golfi Panagiota; Palmisano Ralf; Schmitt-John Thomas; Bartsch Jörg W

    2011-01-01

    Abstract Background The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown but hypotheses about disease mechanisms include oxidative stress, defective axonal transport, mitochondrial dysfunction and disrupted RNA processing. Whereas familial ALS is well represented by transgenic mutant SOD1 mouse models, the mouse mutant wobbler (WR) develops progressive motor neuron degeneration due to a point mutation in the Vps54 gene, and provides an animal model for sporadic ALS. VP...

  12. Effect of IQoro® training on impaired postural control and oropharyngeal motor function in patients with dysphagia after stroke.

    Science.gov (United States)

    Hägg, Mary; Tibbling, Lita

    2016-07-01

    Conclusion All patients with dysphagia after stroke have impaired postural control. IQoro® screen (IQS) training gives a significant and lasting improvement of postural control running parallel with significant improvement of oropharyngeal motor dysfunction (OPMD). Objectives The present investigation aimed at studying the frequency of impaired postural control in patients with stroke-related dysphagia and if IQS training has any effect on impaired postural control in parallel with effect on OPMD. Method A prospective clinical study was carried out with 26 adult patients with stroke-related dysphagia. The training effect was compared between patients consecutively investigated at two different time periods, the first period with 15 patients included in the study more than half a year after stroke, the second period with 11 patients included within 1 month after stroke. Postural control tests and different oropharyngeal motor tests were performed before and after 3 months of oropharyngeal sensorimotor training with an IQS, and at a late follow-up (median 59 weeks after end of training). Result All patients had impaired postural control at baseline. Significant improvement in postural control and OPMD was observed after the completion of IQS training in both intervention groups. The improvements were still present at the late follow-up.

  13. Glutathione prevents ethanol induced gastric mucosal damage and depletion of sulfhydryl compounds in humans.

    OpenAIRE

    Loguercio, C; Taranto, D; Beneduce, F.; del Vecchio Blanco, C; de Vincentiis, A; Nardi, G; M. Romano

    1993-01-01

    Whether parenteral administration of reduced glutathione prevented ethanol induced damage to and depletion of sulfhydryl compounds in the human gastric mucosa was investigated. Ten healthy volunteers underwent endoscopy on three separate occasions. Gastric mucosal damage was induced by spraying 80% ethanol on to the gastric mucosa through the biopsy channel of the endoscope. The gastric mucosal score, total sulfhydryls, glutathione, and cysteine were evaluated in basal conditions and after et...

  14. An opium alkaloid-papaverine ameliorates ethanol-induced hepatotoxicity: Diminution of oxidative stress

    OpenAIRE

    Chandra, Ramesh; Aneja, Ritu; Rewal, Charu; Konduri, Rama; Dass, Sujaka K.; Agarwal, Shefali

    2000-01-01

    In this communication, we show the modulatory potential of papaverine, an opium alkaloid and a well known vasodilator agent on the ethanol-induced hepatic oxidative stress in male Wistar rats. Ethanol treatment (50% v/v) enhanced lipid peroxidation significantly accompanied by a decline in the activities of glutathione peroxidase (G-Px), glutathione reductase (GR) and depletion in levels of hepatic glutathione (GSH). Ethanol administration increased hepatic glutathione-s-transferases (GST). E...

  15. Protective Effects of Manassantin A against Ethanol-Induced Gastric Injury in Rats.

    Science.gov (United States)

    Song, Ji-Won; Seo, Chang-Seob; Kim, Tae-In; Moon, Og-Sung; Won, Young-Suk; Son, Hwa-Young; Son, Jong-Keun; Kwon, Hyo-Jung

    2016-01-01

    Manassantin A, a neolignan isolated from Saururus chinensis, is a major phytochemical compound that has various biological activities, including anti-inflammatory, neuroleptic, and human acyl-CoA : cholesterol acyltransferase (ACAT) inhibitory activities. In this study, we investigated the protective effects of manassantin A against ethanol-induced acute gastric injury in rats. Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the manassantin A group were given oral doses of omeprazole (20 mg/kg) or manassantin A (15 mg/kg), respectively, 1 h prior to the administration of absolute ethanol. Our examinations revealed that manassantin A pretreatment reduced ethanol-induced hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Manassantin A pretreatment also attenuated the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, increased the mucosal glutathione (GSH) content, and enhanced the activities of antioxidant enzymes. The levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were clearly decreased in the manassantin A-pretreated group. In addition, manassantin A pretreatment enhanced the levels of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2 (PGE2) and reduced the inducible nitric oxide synthase (iNOS) overproduction and nuclear factor kappa B (NF-κB) phosphorylation. Collectively, these results indicate that manassantin A protects the gastric mucosa from ethanol-induced acute gastric injury, and suggest that these protective effects might be associated with COX/PGE2 stimulation, inhibition of iNOS production and NF-κB activation, and improvements in the antioxidant and anti-inflammatory status.

  16. Protective effect of Quercetin in the Regression of Ethanol-Induced Hepatotoxicity

    OpenAIRE

    A.Vidhya; M Indira

    2009-01-01

    This study examined the protective effects of quercetin on chronic ethanol-induced liver injury. Rats were treated with ethanol at a dose of 4 g/100 g/day for 90 days. After ethanol intoxication, levels of serum amino transferases were significantly elevated. Decreased activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase was also observed on ethanol administration. Increased amounts of lipid peroxidation products viz. hydroperoxides, conjugated dienes a...

  17. Ghrelin knockout mice show decreased voluntary alcohol consumption and reduced ethanol-induced conditioned place preference.

    Science.gov (United States)

    Bahi, Amine; Tolle, Virginie; Fehrentz, Jean-Alain; Brunel, Luc; Martinez, Jean; Tomasetto, Catherine-Laure; Karam, Sherif M

    2013-05-01

    Recent work suggests that stomach-derived hormone ghrelin receptor (GHS-R1A) antagonism may reduce motivational aspects of ethanol intake. In the current study we hypothesized that the endogenous GHS-R1A agonist ghrelin modulates alcohol reward mechanisms. For this purpose ethanol-induced conditioned place preference (CPP), ethanol-induced locomotor stimulation and voluntary ethanol consumption in a two-bottle choice drinking paradigm were examined under conditions where ghrelin and its receptor were blocked, either using ghrelin knockout (KO) mice or the specific ghrelin receptor (GHS-R1A) antagonist "JMV2959". We showed that ghrelin KO mice displayed lower ethanol-induced CPP than their wild-type (WT) littermates. Consistently, when injected during CPP-acquisition, JMV2959 reduced CPP-expression in C57BL/6 mice. In addition, ethanol-induced locomotor stimulation was lower in ghrelin KO mice. Moreover, GHS-R1A blockade, using JMV2959, reduced alcohol-stimulated locomotion only in WT but not in ghrelin KO mice. When alcohol consumption and preference were assessed using the two-bottle choice test, both genetic deletion of ghrelin and pharmacological antagonism of the GHS-R1A (JMV2959) reduced voluntary alcohol consumption and preference. Finally, JMV2959-induced reduction of alcohol intake was only observed in WT but not in ghrelin KO mice. Taken together, these results suggest that ghrelin neurotransmission is necessary for the stimulatory effect of ethanol to occur, whereas lack of ghrelin leads to changes that reduce the voluntary intake as well as conditioned reward by ethanol. Our findings reveal a major, novel role for ghrelin in mediating ethanol behavior, and add to growing evidence that ghrelin is a key mediator of the effects of multiple abused drugs. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. PRENATAL ETHANOL EXPOSURE LEADS TO GREATER ETHANOL-INDUCED APPETITIVE REINFORCEMENT

    OpenAIRE

    Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.

    2012-01-01

    Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of this effect of prenatal ethanol on the sensitivity to ethanol’s reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol’s aversive consequences. The present study assessed ethanol-induced second-order conditione...

  19. Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

    Science.gov (United States)

    Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

    2011-12-01

    Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Developmental Coordination Disorder, an umbrella term for motor impairments in children: nature and co-morbid disorders

    Directory of Open Access Journals (Sweden)

    Laurence eVaivre-Douret

    2016-04-01

    Full Text Available Background:Developmental Coordination Disorder (DCD defines a heterogeneous class of children exhibiting marked impairment in motor coordination as a general group of deficits in fine and gross motricity (subtype mixed group common to all research studies, and with a variety of other motor disorders that have been little investigated. No consensus about symptoms and aetiology has been established. Methods: Data from 58 children aged 6 to 13 years with DCD were collected on DSM-IV criteria, similar to DSM- 5 criteria. They had no other medical condition and inclusion criteria were strict (born full-term, no medication, no occupational /physical therapy. Multivariate statistical methods were used to evidence relevant interactions between discriminant features in a general DCD subtype group and to highlight specific co-morbidities. The study examined age-calibrated standardized scores from completed assessments of psychological, neuropsychological and neuropsychomotor functions, and more specifically the presence of minor neurological dysfunctions (MND including neurological soft signs (NSS, without evidence of focal neurological brain involvement. These were not considered in most previous studies. Results: Findings show the salient DCD markers for the mixed subtype (imitation of gestures, digital perception, digital praxia, manual dexterity, upper and lower limb coordination, versus surprising co-morbidities, with 33% of MND with mild spasticity from phasic stretch reflex (PSR, not associated with the above impairments but rather with sitting tone (p= .004 and dysdiadochokinesia (p= .011. PSR was not specific to a DCD subtype but was related to increased impairment of coordination between upper and lower limbs and manual dexterity. Our results highlight the major contribution of an extensive neuro-developmental assessment (mental and physical. Discussion: The present study provides important new evidence in favour of a complete physical

  1. Antioxidative Activity of Flavonoids from Abrus cantoniensis against Ethanol-Induced Gastric Ulcer in Mice.

    Science.gov (United States)

    Li, Hui; Song, Zi-Jing; Dai, Yan-Ping; Zhang, Su-Li; He, Xin; Guo, Chang-Run; Zhang, Wen-Jun; Wang, Jiao-Ying; Zhang, Chun-Feng; Wang, Chong-Zhi; Yuan, Chun-Su

    2015-07-01

    The present study investigated the flavonoids from Abrus cantoniensis against ethanol-induced gastric ulcers in mice. The flavonoids from A. cantoniensis were extracted with ethanol and purified by macroporous resin and polyamide. The 2,2-diphenyl-1-picrylhydrazyl assay was used to measure the antioxidative activities in vitro. The ethanol-induced ulcer mouse model was used to evaluate the gastroprotective activities of the flavonoids from A. cantoniensis. In addition, a method was established to ensure accuracy for animal ulcer evaluation. The flavonoids from A. cantoniensis showed a strong free radical scavenging capacity with an IC50 of 43.83 µg/mL in the 2,2-diphenyl-1-picrylhydrazyl assay. At doses between 28.16-112.67 mg/kg, the flavonoids conspicuously reduced the ulcer index in ethanol-induced mice (pglutathione, and myeloperoxidase in the stomach tissues between the flavonoids from the A. cantoniensis groups and the ethanol control group. The gastroprotective effect of the flavonoids from A. cantoniensis could be due to its antioxidative activity of the defensive mechanism. The data revealed that the flavonoids from A. cantoniensis could be a potential therapeutic agent for gastric ulcer prevention and treatment. Georg Thieme Verlag KG Stuttgart · New York.

  2. Role of neutrophilic elastase in ethanol induced injury to the gastric mucosa

    Energy Technology Data Exchange (ETDEWEB)

    Kvietys, P.R.; Carter, P.R. (Louisiana State Univ. Medical Center, Shreveport (United States))

    1990-02-26

    Intragastric administration of ethanol (at concentrations likely to be encountered by the mucosa during acute intoxication) produces gastritis. Recent studies have implicated neutrophils in the gastric mucosal injury induced by luminal ethanol. The objective of the present study was to assess whether neutrophilic elastase contributes to the ethanol-induced gastric mucosal injury. Sprague-Dawley rats were instrumented for perfusion of the gastric lumen with saline or ethanol. Mucosal injury was quantitated by continuously measuring the blood-to-lumen clearance of {sup 51}Cr-EDTA. The experimental protocol consisted of a 40 minute control period (saline perfusion) followed by three successive 40 minute experimental periods (ethanol perfusion). During the three experimental periods the concentration of ethanol was progressively increased to 10, 20, and 30%. The experiments were performed in untreated animals and in animals pretreated with either Eglin c (an inhibitor of elastase and cathepsin G activity) or L 658 (a specific inhibitor of elastase activity). The effects of ethanol on EDTA clearance (x control) in untreated (n = 9) and L658 treated (n = 5) animals are shown in the Table below. Pretreatment with L 658 significantly attenuated the ethanol-induced increases in EDTA clearance. Pretreatment with Eglin c (n = 6) also provided some protection against ethanol-induced injury, but not to the extent as that provided by L658. The results of the authors studies suggest that neutrophilic elastase contributes to a gastric mucosal injury induced by luminal perfusion of the stomach with physiologically relevant concentrations of ethanol.

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

    Directory of Open Access Journals (Sweden)

    Mariko Saito

    2016-08-01

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

  4. Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses.

    Science.gov (United States)

    Kang, Geum-Dan; Kim, Dong-Hyun

    2017-02-01

    Poncirin (PO) and isosakuranetin (or ponciretin [PT]) are compounds found in fruits of the genus Citrus. They are frequently used in traditional Chinese medicine for the treatment of inflammation and asthma. Therefore, we examined their anti-gastritis effects in vitro and in vivo. The anti-inflammatory effects of PO and PT were examined using ethanol- or LPS-stimulated KATO III cells. Gastritis was induced in ICR mice via intragastric injection of absolute ethanol. Levels of inflammatory markers were measured by enzyme-linked immunosorbent assay, immunoblotting, and quantitative polymerase chain reaction. Treatment with PT or PO inhibited the secretion of interleukin (IL)-8 and tumor necrosis factor (TNF) in ethanol- or LPS-stimulated KATO III cells. They also reduced the activation of nuclear factor kappa B (NF-κB). Pre-treatment with PT or PO significantly protected against ethanol-induced hemorrhagic gastritis, characterized by edema, tissue erosions, and mucosal friability in mice. Treatment with PT or PO suppressed ethanol-induced NF-κB activation and the release of TNF, IL-8, and IFN-γ. The protective effect of PT was greater than that of PO and comparable to ranitidine, a positive control. PT may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, including neutrophils, via the regulation of CXCL4 (or IL-8) secretion and the activation NF-κB. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum.

    Science.gov (United States)

    Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A; Handshoe, Jonathan W; Cui, Jiajun; Xu, Wenhua; Chen, Gang

    2015-08-01

    Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1β (IL-1β) secretion, and IL-1β is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1β secretion is inhibited in the developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD).

  6. Gastroprotective effect of (-)-myrtenol against ethanol-induced acute gastric lesions: possible mechanisms.

    Science.gov (United States)

    Viana, Ana Flávia Seraine Custódio; da Silva, Francilene Vieira; Fernandes, Hélio de Barros; Oliveira, Irisdalva Sousa; Braga, Milena Aguiar; Nunes, Paulo Iury Gomes; Viana, Daniel de Araújo; de Sousa, Damião Pergentino; Rao, Vietla Satyanarayana; Oliveira, Rita de Cássia Meneses; Almeida Santos, Flávia

    2016-08-01

    (-)-Myrtenol is a natural fragrance monoterpenoid structurally related to α-pinene found in diverse plant essential oils. This study was aimed to assess the anti-ulcerogenic potential of (-)-myrtenol against ethanol-induced gastric lesions and to elucidate the underlying mechanism(s). Gastroprotective activity of (-)-myrtenol was evaluated using the mouse model of ethanol-induced gastric damage. To elucidate the gastroprotective mechanism(s), the roles of GABA, prostaglandins, nitric oxide and KATP channels were assessed. Besides, the oxidative stress-related parameters and the mucus content in gastric tissues were analysed. (-)-Myrtenol at oral doses of 25, 50 and 100 mg/kg significantly decreased the severity of ethanol-induced gastric lesions affording gastroprotection that was accompanied by a decrease in the activity of myeloperoxidase and malondialdehyde, an increase in GPx, SOD, and catalase activity in gastric tissues, and with well-maintained normal levels of nitrite/nitrate, gastric mucus and NP-SHs. Pretreatment with GABA-A receptor antagonist flumazenil, the COX inhibitor indomethacin, and NO synthesis inhibitor L-NAME but not with KATP channel blocker glibenclamide significantly blocked the (-)-myrtenol gastroprotection. These results provide first-time evidence for the gastroprotective effect of (-)-myrtenol that could be related to GABAA -receptor activation and antioxidant activity. © 2016 Royal Pharmaceutical Society.

  7. Ethanol-induced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice.

    Science.gov (United States)

    Kim, Sun J; Lee, Joo W; Jung, Young S; Kwon, Do Y; Park, Hee K; Ryu, Chang S; Kim, Sang K; Oh, Goo T; Kim, Young C

    2009-06-01

    Oxidative stress via generation of reactive oxygen species is suggested to be the major mechanism of alcohol-induced liver injury. We investigated the effects of glutathione peroxidase-1 and catalase double deficiency (Gpx-1(-/-)/Cat(-/-)) on liver injury and changes in the sulfur amino acid metabolism induced by binge ethanol administration. Ethanol (5 g/kg) was administered orally to the wild-type and the Gpx-1(-/-)/Cat(-/-) mice every 12 h for a total of three doses. Mice were sacrificed 6 h after the final dose. The Gpx-1/Cat deficiency alone increased malondialdehyde levels in liver significantly. Hepatic methionine adenosyltransferase (MAT) activity and S-adenosylmethionine levels were decreased, however, glutathione contents were not changed. Ethanol administration to the Gpx-1(-/-)/Cat(-/-) mice increased the elevation of serum alanine aminotransferase activity, plasma homocysteine levels, hepatic fat accumulation and lipid peroxidation compared with the wild-type animals challenged with ethanol. Also the reduction of MAT activity and S-adenosylmethionine levels was enhanced, but MATI/III expression was increased significantly. The results indicate that Gpx-1 and Cat have critical roles in the protection of liver against binge ethanol exposure. Augmentation of ethanol-induced oxidative stress may be responsible for the impairment of the transsulfuration reactions and the aggravation of acute liver injury in the Gpx-1(-/-)/Cat(-/-) mice.

  8. Functional Balance and Motor Impairment Correlations with Gait Parameters during Timed Up and Go Test across Three Attentional Loading Conditions in Stroke Survivors

    Directory of Open Access Journals (Sweden)

    Haidzir Manaf

    2014-01-01

    Full Text Available The aim of this study was to determine whether stroke survivor’s gait performance during dual-task Timed Up and Go (TUG test is correlated with the level of functional balance and motor impairment. Thirty stroke survivors (22 men, 8 women were recruited for this study. The level of functional balance (Berg Balance Scale and motor impairment (Fugl-Meyer assessment lower extremity were assessed prior to the TUG test. TUG test was conducted under three attentional loading conditions (single, dual motor, and dual-cognitive. The time and number of steps were used to quantify gait parameters. The Spearmen’s rank correlation coefficient was used to evaluate the relationship between these variables. There was moderate to strong negative correlation between functional balance and gait parameters (range −0.53 to −0.73, P<0.05. There was a weak negative correlation observed between the time taken to complete the single task and motor impairment (rs=-0.43; P=0.02 dual motor task and motor impairment (rs=-0.41; P=0.02. However, there were no significant correlations between lower limb motor impairment and the number of steps in all conditions. These findings suggest that functional balance may be an influential domain of successful dual-task TUG in stroke.

  9. Stereopsis impairment is associated with decreased color perception and worse motor performance in Parkinson’s disease

    Science.gov (United States)

    2014-01-01

    Background We conducted this study is to investigate the correlation between stereopsis dysfunction and color perception, as well as whether stereopsis impairment is associated with motor dysfunction in patients with Parkinson’s disease (PD). Method Our present study included 45 PD patients and 50 non-PD control patients attending the Movement Disorder Center at Xuanwu Hospital Capital Medical University in Beijing from July 2011 to November 2011. Neurologic evaluations and visual function assessments were conducted, and the results between two groups of patients were compared. Results We found that the total error scores (TESs) and partial error scores (PESs) for red, green, blue and purple were all significantly higher in PD patients than in control patients. The limited grade on the FLY Stereo Acuity Test with LEA Symbols was significantly lower in PD patients than in control patients (P = 0.0001), whereas the percentage of abnormal stereopsis in PD patients was significantly higher than in control patients (42.2% vs. 12%; P = 0.001). Multiple linear regression analysis showed that PD patients with higher Hoehn and Yahr Scale stage, and those with decreased stereopsis had higher Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores and worse motor function. Furthermore, our study demonstrates that the UPDRS motor scores and total average number of the Purdue Pegboard Test scores of PD patients were significantly improved when they had taken their medications, and the TESs and PESs for green were lower in when they were off their medications. Conclusion Our results provide more information on the underlying mechanisms of vision, motor and stereopsis impairments in PD patients. PMID:24886673

  10. Impaired Retention of Motor Learning of Writing Skills in Patients with Parkinson’s Disease with Freezing of Gait

    Science.gov (United States)

    Heremans, Elke; Nackaerts, Evelien; Vervoort, Griet; Broeder, Sanne; Swinnen, Stephan P.; Nieuwboer, Alice

    2016-01-01

    Background Patients with Parkinson’s disease (PD) and freezing of gait (FOG) suffer from more impaired motor and cognitive functioning than their non-freezing counterparts. This underlies an even higher need for targeted rehabilitation programs in this group. However, so far it is unclear whether FOG affects the ability for consolidation and generalization of motor learning and thus the efficacy of rehabilitation. Objective To investigate the hallmarks of motor learning in people with FOG compared to those without by comparing the effects of an intensive motor learning program to improve handwriting. Methods Thirty five patients with PD, including 19 without and 16 with FOG received six weeks of handwriting training consisting of exercises provided on paper and on a touch-sensitive writing tablet. Writing training was based on single- and dual-task writing and was supported by means of visual target zones. To investigate automatization, generalization and retention of learning, writing performance was assessed before and after training in the presence and absence of cues and dual tasking and after a six-week retention period. Writing amplitude was measured as primary outcome measure and variability of writing and dual-task accuracy as secondary outcomes. Results Significant learning effects were present on all outcome measures in both groups, both for writing under single- and dual-task conditions. However, the gains in writing amplitude were not retained after a retention period of six weeks without training in the patient group without FOG. Furthermore, patients with FOG were highly dependent on the visual target zones, reflecting reduced generalization of learning in this group. Conclusions Although short-term learning effects were present in both groups, generalization and retention of motor learning were specifically impaired in patients with PD and FOG. The results of this study underscore the importance of individualized rehabilitation protocols. PMID

  11. Impaired Retention of Motor Learning of Writing Skills in Patients with Parkinson's Disease with Freezing of Gait.

    Directory of Open Access Journals (Sweden)

    Elke Heremans

    Full Text Available Patients with Parkinson's disease (PD and freezing of gait (FOG suffer from more impaired motor and cognitive functioning than their non-freezing counterparts. This underlies an even higher need for targeted rehabilitation programs in this group. However, so far it is unclear whether FOG affects the ability for consolidation and generalization of motor learning and thus the efficacy of rehabilitation.To investigate the hallmarks of motor learning in people with FOG compared to those without by comparing the effects of an intensive motor learning program to improve handwriting.Thirty five patients with PD, including 19 without and 16 with FOG received six weeks of handwriting training consisting of exercises provided on paper and on a touch-sensitive writing tablet. Writing training was based on single- and dual-task writing and was supported by means of visual target zones. To investigate automatization, generalization and retention of learning, writing performance was assessed before and after training in the presence and absence of cues and dual tasking and after a six-week retention period. Writing amplitude was measured as primary outcome measure and variability of writing and dual-task accuracy as secondary outcomes.Significant learning effects were present on all outcome measures in both groups, both for writing under single- and dual-task conditions. However, the gains in writing amplitude were not retained after a retention period of six weeks without training in the patient group without FOG. Furthermore, patients with FOG were highly dependent on the visual target zones, reflecting reduced generalization of learning in this group.Although short-term learning effects were present in both groups, generalization and retention of motor learning were specifically impaired in patients with PD and FOG. The results of this study underscore the importance of individualized rehabilitation protocols.

  12. Brain implants for substituting lost motor function: state of the art and potential impact on the lives of motor-impaired seniors.

    Science.gov (United States)

    Ramsey, N F; Aarnoutse, E J; Vansteensel, M J

    2014-01-01

    Recent scientific achievements bring the concept of neural prosthetics for reinstating lost motor function closer to medical application. Current research involves severely paralyzed people under the age of 65, but implications for seniors with stroke or trauma-induced impairments are clearly on the horizon. Demographic changes will lead to a shortage of personnel to care for an increasing population of senior citizens, threatening maintenance of an acceptable level of care and urging ways for people to live longer at their home independent from personal assistance. This is particularly challenging when people suffer from disabilities such as partial paralysis after stroke or trauma, where daily personal assistance is required. For some of these people, neural prosthetics can reinstate some lost motor function and/or lost communication, thereby increasing independence and possibly quality of life. In this viewpoint article, we present the state of the art in decoding brain activity in the service of brain-computer interfacing. Although some noninvasive applications produce good results, we focus on brain implants that benefit from better quality brain signals. Fully implantable neural prostheses for home use are not available yet, but clinical trials are being prepared. More sophisticated systems are expected to follow in the years to come, with capabilities of interest for less severe paralysis. Eventually the combination of smart robotics and brain implants is expected to enable people to interact well enough with their environment to live an independent life in spite of motor disabilities. © 2014 S. Karger AG, Basel.

  13. Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

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    Francisco Bruno Teixeira

    Full Text Available Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies, GFAP (a marker of astrocytes and Iba1 (microglia marker in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

  14. Fluoxetine does not impair motor function in patients with Parkinson's disease: Correlation between mood and motor functions with plasma concentrations of fluoxetine/norfluoxetine

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    Kostić Vladimir

    2012-01-01

    Full Text Available Background/Aim. Selective serotonin reuptake inhibitors are the most commonly chosen antidepressants in patients with Parkinson's disease (PD. The aim of our study was to assess the influence of fluoxetine (Flu on motor functions in patients with PD. Methods. In this prospective, controlled, open-label study, 18 patients with PD and mild depression [(10 ≤ Hamilton Rating Scale for Depression (HDRS ≤ 23] without dementia [(25 ≤ Mini-Mental State Examination (MMSE] were treated with Flu. Both single and repeated dose effects of Flu were assessed on days 1-80. Plasma concentrations of Flu and norfluoxetine (NORFlu were correlated with the results of selected motor function performance scores: The Unified Parkinsons Disease Rating Score (UPDRS, Finger Tapping Test (FTT and Purdue Pegboard Test (PPT. Severity of PD, depression and dementia were evaluated using standard tests [(Hoehn and Yahr stages (HY, activity of daily living (ADL, UPDRS, HDRS, MMSE]. Results. Steady-state for Flu/NORFlu was reached after 18 days of treatment. Such a plateau correlated with significant improvements in both scores of depression and Parkinson's disability (HDRS, UPDRS and ADL, respectively. In addition, FTT and PPT scores also increased until day 18, with further slight fluctuations around the plateau. Optimal motor performances correlated with Flu concentrations of approximately 60-110 μg/L. Conclusion. Flu (20 mg/day significantly reduced depression in PD patients while it did not impair their motor performances. Because substantial placebo effects may arise in studies of PD and depression, large, prospective, randomized, placebo-controlled clinical trials are warranted. [Acknowledgment. Projekat Ministarstva nauke Republike Srbije, br. 175090

  15. Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice.

    Science.gov (United States)

    Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Essa, Musthafa Mohamed; Barathidasan, Rajamani; SaravanaBabu, Chidambaram; Guillemin, Gilles J; Khan, Mohammed A S

    2016-01-01

    Parkinson's disease (PD) is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic) neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS) such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS), a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt.) with probenecid (250 mg/kg, s.c.) (MPTP/p) induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks) of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor) impairments, levels and expressions of dopamine (DA), serotonin (5-HT), DAergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporters-2 (VMAT 2) and α-synuclein in nigrostriatal (striatum (ST) and substantia nigra (SN)) and extra-nigrostriatal (hippocampus, cortex and cerebellum) tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.

  16. Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice.

    Directory of Open Access Journals (Sweden)

    Udaiyappan Janakiraman

    Full Text Available Parkinson's disease (PD is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS, a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt. with probenecid (250 mg/kg, s.c. (MPTP/p induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor impairments, levels and expressions of dopamine (DA, serotonin (5-HT, DAergic markers such as tyrosine hydroxylase (TH, dopamine transporter (DAT, vesicular monoamine transporters-2 (VMAT 2 and α-synuclein in nigrostriatal (striatum (ST and substantia nigra (SN and extra-nigrostriatal (hippocampus, cortex and cerebellum tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.

  17. Assessment of gait in toddlers with normal motor development and in hemiplegic children with mild motor impairment: a validity study

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    Priscilla R. P. Figueiredo

    2013-08-01

    Full Text Available BACKGROUND: The optimization of gait performance is an important goal in the rehabilitation of children with cerebral palsy (CP who present a prognosis associated with locomotion. Gait analysis using videos captured by digital cameras requires validation. OBJECTIVE: To evaluate the validity of a method that involves the analysis of videos captured using a digital camera for quantifying the temporal parameters of gait in toddlers with normal motor development and children with CP. METHOD: Eleven toddlers with normal motor development and eight children with spastic hemiplegia who were able to walk without assistive devices were asked to walk through a space contained in the visual field of two instruments: a digital camera and a three-dimensional motion analysis system, Qualisys Pro-Reflex. The duration of the stance and swing phases of gait and of the entire gait cycle were calculated by analyzing videos captured by a digital camera and compared to those obtained by Qualisys Pro-Reflex, which is considered a highly accurate system. RESULTS: The Intraclass Correlation Coefficient (ICC demonstrated excellent agreement (ICC>0.90 between the two procedures for all measurements, except for the swing phase of the normal toddlers (ICC=0.35. The standard error of measurement was less than 0.02 seconds for all measures. CONCLUSIONS: The results reveal similarities between the two instruments, suggesting that digital cameras can be valid instruments for quantifying two temporal parameters of gait. This congruence is of clinical and scientific relevance and validates the use of digital cameras as a resource for helping the assessment and documentation of the therapeutic effects of interventions targeted at the gait of children with CP.

  18. Development and validation of the first robotic scale for the clinical assessment of upper extremity motor impairments in stroke patients.

    Science.gov (United States)

    Einav, Omer; Geva, Diklah; Yoeli, Doron; Kerzhner, Marina; Mauritz, Karl-Heinz

    2011-10-01

    We aimed to develop and validate the first robotic-based instrument and procedure for assessing upper extremity motor impairments in patients with stroke and to test its discriminative power. The ReoGo robotic rehabilitation platform was used to design a novel, upper limb functionality assessment tool, the Reo Scale Assessment (RSA). We used the RSA to evaluate 100 patients with stroke. The RSA items were tested for internal consistency and submitted to factor analysis. The Fugl-Meyer (FM) motor test, the Wolf Motor Function Test (WMFT), and the Action Research Arm Test (ARAT) were used to examine the validity of the RSA. RSA scores were compared and correlated with the scores of the 3 scales. The discriminative power of the RSA was tested against the FM impairment levels by analysis of variance. The total RSA score correlated closely with the upper extremity scores of the FM, WMFT, and ARAT (r = 0.95, 0.93, and 0.90, respectively). The RSA was able to discriminate between low, moderate, and high functioning patients (86% agreement with FM). Principal component analysis revealed that the RSA coefficients loaded on 3 tested components: proximal, distal, and force. Our results provide strong evidence that the validity of the RSA is comparable with that of the FM, WMFT, and ARAT. The objective measuring and scoring systems of the robotic RSA make it an efficient tool for assessing motor function of stroke patients in clinical and research settings. Additional studies are needed to test the reliability and sensitivity of the RSA.

  19. Increased activity in frontal motor cortex compensates impaired speech perception in older adults

    National Research Council Canada - National Science Library

    Du, Yi; Buchsbaum, Bradley R; Grady, Cheryl L; Alain, Claude

    2016-01-01

    .... Here we show that relative to young adults, older adults show higher activation of frontal speech motor areas as measured by functional MRI during a syllable identification task at varying signal-to-noise ratios...

  20. Restauration of age related motor impairment: Role of IGF-1 based gene therapy and microglial activation.

    Directory of Open Access Journals (Sweden)

    Eugenia Falomir Lockhart

    2015-05-01

    In the current study we implemented ICV IGF-I gene therapy in very old rats (28 months and assessed the motor performance pre and 17-days after surgery. Glial immunoreactivity in striatum was evaluated by Iba1 and GFAP markers. Results: As we previously reported, IGF-I restored motor coordination and forelimb grip strength in aged rats (Sanchez et al., 2008. We found that microglia immunoreactivity (Iba-1+ was significantly increased for at least 17 days after treatment with IGF-I (Xm-senil-IGF-I=8.370±0.3297 vs Xm-senil-DsRed= 5.557±0.2553; p<0.0001, astrocytes (GFAP+ showed not changes. Our results identify a novel function of microglia in the maintenance of motor permormance and suggest an original approach for reversing age-associated motor and exploratory performance recorded in rats.

  1. Bilateral subthalamic stimulation impairs cognitive-motor performance in Parkinson's disease patients

    National Research Council Canada - National Science Library

    Alberts, Jay L; Voelcker-Rehage, Claudia; Hallahan, Katie; Vitek, Megan; Bamzai, Rashi; Vitek, Jerrold L

    2008-01-01

    Deep brain stimulation (DBS) is a surgical procedure that has been shown effective in improving the cardinal motor signs of advanced Parkinson's disease, however, declines in cognitive function have been associated...

  2. Motor skills of children with unilateral visual impairment in the Infant Aphakia Treatment Study.

    Science.gov (United States)

    Celano, Marianne; Hartmann, E Eugenie; DuBois, Lindreth G; Drews-Botsch, Carolyn

    2016-02-01

    To assess motor functioning in children aged 4 years 6 months enrolled in the Infant Aphakia Treatment Study, and to determine contributions of visual acuity and stereopsis to measured motor skills. One hundred and four children (53% female) with unilateral aphakia randomized to intraocular lens or contact lens treatment were evaluated at 4 years 6 months (age range 4y 6mo-4y 11mo) for monocular recognition visual acuity, motor skills, and stereopsis by a traveling examiner masked to treatment condition. Motor skills were assessed with the Movement Assessment Battery for Children--Second Edition (MABC-2). Visual acuity was operationalized as log10 of the minimum angle of resolution (logMAR) value for treated eye, best logMAR value for either eye, and intraocular logMAR difference. Student's t-tests showed no significant differences in MABC-2 scores between the intraocular lens and contact lens groups. The mean total score was low (6.43; 18th centile) compared with the normative reference group. Motor functioning was not related to visual acuity in the treated eye or to intraocular logMAR difference, but was predicted in a regression model by the better visual acuity of either eye (usually the fellow eye), even after accounting for the influence of age at surgery, examiner, orthotropic ocular alignment, and stereopsis. Children with unilateral congenital cataract may have delayed motor functioning at 4 years 6 months, which may adversely affect their social and academic functioning. © 2015 Mac Keith Press.

  3. Influence of zinc sulfate intake on acute ethanol-induced liver injury in rats

    Science.gov (United States)

    Bolkent, Sema; Arda-Pirincci, Pelin; Bolkent, Sehnaz; Yanardag, Refiye; Tunali, Sevim; Yildirim, Sukriye

    2006-01-01

    AIM: To investigate the role of metallothionein and proliferating cell nuclear antigen (PCNA) on the morphological and biochemical effects of zinc sulfate in ethanol-induced liver injury. METHODS: Wistar albino rats were divided into four groups. Group I; intact rats, group II; control rats given only zinc, group III; animals given absolute ethanol, group IV; rats given zinc and absolute ethanol. Ethanol-induced injury was produced by the 1 mL of absolute ethanol, administrated by gavage technique to each rat. Animals received 100 mg/kg per day zinc sulfate for 3 d 2 h prior to the administration of absolute ethanol. RESULTS: Increases in metallothionein immunoreactivity in control rats given only zinc and rats given zinc and ethanol were observed. PCNA immunohistochemistry showed that the number of PCNA-positive hepatocytes was increased significantly in the livers of rats administered ethanol + zinc sulfate. Acute ethanol exposure caused degenerative morphological changes in the liver. Blood glutathione levels decreased, serum alkaline phosphatase and aspartate transaminase activities increased in the ethanol group when compared to the control group. Liver glutathione levels were reduced, but lipid peroxidation increased in the livers of the group administered ethanol as compared to the other groups. Administration of zinc sulfate in the ethanol group caused a significant decrease in degenerative changes, lipid peroxidation, and alkaline phosphatase and aspartate transaminase activities, but an increase in liver glutathione. CONCLUSION: Zinc sulfate has a protective effect on ethanol-induced liver injury. In addition, cell proliferation may be related to the increase in metallothionein immunoreactivity in the livers of rats administered ethanol + zinc sulfate. PMID:16865776

  4. Fractalkine is a "find-me" signal released by neurons undergoing ethanol-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Jennifer D Sokolowski

    2014-11-01

    Full Text Available Apoptotic neurons generated during normal brain development or secondary to pathologic insults are efficiently cleared from the central nervous system. Several soluble factors, including nucleotides, cytokines, and chemokines are released from injured neurons, signaling microglia to find and clear debris. One such chemokine that serves as a neuronal-microglial communication factor is fractalkine, with roles demonstrated in several models of adult neurological disorders. Lacking, however, are studies investigating roles for fractalkine in perinatal brain injury, an important clinical problem with no effective therapies. We used a well-characterized mouse model of ethanol-induced apoptosis to assess the role of fractalkine in neuronal-microglial signaling. Quantification of apoptotic debris in fractalkine-knockout and CX3CR1-knockout mice following ethanol treatment revealed increased apoptotic bodies compared to wild type mice. Ethanol-induced injury led to release of soluble, extracellular fractalkine. The extracellular media harvested from apoptotic brains induces microglial migration in a fractalkine-dependent manner that is prevented by neutralization of fractalkine with a blocking antibody or by deficiency in the receptor, CX3CR1. This suggests fractalkine acts as a ‘find-me’ signal, recruiting microglial processes toward apoptotic cells to promote their clearance. Next, we aimed to determine whether there are downstream alterations in cytokine gene expression due to fractalkine signaling. We examined mRNA expression in fractalkine-knockout and CX3CR1-knockout mice after alcohol-induced apoptosis and found differences in cytokine production in the brains of these knockouts by 6 hours after ethanol treatment. Collectively, this suggests that fractalkine acts as a ‘find me’ signal released by apoptotic neurons, and subsequently plays a critical role in modulating both phagocytic clearance and inflammatory cytokine gene expression after

  5. Impaired inhibition of prepotent motor actions in patients with Tourette syndrome.

    Science.gov (United States)

    Wylie, Scott A; Claassen, Daniel O; Kanoff, Kristen E; Ridderinkhof, K Richard; van den Wildenberg, Wery P M

    2013-09-01

    Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses as an act of cognitive control. We tested the hypothesis that individuals with Tourette syndrome show a deficit in inhibiting prepotent motor actions. Healthy controls and older adolescents/adults with persistent Tourette syndrome without a history of obsessive-compulsive disorder or attention-deficit/hyperactivity disorder and presenting with stable mood functioning (i.e., no history of well-treated anxiety or depression) participated in this study. They performed a Simon task that induced conflict between prepotent actions and goal-directed actions. A novel theoretical framework distinguished group differences in acting impulsively (i.e., fast motor errors) from the proficiency of inhibiting interference by prepotent actions (i.e., slope of interference reduction). We included 27 controls and 28 individuals with Tourette syndrome in our study. Both groups showed similar susceptibility to making fast, impulsive motor errors (Tourette syndrome 26% v. control 23%; p = 0.10). The slope (m) reduction of the interference effect was significantly less pronounced among participants with Tourette syndrome than controls (Tourette syndrome: m = -0.07 v. control: m = -0.23; p = 0.022), consistent with deficient inhibitory control over prepotent actions in Tourette syndrome. This study does not address directly the role of psychiatric comorbidities and medication effects on inhibitory control over impulsive actions in individuals with Tourette syndrome. The results offer empirical evidence for deficient inhibitory control over prepotent motor actions in individuals with persistent Tourette syndrome with minimal to absent psychiatric comorbidities. These findings also suggest that the frontal

  6. Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yongke Lu

    2015-10-01

    Full Text Available Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT, CYP2E1 knockout (KO or CYP2E1 humanized transgenic knockin (KI, mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA, an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These

  7. Altered chemomechanical coupling causes impaired motility of the kinesin-4 motors KIF27 and KIF7.

    Science.gov (United States)

    Yue, Yang; Blasius, T Lynne; Zhang, Stephanie; Jariwala, Shashank; Walker, Benjamin; Grant, Barry J; Cochran, Jared C; Verhey, Kristen J

    2018-01-19

    Kinesin-4 motors play important roles in cell division, microtubule organization, and signaling. Understanding how motors perform their functions requires an understanding of their mechanochemical and motility properties. We demonstrate that KIF27 can influence microtubule dynamics, suggesting a conserved function in microtubule organization across the kinesin-4 family. However, kinesin-4 motors display dramatically different motility characteristics: KIF4 and KIF21 motors are fast and processive, KIF7 and its Drosophila melanogaster homologue Costal2 (Cos2) are immotile, and KIF27 is slow and processive. Neither KIF7 nor KIF27 can cooperate for fast processive transport when working in teams. The mechanistic basis of immotile KIF7 behavior arises from an inability to release adenosine diphosphate in response to microtubule binding, whereas slow processive KIF27 behavior arises from a slow adenosine triphosphatase rate and a high affinity for both adenosine triphosphate and microtubules. We suggest that evolutionarily selected sequence differences enable immotile KIF7 and Cos2 motors to function not as transporters but as microtubule-based tethers of signaling complexes. © 2018 Yue et al.

  8. [Clinical research of knee joint motor impairment after fracture operation treated with relaxing needling manipulation combined with exercise therapy].

    Science.gov (United States)

    Luo, Kaimin; Qi, Tianchen; Yang, Lin; Hou, Zhi

    2015-09-01

    To compare the clinical efficacy on the motor impairment of knee joint after tracture operation between the combined therapeutic method of relaxing needling manipulation and exercise therapy and the simple exercise therapy. Sixty-four patients after the operation for the fracture of femoral shaft were randomized into a relaxing needling combined with exercise therapy group (group A) and an exercise therapy group (group B), 32 cases in each one. In the group A, the relaxing needling manipulation was applied to the local painful area of knee or the stiff soft tissues. Additionally, the exercise therapy was used in combination. In the group B, the exercise therapy was applied simply. Hospital for special surgery (HSS) pain score, the range of movement (ROM) of knee joint and Lysholm score were compared before and 60 days after treatment in the patients of the two groups. The efficacy was compared between the two groups. After treatment, HSS pain score, ROM and Lysholm score were all improved in the two groups, presenting the significant differences as compared with those before treatment (all Pexercise therapy achieves the significant efficacy on the motor impairment of knee joint after the operation for the fracture of femoral shaft, superior to the simple exercise therapy.

  9. Motor-based bodily self is selectively impaired in eating disorders

    Science.gov (United States)

    Mansi, Gianluigi; Fumagalli, Alessandra; Fumagalli, Beatrice; Sottocornola, Simona; Molteni, Massimo; Micali, Nadia

    2017-01-01

    Background Body representation disturbances in body schema (i.e. unconscious sensorimotor body representations for action) have been frequently reported in eating disorders. Recently, it has been proposed that body schema relies on adequate functioning of the motor system, which is strongly implicated in discriminating between one’s own and someone else’s body. The present study aimed to investigate the motor-based bodily self in eating disorders and controls, in order to examine the role of the motor system in body representation disturbances at the body schema level. Method Female outpatients diagnosed with eating disorders (N = 15), and healthy controls (N = 18) underwent a hand laterality task, in which their own (self-stimuli) and someone else’s hands (other-stimuli) were displayed at different orientations. Participants had to mentally rotate their own hand in order to provide a laterality judgement. Group differences in motor-based bodily self-recognition—i.e. whether a general advantage occurred when implicitly processing self- vs. other-stimuli − were evaluated, by analyzing response times and accuracy by means of mixed ANOVAs. Results Patients with eating disorders did not show a temporal advantage when mentally rotating self-stimuli compared to other-stimuli, as opposed to controls (F(1, 31) = 5.6, p = 0.02; eating disorders-other = 1092 ±256 msec, eating disorders-self = 1097±254 msec; healthy controls-other = 1239±233 msec, healthy controls -self = 1192±232 msec). Conclusion This study provides initial indication that high-level motor functions might be compromised as part of body schema disturbances in eating disorders. Further larger investigations are required to test motor system abnormalities in the context of body schema disturbance in eating disorders. PMID:29091967

  10. Motor-based bodily self is selectively impaired in eating disorders.

    Science.gov (United States)

    Campione, Giovanna Cristina; Mansi, Gianluigi; Fumagalli, Alessandra; Fumagalli, Beatrice; Sottocornola, Simona; Molteni, Massimo; Micali, Nadia

    2017-01-01

    Body representation disturbances in body schema (i.e. unconscious sensorimotor body representations for action) have been frequently reported in eating disorders. Recently, it has been proposed that body schema relies on adequate functioning of the motor system, which is strongly implicated in discriminating between one's own and someone else's body. The present study aimed to investigate the motor-based bodily self in eating disorders and controls, in order to examine the role of the motor system in body representation disturbances at the body schema level. Female outpatients diagnosed with eating disorders (N = 15), and healthy controls (N = 18) underwent a hand laterality task, in which their own (self-stimuli) and someone else's hands (other-stimuli) were displayed at different orientations. Participants had to mentally rotate their own hand in order to provide a laterality judgement. Group differences in motor-based bodily self-recognition-i.e. whether a general advantage occurred when implicitly processing self- vs. other-stimuli - were evaluated, by analyzing response times and accuracy by means of mixed ANOVAs. Patients with eating disorders did not show a temporal advantage when mentally rotating self-stimuli compared to other-stimuli, as opposed to controls (F(1, 31) = 5.6, p = 0.02; eating disorders-other = 1092 ±256 msec, eating disorders-self = 1097±254 msec; healthy controls-other = 1239±233 msec, healthy controls -self = 1192±232 msec). This study provides initial indication that high-level motor functions might be compromised as part of body schema disturbances in eating disorders. Further larger investigations are required to test motor system abnormalities in the context of body schema disturbance in eating disorders.

  11. Effects of Ai Chi on balance, quality of life, functional mobility, and motor impairment in patients with Parkinson's disease.

    Science.gov (United States)

    Kurt, Emine Eda; Büyükturan, Buket; Büyükturan, Öznur; Erdem, Hatice Rana; Tuncay, Figen

    2018-04-01

    In this study, we aimed to investigate effects of Ai Chi on balance, functional mobility, health-related quality of life, and motor impairment in patients with Parkinson's disease. This study was conducted as an open-label randomized controlled trial (ISRCTN26292510) with repeated measures. Forty patients with Parkinson's disease stages 2 to 3 according to the Hoehn and Yahr Scale were randomly allocated to either an Ai Chi exercise group or a land-based exercise control group for 5 weeks. Balance was measured using the Biodex-3,1 and the Berg Balance Scale. Functional mobility was evaluated using the Timed Up and Go Test. Additionally, health-related quality of life and motor activity were assessed with the Parkinson's Disease Questionnaire-39 and the Unified Parkinson's Disease Rating Scale-III. Although patients in both groups showed significant improvement in all outcome variables, improvement of dynamic balance was significantly greater in the Ai Chi group (p Parkinson's Disease Questionnaire-39 (p Parkinson's Disease Rating Scale-III (p Parkinson's disease. Implications for rehabilitation Ai Chi exercises (aquatic exercises) may help improve balance, functional mobility, health-related quality of life, and motor ability in patients with mild to moderate Parkinson's disease more efficiently than similar land-based exercises. Ai Chi exercises should be considered as a rehabilitation option for treatment of patients with mild or moderate Parkinson's disease.

  12. Neuroprotective profile of pyruvate against ethanol-induced neurodegeneration in developing mice brain.

    Science.gov (United States)

    Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Kim, Tae Hyun; Lee, Hae Young; Kim, Myeong Ok

    2013-12-01

    Exposure to ethanol during developmental stages leads to several types of neurological disorders. Apoptotic neurodegeneration due to ethanol exposure is a main feature in alcoholism. Exposure of developing animals to alcohol induces apoptotic neuronal death and causes fetal alcohol syndrome. In the present study, we observed the possible protective effect of pyruvate against ethanol-induced neurodegeneration. Exposure of developing mice to ethanol (2.5 g/kg) induces apoptotic neurodegeneration and widespread neuronal cell death in the cortex and thalamus. Co-treatment of pyruvate (500 mg/kg) protects neuronal cell against ethanol by the reduced expression of caspase-3 in these brain regions. Immunohistochemical analysis and TUNNEL at 24 h showed that apoptotic cell death induced by ethanol in the cortex and thalamus is reduced by pyruvate. Histomorphological analysis at 24 h with cresyl violet staining also proved that pyruvate reduced the number of neuronal cell loss in the cortex and thalamus. The results showed that ethanol increased the expression of caspase-3 and thus induced apoptotic neurodegeneration in the developing mice cortex and thalamus, while co-treatment of pyruvate inhibits the induction of caspase-3 and reduced the cell death in these brain regions. These findings, therefore, showed that treatment of pyruvate inhibits ethanol-induced neuronal cell loss in the postnatal seven (P7) developing mice brain and may appear as a safe neuroprotectant for treating neurodegenerative disorders in newborns and infants.

  13. Structure and preventive effects against ethanol-induced gastric ulcer of an expolysaccharide from Lachnum sp.

    Science.gov (United States)

    Xu, Ping; Yang, Liu; Yuan, Ru-Yue; Ye, Zi-Yang; Ye, Hui-Ran; Ye, Ming

    2016-05-01

    An extracellular polysaccharide of Lachnum sp. (LEP) was purified by DEAE-cellulose 52 column chromatography and Sepharose CL-6B column chromatography. LEP-2a was identified to be a homogeneous component with an average molecular weight of 3.22 × 10(4)Da. The structure of LEP-2a was characterized by chemical and spectroscopic methods, including methylation analysis, periodate oxidation-smith degradation, infrared spectroscopy and NMR analysis. Results indicated that LEP-2a was a (1→3)-,(1→6)-β-D-Glcp, whose branch chain was consist of two d-glucopyranosyl residues linked by β-1,3-glycosidic linkage, which was linked at C6 of the backbone chain by β-1,6-glycosidic linkage. To study the protective effects of LEP-2a on the ethanol-induced gastric ulcer in mice, LEP-2a (100, 200 and 400mg/kg/d) was given to mice by gavage for 2 weeks. Results showed that LEP-2a significantly decreased the ulcer bleeding areas, pepsin activity, gastric juice volume, gastric juice total acidity and the malondialdehyde (MDA) content in serum. Meanwhile, the superoxide dismutase (SOD) increased significantly. The above findings suggested that LEP-2a had a significant preventive effect against the ethanol-induced gastric ulcer. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Protective effect of [6]-gingerol on the ethanol-induced teratogenesis of cultured mouse embryos.

    Science.gov (United States)

    Yon, Jung-Min; Baek, In-Jeoung; Lee, Se-Ra; Kim, Mi-Ra; Hong, Jin Tae; Yong, Hwanyul; Lee, Beom Jun; Yun, Young Won; Nam, Sang-Yoon

    2012-01-01

    Excessive ethanol consumption during pregnancy causes fetal alcohol syndrome. We investigated the effect of [6]-gingerol on ethanol-induced embryotoxicity using a whole embryo culture system. The morphological changes of embryos and the gene expression patterns of the antioxidant enzymes cytosolic glutathione peroxidase (cGPx), cytoplasmic Cu/Zn superoxide dismutase (SOD1), and Mn-SOD (SOD2), and SOD activity were examined in the cultured mouse embryos exposed to ethanol (5 μL/3 mL) and/or [6]-gingerol (1×10(-8) or 1×10(-7) μg/mL) for 2 days. In ethanol-exposed embryos, the standard morphological score of embryos was significantly decreased compared with those of the control (vehicle) group. However, cotreatment of embryos with [6]-gingerol and ethanol significantly improved all of the developmental parameters except crownrump length and head length, compared with those of the ethanol alone group. The mRNA expression levels of cGPx and SOD2, not SOD1, were decreased consistently, SOD activity were significantly decreased compared with the control group. However, the decreases in mRNA levels of antioxidant enzymes and SOD activity were significantly restored to the control levels by [6]-gingerol supplement. These results indicate that [6]-gingerol has a protective effect against ethanol-induced teratogenicity during mouse embryogenesis.

  15. Protective effects of pogostone from Pogostemonis Herba against ethanol-induced gastric ulcer in rats.

    Science.gov (United States)

    Chen, Haiming; Liao, Huijun; Liu, Yuhong; Zheng, Yifeng; Wu, Xiaoli; Su, Zuqing; Zhang, Xie; Lai, Zhengquan; Lai, Xiaoping; Lin, Zhi-Xiu; Su, Ziren

    2015-01-01

    We examined the protective effect of pogostone (PO), a chemical constituent isolated from Pogostemonis Herba, on the ethanol-induced gastric ulcer in rats. Administration of PO at doses of 10, 20 and 40 mg/kg body weight prior to ethanol ingestion effectively protected the stomach from ulceration. The gastric lesions were significantly ameliorated by all doses of PO as compared to the vehicle group. Pre-treatment with PO prevented the oxidative damage and the decrease of prostaglandin E2 (PGE2) content. In addition, PO pretreatment markedly increased the mucosa levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and decreased gastric malonaldehyde (MDA), relative to the vehicle group. In the mechanistic study, significant elevation of non-protein-sulfhydryl (NP-SH) was observed in the gastric mucosa pretreated by PO. Analysis of serum cytokines indicated that PO pretreatment obviously elevated the decrease of interleukin-10 (IL-10) level, while markedly mitigated the increment of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretions in ethanol-induced rats. Taken together, these results strongly indicate that PO could exert a gastro-protective effect against gastric ulceration, and the underlying mechanism might be associated with the stimulation of PGE2, improvement of antioxidant and anti-inflammatory status, as well as preservation of NP-SH. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Hepatoprotective effect of aqueous extract of Aframomum melegueta on ethanol-induced toxicity in rats.

    Science.gov (United States)

    Nwozo, Sarah O; Oyinloye, Babatunji E

    2011-01-01

    In recent years there have been remarkable developments in the prevention of diseases, especially with regards to the role of free radicals and antioxidants. Ethanol-induced oxidative stress appears to be one mechanism by which ethanol causes liver injury. The protective effect of aqueous plant extract of Aframomum melegueta on ethanol-induced toxicity was investigated in male Wistar rats. The rats were treated with 45 % ethanol (4.8 g/kg b.w.t.) for 16 days to induce alcoholic diseases in the liver. The activities of alanine aminotransferase, aspartate aminotransferase and triglyceride were monitored and the histological changes in liver examined in order to evaluate the protective effects of the plant extract. Hepatic malondialdehyde and reduced glutathione, as well as superoxide dismutase and glutathione-S-transferase activities were determined for the antioxidant status. Chronic ethanol administration resulted in a statistically significant elevation of serum alanine aminotransferases and triglyceride levels, as well as a decrease in reduced glutathione and superoxide dismutase which was dramatically attenuated by the co-administration of the plant extract. Histological changes were related to these indices. Co-administration of the plant extract suppressed the elevation of lipid peroxidation, restored the reduced glutathion, and enhanced the superoxide dismutase activity. These results highlight the ability of Aframomum melegueta to ameliorate oxidative damage in the liver and the observed effects are associated with its antioxidant activities.

  17. Camellia sinensis (L. Kuntze Extract Ameliorates Chronic Ethanol-Induced Hepatotoxicity in Albino Rats

    Directory of Open Access Journals (Sweden)

    Poonam Lodhi

    2014-01-01

    Full Text Available The goal of this study was to investigate the hepatoprotective effects of aqueous extract of Camellia sinensis or green tea extract (AQGTE in chronic ethanol-induced albino rats. All animals were divided into 4 groups in the study for a 5-week duration. 50% ethanol was given orally to the rats with two doses (5 mg/kg bw and 10 mg/kg bw of AQGTE. Ethanol administration caused a significant increase in the levels of plasma and serum enzymatic markers, alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP, and nonenzymatic markers (cholesterol and triglycerides, lipid peroxidation contents, malondialdehyde (MDA, and glutathione-S-transferase (GST, and decreased the activities of total proteins, albumin, and cellular antioxidant defense enzymes such as superoxide dismutase (SOD. The elevation and reduction in these biochemical enzymes caused the damage in hepatocytes histologically due to the high production of ROS, which retards the antioxidant defense capacity of cell. AQGTE was capable of recovering the level of these markers and the damaged hepatocytes to their normal structures. These results support the suggestion that AQGTE was able to enhance hepatoprotective and antioxidant effects in vivo against ethanol-induced toxicity.

  18. 1,8-cineol, a food flavoring agent, prevents ethanol-induced gastric injury in rats.

    Science.gov (United States)

    Santos, F A; Rao, V S

    2001-02-01

    This study investigated the gastroptrotective effect of 1,8-cineole (cineole) on ethanol-induced gastric mucosal damage in rats and the possible mechanisms involved. 1,8-Cineole (50-200 mg/kg), given orally 1 hr before administration of 1 ml of absolute ethanol significantly attenuated the ethanol-induced gastric injury in a manner similar to nordihydroguairetic acid, a known lipoxygenase inhibitor. 1,8-Cineole showed a tendency to restore the ethanol-associated decreases in nonprotein sulfhydryls, suggesting a possible antioxidant effect. In gastric secretion studies, 1,8-cineole, similar to cimetidine, a known histamine-2 receptor antagonist, demonstrated significant inhibitions of both gastric juice volume as well as total acid output. The protection offered by 1,8-cineole was found to be unaltered by 8-phenyltheophylline or L-NAME, indicating that its effect is not mediated by endogenous adenosine or nitric oxide. These results, taken together with the earlier reports, suggest that the antioxidant and lipoxygenase inhibitory actions of 1,8-cineole are of prime importance in affording gastroprotection against ethanol injury in the rat.

  19. Protective effect of arctigenin on ethanol-induced neurotoxicity in PC12 cells.

    Science.gov (United States)

    Huang, Jia; Xiao, Lan; Wei, Jing-Xiang; Shu, Ya-Hai; Fang, Shi-Qi; Wang, Yong-Tang; Lu, Xiu-Min

    2017-04-01

    As a neurotropic substance, ethanol can damage nerve cells through an increase in the production of free radicals, interference of neurotrophic factor signaling pathways, activation of endogenous apoptotic signals and other molecular mechanisms. Previous studies have revealed that a number of natural drugs extracted from plants offer protection of nerve cells from damage. Among these, arctigenin (ATG) is a lignine extracted from Arctium lappa (L.), which has been found to exert a neuroprotective effect on scopolamine‑induced memory deficits in mice with Alzheimer's disease and glutamate-induced neurotoxicity in primary neurons. As a result, it may offer beneficial effects on ethanol-induced neurotoxicity. However, the effects of ATG on ethanol‑induced nerve damage remain to be elucidated. To address this issue, the present study used rat pheochromocytoma PC12 cells to investigate the neuroprotective effects of ATG on ethanol-induced cell damage by performing an MTT reduction assay, cell cycle analysis, Hoechst33342/propidium iodide fluorescence staining and flow cytometry to examine apoptosis. The results showed that 10 µM ATG effectively promoted the proliferation of damaged cells, and increased the distribution ratio of the cells at the G2/M and S phases (P<0.05). In addition, the apoptosis and necrosis of the PC12 cells were significantly decreased following treatment with ATG. Therefore, it was concluded that 10 µM ATG had a protective effect on ethanol‑induced injury in PC12 cells.

  20. Gastroprotective effects of CoQ10 on ethanol-induced acute gastric lesions.

    Science.gov (United States)

    Karakaya, K; Barut, F; Hanci, V; Can, M; Comert, M; Ucan, H B; Cakmak, G K; Irkorucu, O; Tascilar, O; Emre, A U

    2015-01-01

    Alcohol consumption is frequently associated with gastric mucosal lesions. The purpose of this study was to determine the effect of Coenzyme-Q10 (CoQ10) supplementation on the ethanol-induced gastric mucosal damage in a rat model. Sixty-four female wistar albino rats were randomly divided into 8 groups (n = 8). Studies were performed in ethanol induced gastric ulcer model in Wistar albino rats. Famotidine at a dose of 5 mg/kg or 20 mg/kg and CoQ10 at a single dose of 10 mg/kg or 20 mg/kg and 30 mg/kg for 7 days were administered as pretreatment. All the rats in study groups received 2 ml/kg ethanol 95 % intragastrically, 30 minutes after pretreatment. Four hour after ethanol administration, all rats were sacrificed and their stomachs were removed under ketamin anaesthesia. Gastric protection was evaluated by measuring the ulcer index, MDA concentrations, and histopathological studies. Rats pretreated either with famotidine or CoQ10 had significantly diminished gastric mucosal damage which was assessed with gross and microscopic analysis (p < 0.00625). MDA levels were significantly lower in famotidine 20 mg/kg and CoQ10 pretreatment for 7 days group (p < 0.00625).

  1. Influence of aging on ethanol-induced oxidative stress in digestive tract of rats.

    Science.gov (United States)

    Vucević, D; Mladenović, D; Ninković, M; Stanković, Mn; Jorgacević, B; Stanković, Ms; de Luka, S; Radosavljević, T

    2013-07-01

    Aging and ethanol induce oxidative stress due to increased prooxidant production and decreased antioxidative capacity. The aim was to investigate the influence of aging on oxidative stress in liver, stomach and pancreas in acute ethanol intoxication. Adult (3 months) and old (18 months) male Wistar rats were divided into the following groups: control (control group rats aged 3 months (C3) and control group rats aged 18 months (C18)) and ethanol-treated groups (ethanol-treated 3-month-old rats (E3) and ethanol-treated 18-month-old rats (E18)). Ethanol was administered in five doses of 2 g/kg at 12-h intervals by orogastric tube. Tissue samples were collected for the determination of oxidative stress parameters. Malondialdehyde (MDA) concentration was increased in all the experimental groups and investigated organs versus C3 group ( p Aging potentiates ethanol-induced oxidative stress in liver, stomach and pancreas due to increased lipid peroxidation and nitrosative stress and decreased antioxidative tissue capacity.

  2. Gastroprotective Effects of Sulphated Polysaccharides from the Alga Caulerpa mexicana Reducing Ethanol-Induced Gastric Damage

    Directory of Open Access Journals (Sweden)

    José Gerardo Carneiro

    2018-01-01

    Full Text Available The development of the gastric lesion is complex and the result of the imbalance between aggressive and protective factors, involving the generation of free radicals and disturbance in nitric oxide (NO production. Sulphated polysaccharides (SP, from marine algae, are widely used in biotechnological and pharmaceutical areas. In this study, we evaluated the effects of SP from the green marine alga Caulerpa mexicana (Cm-SP in ethanol-induced gastric damage models in mice. Cm-SP (2, 20, or 200 mg/kg, administered p.o., significantly reduced gastric damage, and these effects were inhibited through pretreatment with indomethacin. Cm-SP (200 mg/kg prevented the ethanol-induced decline in glutathione and restored its normal level. Moreover, it was able to normalize the elevated thiobarbituric acid reactive substance levels. However, Cm-SP did not show any significant effects on NO2/NO3 level, when compared to the ethanol group. The pretreatment with L- NAME induced gastric mucosal damage and did not inhibit the gastroprotective effect of Cm-SP (200 mg/kg. In conclusion, the gastroprotective effects of Cm-SP in mice involve prostaglandins and reduction in the oxidative stress and are independent of NO.

  3. Gastroprotective Effects of Sulphated Polysaccharides from the Alga Caulerpa mexicana Reducing Ethanol-Induced Gastric Damage.

    Science.gov (United States)

    Carneiro, José Gerardo; Holanda, Ticiana de Brito Lima; Quinderé, Ana Luíza Gomes; Frota, Annyta Fernandes; Soares, Vitória Virgínia Magalhães; Sousa, Rayane Siqueira de; Carneiro, Manuela Araújo; Martins, Dainesy Santos; Gomes Duarte, Antoniella Souza; Benevides, Norma Maria Barros

    2018-01-20

    The development of the gastric lesion is complex and the result of the imbalance between aggressive and protective factors, involving the generation of free radicals and disturbance in nitric oxide (NO) production. Sulphated polysaccharides (SP), from marine algae, are widely used in biotechnological and pharmaceutical areas. In this study, we evaluated the effects of SP from the green marine alga Caulerpa mexicana (Cm-SP) in ethanol-induced gastric damage models in mice. Cm-SP (2, 20, or 200 mg/kg), administered p.o., significantly reduced gastric damage, and these effects were inhibited through pretreatment with indomethacin. Cm-SP (200 mg/kg) prevented the ethanol-induced decline in glutathione and restored its normal level. Moreover, it was able to normalize the elevated thiobarbituric acid reactive substance levels. However, Cm-SP did not show any significant effects on NO₂/NO₃ level, when compared to the ethanol group. The pretreatment with L- NAME induced gastric mucosal damage and did not inhibit the gastroprotective effect of Cm-SP (200 mg/kg). In conclusion, the gastroprotective effects of Cm-SP in mice involve prostaglandins and reduction in the oxidative stress and are independent of NO.

  4. The Influence of Motor Impairment on Autonomic Heart Rate Modulation among Children with Cerebral Palsy

    Science.gov (United States)

    Zamuner, Antonio Roberto; Cunha, Andrea Baraldi; da Silva, Ester; Negri, Ana Paola; Tudella, Eloisa; Moreno, Marlene Aparecida

    2011-01-01

    The study of heart rate variability is an important tool for a noninvasive evaluation of the neurocardiac integrity. The present study aims to evaluate the autonomic heart rate modulation in supine and standing positions in 12 children diagnosed with cerebral palsy and 16 children with typical motor development (control group), as well as to…

  5. Pistachio supplementation attenuates motor and cognition impairments induced by cisplatin or vincristine in rats

    Directory of Open Access Journals (Sweden)

    Leila Golchin

    2015-01-01

    Conclusion: We conclude that pistachio in the diet following anticancer drugs such as cisplatin and vincristine might have a protective effect against anticancer drug-induced disruptions in motor and cognitive function. However, further studies are needed to elucidate the exact mechanisms of this protective effect of pistachio.

  6. Motor nervous system impairment persists in long-term survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Lehtinen, Satu S; Huuskonen, Usko E; Harila-Saari, Arja H; Tolonen, Uolevi; Vainionpää, Leena K; Lanning, B Marjatta

    2002-05-01

    The objective of the current study was to determine whether therapy for childhood acute lymphoblastic leukemia (ALL) results in long-lasting neurologic signs or electrophysiologic injuries within the motor tracts. Twenty-seven children who were treated for ALL were studied clinically 5 years after the cessation of therapy by means of motor-evoked potentials (MEPs) elicited by magnetic stimulation transcranially and peripherally. An equal number of healthy children matched with regard to age, gender, and height served as the control group. The MEP latencies to the hands and legs elicited by stimulation at the cortex were prolonged significantly in the children treated for ALL compared with the control group, with the differences being 2.2 milliseconds [ms] (P motor difficulties and dysdiadochokinesia. Neurologic signs still persisted 5 years after therapy for ALL. Approximately 33% of the patients had fine or gross motor difficulties and dysdiadochokinesia, and demyelinative injuries to the peripheral nerve tracts were found proximally but not within the central nervous system. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10503

  7. Farnesoid X receptor regulates forkhead Box O3a activation in ethanol-induced autophagy and hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Sharon Manley

    2014-01-01

    Full Text Available Alcoholic liver disease encompasses a wide spectrum of pathogenesis including steatosis, fibrosis, cirrhosis, and alcoholic steatohepatitis. Autophagy is a lysosomal degradation process that degrades cellular proteins and damaged/excess organelles, and serves as a protective mechanism in response to various stresses. Acute alcohol treatment induces autophagy via FoxO3a-mediated autophagy gene expression and protects against alcohol-induced steatosis and liver injury in mice. Farnesoid X Receptor (FXR is a nuclear receptor that regulates cellular bile acid homeostasis. In the present study, wild type and FXR knockout (KO mice were treated with acute ethanol for 16 h. We found that ethanol treated-FXR KO mice had exacerbated hepatotoxicity and steatosis compared to wild type mice. Furthermore, we found that ethanol treatment had decreased expression of various essential autophagy genes and several other FoxO3 target genes in FXR KO mice compared with wild type mice. Mechanistically, we did not find a direct interaction between FXR and FoxO3. Ethanol-treated FXR KO mice had increased Akt activation, increased phosphorylation of FoxO3 resulting in decreased FoxO3a nuclear retention and DNA binding. Furthermore, ethanol treatment induced hepatic mitochondrial spheroid formation in FXR KO mice but not in wild type mice, which may serve as a compensatory alternative pathway to remove ethanol-induced damaged mitochondria in FXR KO mice. These results suggest that lack of FXR impaired FoxO3a-mediated autophagy and in turn exacerbated alcohol-induced liver injury.

  8. Post-retrieval propranolol treatment does not modulate reconsolidation or extinction of ethanol-induced conditioned place preference.

    Science.gov (United States)

    Font, Laura; Cunningham, Christopher L

    2012-04-01

    The reconsolidation hypothesis posits that established emotional memories, when reactivated, become labile and susceptible to disruption. Post-retrieval injection of propranolol (PRO), a nonspecific β-adrenergic receptor antagonist, impairs subsequent retention performance of a cocaine- and a morphine-induced conditioned place preference (CPP), implicating the noradrenergic system in the reconsolidation processes of drug-seeking behavior. An important question is whether post-retrieval PRO disrupts memory for the drug-cue associations, or instead interferes with extinction. In the present study, we evaluated the role of the β-adrenergic system on the reconsolidation and extinction of ethanol-induced CPP. Male DBA/2J mice were trained using a weak or a strong conditioning procedure, achieved by varying the ethanol conditioning dose (1 or 2 g/kg) and the number of ethanol trials (2 or 4). After acquisition of ethanol CPP, animals were given a single post-retrieval injection of PRO (0, 10 or 30 mg/kg) and tested for memory reconsolidation 24 h later. Also, after the first reconsolidation test, mice received 18 additional 15-min choice extinction tests in which PRO was injected immediately after every test. Contrary to the prediction of the reconsolidation hypothesis, a single PRO injection after the retrieval test did not modify subsequent memory retention. In addition, repeated post-retrieval administration of PRO did not interfere with extinction of CPP in mice. Overall, our data suggest that the β-adrenergic receptor does not modulate the associative processes underlying ethanol CPP. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Identifying and treating phonological and motor errors in acquired speech impairment

    Directory of Open Access Journals (Sweden)

    Adam Buchwald

    2015-04-01

    Table 1 presents the results from both components of this analysis. The two individuals who produced phonological processing errors (i.e., singleton timing did not change in accuracy at post-test. The three other individuals whose errors indicated motor planning errors (i.e., cluster timing improved their cluster production accuracy for trained and untrained words (M1, M2 or substantially decreased their self-corrections. Discussion This study replicated and expanded on previous work indicating that the acoustic/articulatory properties of errors can help identify error types and predict responsiveness to treatment via repetition. These crucial findings are consistent with speech motor learning research (Maas et al., 2008 and suggest a promising direction for exploring the differential diagnosis and treatment of acquired sound production disorders.

  10. Selective, non-lateralized impairment of motor imagery following right parietal damage.

    Science.gov (United States)

    Danckert, James; Ferber, Susanne; Doherty, Timothy; Steinmetz, Helena; Nicolle, David; Goodale, Melvyn A

    2002-01-01

    Using variants of a visually guided pointing task, in which subjects make pointing movements towards targets of varying sizes, we explored motor imagery in a patient with visual neglect. When this patient actually pointed towards targets of different sizes he showed the normal correlation between movement duration (MD) and target size, such that MD increased as target size decreased. In contrast, his imagined movements did not show the same speed-accuracy trade-off observed for actual movements. This was true regardless of the hand used or the initial direction of movement (left versus right). The patient performed normally on several tasks of visual imagery, including size estimation, perceptual discrimination and localization of cities on an imagined map. This patient's performance suggests that the networks in the right parietal lobe play an important role in the generation of internal models of motor movements regardless of the hand used to perform the task.

  11. Short-term effects of vibration therapy on motor impairments in Parkinson's disease.

    Science.gov (United States)

    King, Lauren K; Almeida, Quincy J; Ahonen, Heidi

    2009-01-01

    Recent studies have suggested that vibration therapy may have a positive influence on motor symptoms in individuals with Parkinson's disease (PD). However, quantitative evidence of these benefits is scarce, and the concept of "whole-body" vibration in these studies is vague. The objectives of the current study were to evaluate the influence of vibration on motor symptoms and functional measures in PD by delivering sound waves to the entire body. We delivered whole body sound wave vibration to 40 individuals with PD using a Physioacoustic Chair, a piece of equipment with speakers spaced throughout the chair permitting a series of programmed low frequency sound waves through the body. Using a parallel cross-over design we utilized the Unified Parkinson's Disease Rating Scale (UPDRS), quantitative gait assessments, and a grooved pegboard for upper limb control. Improvements were seen in all symptom, motor control and functional outcome measures at the time of assessment. Specifically, a significant decrease in rigidity, and tremor were shown, as well as a significant increase in step length and improved speed on the grooved pegboard task. Results of this initial investigation provide support for vibration therapy as a non-pharmacological treatment alternative. Long-term benefits of vibration therapy will require further research.

  12. Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort

    DEFF Research Database (Denmark)

    Ryberg, C; Rostrup, E; Paulson, O B

    2011-01-01

    The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS......) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive...

  13. Homocysteine aggravates ROS-induced depression of transmitter release from motor nerve terminals: potential mechanism of peripheral impairment in motor neuron diseases associated with hyperhomocysteinemia

    Directory of Open Access Journals (Sweden)

    Ellya eBukharaeva

    2015-10-01

    Full Text Available Homocysteine (HCY is a pro-inflammatory sulphur-containing redox active endogenous amino acid, which concentration increases in neurodegenerative disorders including amyotrophic lateral sclerosis (ALS. A widely held view suggests that HCY could contribute to neurodegeneration via promotion of oxidative stress. However, the action of HCY on motor nerve terminals has not been investigated so far. We previously reported that oxidative stress inhibited synaptic transmission at the neuromuscular junction, targeting primarily the motor nerve terminals. In the current study, we investigated the effect of HCY on oxidative stress-induced impairment of transmitter release at the mouse diaphragm muscle. The mild oxidant H2O2 decreased the intensity of spontaneous quantum release from nerve terminals (measured as the frequency of miniature endplate potentials, MEPPs without changes in the amplitude of MEPPs, indicating a presynaptic effect. Pre-treatment with HCY for 2 h only slightly affected both amplitude and frequency of MEPPs but increased the inhibitory potency of H2O2 almost two fold. As HCY can activate certain subtypes of glutamate NMDA receptors we tested the role of NMDA receptors in the sensitizing action of HCY. Remarkably, the selective blocker of NMDA receptors, AP-5 completely removed the sensitizing effect of HCY on the H2O2-induced presynaptic depressant effect. Thus, at the mammalian neuromuscular junction HCY largely increases the inhibitory effect of oxidative stress on transmitter release, via NMDA receptors activation. This combined effect of HCY and local oxidative stress can specifically contribute to the damage of presynaptic terminals in neurodegenerative motoneuron diseases, including ALS.

  14. Gross motor function in children with spastic Cerebral Palsy and Cerebral Visual Impairment: A comparison between outcomes of the original and the Cerebral Visual Impairment adapted Gross Motor Function Measure-88 (GMFM-88-CVI).

    Science.gov (United States)

    Salavati, M; Rameckers, E A A; Waninge, A; Krijnen, W P; Steenbergen, B; van der Schans, C P

    2017-01-01

    To investigate whether the adapted version of the Gross Motor Function Measure-88 (GMFM-88) for children with Cerebral Palsy (CP) and Cerebral Visual Impairment (CVI) results in higher scores. This is most likely to be a reflection of their gross motor function, however it may be the result of a better comprehension of the instruction of the adapted version. The scores of the original and adapted GMFM-88 were compared in the same group of children (n=21 boys and n=16 girls), mean (SD) age 113 (30) months with CP and CVI, within a time span of two weeks. A paediatric physical therapist familiar with the child assessed both tests in random order. The GMFCS level, mental development and age at testing were also collected. The Wilcoxon signed-rank test was used to compare two different measurements (the original and adapted GMFM-88) on a single sample, (the same child with CP and CVI; pchildren with CP and CVI showed a positive difference in percentage score on at least one of the five dimensions and positive percentage scores for the two versions differed on all five dimensions for fourteen children. For six children a difference was seen in four dimensions and in 10 children difference was present in three dimensions (GMFM dimension A, B& C or C, D & E) (pchildren with CP and CVI that is not adversely impacted bytheir visual problems. On the basis of these findings, we recommend using the adapted GMFM-88 to measure gross motor functioning in children with CP and CVI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The wake-promoting drug Modafinil prevents motor impairment in sickness behavior induced by LPS in mice

    DEFF Research Database (Denmark)

    Zager, Adriano; Brandão, Wesley Nogueira; Margatho, Rafael Oliveira

    2018-01-01

    blockage of the dopaminergic D1R by the drug SCH-23390 counteracted the effect of Modafinil on locomotion and anxiety-like behavior, but not on depressive-like behavior and brain immune cells. The dopaminergic D1 receptor signaling is essential to the Modafinil effects on LPS-induced alterations......The wake-promoting drug Modafinil has been used for many years for treatment of Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related psychostimulant action. Recent studies have indicated that Modafinil prevents neuroinflammation in animal models. Thus, the aim of the present study...... to the open field and elevated plus maze test 2h later. After 24h, mice were subjected to tail suspension test, followed by either flow cytometry with whole brain for CD11b+CD45+ cells or qPCR in brain areas for cytokine gene expression. Modafinil treatment prevented the LPS-induced motor impairment, anxiety...

  16. Intravenous immunoglobulin (IVIg) with methylprednisolone pulse therapy for motor impairment of neuralgic amyotrophy: clinical observations in 10 cases.

    Science.gov (United States)

    Naito, Ko-suke; Fukushima, Kazuhiro; Suzuki, Seiko; Kuwahara, Motoi; Morita, Hiroshi; Kusunoki, Susumu; Ikeda, Shu-ichi

    2012-01-01

    Neuralgic amyotrophy (NA) is a distinct peripheral nervous system disorder characterized by attacks of acute neuropathic pain and rapid multifocal weakness and atrophy unilaterally in the upper limb. The current hypothesis is that the episodes are caused by an immune-mediated response to the brachial plexus, however, therapeutic strategies for NA have not been well established. We retrospectively reviewed 15 case series of NA; 10 of the 15 patients received intravenous immunoglobulin (IVIg) with methylprednisolone pulse therapy (MPPT) and 9 of these 0 patients showed clinical improvement of motor impairment. Our clinical observations do not contradict the possibility that IVIg with MPPT may be one of the potential therapeutics for NA, however the efficacy remains to be established. Further confirmatory trials are needed in patients with various clinical severities and phases of NA. Further basic research and confirmatory trials should be performed to survey the efficacy of such immunomodulation therapy for NA.

  17. Genetic impairment of parasite myosin motors uncovers the contribution of host cell membrane dynamics to Toxoplasma invasion forces.

    Science.gov (United States)

    Bichet, Marion; Touquet, Bastien; Gonzalez, Virginie; Florent, Isabelle; Meissner, Markus; Tardieux, Isabelle

    2016-11-09

    The several-micrometer-sized Toxoplasma gondii protozoan parasite invades virtually any type of nucleated cell from a warm-blooded animal within seconds. Toxoplasma initiates the formation of a tight ring-like junction bridging its apical pole with the host cell membrane. The parasite then actively moves through the junction into a host cell plasma membrane invagination that delineates a nascent vacuole. Recent high resolution imaging and kinematics analysis showed that the host cell cortical actin dynamics occurs at the site of entry while gene silencing approaches allowed motor-deficient parasites to be generated, and suggested that the host cell could contribute energetically to invasion. In this study we further investigate this possibility by analyzing the behavior of parasites genetically impaired in different motor components, and discuss how the uncovered mechanisms illuminate our current understanding of the invasion process by motor-competent parasites. By simultaneously tracking host cell membrane and cortex dynamics at the site of interaction with myosin A-deficient Toxoplasma, the junction assembly step could be decoupled from the engagement of the Toxoplasma invasive force. Kinematics combined with functional analysis revealed that myosin A-deficient Toxoplasma had a distinct host cell-dependent mode of entry when compared to wild-type or myosin B/C-deficient Toxoplasma. Following the junction assembly step, the host cell formed actin-driven membrane protrusions that surrounded the myosin A-deficient mutant and drove it through the junction into a typical vacuole. However, this parasite-entry mode appeared suboptimal, with about 40 % abortive events for which the host cell membrane expansions failed to cover the parasite body and instead could apply deleterious compressive forces on the apical pole of the zoite. This study not only clarifies the key contribution of T. gondii tachyzoite myosin A to the invasive force, but it also highlights a new mode

  18. Brain Damage and Motor Cortex Impairment in Chronic Obstructive Pulmonary Disease: Implication of Nonrapid Eye Movement Sleep Desaturation.

    Science.gov (United States)

    Alexandre, Francois; Heraud, Nelly; Sanchez, Anthony M J; Tremey, Emilie; Oliver, Nicolas; Guerin, Philippe; Varray, Alain

    2016-02-01

    Nonrapid eye movement (NREM) sleep desaturation may cause neuronal damage due to the withdrawal of cerebrovascular reactivity. The current study (1) assessed the prevalence of NREM sleep desaturation in nonhypoxemic patients with chronic obstructive pulmonary disease (COPD) and (2) compared a biological marker of cerebral lesion and neuromuscular function in patients with and without NREM sleep desaturation. One hundred fifteen patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 2 and 3), resting PaO2 of 60-80 mmHg, aged between 40 and 80 y, and without sleep apnea (apnea-hypopnea index sleep recordings. In addition, twenty-nine patients (substudy) were assessed i) for brain impairment by serum S100B (biological marker of cerebral lesion), and ii) for neuromuscular function via motor cortex activation and excitability and maximal voluntary quadriceps strength measurement. A total of 51.3% patients (n = 59) had NREM sleep desaturation (NREMDes). Serum S100B was higher in the NREMDes patients of the substudy (n = 14): 45.1 [Q1: 37.7, Q3: 62.8] versus 32.9 [Q1: 25.7, Q3: 39.5] pg.ml(-1) (P = 0.028). Motor cortex activation and excitability were lower in NREMDes patients (both P = 0.03), but muscle strength was comparable between groups (P = 0.58). Over half the nonhypoxemic COPD patients exhibited NREM sleep desaturation associated with higher values of the cerebral lesion biomarker and lower neural drive reaching the quadriceps during maximal voluntary contraction. The lack of muscle strength differences between groups suggests a compensatory mechanism(s). Altogether, the results are consistent with an involvement of NREM sleep desaturation in COPD brain impairment. The study was registered at www.clinicaltrials.gov as NCT01679782. © 2016 Associated Professional Sleep Societies, LLC.

  19. Protection of hepatotoxicity using Spondias pinnata by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers in Wistar rats

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    Shoaib Shadab Iqbal

    2016-12-01

    Conclusion: S. pinnata extracts AE and EE possess a potent hepatoprotective effect against ethanol-induced liver injury in Wistar rats, and protect them from hepatotoxicity by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers.

  20. Involvement of the N-methyl-d-aspartate receptor GluN2D subunit in phencyclidine-induced motor impairment, gene expression, and increased Fos immunoreactivity

    Science.gov (United States)

    2013-01-01

    Background Noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists evoke a behavioral and neurobiological syndrome in experimental animals. We previously reported that phencyclidine (PCP), an NMDA receptor antagonist, increased locomotor activity in wildtype (WT) mice but not GluN2D subunit knockout mice. Thus, the aim of the present study was to determine whether the GluN2D subunit is involved in PCP-induced motor impairment. Results PCP or UBP141 (a GluN2D antagonist) induced potent motor impairment in WT mice but not GluN2D KO mice. By contrast, CIQ, a GluN2C/2D potentiator, induced severe motor impairment in GluN2D KO mice but not WT mice, suggesting that the GluN2D subunit plays an essential role in the effects of PCP and UBP141, and an appropriate balance between GluN2C and GluN2D subunits might be needed for appropriate motor performance. The level of the GluN2D subunit in the mature mouse brain is very low and restricted. GluN2D subunits exist in brainstem structures, the globus pallidus, thalamus, and subthalamic nucleus. We found that the expression of the c-fos gene increased the most among PCP-dependent differentially expressed genes between WT and GluN2D KO mice, and the number of Fos-positive cells increased after PCP administration in the basal ganglia motor circuit in WT mice but not GluN2D KO mice. Conclusion These results suggest that the GluN2D subunit within the motor circuitry is a key subunit for PCP-induced motor impairment, which requires an intricate balance between GluN2C- and GluN2D-mediated excitatory outputs. PMID:24330819

  1. Effect of motor cognition program for improving temporal-spatial timing memory ability with mild cognitive impairment patients.

    Science.gov (United States)

    Kim, Sooyeon

    2017-08-01

    This exploratory study evaluated motor cognition program for improving temporal-spatial timing memory ability with mild cognitive impairment (MCI) patients. The purpose was to explore the efficacies of motor cognition program according to practice methods, centering on coordination and observation pattern. Two practice methods were applied to the 40 MCI elder. In experiment 1, participants divided into two group as, one-hand practice group (n=20) and both-hands practice group (n=20). In experiment 2, participants divided into two group as, active observation group (n=20) and passive observation group (n=20). The participant was asked to alternatively press two buttons 6 times with the index finger hand with goal rhythm pattern (3,600 msec in total duration). In coordination pattern, bimanual practice was more effective for improving temporal-spatial timing memory ability than unilateral practice. In observation pattern, active observation showed better learning effect than passive observation. However, there was a learning effect even in passive observation pattern. Such a result claimed for the elderly, who has problem to do daily activity, could use observation of temporal-spatial timing task for improving cognitive ability.

  2. Children with Motor Impairments Play a Kinect Learning Game: First Findings from a Pilot Case in an Authentic Classroom Environment

    Directory of Open Access Journals (Sweden)

    Symeon Retalis

    2014-02-01

    Full Text Available This paper presents the first very positive findings from an empirical study about the effectiveness of the use of a Kinect learning game for children with gross motor skills problems and motor impairments. This game follows the principles of a newly presented approach, called Kinems, which advocates that special educators and therapists should use learning games that via embodied touchless interaction – thanks to the Microsoft Kinect camera- children with dyspraxia and other related disorders such as autism, Asperger's Syndrome, and Attention Deficit Disorder, can improve related skills. Several Kinems games have been proposed (http://www.kinems.com. These games are innovative and are played with hand and body gestures. Kinems suggests that games should be highly configurable so that a teacher can modify the settings (e.g. difficult level, time settings, etc. for the individual needs of each child. Also, a teacher should have access to kinetic and learning analytics of the child’s interaction progress and achievements should be safely stored and vividly presented.

  3. Voluntary Physical Exercise Improves Subsequent Motor and Cognitive Impairments in a Rat Model of Parkinson’s Disease

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    Shih-Chang Hsueh

    2018-02-01

    Full Text Available Background: Parkinson’s disease (PD is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegenerative disease. Methods: In this study, we investigated the long-term effects of voluntary running wheel exercise on gait phenotypes, depression, cognitive, rotational behaviors as well as histology in a 6-OHDA-lesioned rat model of PD. Results: We observed that, when compared with the non-exercise controls, five-week voluntary exercise alleviated and postponed the 6-OHDA-induced gait deficits, including a significantly improved walking speed, step/stride length, base of support and print length. In addition, we found that the non-motor functions, such as novel object recognition and forced swim test, were also ameliorated by voluntary exercise. However, the rotational behavior of the exercise group did not show significant differences when compared with the non-exercise group. Conclusions: We first analyzed the detailed spatiotemporal changes of gait pattern to investigate the potential benefits after long-term exercise in the rat model of PD, which could be useful for future objective assessment of locomotor function in PD or other neurological animal models. Furthermore, these results suggest that short-term voluntary exercise is sufficient to alleviate cognition deficits and depressive behavior in 6-OHDA lesioned rats and long-term treatment reduces the progression of motor symptoms and elevates tyrosine hydroxylase (TH, Brain-derived neurotrophic factor (BDNF, bone marrow tyrosine kinase in chromosome X (BMX protein expression level without affecting dopaminergic (DA neuron loss in this PD rat model.

  4. Protective effect of δ-amyrone against ethanol-induced gastric ulcer in mice.

    Science.gov (United States)

    Li, Weifeng; Yao, Huan; Niu, Xiaofeng; Wang, Yu; Zhang, Hailin; Li, Huani; Mu, Qingli

    2015-06-01

    The purpose of this study is to examine the protective effect of δ-amyrone on ethanol-induced gastric ulcer in mice. The mice intragastric administration 75% (0.5 mL/100g) ethanol was pretreated with δ-amyrone (4 and 8 mg/kg) and cimetidine (100 mg/kg) or vehicles in different experimental groups for a continuous three-day, and animals were euthanized 3h after ethanol ingestion. The gastric lesions were significantly attenuated by δ-amyrone (4 and 8 mg/kg) as compared to the ulcer control group. Pre-treatment with δ-amyrone prevented the myeloperoxidase (MPO) activity, production of nitric oxide (NO) in serum, expression of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) p65 protein expression. Analysis of cytokines in gastric tissue and serum of ethanol-induced mice showed the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased by δ-amyrone in response to NF-κB p65. These results suggested that δ-amyrone exerts its protective effect on experimental gastric ulcer by inhibiting NF-κB signaling pathways, which subsequently reduces overproduction of the inducible enzymes iNOS and suppresses the release of the inflammatory factors TNF-α, IL-6 and NO. Thus, δ-amyrone shows promise as a therapeutic agent in experimental gastric ulcer. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice.

    Science.gov (United States)

    Li, Wei-Feng; Hao, Ding-Jun; Fan, Ting; Huang, Hui-Min; Yao, Huan; Niu, Xiao-Feng

    2014-02-05

    The quaternary benzo[c]phenanthridine alkaloid, chelerythrine (CHE), is of great practical and research interest because of its pronounced, widespread physiological effects, primarily antimicrobial and anti-inflammatory, arising from its ability to interact with proteins and DNA. Although CHE was originally shown to possess anti-inflammatory properties, its effects on acute gastric ulcer have not been previously explored. The aim of the present study is to evaluate the protective effect of CHE on ethanol induced gastric ulcer in mice. Administration of CHE at doses of 1, 5 and 10mg/kg bodyweight prior to ethanol ingestion dose-dependently inhibited gastric ulcer. The gastric mucosal lesion was assessed by ulcer area, gastric juice acidity, myeloperoxidase (MPO) activities, macroscopic and histopathological examinations. CHE significantly reduced the gastric ulcer index, myeloperoxidase activities, macroscopic and histological score in a dose-dependent manner. In addition, CHE also significantly inhibited nitric oxide (NO) concentration, pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) level in serum and gastric mucosal in the mice exposed to ethanol induced ulceration in a dose-dependent manner. In addition, immunohistochemical analysis revealed that CHE markedly attenuated the overexpression of nuclear factor-κB in gastric mucosa of mice. It was concluded that CHE represents a potential therapeutic option to reduce the risk of gastric ulceration. In addition, acute toxicity study revealed no abnormal sign to the mice treated with CHE (15mg/kg). These findings suggest that the gastroprotective activity of CHE might contribute in adjusting the inflammatory cytokine by regulating the NF-κB signalling pathway. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Protective Effects of Hydrolyzed Nucleoproteins from Salmon Milt against Ethanol-Induced Liver Injury in Rats

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    Akiko Kojima-Yuasa

    2016-12-01

    Full Text Available Dietary nucleotides play a role in maintaining the immune responses of both animals and humans. Oral administration of nucleic acids from salmon milt have physiological functions in the cellular metabolism, proliferation, differentiation, and apoptosis of human small intestinal epithelial cells. In this study, we examined the effects of DNA-rich nucleic acids prepared from salmon milt (DNSM on the development of liver fibrosis in an in vivo ethanol-carbon tetrachloride cirrhosis model. Plasma aspartate transaminase and alanine transaminase were significantly less active in the DNSM-treated group than in the ethanol plus carbon tetrachloride (CCl4-treated group. Collagen accumulation in the liver and hepatic necrosis were observed histologically in ethanol plus CCl4-treated rats; however, DNSM-treatment fully protected rats against ethanol plus CCl4-induced liver fibrosis and necrosis. Furthermore, we examined whether DNSM had a preventive effect against alcohol-induced liver injury by regulating the cytochrome p450 2E1 (CYP2E1-mediated oxidative stress pathway in an in vivo model. In this model, CYP2E1 activity in ethanol plus CCl4-treated rats increased significantly, but DNSM-treatment suppressed the enzyme’s activity and reduced intracellular thiobarbituric acid reactive substances (TBARS levels. Furthermore, the hepatocytes treated with 100 mM ethanol induced an increase in cell death and were not restored to the control levels when treated with DNSM, suggesting that digestive products of DNSM are effective for the prevention of alcohol-induced liver injury. Deoxyadenosine suppressed the ethanol-induced increase in cell death and increased the activity of alcohol dehydrogenase. These results suggest that DNSM treatment represents a novel tool for the prevention of alcohol-induced liver injury.

  7. Comparison of Cannabidiol, Antioxidants, and Diuretics in Reversing Binge Ethanol-Induced Neurotoxicity

    Science.gov (United States)

    Hamelink, Carol; Hampson, Aidan; Wink, David A.; Eiden, Lee E.; Eskay, Robert L.

    2014-01-01

    Binge alcohol consumption in the rat induces substantial neurodegeneration in the hippocampus and entorhinal cortex. Oxidative stress and cytotoxic edema have both been shown to be involved in such neurotoxicity, whereas N-methyl-D-aspartate (NMDA) receptor activity has been implicated in alcohol withdrawal and excitoxic injury. Because the nonpsychoactive cannabinoid cannabidiol (CBD) was previously shown in vitro to prevent glutamate toxicity through its ability to reduce oxidative stress, we evaluated CBD as a neuroprotectant in a rat binge ethanol model. When administered concurrently with binge ethanol exposure, CBD protected against hippocampal and entorhinal cortical neurodegeneration in a dose-dependent manner. Similarly, the common antioxidants butylated hydroxytoluene and α-tocopherol also afforded significant protection. In contrast, the NMDA receptor antagonists dizocilpine (MK-801) and memantine did not prevent cell death. Of the diuretics tested, furosemide was protective, whereas the other two anion exchanger inhibitors, L-644,711 [(R)-(+)-(5,6-dichloro2,3,9,9a-tetrahydro 3-oxo-9a-propyl-1H-fluoren-7-yl)oxy acetic acid] and bumetanide, were ineffective. In vitro comparison of these diuretics indicated that furosemide is also a potent antioxidant, whereas the nonprotective diuretics are not. The lack of efficacy of L-644,711 and bumetanide suggests that the antioxidant rather than the diuretic properties of furosemide contribute most critically to its efficacy in reversing ethanol-induced neurotoxicity in vitro, in our model. This study provides the first demonstration of CBD as an in vivo neuroprotectant and shows the efficacy of lipophilic antioxidants in preventing binge ethanol-induced brain injury. PMID:15878999

  8. Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant enzyme activities in rats.

    Science.gov (United States)

    Alirezaei, Masoud; Dezfoulian, Omid; Neamati, Shima; Rashidipour, Marzyeh; Tanideh, Nader; Kheradmand, Arash

    2012-12-01

    Purified oleuropein from olive leaf extract has been shown to have antioxidant effects in our recent studies. Thus, the aim of this study was to assess the antioxidant abilities of oleuropein in comparison with ranitidine in ethanol-induced gastric damages via evaluation of ulcer index inhibition, antioxidant enzyme activities, and lipid peroxidation level. Fifty-six adult male Sprague-Dawley rats were divided into seven equal groups as follows: control group, ethanol group (absolute ethanol 1 ml/rat), oleuropein group (12 mg/kg), and oleuropein (6, 12, and 18 mg/kg) plus ethanol groups, as well as ranitidine (50 mg/kg) plus ethanol group. Pretreatment with oleuropein (12 and 18 mg/kg) significantly increased the ulcer index inhibition (percent), in comparison with oleuropein (6 mg/kg). Glutathione peroxidase (GPx) activity was significantly lower in the ethanol group when compared with the other groups whereas, treatment of rats with oleuropein (12 mg/kg) significantly increased glutathione content in gastric tissue when compared with the other groups, and lipid peroxidation was significantly reduced in the oleuropein- (12 and 18 mg/kg) and ranitidine-treated animals. Superoxide dismutase (SOD) and catalase (CAT) activities were both much higher in oleuropein-treated rats than the ethanol group, and although there was a moderate increase in SOD and CAT activities in ranitidine-treated rats, the differences were not significant. These findings suggest that oleuropein has beneficial antioxidant properties against ethanol-induced gastric damages in the rat. Therefore, it seems that a combination regimen including both antioxidant and antisecretory drugs may be beneficial in prevention of ethanol-mediated gastric mucosal damages.

  9. Gastroprotective effect of aucubin against ethanol-induced gastric mucosal injury in mice.

    Science.gov (United States)

    Yang, Yang; Yin, Bing; Lv, Le; Wang, Ziye; He, Jiao; Chen, Ziyang; Wen, Xin; Zhang, Yongmin; Sun, Wenji; Li, Yang; Zhao, Ye

    2017-11-15

    Aucubin, an iridoid glycoside, was isolated from seeds of Eucommia ulmoides Oliver. This study was aimed to evaluate the protective effect of aucubin against ethanol-induced gastric mucosal injury in mice. Mice were orally administrated with aucubin (20, 40 and 80mg/kg) for 3 consecutive days. On the 3rd day, the mice of gastric mucosal injury were induced with 70% ethanol after the last administration of aucubin. Gastric tissue of mice were submitted for evaluating the severity of gastric mucosal injury. The protective effect of aucubin was evaluated by the gastric ulcer index and histological examinations and determining the levels of inflammatory cytokines, oxidative stress and some gastric mucosal protection factors. Prophylactic oral administration of aucubin decreased gastric ulcer indexes and histological scores. A significant decrease of myeloperoxidase (MPO) activity and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were observed in aucubin administrated groups. In addition, mice administrated with aucubin increased glutathione (GSH) and heat shock protein-70 (HSP-70) levels and superoxide dismutase (SOD) activity, as well as normalized the levels of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and cyclooxygenase-1 (COX-1) in gastric tissue of mice. The findings of this study demonstrated that aucubin shows protective effect against ethanol-induced acute gastric mucosal injury through its anti-inflammatory and anti-oxidant effects. Furthermore, aucubin enhanced gastric mucosal protection by up-regulation of HSP-70 level and normalization of EGF, VEGF and COX-1 levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Ameliorative effect of Opuntia ficus indica juice on ethanol-induced oxidative stress in rat erythrocytes.

    Science.gov (United States)

    Alimi, Hichem; Hfaeidh, Najla; Bouoni, Zouhour; Sakly, Mohsen; Rhouma, Khémais Ben

    2013-05-01

    The aim of the present study was to investigate the efficacy of Opuntia ficus indica f. inermis fruit juice (OFIj) on reversing oxidative damages induced by chronic ethanol intake in rat erythrocytes. OFIj was firstly analyzed with HPLC for phenolic and flavonoids content. Secondly, 40 adult male Wistar rats were equally divided into five groups and treated for 90 days as follows: control (C), ethanol-only 3 g/kg body weight (b.w) (E), low dose of OFIj 2 ml/100 g b.w+ethanol (Ldj+E), high dose of OFIj 4 ml/100 g b.w+ethanol (Hdj+E), and only a high dose of OFIj 4 ml/100g b.w (Hdj). HPLC analysis indicated high concentrations of phenolic acids and flavonoids in OFIj. Ethanol treatment markedly decreased the activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and the level of reduced glutathione (GSH). Changes in the erythrocyte's antioxidant ability were accompanied by enhanced oxidative modification of lipids (increase of malondialdeyde level) and proteins (increase in carbonyl groups). Interestingly, pre-administration of either 2 ml/100 g b.w or 4 ml/100 g b.w of OFIj to ethanol-intoxicated rats significantly reversed decreases in enzymatic as well as non enzymatic antioxidants parameters in erythrocytes. Also, the administration of OFIj significantly protected lipids and proteins against ethanol-induced oxidative modifications in rat erythrocytes. The beneficial effect of OFIj can result from the inhibition of ethanol-induced free radicals chain reactions in rat erythrocytes or from the enhancement of the endogenous antioxidants activities. Copyright © 2011 Elsevier GmbH. All rights reserved.

  11. Participation of the cholinergic system in the ethanol-induced suppression of paradoxical sleep in rats

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    L.A. Papale

    2008-09-01

    Full Text Available Sleep disturbance is among the many consequences of ethanol abuse in both humans and rodents. Ethanol consumption can reduce REM or paradoxical sleep (PS in humans and rats, respectively. The first aim of this study was to develop an animal model of ethanol-induced PS suppression. This model administered intragastrically (by gavage to male Wistar rats (3 months old, 200-250 g 0.5 to 3.5 g/kg ethanol. The 3.5 g/kg dose of ethanol suppressed the PS stage compared with the vehicle group (distilled water during the first 2-h interval (0-2 h; 1.3 vs 10.2; P < 0.001. The second aim of this study was to investigate the mechanisms by which ethanol suppresses PS. We examined the effects of cholinergic drug pretreatment. The cholinergic system was chosen because of the involvement of cholinergic neurotransmitters in regulating the sleep-wake cycle. A second set of animals was pretreated with 2.5, 5.0, and 10 mg/kg pilocarpine (cholinergic agonist or atropine (cholinergic antagonist. These drugs were administered 1 h prior to ethanol (3.5 g/kg or vehicle. Treatment with atropine prior to vehicle or ethanol produced a statistically significant decrease in PS, whereas pilocarpine had no effect on minutes of PS. Although the mechanism by which ethanol induces PS suppression is not fully understood, these data suggest that the cholinergic system is not the only system involved in this interaction.

  12. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ruibing [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Lihui [Shandong Normal University, Jinan, Shandong Province 250012 (China); Luo, Zheng; Guo, Xiaolan [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Ming, E-mail: ymylh@163.com [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China)

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  13. Prenatal exposure of ethanol induces increased glutamatergic neuronal differentiation of neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Han Seol-Heui

    2010-11-01

    Full Text Available Abstract Background Prenatal ethanol exposure during pregnancy induces a spectrum of mental and physical disorders called fetal alcohol spectrum disorder (FASD. The central nervous system is the main organ influenced by FASD, and neurological symptoms include mental retardation, learning abnormalities, hyperactivity and seizure susceptibility in childhood along with the microcephaly. In this study, we examined whether ethanol exposure adversely affects the proliferation of NPC and de-regulates the normal ratio between glutamatergic and GABAergic neuronal differentiation using primary neural progenitor culture (NPC and in vivo FASD models. Methods Neural progenitor cells were cultured from E14 embryo brain of Sprague-Dawley rat. Pregnant mice and rats were treated with ethanol (2 or 4 g/kg/day diluted with normal saline from E7 to E16 for in vivo FASD animal models. Expression level of proteins was investigated by western blot analysis and immunocytochemical assays. MTT was used for cell viability. Proliferative activity of NPCs was identified by BrdU incorporation, immunocytochemistry and FACS analysis. Results Reduced proliferation of NPCs by ethanol was demonstrated using BrdU incorporation, immunocytochemistry and FACS analysis. In addition, ethanol induced the imbalance between glutamatergic and GABAergic neuronal differentiation via transient increase in the expression of Pax6, Ngn2 and NeuroD with concomitant decrease in the expression of Mash1. Similar pattern of expression of those transcription factors was observed using an in vivo model of FASD as well as the increased expression of PSD-95 and decreased expression of GAD67. Conclusions These results suggest that ethanol induces hyper-differentiation of glutamatergic neuron through Pax6 pathway, which may underlie the hyper-excitability phenotype such as hyperactivity or seizure susceptibility in FASD patients.

  14. Expression of ethanol-induced behavioral sensitization is associated with alteration of chromatin remodeling in mice.

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    Béatrice Botia

    Full Text Available BACKGROUND: Ethanol-induced behavioral sensitization (EIBS is proposed to play a role in early and recurring steps of addiction. EIBS does not occur uniformly in all animals even from the same inbred strain. Since recent data demonstrate that epigenetic mechanisms are likely to be involved in the development and the persistence of ethanol-related behaviors, we explored the involvement of epigenetic mechanisms in ethanol response after EIBS development. METHODOLOGY: DBA/2J mice were i.p. injected with saline or ethanol (2 g/kg once a day for 10 consecutive days. At day 17, ethanol-treated mice were split in resistant and sensitized groups. Brains were then removed 30 min after a saline or 2 g/kg ethanol challenge to assess i gene expression using PCR array targeting 84 epigenetic-related genes and ii histone deacetylases (HDAC, histone acetylases (HAT and DNA methyltransferases (DNMT activities as well as H4K12 acetylation. PRINCIPAL FINDINGS: Acute ethanol administration decreased dnmt1, esco2 and rps6ka5 genes expression. These genes were similarly altered in sensitized but not in resistant mice after an ethanol challenge, suggesting that resistant mice were tolerant to the transcriptional outcomes of an ethanol challenge. Whereas global HAT or DNMT activity was not affected, global HDAC activity was reduced after an acute ethanol injection. HDAC inhibition occurred in all ethanol-treated mice but with a lesser extent in sensitized animals. As a consequence, H4 acetylation was specifically potentiated in the core of the Nac proportionally to the striatal HDAC activity decrease. CONCLUSIONS/SIGNIFICANCE: The present study highlights that the contrasted behavioral response to an ethanol challenge between resistant and sensitized mice may be mediated by epigenetic mechanisms occurring specifically in the striatum. Here we show that vulnerability to ethanol dependence and relapse could be, at least in part, due to individual variability in acute

  15. Comparison of cannabidiol, antioxidants, and diuretics in reversing binge ethanol-induced neurotoxicity.

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    Hamelink, Carol; Hampson, Aidan; Wink, David A; Eiden, Lee E; Eskay, Robert L

    2005-08-01

    Binge alcohol consumption in the rat induces substantial neurodegeneration in the hippocampus and entorhinal cortex. Oxidative stress and cytotoxic edema have both been shown to be involved in such neurotoxicity, whereas N-methyl-d-aspartate (NMDA) receptor activity has been implicated in alcohol withdrawal and excitoxic injury. Because the nonpsychoactive cannabinoid cannabidiol (CBD) was previously shown in vitro to prevent glutamate toxicity through its ability to reduce oxidative stress, we evaluated CBD as a neuroprotectant in a rat binge ethanol model. When administered concurrently with binge ethanol exposure, CBD protected against hippocampal and entorhinal cortical neurodegeneration in a dose-dependent manner. Similarly, the common antioxidants butylated hydroxytoluene and alpha-tocopherol also afforded significant protection. In contrast, the NMDA receptor antagonists dizocilpine (MK-801) and memantine did not prevent cell death. Of the diuretics tested, furosemide was protective, whereas the other two anion exchanger inhibitors, L-644,711 [(R)-(+)-(5,6-dichloro2,3,9,9a-tetrahydro 3-oxo-9a-propyl-1H-fluoren-7-yl)oxy acetic acid] and bumetanide, were ineffective. In vitro comparison of these diuretics indicated that furosemide is also a potent antioxidant, whereas the nonprotective diuretics are not. The lack of efficacy of L-644,711 and bumetanide suggests that the antioxidant rather than the diuretic properties of furosemide contribute most critically to its efficacy in reversing ethanol-induced neurotoxicity in vitro, in our model. This study provides the first demonstration of CBD as an in vivo neuroprotectant and shows the efficacy of lipophilic antioxidants in preventing binge ethanol-induced brain injury.

  16. SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

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    The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

  17. Ethanol-Induced TLR4/NLRP3 Neuroinflammatory Response in Microglial Cells Promotes Leukocyte Infiltration Across the BBB.

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    Alfonso-Loeches, Silvia; Ureña-Peralta, Juan; Morillo-Bargues, M José; Gómez-Pinedo, Ulises; Guerri, Consuelo

    2016-02-01

    We reported that the ethanol-induced innate immune response by activating TLR4 signaling triggers gliosis and neuroinflammation. Ethanol also activates other immune receptors, such as NOD-like-receptors, and specifically NLRP3-inflammasome in astroglial cells, to stimulate caspase-1 cleavage and IL-1β and IL-18 cytokines production. Yet, whether microglia NLRs are also sensitive to the ethanol effects that contribute to neuroinflammation is uncertain. Using cerebral cortexes of the chronic alcohol-fed WT and TLR4(-/-) mice, we demonstrated that chronic ethanol treatment enhanced TLR4 mediated-NLRP3/Caspase-1 complex activation, and up-regulated pro-inflammatory cytokines and chemokines levels. Ethanol-induced NLRP3-inflammasome activation and mitochondria-ROS generation were also observed in cultured microglial cells. The up-regulation of CD45(high)/CD11b(+) cell populations and matrix metalloproteinase-9 levels was also noted in the cortexes of the ethanol-treated WT mice. Notably, elimination of the TLR4 function abolished most ethanol-induced neuroinflammatory effects. Thus, our results demonstrate that ethanol triggers TLR4-mediated NLRP3-inflammasome activation in glial cells, and suggest that microglia stimulation may compromise the permeability of blood-brain barrier events to contribute to ethanol-induced neuroinflammation and brain damage.

  18. Protective Effects of the Traditional Herbal Formula Oryeongsan Water Extract on Ethanol-Induced Acute Gastric Mucosal Injury in Rats

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    Woo-Young Jeon

    2012-01-01

    Full Text Available This study was performed to evaluate the protective effect and safety of Oryeongsan water extract (OSWE on ethanol-induced acute gastric mucosal injury and an acute toxicity study in rats. Acute gastric lesions were induced via intragastric oral administration of absolute ethanol at a dose of 5 mL/kg. OSWE (100 and 200 mg/kg was administered to rats 2 h prior to the oral administration of absolute ethanol. The stomach of animal models was opened and gastric mucosal lesions were examined. Gastric mucosal injuries were evaluated by measuring the levels of malondialdehyde (MDA, glutathione (GSH, and the activity of antioxidant enzymes. In the acute toxicity study, no adverse effects of OSWE were observed at doses up to 2000 mg/kg/day. Administration of OSWE reduced the damage by conditioning the gastric mucosa against ethanol-induced acute gastric injury, which included hemorrhage, hyperemia, and loss of epithelial cells. The level of MDA was reduced in OSWE-treated groups compared with the ethanol-induced group. Moreover, the level of GSH and the activity of antioxidant enzymes were significantly increased in the OSWE-treated groups. Our findings suggest that OSWE has a protective effect on the gastric mucosa against ethanol-induced acute gastric injury via the upregulation of antioxidant enzymes.

  19. Gross motor function, functional skills and caregiver assistance in children with spastic cerebral palsy (CP) with and without cerebral visual impairment (CVI)

    NARCIS (Netherlands)

    Salavati, M.; Rameckers, E.A.A.; Steenbergen, B.; Schans, C.P. van der

    2014-01-01

    Aim: To determine whether the level of gross motor function and functional skills in children with cerebral palsy (CP) and cerebral visual impairment (CVI) as well as caregiver assistance are lower in comparison with the corresponding group of children experiencing CP without CVI. Method: Data

  20. New Approaches to Exciting Exergame-Experiences for People with Motor Function Impairments.

    Science.gov (United States)

    Eckert, Martina; Gómez-Martinho, Ignacio; Meneses, Juan; Martínez, José-Fernán

    2017-02-12

    The work presented here suggests new ways to tackle exergames for physical rehabilitation and to improve the players' immersion and involvement. The primary (but not exclusive) purpose is to increase the motivation of children and adolescents with severe physical impairments, for doing their required exercises while playing. The proposed gaming environment is based on the Kinect sensor and the Blender Game Engine. A middleware has been implemented that efficiently transmits the data from the sensor to the game. Inside the game, different newly proposed mechanisms have been developed to distinguish pure exercise-gestures from other movements used to control the game (e.g., opening a menu). The main contribution is the amplification of weak movements, which allows the physically impaired to have similar gaming experiences as the average population. To test the feasibility of the proposed methods, four mini-games were implemented and tested by a group of 11 volunteers with different disabilities, most of them bound to a wheelchair. Their performance has also been compared to that of a healthy control group. Results are generally positive and motivating, although there is much to do to improve the functionalities. There is a major demand for applications that help to include disabled people in society and to improve their life conditions. This work will contribute towards providing them with more fun during exercise.

  1. Impact of Cerebral Visual Impairments on Motor Skills: Implications for Developmental Coordination Disorders

    Science.gov (United States)

    Chokron, Sylvie; Dutton, Gordon N.

    2016-01-01

    Cerebral visual impairment (CVI) has become the primary cause of visual impairment and blindness in children in industrialized countries. Its prevalence has increased sharply, due to increased survival rates of children who sustain severe neurological conditions during the perinatal period. Improved diagnosis has probably contributed to this increase. As in adults, the nature and severity of CVI in children relate to the cause, location and extent of damage to the brain. In the present paper, we define CVI and how this impacts on visual function. We then define developmental coordination disorder (DCD) and discuss the link between CVI and DCD. The neuroanatomical correlates and aetiologies of DCD are also presented in relationship with CVI as well as the consequences of perinatal asphyxia (PA) and preterm birth on the occurrence and nature of DCD and CVI. This paper underlines why there are both clinical and theoretical reasons to disentangle CVI and DCD, and to categorize the features with more precision. In order to offer the most appropriate rehabilitation, we propose a systematic and rapid evaluation of visual function in at-risk children who have survived preterm birth or PA whether or not they have been diagnosed with cerebral palsy or DCD. PMID:27757087

  2. Impact of cerebral visual impairments on motor skills : implications for developmental coordination disorders.

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    Sylvie Chokron

    2016-10-01

    Full Text Available Cerebral visual impairment (CVI has become the primary cause of visual impairment and blindness in children in industrialized countries. Its prevalence has increased sharply, due to increased survival rates of children who sustain severe neurological conditions during the perinatal period. Improved diagnosis has probably contributed to this increase. As in adults, the nature and severity of CVI in children relate to the cause, location and extent of damage to the brain. In the present paper, we define CVI and how this impacts on visual function. We then define DCD and discuss the link between CVI and DCD. The neuroanatomical correlates and aetiologies of DCD are also presented in relationship with CVI as well as the consequences of perinatal asphyxia and preterm birth on the occurrence and nature of DCD and CVI. This paper underlines why there are both clinical and theoretical reasons to disentangle CVI and DCD, and to categorise the features with more precision. In order to offer the most appropriate rehabilitation, we propose a systematic and rapid evaluation of visual function in at-risk children who have survived preterm birth or perinatal asphyxia whether or not they have been diagnosed with cerebral palsy or DCD.

  3. New Approaches to Exciting Exergame-Experiences for People with Motor Function Impairments

    Directory of Open Access Journals (Sweden)

    Martina Eckert

    2017-02-01

    Full Text Available The work presented here suggests new ways to tackle exergames for physical rehabilitation and to improve the players’ immersion and involvement. The primary (but not exclusive purpose is to increase the motivation of children and adolescents with severe physical impairments, for doing their required exercises while playing. The proposed gaming environment is based on the Kinect sensor and the Blender Game Engine. A middleware has been implemented that efficiently transmits the data from the sensor to the game. Inside the game, different newly proposed mechanisms have been developed to distinguish pure exercise-gestures from other movements used to control the game (e.g., opening a menu. The main contribution is the amplification of weak movements, which allows the physically impaired to have similar gaming experiences as the average population. To test the feasibility of the proposed methods, four mini-games were implemented and tested by a group of 11 volunteers with different disabilities, most of them bound to a wheelchair. Their performance has also been compared to that of a healthy control group. Results are generally positive and motivating, although there is much to do to improve the functionalities. There is a major demand for applications that help to include disabled people in society and to improve their life conditions. This work will contribute towards providing them with more fun during exercise.

  4. Apocynin protects against ethanol-induced gastric ulcer in rats by attenuating the upregulation of NADPH oxidases 1 and 4.

    Science.gov (United States)

    El-Naga, Reem N

    2015-12-05

    Gastric ulcer is a common gastrointestinal disorder affecting many people all over the world. Absolute ethanol (5 ml/kg) was used to induce gastric ulceration in rats. Apocynin (50 mg/kg) was given orally one hour before the administration of absolute ethanol. Omeprazole (20 mg/kg) was used as a standard. Interestingly, apocynin pre-treatment provided 93.5% gastroprotection against ethanol-induced ulceration. Biochemically, gastric mucin content was significantly increased with apocynin pre-treatment. This finding was further supported by alcian blue staining of stomach sections obtained from the different treated groups. Also, gastric juice volume and acidity were significantly reduced. Apocynin significantly ameliorated ethanol-induced oxidative stress by replenishing reduced glutathione and superoxide dismutase levels as well as reducing elevated malondialdehyde levels in gastric tissues. Besides, ethanol-induced pro-inflammatory response was significantly decreased by apocynin pre-treatment via reducing elevated levels of pro-inflammatory markers; interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2 and inducible nitric oxide synthase. Additionally, caspase-3 tissue level was significantly reduced in apocynin pre-treated group. Interestingly, NADPH oxidase-1 (NOX-1) and NOX-4 up-regulation was shown to be partially involved in the pathogenesis of ethanol-induced gastric ulceration and was significantly reversed by apocynin pre-treatment. Gastroprotective properties of apocynin were confirmed by histopathological examination. It is worth mentioning that apocynin was superior in all aspects except gastric mucin content parameter where it was significantly increased by 13.5 folds in the omeprazole pre-treated group. This study was the first to show that apocynin is a promising gastroprotective agent against ethanol-induced gastric ulceration, partially via its anti-oxidant, anti-inflammatory, anti-apoptotic effects as well as down-regulating NOX-1 and NOX-4

  5. Shared and differentiated motor skill impairments in children with dyslexia and/or attention deficit disorder: From simple to complex sequential coordination.

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    Marchand-Krynski, Marie-Ève; Morin-Moncet, Olivier; Bélanger, Anne-Marie; Beauchamp, Miriam H; Leonard, Gabriel

    2017-01-01

    Dyslexia and Attention deficit disorder (AD) are prevalent neurodevelopmental conditions in children and adolescents. They have high comorbidity rates and have both been associated with motor difficulties. Little is known, however, about what is shared or differentiated in dyslexia and AD in terms of motor abilities. Even when motor skill problems are identified, few studies have used the same measurement tools, resulting in inconstant findings. The present study assessed increasingly complex gross motor skills in children and adolescents with dyslexia, AD, and with both Dyslexia and AD. Our results suggest normal performance on simple motor-speed tests, whereas all three groups share a common impairment on unimanual and bimanual sequential motor tasks. Children in these groups generally improve with practice to the same level as normal subjects, though they make more errors. In addition, children with AD are the most impaired on complex bimanual out-of-phase movements and with manual dexterity. These latter findings are examined in light of the Multiple Deficit Model.

  6. Shared and differentiated motor skill impairments in children with dyslexia and/or attention deficit disorder: From simple to complex sequential coordination.

    Directory of Open Access Journals (Sweden)

    Marie-Ève Marchand-Krynski

    Full Text Available Dyslexia and Attention deficit disorder (AD are prevalent neurodevelopmental conditions in children and adolescents. They have high comorbidity rates and have both been associated with motor difficulties. Little is known, however, about what is shared or differentiated in dyslexia and AD in terms of motor abilities. Even when motor skill problems are identified, few studies have used the same measurement tools, resulting in inconstant findings. The present study assessed increasingly complex gross motor skills in children and adolescents with dyslexia, AD, and with both Dyslexia and AD. Our results suggest normal performance on simple motor-speed tests, whereas all three groups share a common impairment on unimanual and bimanual sequential motor tasks. Children in these groups generally improve with practice to the same level as normal subjects, though they make more errors. In addition, children with AD are the most impaired on complex bimanual out-of-phase movements and with manual dexterity. These latter findings are examined in light of the Multiple Deficit Model.

  7. Neuroinflammation increases GABAergic tone and impairs cognitive and motor function in hyperammonemia by increasing GAT-3 membrane expression. Reversal by sulforaphane by promoting M2 polarization of microglia.

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    Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Gonzalez-Usano, Alba; Agusti, Ana; Balzano, Tiziano; Llansola, Marta; Felipo, Vicente

    2016-04-18

    Hyperammonemia induces neuroinflammation and increases GABAergic tone in the cerebellum which contributes to cognitive and motor impairment in hepatic encephalopathy (HE). The link between neuroinflammation and GABAergic tone remains unknown. New treatments reducing neuroinflammation and GABAergic tone could improve neurological impairment. The aims were, in hyperammonemic rats, to assess whether: (a) Enhancing endogenous anti-inflammatory mechanisms by sulforaphane treatment reduces neuroinflammation and restores learning and motor coordination. (b) Reduction of neuroinflammation by sulforaphane normalizes extracellular GABA and glutamate-NO-cGMP pathway and identify underlying mechanisms. (c) Identify steps by which hyperammonemia-induced microglial activation impairs cognitive and motor function and how sulforaphane restores them. We analyzed in control and hyperammonemic rats, treated or not with sulforaphane, (a) learning in the Y maze; (b) motor coordination in the beam walking; (c) glutamate-NO-cGMP pathway and extracellular GABA by microdialysis; (d) microglial activation, by analyzing by immunohistochemistry or Western blot markers of pro-inflammatory (M1) (IL-1b, Iba-1) and anti-inflammatory (M2) microglia (Iba1, IL-4, IL-10, Arg1, YM-1); and (e) membrane expression of the GABA transporter GAT-3. Hyperammonemia induces activation of astrocytes and microglia in the cerebellum as assessed by immunohistochemistry. Hyperammonemia-induced neuroinflammation is associated with increased membrane expression of the GABA transporter GAT-3, mainly in activated astrocytes. This is also associated with increased extracellular GABA in the cerebellum and with motor in-coordination and impaired learning ability in the Y maze. Sulforaphane promotes polarization of microglia from the M1 to the M2 phenotype, reducing IL-1b and increasing IL-4, IL-10, Arg1, and YM-1 in the cerebellum. This is associated with astrocytes deactivation and normalization of GAT-3 membrane

  8. Evaluation of cell proliferation, apoptosis, and DNA-repair genes as potential biomarkers for ethanol-induced CNS alterations.

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    Hicks, Steven D; Lewis, Lambert; Ritchie, Julie; Burke, Patrick; Abdul-Malak, Ynesse; Adackapara, Nyssa; Canfield, Kelly; Shwarts, Erik; Gentile, Karen; Meszaros, Zsuzsa Szombathyne; Middleton, Frank A

    2012-10-25

    Alcohol use disorders (AUDs) lead to alterations in central nervous system (CNS) architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs) produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure. Remarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs) of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP) assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1) was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5) showed a highly significant correlation with AUD-induced decreases in the volume of the left parietal supramarginal gyrus and

  9. Evaluation of cell proliferation, apoptosis, and dna-repair genes as potential biomarkers for ethanol-induced cns alterations

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    Hicks Steven D

    2012-10-01

    Full Text Available Abstract Background Alcohol use disorders (AUDs lead to alterations in central nervous system (CNS architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure. Results Remarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1 was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5 showed a highly significant correlation with AUD-induced decreases in the volume of the left

  10. Increased sleep fragmentation leads to impaired off-line consolidation of motor memories in humans.

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    Ina Djonlagic

    Full Text Available A growing literature supports a role for sleep after training in long-term memory consolidation and enhancement. Consequently, interrupted sleep should result in cognitive deficits. Recent evidence from an animal study indeed showed that optimal memory consolidation during sleep requires a certain amount of uninterrupted sleep. Sleep continuity is disrupted in various medical disorders. We compared performance on a motor sequence learning task (MST in relatively young subjects with obstructive sleep apnea (n = 16; apnea-hypopnea index 17.1±2.6/h [SEM] to a carefully matched control group (n = 15, apnea-hypopnea index 3.7±0.4/h, p<0.001. Apart from AHI, oxygen nadir and arousal index, there were no significant differences between groups in total sleep time, sleep efficiency and sleep architecture as well as subjective measures of sleepiness based on standard questionnaires. In addition performance on the psychomotor vigilance task (reaction time and lapses, which is highly sensitive to sleep deprivation showed no differences as well as initial learning performance during the training phase. However there was a significant difference in the primary outcome of immediate overnight improvement on the MST between the two groups (controls = 14.7±4%, patients = 1.1±3.6%; P = 0.023 as well as plateau performance (controls = 24.0±5.3%, patients = 10.1±2.0%; P = 0.017 and this difference was predicted by the arousal index (p = 0.02 rather than oxygen saturation (nadir and time below 90% saturation. Taken together, this outcome provides evidence that there is a clear minimum requirement of sleep continuity in humans to ensure optimal sleep dependent memory processes. It also provides important new information about the cognitive impact of obstructive sleep apnea and challenges its current definitions.

  11. Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation.

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    Magen, Iddo; Avraham, Yosefa; Ackerman, Zvi; Vorobiev, Lia; Mechoulam, Raphael; Berry, Elliot M

    2009-09-01

    The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease. CBD (5mg/kg; i.p.) was administered over 4weeks to mice that had undergone BDL. Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-alpha-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-alpha receptor 1 expression were blocked by ZM241385, an A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor. The effects of BDL apparently result in part from down-regulation of A(2)A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.

  12. Learning “How to Learn”: Super Declarative Motor Learning Is Impaired in Parkinson's Disease

    Science.gov (United States)

    Fattapposta, Francesco; Abbruzzese, Giovanni

    2017-01-01

    Learning new information is crucial in daily activities and occurs continuously during a subject's lifetime. Retention of learned material is required for later recall and reuse, although learning capacity is limited and interference between consecutively learned information may occur. Learning processes are impaired in Parkinson's disease (PD); however, little is known about the processes related to retention and interference. The aim of this study is to investigate the retention and anterograde interference using a declarative sequence learning task in drug-naive patients in the disease's early stages. Eleven patients with PD and eleven age-matched controls learned a visuomotor sequence, SEQ1, during Day1; the following day, retention of SEQ1 was assessed and, immediately after, a new sequence of comparable complexity, SEQ2, was learned. The comparison of the learning rates of SEQ1 on Day1 and SEQ2 on Day2 assessed the anterograde interference of SEQ1 on SEQ2. We found that SEQ1 performance improved in both patients and controls on Day2. Surprisingly, controls learned SEQ2 better than SEQ1, suggesting the absence of anterograde interference and the occurrence of learning optimization, a process that we defined as “learning how to learn.” Patients with PD lacked such improvement, suggesting defective performance optimization processes. PMID:28828186

  13. Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions

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    Mario U Manto

    2015-03-01

    Full Text Available Autoantibodies to the smaller isoform of glutamate decarboxylase can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct glutamate decarboxylase autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal glutamate decarboxylase antibodies. We found that glutamate decarboxylase autoantibodies present in patients with stiff person syndrome (n = 7 and cerebellar ataxia (n = 15 recognized an epitope distinct from that recognized by glutamate decarboxylase autoantibodies present in patients with type 1 diabetes mellitus (n = 10 or limbic encephalitis (n = 4. We demonstrated that the administration of a monoclonal glutamate decarboxylase antibody representing this epitope specificity (1 disrupted in vitro the association of glutamate decarboxylase with γ-Aminobutyric acid containing synaptic vesicles, (2 depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect, (3 significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task, (4 markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm, and (5 induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of glutamate decarboxylase by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such glutamate decarboxylase antibodies could be envisioned.

  14. Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons

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    Ullah Ikram

    2012-01-01

    Full Text Available Abstract Background Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met and thymoquinone (TQ during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD 17.5. Results We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca2+]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (ΔψM, which is typically lowered by ethanol exposure. Increased cytosolic free [Ca2+]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2, increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death. Conclusion These findings suggested that Met and TQ are strong protective agents against ethanol-induced

  15. Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kai Connie [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

    2012-08-01

    Oxidative stress and lipid accumulation play important roles in alcohol-induced liver injury. Previous reports showed that, in livers of nuclear factor erythroid 2-related factor 2 (Nrf2)-activated mice, genes involved in antioxidant defense are induced, whereas genes involved in lipid biosynthesis are suppressed. To investigate the role of Nrf2 in ethanol-induced hepatic alterations, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation, were treated with ethanol (5 g/kg, po). Blood and liver samples were collected 6 h thereafter. Ethanol increased alanine aminotransferase and lactate dehydrogenase activities as well as thiobarbituric acid reactive substances in serum of Nrf2-null and wild-type mice, but not in Nrf2-enhanced mice. After ethanol administration, mitochondrial glutathione concentrations decreased markedly in Nrf2-null mice but not in Nrf2-enhanced mice. H{sub 2}DCFDA staining of primary hepatocytes isolated from the four genotypes of mice indicates that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. Ethanol increased serum triglycerides and hepatic free fatty acids in Nrf2-null mice, and these increases were blunted in Nrf2-enhanced mice. In addition, the basal mRNA and nuclear protein levels of sterol regulatory element-binding protein 1(Srebp-1) were decreased with graded Nrf2 activation. Ethanol further induced Srebp-1 mRNA in Nrf2-null mice but not in Nrf2-enhanced mice. In conclusion, Nrf2 activation prevented alcohol-induced oxidative stress and accumulation of free fatty acids in liver by increasing genes involved in antioxidant defense and decreasing genes involved in lipogenesis. -- Highlights: ► Ethanol depleted mitochondrial GSH in Nrf2-null mice but not in Keap1-KD mice. ► Ethanol increased ROS in hepatocytes isolated from Nrf2-null and wild

  16. Prenatal ethanol exposure alters ethanol-induced Fos immunoreactivity and dopaminergic activity in the mesocorticolimbic pathway of the adolescent brain.

    Science.gov (United States)

    Fabio, M C; Vivas, L M; Pautassi, R M

    2015-08-20

    Prenatal ethanol exposure (PEE) promotes alcohol intake during adolescence, as shown in clinical and pre-clinical animal models. The mechanisms underlying this effect of prenatal ethanol exposure on postnatal ethanol intake remain, however, mostly unknown. Few studies assessed the effects of moderate doses of prenatal ethanol on spontaneous and ethanol-induced brain activity on adolescence. This study measured, in adolescent (female) Wistar rats prenatally exposed to ethanol (0.0 or 2.0g/kg/day, gestational days 17-20) or non-manipulated (NM group) throughout pregnancy, baseline and ethanol-induced cathecolaminergic activity (i.e., colocalization of c-Fos and tyrosine hydroxylase) in ventral tegmental area (VTA), and baseline and ethanol-induced Fos immunoreactivity (ir) in nucleus accumbens shell and core (AcbSh and AcbC, respectively) and prelimbic (PrL) and infralimbic (IL) prefrontal cortex. The rats were challenged with ethanol (dose: 0.0, 1.25, 2.5 or 3.25g/kg, i.p.) at postnatal day 37. Rats exposed to vehicle prenatally (VE group) exhibited reduced baseline dopaminergic tone in VTA; an effect that was inhibited by prenatal ethanol exposure (PEE group). Dopaminergic activity in VTA after the postnatal ethanol challenge was greater in PEE than in VE or NM animals. Ethanol-induced Fos-ir at AcbSh was found after 1.25g/kg and 2.5g/kg ethanol, in VE and PEE rats, respectively. PEE did not alter ethanol-induced Fos-ir at IL but reduced ethanol-induced Fos-ir at PrL. These results suggest that prenatal ethanol exposure heightens dopaminergic activity in the VTA and alters the response of the mesocorticolimbic pathway to postnatal ethanol exposure. These effects may underlie the enhanced vulnerability to develop alcohol-use disorders of adolescents with a history of in utero ethanol exposure. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Intralimb coordination as a sensitive indicator of motor-control impairment after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Lea eAwai

    2014-03-01

    Full Text Available Background: Recovery of walking function after neurotrauma, e.g. after spinal cord injury, is routinely captured using standardized walking outcome measures of time and distance. However, these measures do not provide information on possible underlying mechanisms of recovery, nor do they tell anything about the quality of gait. Subjects with an incomplete spinal cord injury are a very heterogeneous group of people with a wide range of functional impairments. A stratification of these subjects would allow increasing sensitivity for hypothesis testing and a more targeted treatment strategy.Methods: The gait of incomplete spinal cord injured subjects was compared to healthy control subjects by analyzing kinematic data obtained by a 3-D motion capture system. Hip-knee angle-angle plots (cyclograms informed on the qualitative aspect of gait and the intralimb coordination. Features of the cyclogram, e.g. shape of the cyclogram, cycle-to-cycle consistency and its modulation due to changes in walking speed were discerned and used to stratify spinal cord injured subjects.Results: Spinal cord injured subjects were unable to modulate their cyclogram configuration when increasing speed from slow to preferred. Their gait quality remained clearly aberrant and showed even higher deviations from normal when walking at preferred speed. Qualitative categorization of spinal cord injured subjects based on their intralimb coordination was complemented by quantitative measures of cyclogram shape comparison.Discussion: Spinal cord injured subjects showed distinct distortions of intralimb coordination as well as limited modulation to changes in walking speed. The specific changes of the cyclograms revealed complementary insight in the disturbance of lower-limb control in addition to measures of time and distance and may be a useful tool for patient categorization and stratification prior to clinical trial inclusion.

  18. Development and testing an online near-infrared spectroscopy brain-computer interface tailored to an individual with severe congenital motor impairments.

    Science.gov (United States)

    Schudlo, Larissa C; Chau, Tom

    2017-07-31

    For non-verbal individuals, brain-computer interfaces (BCIs) are a potential means of communication. Near-infrared spectroscopy (NIRS) is a brain-monitoring modality that has been considered for BCIs. To date, limited NIRS-BCI testing has involved online classification, particularly with individuals with severe motor impairments. We tested an online NIRS-BCI developed for a non-verbal individual with severe congenital motor impairments. The binary BCI differentiated categorical verbal fluency task (VFT) performance and rest using prefrontal measurements. The participant attended five sessions, the last two of which were online with classification feedback. An online classification accuracy of 63.33% was achieved using a linear discriminant classifier trained on a four-dimensional feature set. An offline, cross-validation analysis of all data yielded an optimal adjusted classification accuracy of 66.6 ± 9.11%. Inconsistent functional responses, contradictory effects of feedback, participant fatigue and motion artefacts were identified as challenges to online classification specific to this participant. Results suggest potential in using an NIRS-BCI controlled by the VFT in instances of severe congenital impairments. Further testing with users with severe disabilities is necessary. Implications for Rehabilitation Brain-computer interfaces (BCIs) can provide a non-motor based means of communication for individuals with severe motor impairments. Near-infrared spectroscopy (NIRS) is a haemodynamic-based brain-imaging modality used in BCIs. To date, NIRS-BCIs have not been thoroughly tested with potential target users. This case study shows that NIRS-BCIs may offer a means of practical communication for individuals with severe congenital impairments and continued exploration is advisable.

  19. Impaired motor preparation and execution during standing reach in people with chronic stroke.

    Science.gov (United States)

    McCombe Waller, Sandy; Yang, Chieh-Ling; Magder, Laurence; Yungher, Don; Creath, Rob; Gray, Vicki; Rogers, Mark W

    2016-09-06

    be indicative of interference of a classical startle reflex activating elbow flexors. Results indicated impairments in movement preparation of both APA's and goal directed UE movement in individuals with stroke which impact the functional performance of reaching in the standing position. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Technology to help persons with extensive neuro-motor impairment and lack of speech with their leisure occupation and communication.

    Science.gov (United States)

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; D'Amico, Fiora; Addante, Luigi M; Ferlisi, Gabriele; Zullo, Valeria; Oliva, Doretta; Megna, Marisa

    2014-03-01

    These two studies were aimed at extending the assessment of technology-aided programs to enhance leisure occupation or communication with persons with extensive neuro-motor impairment and lack of speech. Specifically, Study I implemented the program for leisure occupation with two post-stroke patients. Study II implemented the program for communication with two persons affected by amyotrophic lateral sclerosis (ALS). In Study I, a computer system presented the participants with a variety of stimuli. The participants could select/access those stimuli by microswitch activation or could bypass them by abstaining from microswitch responses. In Study II, the participants used a computer-aided telephone system that allowed them to choose via microswitch activation the persons to call. On the computer screen, they also had words and phrases that they could activate during the calls to influence the conversation with the persons called. Data from both studies were largely positive. The post-stroke patients showed high levels of stimulus selection (access) and extended engagement. The patients with ALS were able to make phone calls and to select the words/phrases to influence the conversations. The relevance of technology-aided programs for leisure occupation and communication of persons with extensive multiple disabilities was discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD+ Depletion in Human Astroglial Cells

    Directory of Open Access Journals (Sweden)

    Jade Guest

    2015-01-01

    Full Text Available Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD+ levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11 mM, 22 mM, 65 mM, and 100 mM for ≤ 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose polymer production. Significant decreases in total NAD(H and sirtuin 1 activity were also observed at concentrations ≥ 22 mM. Similar to U251 cells, exposure to ethanol (≥22 mM decreased levels of NAD(H in primary human astrocytes. NAD(H depletion in primary astrocytes was prevented by pretreatment with 1 μM of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ≥ 5 μM resulted in significant reductions in [NAD(H]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene.

  2. Protective effects of bilobalide against ethanol-induced gastric ulcer in vivo/vitro.

    Science.gov (United States)

    Hui, Shi; Fangyu, Wang

    2017-01-01

    Bilobalide (BI) has been widely known as a unique constituent extracted from Ginkgo biloba. The aim of the current study was to reveal the potential efficacy as well as the underlying mechanism of the action of BI on ethanol-induced lesion in gastric mucosa in vivo/vitro. Ethanol (0.2ml/kg) was applied to induce gastric ulcer mice model. Our results indicated that treatment with BI markedly decreased the levels of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) in vivo. Additionally, BI intervation exhibited elevated myeloperoxidase (MPO) level in stomach, increased superoxide dismutase (SOD) activity and decreased malonaldehyde (MDA) content in serum and stomach when compared with those of the model group. It could be also observed that inhibited MAPK/NF-κB pathway expressions occurred after BI treatment both in vivo and in vitro. Taken together, BI exerted a gastro-protective effect against gastric ulceration, which was presumed to be associated with MAPK/NF-κB pathway. Copyright © 2016. Published by Elsevier Masson SAS.

  3. Relation between ethanol induced changes in plasma catecholines during stress and voluntary ethanol preference

    Energy Technology Data Exchange (ETDEWEB)

    Pashko, S.

    1986-03-01

    N/NIH rats (N = 10) were implanted with venous catheters to permit stressless chronic, repeated blood withdrawal. Following surgical recovery, the rats were restrained to a lab counter top for 30 min after injection with saline or low dose (0.5 g/kg) ethanol. Blood was repeatedly withdrawn to determine AUC production of NE and E to assess the effect that low dose ethanol has on stress responsiveness. Between saline injection restraint and ethanol injection restraint conditions no differences in NE or E AUC were apparent. A 2- bottle preference test for ethanol was then performed over 21 days. Multiple regression analyses of NE saline restraint and ethanol restraint could predict ethanol consumption to the p = .02 level with R/sup 2/ = .681. Multiple regressions of E saline restraint and E ethanol restraint could predict ethanol consumption to the p = .01 level with R/sup 2/ = .746. These data suggest that ethanol induced increases in plasma NE and E during stress can predict later voluntary ethanol consumption between the ranges of .13 and 1.05 g ethanol/kg/day. This data seems to be more in line with an arousal or withdrawal relationship between ethanol consumption and stress than by a simple tension reduction formulation based on plasma NE or E.

  4. Acute Ethanol-Induced Changes in Edema and Metabolite Concentrations in Rat Brain

    Directory of Open Access Journals (Sweden)

    Huimin Liu

    2014-01-01

    Full Text Available The aim of this study is to describe the acute effects of EtOH on brain edema and cerebral metabolites, using diffusion weight imaging (DWI and proton magnetic resonance spectroscopy (1H-MRS at a 7.0T MR and to define changes in apparent diffusion coefficient (ADC values and the concentration of metabolites in the rat brain after acute EtOH intoxication. ADC values in each ROI decreased significantly at 1 h and 3 h after ethanol administration. ADC values in frontal lobe were decreased significantly compared with other regions at 3 h. For EtOH/Cr+PCr and cerebral metabolites (Cho, Tau, and Glu differing over time, no significant differences for Ins, NAA, and Cr were observed in frontal lobes. Regression analysis revealed a significant association between TSEtOH/Cr+PCr and TSCho, TSTau, TSGlu, and TSADC. The changes of ADC values in different brain regions reflect the process of the cytotoxic edema in vivo. The characterization of frontal lobes metabolites changes and the correlations between TSEtOH/Cr+PCr and TSCho, TSTau, and TSGlu provide a better understanding for the biological mechanisms in neurotoxic effects of EtOH on the brain. In addition, the correlations between TSEtOH/Cr+PCr and TSADC will help us to understand development of the ethanol-induced brain cytotoxic edema.

  5. Novel ethanol-induced pectin-xanthan aerogel coatings for orthopedic applications.

    Science.gov (United States)

    Horvat, Gabrijela; Xhanari, Klodian; Finšgar, Matjaž; Gradišnik, Lidija; Maver, Uroš; Knez, Željko; Novak, Zoran

    2017-06-15

    In this study, we developed a novel high methoxyl pectin-xanthan aerogel coating on medical-grade stainless steel, prepared by ethanol-induced gelation and subsequent supercritical drying. Two non-steroidal anti-inflammatory drugs, i.e. diclofenac sodium and indomethacin, were incorporated into the aerogel coating. Electrochemical analyses were performed on the coated samples using electrochemical impedance spectroscopy and cyclic polarization techniques. The results showed that all passivated samples were highly resistant to general corrosion. The release of both non-steroidal anti-inflammatory drugs was complete after 24h, as confirmed by the plateau in the drug release profiles as well as by IR spectroscopy after the final release point. The potential of samples for use in orthopedic applications was evaluated on a human bone-derived osteoblast cell and all samples were shown to be biocompatible. The increased viability of some samples indicates the high potential of the developed approach for future evaluation of possible clinical use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Rutin attenuates ethanol-induced neurotoxicity in hippocampal neuronal cells by increasing aldehyde dehydrogenase 2.

    Science.gov (United States)

    Song, Kibbeum; Kim, Sokho; Na, Ji-Young; Park, Jong-Heum; Kim, Jae-Kyung; Kim, Jae-Hun; Kwon, Jungkee

    2014-10-01

    Rutin is derived from buckwheat, apples, and black tea. It has been shown to have beneficial anti-inflammatory and antioxidant effects. Ethanol is a central nervous system depressant and neurotoxin. Its metabolite, acetaldehyde, is critically toxic. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde into nontoxic acetate. This study examined rutin's effects on ALDH2 activity in hippocampal neuronal cells (HT22 cells). Rutin's protective effects against acetaldehyde-based ethanol neurotoxicity were confirmed. Daidzin, an ALDH2 inhibitor, was used to clarify the mechanisms of rutin's protective effects. Cell viability was significantly increased after rutin treatment. Rutin significantly reversed ethanol-increased Bax, cytochrome c expression and caspase 3 activity, and decreased Bcl-2 and Bcl-xL protein expression in HT22 cells. Interestingly, rutin increased ALDH2 expression, while daidzin reversed this beneficial effect. Thus, this study demonstrates rutin protects HT22 cells against ethanol-induced neurotoxicity by increasing ALDH2 activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Protective effect of Cistanchis A on ethanol-induced damage in primary cultured mouse hepatocytes.

    Science.gov (United States)

    Luo, Huiying; Cao, Rongrong; Wang, Lijuan; Zhu, Lijuan

    2016-10-01

    Cistanoside A (C. A) was one of phenylethanol glycosides isolated from Cistanche deserticola, a tonic in traditional Chinese medicine. In our previous research, we demonstrated that Cistanoside A (C. A) possess the protective activities on CCl4 induced hepatotoxicity in mice, such as increasing free radicals clearing activities, alleviating lipid-overoxidation damage, and improving respiratory chain function in mitochondria. Meanwhile, our previous research also demonstrated C.A possess protective activities on alcohol induced hepatotoxicity in mice, shown in ameliorate the hepatic function indices, lightening steatosis and inflammatory infiltration, increasing free radicals clearing activities, alleviating lipid-overoxidation damage, and alleviating energy metabolism in mitochondria. The aim of this research was to evaluate the effects of Cistanoside A (C. A) on ethanol-induced damage in primary cultured mouse hepatocytes, and probe into the mechanism related. Using fluorescent staining, flow cytometer, immunohistochemistry analysis, and Western blotting, we demonstrated that C.A could enhance the survival rate of the primary cultured hepatocytes, alleviate apoptosis and necrosis, the mechanism was involved with enhance the expression of apoptosis inhibition factor bcl-2, and inhibition the expression of immediate early genes c-fos. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Surface-directed and ethanol-induced DNA condensation on mica.

    Science.gov (United States)

    Zhang, Ce; van der Maarel, Johan R C

    2008-03-20

    The adsorption of lambda-phage DNA onto mica was investigated with atomic force microscopy. We found that the morphologies depended on the solvent conditions in the sample preparation procedure. Flat-lying networks of hybridized single-stranded DNA were obtained if ultrapure water was used. If buffered conditions are maintained during the whole of the preparation procedure, single double-stranded DNA molecules are adsorbed. The adsorbed double-stranded DNA molecules subsequently can be condensed in situ on the surface by a brief rinse with anhydrous ethanol in the presence of divalent magnesium cations. The majority of these surface-directed and ethanol-induced condensed structures are toroids, but a small fraction of rods also has been observed. Analysis of the height and lateral dimensions shows that the toroids are single-molecular and disk-like with a height of one to two DNA diameters. The thin toroid morphology appears to be a general phenomenon of surface-directed condensation, irrespective of the nature of the condensing ligands and the specific surface interaction.

  9. The Zebrafish, a Novel Model Organism for Screening Compounds Affecting Acute and Chronic Ethanol-Induced Effects.

    Science.gov (United States)

    Tran, S; Facciol, A; Gerlai, R

    2016-01-01

    Alcohol addiction is a major unmet medical and economic issue for which very few efficacious pharmacological treatment options are currently available. The development and identification of new compounds and drugs to treat alcohol addiction is hampered by the high costs and low amenability of traditional laboratory rodents to high-throughput behavioral screens. The zebrafish represents an excellent compromise between systems complexity and practical simplicity by overcoming many limitations inherent in these rodent models. In this chapter, we review current advances in the behavioral and neurochemical characterization of ethanol-induced changes in zebrafish. We also discuss the basic principles and methods of and the most recent advances in using paradigms with which one can screen for compounds altering acute and chronic ethanol-induced effects in zebrafish. © 2016 Elsevier Inc. All rights reserved.

  10. Banhabaekchulchunma-tang, a traditional herbal formula attenuates absolute ethanol-induced gastric injury by enhancing the antioxidant status.

    Science.gov (United States)

    Shin, In-Sik; Jeon, Woo-Young; Shin, Hyeun-Kyoo; Cha, Sin-Woo; Lee, Mee-Young

    2013-07-12

    Banhabaekchulchunma-tang (hange-byakujutsu-tenma-to in Japanese and banxia-baizhu-tianma-tang in Chinese) is a mixture of fourteen herbs. It is used traditionally for the treatment of anemia, anorexia, general weakness, and female infertility in China, Japan, and Korea. In this study, we investigated the protective effects of a Banhabaekchulchunma-tang water extract (BCT) against ethanol-induced acute gastric injury in rats. Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the BCT group were given oral doses of omeprazole (50 mg/kg) or BCT (400 mg/kg), respectively, 2 h prior to the administration of absolute ethanol. The stomach of each animal was excised and examined for gastric mucosal lesions. To confirm the protective effects of BCT, we evaluated the degree of lipid peroxidation, the level of reduced glutathione (GSH), and the activities of the antioxidant enzymes catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase in the stomach. In addition, we conducted an acute toxicity study to evaluate the safety of BCT according to OECD guideline. BCT reduced ethanol-induced hemorrhage, hyperemia, and loss of epithelial cell in the gastric mucosa. BCT reduced the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, and increased the mucosal GSH content and the activities of antioxidant enzymes. In addition, BCT did not cause any adverse effects at up to 5000 mg/kg. These results indicate that BCT protects the gastric mucosa against ethanol-induced gastric injury by increasing the antioxidant status. We suggest that BCT could be developed as an effective drug for the treatment of gastric injury caused by alcohol intake.

  11. Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats.

    Science.gov (United States)

    Sathiavelu, Jayanthi; Senapathy, Giftson Jebakkan; Devaraj, Rajkumar; Namasivayam, Nalini

    2009-06-01

    To evaluate the effect of chrysin, a natural, biologically active compound extracted from many plants, honey and propolis, on the tissue and circulatory antioxidant status, and lipid peroxidation in ethanol-induced hepatotoxicity in rats. Rats were divided into four groups. Groups 1 and 2 received isocaloric glucose. Groups 3 and 4 received 20% ethanol, equivalent to 5 g/kg bodyweight every day. Groups 2 and 4 received chrysin (20 mg/kg bodyweight) dissolved in 0.5% dimethylsulfoxide. The results showed significantly elevated levels of tissue and circulatory thiobarbituric acid reactive substances, conjugated dienes and lipid hydroperoxides, and significantly lowered enzymic and non-enzymic antioxidant activity of superoxide dismutase, catalase and glutathione-related enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin C and vitamin E in ethanol-treated rats compared with the control. Chrysin administration to rats with ethanol-induced liver injury significantly decreased the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, and significantly elevated the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and the levels of reduced glutathione, vitamin C and vitamin E in the tissues and circulation compared with those of the unsupplemented ethanol-treated rats. The histological changes observed in the liver and kidney correlated with the biochemical findings. Chrysin offers protection against free radical-mediated oxidative stress in rats with ethanol-induced liver injury.

  12. Turmeric Extract Rescues Ethanol-Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD).

    Science.gov (United States)

    Muralidharan, Pooja; Connors, Craig T; Mohammed, Arooj S; Sarmah, Swapnalee; Marrs, Kathleen; Marrs, James A; Chism, Grady W

    2017-09-01

    Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol-induced developmental defect using zebrafish as a model was determined. Ethanol-induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol-induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol-treated embryos. The mechanism underlying the rescue remains to be determined. © 2017 Institute of Food Technologists®.

  13. The effect of thalidomide on ethanol-induced gastric mucosal damage in mice: involvement of inflammatory cytokines and nitric oxide.

    Science.gov (United States)

    Amirshahrokhi, Keyvan; Khalili, Ali-Reza

    2015-01-05

    Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Antioxidant and antiulcer potential of aqueous leaf extract of Kigelia africana against ethanol-induced ulcer in rats

    Science.gov (United States)

    dos Santos, Matheus M; Olaleye, Mary T; Ineu, Rafael P; Boligon, Aline A; Athayde, Margareth L; Barbosa, Nilda BV; Rocha, João Batista Teixeira

    2014-01-01

    Ethnobotanical claims regarding Kigelia africana reported antiulcer properties as part of its medicinal application. In this work, aqueous leaf extract from K. africana was investigated for its phytochemical constituents and antiulcer potential against ethanol-induced ulcer in rats. The participation of oxidative stress on ethanol-induced ulcer and the potential protective antioxidant activity of K. africana extracts were investigated by determining vitamin C and thiobarbituric acid reactive species (TBARS) contents in the gastric mucosa of rats. The HPLC analysis showed the presence of gallic acid, chlorogenic acid, caffeic acid and also the flavonoids rutin, quercetin and kaempferol in the aqueous plant extract. Oral treatment with K. africana extract (1.75; 3.5; 7 and 14 mg/kg) one hour after ulcer induction with ethanol decreased in a dose dependent manner the ulcer index. Ethanol increased significantly stomachal TBARS levels and decreased vitamin C content when compared to the control animals. K. africana blunted the ethanol-induced oxidative stress and restored vitamin C content to the control levels. The present results indicate that the aqueous leaf extract from K. africana possesses antiulcer potential. The presence of flavonoids in plant extract suggests that its antiulcerogenic potential is associated with antioxidant activity. Of particular therapeutic potential, K. africana was effective against ethanol even after the induction of ulcer, indicating that it can have protective and curative effects against gastric lesion. PMID:26417263

  15. The Effects of Combination of Robot-Assisted Therapy With Task-Specific or Impairment-Oriented Training on Motor Function and Quality of Life in Chronic Stroke.

    Science.gov (United States)

    Hung, Chung-Shan; Hsieh, Yu-Wei; Wu, Ching-Yi; Lin, Yi-Ting; Lin, Keh-Chung; Chen, Chia-Ling

    2016-08-01

    Robot-assisted therapy (RT) is a promising intervention for stroke rehabilitation. RT hybridized with therapist-mediated therapy (eg, RT plus task-specific or impairment-oriented training) may possibly yield functionally relevant improvements. A comparative study of the different combination regimens is needed. To investigate the efficacy of RT combined with task-specific training or impairment-oriented training on motor function and quality of life in patients with chronic stroke. A single-blind, randomized comparative efficacy study. Two medical centers in Taiwan. Twenty-one subjects with chronic stroke. Participants were recruited and randomized into 1 of 2 groups: (1) RT combined with task-specific (RTT) training (enrolled, n = 11; completed, n = 11) or (2) RT combined with impairment-oriented (RTI) training (enrolled, n = 10; completed, n = 9). Participants received 20 intervention sessions (90-100 min/d, 5 d/wk for 4 weeks). The Fugl-Meyer Motor Assessment Upper Extremity subscale, Stroke Impact Scale, Action Research Arm Test, and Medical Research Council Scale were administered at baseline, posttreatment, and at 3-month follow-up. Two-way repeated-measures analysis of variance was used to investigate the treatment effects. The improvements of the RTT group in motor function measured by the Fugl-Meyer Motor Assessment Upper Extremity subscale and quality of life assessed by the Stroke Impact Scale were significantly superior to the RTI group after the interventions. The improvements of the RTT group were maintained for 3 months. Both groups demonstrated significant within-group improvements in motor function, muscle power, and quality of life. RTT may be a more compelling approach to enhance motor function and quality of life for a long-term period than RTI. The combination of RT with task-specific training and with impairment-oriented training had similar benefits on upper limb motor function and muscle strength immediately after the interventions

  16. Synaptic input changes to spinal cord motoneurons correlate with motor control impairments in a type 1 diabetes mellitus model.

    Science.gov (United States)

    Benitez, Suzana Ulian; Carneiro, Everardo Magalhães; de Oliveira, Alexandre Leite Rodrigues

    2015-10-01

    Hyperglycemia is the main cause of diabetic complications, contributing to a widespread degeneration of the nervous system. Nevertheless, the main focus has been the sensory neurons because of neuropathic pain, while the impairments associated with the spinal cord and motor deficits, mostly of those initiated at early stages of the disease, have been poorly investigated. In this way, the present study used the nonobese diabetic mouse model to evaluate the microenvironment around motoneurons at ventral horn of the spinal cord, following prolonged hyperglycemia. Adult female mice were divided into two groups: spontaneously diabetic (n = 33) and nondiabetic (n = 26). Mice were considered hyperglycemic when blood glucose surpassed 400 mg/dL. Following 2 weeks from that stage, part of the animals was euthanized and the lumbar intumescences were obtained and processed for immunohistochemistry and transmission electron microscopy. For immunohistochemistry, the antibodies used for integrated density of pixels quantification were anti-synaptophysin, anti-GFAP, and anti-Iba1. The functional analysis was monitored with the walking track test (CatWalk system) during 4 weeks. The results revealed significant motor impairment in diabetic animals in comparison to the control group. Such loss of motor control correlated with a significant reduction in presynaptic terminals apposed to the motoneurons. Nevertheless, there were no significant changes in glial reaction in the spinal cord. Overall, the results herein revealed central nervous system changes at early stages of the disease that may in turn contribute to the motor deficit. Such changes open a new window of investigation in early stages of diabetes to better comprehend motor impairment as a long-term complication of the disease.

  17. Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort.

    Science.gov (United States)

    Ryberg, C; Rostrup, E; Paulson, O B; Barkhof, F; Scheltens, P; van Straaten, E C W; van der Flier, W M; Fazekas, F; Schmidt, R; Ferro, J M; Baezner, H; Erkinjuntti, T; Jokinen, H; Wahlund, L-O; Poggesi, A; Pantoni, L; Inzitari, D; Waldemar, G

    2011-08-15

    The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (pCC1, pCC5), motor function (pCC2 and CC5), and walking speed (pCC2 and CC5, pCC3 and total CC), and with development of dementia at 3 years (pCC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Reliability and Validity of Standing Back Extension Test for Detecting Motor Control Impairment in Subjects with Low Back Pain.

    Science.gov (United States)

    Gondhalekar, Gauri A; Kumar, Senthil P; Eapen, Charu; Mahale, Ajit

    2016-01-01

    Low back pain is a chronic health problem with high socioeconomic impact. Specific diagnosis or treatment approach has not yet effectively established to treat chronic low back pain. Standing Back Extension Test is one of the clinical measures to detect the passive extension subgroup of Motor Control Impairment (MCI); which could have an impact on spinal stability leading to recurrent chronic low back pain. Reliability and validity of this test is not fully established. To determine the intra-rater and inter-rater reliability and concurrent validity of the Standing Back Extension Test for detecting MCI of the lumbar spine. A total of 50 subjects were included in the study, 25 patients with Non Specific Low Back Pain (NSLBP) (12 men, 13 women) and 25 healthy controls (12 men, 13 women) were recruited into the study. All subjects performed the test movement. Two raters blinded to the subjects rated the test performance as either 'Positive' or 'Negative' based on the predetermined rating protocol. The thickness of Transverse Abdominis (TrA) muscle was assessed using Rehabilitative Ultrasound Imaging (RUSI). For reliability, the kappa coefficient with percent agreement was calculated and for assessing the validity Receiver Operator Characteristic (ROC) curves and Area under the Curve (AUC) were constructed. The standing back extension test showed very good intra-rater (k=0.87 with an agreement of 96%) and good inter-rater (k=0.78 with an agreement of 94%) reliability and high AUC for TrA muscle. The standing back extension test was found to be a reliable and a valid measure to detect passive extension subgroup for MCI in subjects with low back pain.

  19. Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers

    Science.gov (United States)

    Albaayit, Shaymaa Fadhel Abbas; Abba, Yusuf; Abdullah, Rasedee; Abdullah, Noorlidah

    2016-01-01

    Clausena excavata is a natural herb with both antioxidant and anti-inflammatory properties. It has been used for decades in folkloric practice for the amelioration of various ailments. In this study, the gastroprotective activity of methanolic extract of C. excavata leaves (MECE) was determined in the Sprague Dawley rat ethanol-induced gastric ulcer model. Rats were pretreated with a single dose of vehicle (5% Tween 20), 20 mg/mL omeprazole, 400 and 200 mg/mL of MECE dissolved in 5% Tween 20. Ulcer was induced with 5 mL/kg of ethanol and stomach tissue was obtained after 1 hour. Histological examination was done on hematoxylin and eosin, periodic acid-Schiff, and immunochemically stained gastric mucosal tissues. Prostaglandin E2, superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation levels of the gastric tissue homogenates were also determined. Significantly (Pulcer areas, less intense edema, and fewer leukocytes’ infiltration were observed in MECE- and omeprazole-treated than in untreated gastric mucosa with ulcer. The gastric pH, mucus production, superoxide dismutase, catalase, and glutathione peroxidase contents increased, while the lipid peroxidation content decreased as a result of MECE treatment. Bcl-2-associated X protein was underexpressed, while heat shock protein 70 and transforming growth factor-beta protein were overexpressed in the ulcerated gastric mucosa tissues treated with omeprazole and MECE. Similarly, there was a reduction in the levels of tumor necrotic factor-alpha and interleukin-6, while the level of interleukin-10 was increased. This study showed that the gastroprotective effect of MECE is achieved through inhibition of gastric juice secretion and ulcer lesion development, stimulation of mucus secretion, elevation of gastric pH, reduction of reactive oxygen species production, inhibition of apoptosis in the gastric mucosa, and modulation of inflammatory cytokines. PMID:27366052

  20. Pdgfra protects against ethanol-induced craniofacial defects in a zebrafish model of FASD

    Science.gov (United States)

    McCarthy, Neil; Wetherill, Leah; Lovely, C. Ben; Swartz, Mary E.; Foroud, Tatiana M.; Eberhart, Johann K.

    2013-01-01

    Human birth defects are highly variable and this phenotypic variability can be influenced by both the environment and genetics. However, the synergistic interactions between these two variables are not well understood. Fetal alcohol spectrum disorders (FASD) is the umbrella term used to describe the wide range of deleterious outcomes following prenatal alcohol exposure. Although FASD are caused by prenatal ethanol exposure, FASD are thought to be genetically modulated, although the genes regulating sensitivity to ethanol teratogenesis are largely unknown. To identify potential ethanol-sensitive genes, we tested five known craniofacial mutants for ethanol sensitivity: cyp26b1, gata3, pdgfra, smad5 and smoothened. We found that only platelet-derived growth factor receptor alpha (pdgfra) interacted with ethanol during zebrafish craniofacial development. Analysis of the PDGF family in a human FASD genome-wide dataset links PDGFRA to craniofacial phenotypes in FASD, prompting a mechanistic understanding of this interaction. In zebrafish, untreated pdgfra mutants have cleft palate due to defective neural crest cell migration, whereas pdgfra heterozygotes develop normally. Ethanol-exposed pdgfra mutants have profound craniofacial defects that include the loss of the palatal skeleton and hypoplasia of the pharyngeal skeleton. Furthermore, ethanol treatment revealed latent haploinsufficiency, causing palatal defects in ∼62% of pdgfra heterozygotes. Neural crest apoptosis partially underlies these ethanol-induced defects in pdgfra mutants, demonstrating a protective role for Pdgfra. This protective role is mediated by the PI3K/mTOR pathway. Collectively, our results suggest a model where combined genetic and environmental inhibition of PI3K/mTOR signaling leads to variability within FASD. PMID:23861062

  1. Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury

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    Sun-Hee Jang

    2014-09-01

    Full Text Available Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP against hepatotoxicity induced by acute ethanol (EtOH intoxication in rats. Methods: Sprague-Dawley (SD rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW. The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14 and Taechung (LR3. A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. Results: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST enzyme. It also significantly ameliorated the superoxide dismutase (SOD and the catalase (CAT activities. Conclusion: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol metabolizing enzymes and by attenuating oxidative stress.

  2. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

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    Hany H Arab

    Full Text Available Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o. attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO and tumor necrosis factor-α (TNF-α levels along with nuclear factor kappa B (NF-κB p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10 levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH, glutathione peroxidase (GPx and the total antioxidant capacity (TAC. With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2 in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2 and nitric oxide (NO. Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.

  3. Diosmin Protects against Ethanol-Induced Gastric Injury in Rats: Novel Anti-Ulcer Actions

    Science.gov (United States)

    Arab, Hany H.; Salama, Samir A.; Omar, Hany A.; Arafa, El-Shaimaa A.; Maghrabi, Ibrahim A.

    2015-01-01

    Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels along with nuclear factor kappa B (NF-κB) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses. PMID:25821971

  4. High frequency stimulation alters motor maps, impairs skilled reaching performance and is accompanied by an upregulation of specific GABA, glutamate and NMDA receptor subunits.

    Science.gov (United States)

    Henderson, A K; Pittman, Q J; Teskey, G C

    2012-07-26

    High frequency stimulation (HFS) has the potential to interfere with learning and memory. HFS and motor skill training both lead to potentiation of the stimulated network and alter motor map expression. However, the extent to which HFS can interfere with the learning and performance of a skilled motor task and the resulting effect on the representation of movement has not been examined. Moreover, the molecular mechanisms associated with HFS and skilled motor training on the motor cortex are not known. We hypothesized that HFS would impair performance on a skilled reaching task, and would be associated with alterations in motor map expression and protein levels compared to non-stimulated and untrained controls. Long Evans Hooded rats were chronically implanted with stimulating and recording electrodes in the corpus callosum and frontal neocortex, respectively. High frequency theta burst stimulation or sham stimulation was applied once daily for 20 sessions. The rats were divided into five groups: control, HFS and assessed at 1 week post stimulation, HFS and assessed 3 weeks post stimulation, reach trained, and HFS and reach trained. A subset of rats from each group was assessed with either intracortical microstimulation (ICMS) to examine motor map expression or Western blot techniques to determine protein expression of several excitatory and inhibitory receptor subunits. Firstly, we found that HFS resulted in larger and reorganized motor maps, and lower movement thresholds compared to controls. This was associated with an up-regulation of the GABA(A)α1 and NR1 receptor subunits 3 weeks after the last stimulation session only. Stimulation affected skilled reaching performance in a subset of all stimulated rats. Rats that were poor performers had larger rostral forelimb areas, higher proximal and lower distal movement thresholds compared to rats that were good performers after stimulation. Reach training alone was associated with an up-regulation of GABA(A)α1, α2

  5. Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers

    Directory of Open Access Journals (Sweden)

    Albaayit SFA

    2016-06-01

    Full Text Available Shaymaa Fadhel Abbas Albaayit,1,2 Yusuf Abba,3 Rasedee Abdullah,4 Noorlidah Abdullah1 1Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq; 3Department of Veterinary Pathology and Microbiology, 4Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Clausena excavata is a natural herb with both antioxidant and anti-inflammatory properties. It has been used for decades in folkloric practice for the amelioration of various ailments. In this study, the gastroprotective activity of methanolic extract of C. excavata leaves (MECE was determined in the Sprague Dawley rat ethanol-induced gastric ulcer model. Rats were pretreated with a single dose of vehicle (5% Tween 20, 20 mg/mL omeprazole, 400 and 200 mg/mL of MECE dissolved in 5% Tween 20. Ulcer was induced with 5 mL/kg of ethanol and stomach tissue was obtained after 1 hour. Histological examination was done on hematoxylin and eosin, periodic acid-Schiff, and immunochemically stained gastric mucosal tissues. Prostaglandin E2, superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation levels of the gastric tissue homogenates were also determined. Significantly (P<0.05 smaller ulcer areas, less intense edema, and fewer leukocytes’ infiltration were observed in MECE- and omeprazole-treated than in untreated gastric mucosa with ulcer. The gastric pH, mucus production, superoxide dismutase, catalase, and glutathione peroxidase contents increased, while the lipid peroxidation content decreased as a result of MECE treatment. Bcl-2-associated X protein was underexpressed, while heat shock protein 70 and transforming growth factor-beta protein were overexpressed in the ulcerated gastric mucosa tissues treated with omeprazole and MECE. Similarly, there was a reduction in

  6. Effects of a novel cognition-enhancing agent on fetal ethanol-induced learning deficits.

    Science.gov (United States)

    Savage, Daniel D; Rosenberg, Martina J; Wolff, Christina R; Akers, Katherine G; El-Emawy, Ahmed; Staples, Miranda C; Varaschin, Rafael K; Wright, Carrie A; Seidel, Jessica L; Caldwell, Kevin K; Hamilton, Derek A

    2010-10-01

    Drinking during pregnancy has been associated with learning disabilities in affected offspring. At present, there are no clinically effective pharmacotherapeutic interventions for these learning deficits. Here, we examined the effects of ABT-239, a histamine H₃ receptor antagonist, on fetal ethanol-induced fear conditioning and spatial memory deficits. Long-Evans rat dams stably consumed a mean of 2.82 g ethanol/kg during a 4-hour period each day during pregnancy. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, litter size and birth weights were not different between the ethanol-consuming and control groups. Female adult offspring from the control and fetal alcohol-exposed (FAE) groups received saline or 1 mg ABT-239/kg 30 minutes prior to fear conditioning training. Three days later, freezing time to the context was significantly reduced in saline-treated FAE rats compared to control. Freezing time in ABT-239-treated FAE rats was not different than that in controls. In the spatial navigation study, adult male offspring received a single injection of saline or ABT-239 30 minutes prior to 12 training trials on a fixed platform version of the Morris Water Task. All rats reached the same performance asymptote on Trials 9 to 12 on Day 1. However, 4 days later, first-trial retention of platform location was significantly worse in the saline-treated FAE rats compared control offspring. Retention by ABT-239-treated FAE rats was similar to that by controls. ABT-239's effect on spatial memory retention in FAE rats was dose dependent. These results suggest that ABT-239 administered prior to training can improve retention of acquired information by FAE offspring on more challenging versions of hippocampal-sensitive learning tasks. Further, the differential effects of ABT-239 in FAE offspring compared to controls raises questions about the impact of fetal ethanol exposure on histaminergic neurotransmission in

  7. Hepatoprotective Effect Of Crude Aqueous Leaf Extract Of Fig Tree Ficus Benjamina On Ethanol-Induced Liver Damage In Mice

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    Aimee Lynne Pilapil

    2017-06-01

    Full Text Available Alcoholic abuse remains to be the most common cause of liver cirrhosis with significant morbidity and mortality worldwide. Herbal supplements are being used to prevent damage in excessive alcohol intake and including hepatitis from other causes as hepatoprotective agents. Fig tree is currently being utilized in studies as a potential candidate for hepatoprotection but with limited success. This study determined the hepatoprotective effect of crude aqueous leaf extract of fig tree Ficus benjamina on ethanol-induced hepatotoxicity in mice. In this study fifteen Balbc mice were assigned to negative control positive control and treatment groups which received distilled water Silymarin and F. benjamina crude aqueous leaf extract respectively on day 0 to day 14. Ethanol-induced hepatotoxicity was done on day 7 to day 14 using ethanol given by oral gavage. Assessment of liver function and histology was done with the use of alanine aminotransferase ALT assay and histopathological study respectively. Results showed significant reduction of ALT levels in the treatment 52.40 UL and the positive control groups 42.58 UL as compared with the negative control group with a mean of 196.88 UL P0.05. The difference between the positive and treatment groups was not significant P0.05. The degree of hepatic injury was significantly severe in the negative control group than with the treatment and positive control groups P0.05. On the other hand the degree of hepatic injury showed no significant difference between the positive and treatment groups P0.05. Thus the crude aqueous leaf extract of F. benjamina has hepatoprotective property on ethanol-induced hepatotoxicity in mice similar to Silymarin. F. benjamina as an ornamental plant may be a source of phytochemical with potential pharmaceutical and functional activities.

  8. Gastroprotective effect of heme-oxygenase 1/biliverdin/CO pathway in ethanol-induced gastric damage in mice.

    Science.gov (United States)

    Gomes, Antoniella S; Gadelha, Gemima G; Lima, Samara J; Garcia, Joyce A; Medeiros, Jand Venes R; Havt, Alexandre; Lima, Aldo A; Ribeiro, Ronaldo A; Brito, Gerly Anne C; Cunha, Fernando Q; Souza, Marcellus H L P

    2010-09-10

    Our objective was to evaluate the role of heme-oxygenase 1 (HO-1)/biliverdin/CO pathway in gastric defense against ethanol-induced gastric damage in mice. Mice were pre-treated with saline, hemin (HO-1 inducer), biliverdin (HO-1 product), dimanganese decacarbonyl (DMDC, CO donor) or zinc protoporphyrin IX (ZnPP IX, HO-1 antagonist). Another group received soluble guanylate cyclase (sGC) inhibitor (ODQ) 30 min before hemin, biliverdin or DMDC. After 30 min, gastric damage was induced by ethanol. After one hour, rats were sacrificed. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malonylaldehyde (MDA), glutathione (GSH) or bilirubin. HO-1 expression was determined after saline or ethanol administration by polymerase chain reaction (PCR) or immunohistochemistry. Ethanol (25% or 50%) induced gastric damage, increased MDA levels and reduced GSH in the gastric tissue. Ethanol 50% increased HO-1 mRNA transcripts, HO-1 immunoreactivity, and bilirubin concentration in gastric mucosa. Pre-treatment with hemin reduced gastric damage and MDA formation and increased GSH concentration in the gastric mucosa. ZnPP IX amplified the ethanol-induced gastric lesion, increased MDA formation and decreased GSH concentration in gastric mucosa. Biliverdin and DMDC reduced gastric damage and MDA formation and increased GSH concentration in the gastric tissue. ODQ completely abolished the DMDC protective gastric effect. However, effects of hemin or biliverdin did not change with ODQ treatment. Our results suggest that HO-1/biliverdin/CO pathway plays a protective role against ethanol-induced gastric damage through mechanisms that can be dependent (CO) or independent (biliverdin) of sGC activation. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  9. Microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity via TLR7.

    Science.gov (United States)

    Coleman, Leon G; Zou, Jian; Crews, Fulton T

    2017-01-25

    Toll-like receptor (TLR) signaling is emerging as an important component of neurodegeneration. TLR7 senses viral RNA and certain endogenous miRNAs to initiate innate immune responses leading to neurodegeneration. Alcoholism is associated with hippocampal degeneration, with preclinical studies linking ethanol-induced neurodegeneration with central innate immune induction and TLR activation. The endogenous miRNA let-7b binds TLR7 to cause neurodegeneration. TLR7 and other immune markers were assessed in postmortem human hippocampal tissue that was obtained from the New South Wales Tissue Bank. Rat hippocampal-entorhinal cortex (HEC) slice culture was used to assess specific effects of ethanol on TLR7, let-7b, and microvesicles. We report here that hippocampal tissue from postmortem human alcoholic brains shows increased expression of TLR7 and increased microglial activation. Using HEC slice culture, we found that ethanol induces TLR7 and let-7b expression. Ethanol caused TLR7-associated neuroimmune gene induction and initiated the release let-7b in microvesicles (MVs), enhancing TLR7-mediated neurotoxicity. Further, ethanol increased let-7b binding to the danger signaling molecule high mobility group box-1 (HMGB1) in MVs, while reducing let-7 binding to classical chaperone protein argonaute (Ago2). Flow cytometric analysis of MVs from HEC media and analysis of MVs from brain cell culture lines found that microglia were the primary source of let-7b and HMGB1-containing MVs. Our results identify that ethanol induces neuroimmune pathology involving the release of let-7b/HMGB1 complexes in microglia-derived microvesicles. This contributes to hippocampal neurodegeneration and may play a role in the pathology of alcoholism.

  10. Hepatoprotective effects of aqueous leaf extract and crude isolates of Murraya koenigii against in vitro ethanol-induced hepatotoxicity model.

    Science.gov (United States)

    Sathaye, Sadhana; Bagul, Yogita; Gupta, Sanjay; Kaur, Harpreet; Redkar, Roopali

    2011-09-01

    Medicinal plants constitute a principal health care resource corroborating their gradual acceptance by the global population. The ethno medicinal plant, Murraya koeniggi (Curry-leaf tree) as is native to India exhibits diverse biological activities. Unpublished data from our laboratory revealed hepatoprotective activity of its crude aqueous extract against ethanol-induced hepatotoxicity in experimental animals. Chronic ethanol consumption diminishes the cellular antioxidant levels through free radical induced injury causing hepatitis and cirrhosis with mortality in severe cases. This provided a rationale for studying its mechanistic approaches in terms of modulation of antioxidant defenses for probable hepatoprotective activity against ethanol-induced hepatotoxicity in vitro. Based on the inhibitory concentration (IC(50)) obtained from the cell viability assay, graded concentrations of 100 μg/ml and 500 μg/ml of aqueous extract (WE), isolated carbazole alkaloids (CA) and tannin (T) fraction were chosen to study the hepatoprotective activity against ethanol-induced hepatotoxicity using liver carcinoma cell lines (Hep G(2)). Their antioxidant activity with anti-lipid peroxidation potential (LPO), effects on protein content, liver metabolizing enzymes viz., glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and the morphology of the cells were studied as parameters of hepatoprotection. The tannins and the carbazole alkaloids from the aqueous extract exhibited excellent hepatoprotective activity with respect to the different parameters studied and maintained normal morphology even after ethanolic challenge to the cells as comparable to the protection offered by the standard drug L-ornithine L-aspartate (LOLA). The modulating effect of the aqueous extract and isolates on liver metabolizing enzymes, reduction in lipid peroxidation and decreased cellular damage were found to contribute to the hepatoprotective activity. Copyright © 2010 Elsevier GmbH. All

  11. Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat

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    Han JH

    2015-06-01

    Full Text Available Jin-hong Han,1,2 Hong-zhao Tian,2 Yang-yang Lian,1 Yi Yu,1 Cheng-biao Lu,2 Xin-min Li,3 Rui-ling Zhang,1 Haiyun Xu4 1The Second Affiliated Hospital of Xinxiang Medical University, 2School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 4The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with

  12. Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

    Science.gov (United States)

    Guo, Rui; Ren, Jun

    2010-01-18

    Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2) (*-). Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF. Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

  13. Hepato- and neuro-protective effects of watermelon juice on acute ethanol-induced oxidative stress in rats

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    Omolola R. Oyenihi

    2016-01-01

    Oral administration of watermelon juice for fifteen (15 days prior to ethanol intoxication, significantly reduced the concentration of MDA in the liver and brain of rats. In addition, water melon pre-treatment increased the concentration of GSH and normalized catalase activity in both tissues in comparison to the ethanol control group. Phytochemical analysis revealed the presence of phenol, alkaloids, saponins, tannins and steroids in watermelon juice. Our findings indicate that watermelon juice demonstrate anti-oxidative effects in ethanol-induced oxidation in the liver and brain of rats; which could be associated with the plethora of antioxidant phyto-constituents present there-in.

  14. Multiple factors, including non-motor impairments, influence decision making with regard to exercise participation in Parkinson's disease: a qualitative enquiry.

    Science.gov (United States)

    O'Brien, Christine; Clemson, Lindy; Canning, Colleen G

    2016-01-01

    To explore how the meaning of exercise and other factors interact and influence the exercise behaviour of individuals with Parkinson's disease (PD) enrolled in a 6-month minimally supervised exercise program to prevent falls, regardless of whether they completed the prescribed exercise or not. This qualitative study utilised in-depth semi-structured interviews analysed using grounded theory methodology. Four main themes were constructed from the data: adapting to change and loss, the influence of others, making sense of the exercise experience and hope for a more active future. Participation in the PD-specific physiotherapy program involving group exercise provided an opportunity for participants to reframe their identity of their "active" self. Three new influences on exercise participation were identified and explored: non-motor impairments of apathy and fatigue, the belief in a finite energy quota, and the importance of feedback. A model was developed incorporating the themes and influences to explain decision-making for exercise participation in this group. Complex and interacting issues, including non-motor impairments, need to be considered in order to enhance the development and ongoing implementation of effective exercise programmes for people with PD. Exercise participation can assist individuals to reframe their identity as they are faced with losses associated with Parkinson's disease and ageing. Non-motor impairments of apathy and fatigue may influence exercise participation in people with Parkinson's disease. Particular attention needs to be paid to the provision of feedback in exercise programs for people with Parkinson's disease as it important for their decision-making about continuing exercise.

  15. Efficacy of Bobath versus orthopaedic approach on impairment and function at different motor recovery stages after stroke: a randomized controlled study.

    Science.gov (United States)

    Wang, Ray-Yau; Chen, Hsiu-I; Chen, Chen-Yin; Yang, Yea-Ru

    2005-03-01

    To investigate the effectiveness of Bobath on stroke patients at different motor stages by comparing their treatment with orthopaedic treatment. A single-blind study, with random assignment to Bobath or orthopaedic group. Physical therapy department of a medical centre. Twenty-one patients with stroke with spasticity and 23 patients with stroke at relative recovery stages participated. Twenty sessions of Bobath programme or orthopaedic treatment programme given in four weeks. Stroke Impairment Assessment Set (SIAS), Motor Assessment Scale (MAS), Berg Balance Scale (BBS) and Stroke Impact Scale (SIS) for impairment and functional limitation level. Participants with spasticity showed greater improvement in tone control (change score: 1.20 +/- 1.03 versus 0.08 +/- 0.67, p = 0.006), MAS (change score: 7.64 +/- 4.03 versus 4.00 +/- 1.95, p = 0.011), and SIS (change score: 7.30 +/- 6.24 versus 1.25 +/- 5.33, p = 0.023) after 20 sessions of Bobath treatment than with orthopaedic treatment. Participants with relative recovery receiving Bobath treatment showed greater improvement in MAS (change score: 6.14 +/- 5.55 versus 2.77 +/- 9.89, p = 0.007), BBS (change score: 19.18 +/- 15.94 versus 6.85 +/- 5.23, p = 0.015), and SIS scores (change score: 8.50 +/- 3.41 versus 3.62 +/- 4.07, p = 0.006) than those with orthopaedic treatment. Bobath or orthopaedic treatment paired with spontaneous recovery resulted in improvements in impairment and functional levels for patient with stroke. Patients benefit more from the Bobath treatment in MAS and SIS scores than from the orthopaedic treatment programme regardless of their motor recovery stages.

  16. Abbreviated exposure to hypoxia is sufficient to induce CNS dysmyelination, modulate spinal motor neuron composition, and impair motor development in neonatal mice.

    Directory of Open Access Journals (Sweden)

    Jens O Watzlawik

    Full Text Available Neonatal white matter injury (nWMI is an increasingly common cause of cerebral palsy that results predominantly from hypoxic injury to progenitor cells including those of the oligodendrocyte lineage. Existing mouse models of nWMI utilize prolonged periods of hypoxia during the neonatal period, require complex cross-fostering and exhibit poor growth and high mortality rates. Abnormal CNS myelin composition serves as the major explanation for persistent neuro-motor deficits. Here we developed a simplified model of nWMI with low mortality rates and improved growth without cross-fostering. Neonatal mice are exposed to low oxygen from postnatal day (P 3 to P7, which roughly corresponds to the period of human brain development between gestational weeks 32 and 36. CNS hypomyelination is detectable for 2-3 weeks post injury and strongly correlates with levels of body and brain weight loss. Immediately following hypoxia treatment, cell death was evident in multiple brain regions, most notably in superficial and deep cortical layers as well as the subventricular zone progenitor compartment. PDGFαR, Nkx2.2, and Olig2 positive oligodendrocyte progenitor cell were significantly reduced until postnatal day 27. In addition to CNS dysmyelination we identified a novel pathological marker for adult hypoxic animals that strongly correlates with life-long neuro-motor deficits. Mice reared under hypoxia reveal an abnormal spinal neuron composition with increased small and medium diameter axons and decreased large diameter axons in thoracic lateral and anterior funiculi. Differences were particularly pronounced in white matter motor tracts left and right of the anterior median fissure. Our findings suggest that 4 days of exposure to hypoxia are sufficient to induce experimental nWMI in CD1 mice, thus providing a model to test new therapeutics. Pathological hallmarks of this model include early cell death, decreased OPCs and hypomyelination in early postnatal life

  17. The effect of motor control and tactile acuity training on patients with non-specific low back pain and movement control impairment.

    Science.gov (United States)

    Gutknecht, Magdalena; Mannig, Angelika; Waldvogel, Anja; Wand, Benedict M; Luomajoki, Hannu

    2015-10-01

    Movement control impairment is a clinical subgroup of non-specific low back pain which can be assessed reliably. There is a strong correlation between tactile acuity and movement control suggesting these two treatments might have additive effects. The first research aim was to determine if patients with a motor control impairment demonstrated improvement in outcome with combined tactile acuity and motor control training. The second aim was to determine if tactile acuity training enhanced the effect of motor control training. The primary study was a single-arm cohort study conducted in three physiotherapy practices in the German-speaking part of Switzerland. 40 patients (23 males and 17 females) suffering from non-specific low back pain (NSLBP) and movement control impairment were treated. Patients were assessed at baseline and immediately post treatment. Treatment included exercises to lumbopelvic control and graphesthesia training to improve tactile acuity. Treatment effects were evaluated using the Roland Morris disability questionnaire (RMQ) and the patient-specific functional scale (PSFS). The performance on a set of six movement control tests and lumbar two-point discrimination were also assessed. The results of this cohort study were compared with a historic control group which was comparable with the primary study but included only motor control exercises. All the outcomes improved significantly with the combined training (RMQ - 2.2 pts., PSFS - 2.8 pts.; MCTB - 2.02 pts. & TPD - 17.07 mm; all p control, there was no significant differences in movement control, patient-specific functional complaints or disability between the groups. The results of this study, based on a before and after intervention comparison, showed that outcome improved significantly following combined tactile acuity and motor control training. However, compared to an earlier study, the tactile acuity training did not have an additional effect to the results. The use of historical

  18. Participation in Physical Play and Leisure in Children With Motor Impairments: Mixed-Methods Study to Generate Evidence for Developing an Intervention.

    Science.gov (United States)

    Kolehmainen, Niina; Ramsay, Craig; McKee, Lorna; Missiuna, Cheryl; Owen, Christine; Francis, Jill

    2015-10-01

    Participation in physical play/leisure (PPP) is an important therapy goal of children with motor impairments. Evidence for interventions promoting PPP in these children is scarce. The first step is to identify modifiable, clinically meaningful predictors of PPP for targeting by interventions. The study objective was to identify, in children with motor impairments, body function and structure, activity, environmental, and personal factors related to PPP and modifiable by therapists. This was a mixed-methods, intervention development study. The World Health Organization framework International Classification of Functioning, Disability and Health was used. Participants were children (6-8 years old) with motor impairments, mobilizing independently with or without equipment and seen by physical therapists or occupational therapists in 6 regions in the United Kingdom, and their parents. Self-reported PPP was assessed with the Children's Assessment of Participation and Enjoyment. Modifiable-factor data were collected with therapists' observations, parent questionnaires, and child-friendly interviews. The Children's Assessment of Participation and Enjoyment, therapist, and parent data were analyzed using descriptive statistics and linear regression. Interview data were analyzed for emerging themes. Children's (n=195) PPP (X=18 times per week, interquartile range=11-25) was mainly 'recreational' (eg, pretend play, playing with pets) rather than 'active physical' (eg, riding a bike/scooter). Parents (n=152) reported positive beliefs about children's PPP but various levels of family PPP. Therapists reported 23 unique impairments (eg, muscle tone), 16 activity limitations (eg, walking), and 3 personal factors (eg, child's PPP confidence). Children interviewed (n=17) reported a strong preference for active play but indicated that adults regulated their PPP. Family PPP and impairment in the child's movement-related body structures explained 18% of the variation in PPP. Family

  19. Raf-1 kinase inhibitory protein (RKIP) mediates ethanol-induced sensitization of secretagogue signaling in pancreatic acinar cells.

    Science.gov (United States)

    Kim, Sung Ok; Ives, Kirk L; Wang, Xiaofu; Davey, Robert A; Chao, Celia; Hellmich, Mark R

    2012-09-28

    Excessive alcohol consumption is associated with most cases of chronic pancreatitis, a progressive necrotizing inflammatory disease that can result in pancreatic insufficiency due to acinar atrophy and fibrosis and an increased risk of pancreatic cancer. At a cellular level acute alcohol exposure can sensitize pancreatic acinar cells to secretagogue stimulation, resulting in dysregulation of intracellular Ca(2+) homeostasis and premature digestive enzyme activation; however, the molecular mechanisms by which ethanol exerts these toxic effects have remained undefined. In this study we identify Raf-1 kinase inhibitory protein as an essential mediator of ethanol-induced sensitization of cholecystokinin- and carbachol-regulated Ca(2+) signaling in pancreatic acinar cells. We show that exposure of rodent acinar cells to ethanol induces protein kinase C-dependent Raf-1 kinase inhibitory protein phosphorylation, sensitization of cholecystokinin-stimulated Ca(2+) signaling, and potentiation of both basal and cholecystokinin-stimulated extracellular signal-regulated kinase activation. Furthermore, we show that either suppression of Raf-1 kinase inhibitory protein expression using short hairpin RNA or gene ablation prevented the sensitizing effects of ethanol on cholecystokinin- and carbachol-stimulated Ca(2+) signaling and intracellular chymotrypsin activation in pancreatic acinar cells, suggesting that the modulation of Raf-1 inhibitory protein expression may have future therapeutic utility in the prevention or treatment of alcohol-associated pancreatitis.

  20. beta-Carotene exhibits antioxidant and anti-apoptotic properties to prevent ethanol-induced cytotoxicity in isolated rat hepatocytes.

    Science.gov (United States)

    Peng, Hsiang-Chi; Chen, Jiun-Rong; Chen, Ya-Ling; Yang, Suh-Ching; Yang, Sien-Sing

    2010-06-01

    The study was designed to evaluate the effects of 1 microM beta-carotene on antioxidant status in ethanol-treated rat hepatocytes and investigate possible anti-apoptotic mechanisms of beta-carotene in protecting ethanol-induced cytotoxicity. The isolated rat hepatocytes were incubated for 48 h in a medium with or without alcohol (100 mM) and mu-carotene (1 microM) using the following groups: the control (C), beta-carotene (CB), ethanol (E), and ethanol + beta-carotene (EB) groups. The cell viability, antioxidative status, cytochrome P450 2E1 (CYP2E1) and caspase expressions in hepatocytes were measured. The E group demonstrated lower cell viability, glutathione (GSH) levels, and lipid peroxide accumulation in rat hepatocytes; meanwhile, CYP2E1, caspase-3, and caspase-9 expressions increased. In contrast, cell viability, GSH levels, and glutathione reductase (GRD) activity significantly increased while lipid peroxides and expressions of CYP2E1, casapse-3, and caspase-9 decreased in the EB group. The results suggest that ethanol treatment decreases cell viability in rat hepatocytes via induced oxidative stress. 1 muM beta-carotene decreased oxidative stress and prevented ethanol-induced cell death by inhibiting caspase-9 and caspase-3 expression.

  1. Sulfated-Polysaccharide Fraction from Red Algae Gracilaria caudata Protects Mice Gut Against Ethanol-Induced Damage

    Science.gov (United States)

    Silva, Renan Oliveira; dos Santos, Geice Maria Pereira; Nicolau, Lucas Antonio Duarte; Lucetti, Larisse Tavares; Santana, Ana Paula Macedo; de Souza Chaves, Luciano; Barros, Francisco Clark Nogueira; Freitas, Ana Lúcia Ponte; Souza, Marcellus Henrique Loiola Ponte; Medeiros, Jand-Venes Rolim

    2011-01-01

    The aim of the present study was to investigate the gastroprotective activity of a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae Gracilaria caudata and the mechanism underlying the gastroprotective activity. Male Swiss mice were treated with PLS (3, 10, 30 and 90 mg·kg−1, p.o.), and after 30 min, they were administered 50% ethanol (0.5 mL/25 g−1, p.o.). One hour later, gastric damage was measured using a planimeter. Samples of the stomach tissue were also obtained for histopathological assessment and for assays of glutathione (GSH) and malondialdehyde (MDA). Other groups were pretreated with l-NAME (10 mg·kg−1, i.p.), dl-propargylglycine (PAG, 50 mg·kg−1, p.o.) or glibenclamide (5 mg·kg−1, i.p.). After 1 h, PLS (30 mg·kg−1, p.o.) was administered. After 30 min, ethanol 50% was administered (0.5 mL/25g−1, p.o.), followed by sacrifice after 60 min. PLS prevented-ethanol-induced macroscopic and microscopic gastric injury in a dose-dependent manner. However, treatment with l-NAME or glibenclamide reversed this gastroprotective effect. Administration of propargylglycine did not influence the effect of PLS. Our results suggest that PLS has a protective effect against ethanol-induced gastric damage in mice via activation of the NO/KATP pathway. PMID:22163181

  2. Gastroprotective effect of the traditional herbal medicine, Sipjeondaebo-tang water extract, against ethanol-induced gastric mucosal injury.

    Science.gov (United States)

    Jeon, Woo-Young; Shin, In-Sik; Shin, Hyeun-Kyoo; Lee, Mee-Young

    2014-10-04

    Sipjeondaebo-tang, a traditional herbal medicine, has been reported to activate the immune response. Although, most research has focused on its anticancer activity. The purpose of this study was to determine whether Sipjeondaebo-tang exerts antioxidant activity against ethanol-induced gastric injury. Gastric mucosal injury was induced by the oral administration of absolute ethanol at 5 mL/kg to rats after 18 h fast. Sipjeondaebo-tang water extract (SDTW; 200 mg/kg of body weight) was administered to rats 2 h before the oral administration of absolute ethanol. Gastric mucosal injury was evaluated by measuring the gastric injury, such as extent of lesions, malondialdehyde (MDA) concentration, glutathione (GSH) content and activities of antioxidant enzymes including catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, and superoxide dismutase in stomach tissue. Oral administration of SDTW markedly decreased the damage by conditioning the gastric mucosa such as hemorrhage, hyperemia. Pretreatment with SDTW significantly reduced MDA concentration and significantly increased GSH content and the activities of antioxidant enzymes. In an acute toxicity study, no adverse effects of SDTW were observed at doses up to 5000 mg/kg/day. SDTW may protect the gastric mucosa against ethanol-induced gastric mucosa injury. These results suggested that SDTW might also play an important role in the gastroprotection based on their antioxidant effect.

  3. Synbiotics reduce ethanol-induced hepatic steatosis and inflammation by improving intestinal permeability and microbiota in rats.

    Science.gov (United States)

    Chiu, Wan-Chun; Huang, Ya-Li; Chen, Ya-Ling; Peng, Hsiang-Chi; Liao, Wei-Hsiang; Chuang, Hsiao-Li; Chen, Jiun-Rong; Yang, Suh-Ching

    2015-05-01

    Clinical and animal experiments indicated that gut-derived endotoxin and imbalanced intestinal microbiota contribute to the pathogenesis of alcoholic liver disease (ALD). In this study, we investigated whether synbiotic supplementation could improve ALD in rats by altering the intestinal microbial composition and improving the intestinal integrity. Male Wistar rats were divided into four groups according to plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and subjected to either a normal liquid diet (C), a normal liquid diet with synbiotic supplementation (C + S), an ethanol liquid diet (E), or an ethanol liquid diet with synbiotic supplementation (E + S) for 12 weeks. Results revealed that the ethanol-fed group showed increases in plasma AST and ALT activities, the endotoxin level, the hepatic triglyceride (TG) level, and hepatic tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 levels, and a decrease in the hepatic IL-10 level. Ethanol-feeding also contributed to increased intestinal permeability and decreased fecal bifidobacteria and lactobacilli amounts. However, synbiotic supplementation effectively attenuated the plasma endotoxin, hepatic TG and TNF-α levels, and increased the hepatic IL-10 level. Furthermore, synbiotic supplementation protected the rats against ethanol-induced hyperpermeability of the intestine, and significantly increased amounts of bifidobacteria and lactobacilli in the feces. This study demonstrated that synbiotics possess a novel hepatoprotective function by improving the intestinal permeability and microbiota in rats with ethanol-induced liver injury.

  4. Sodium selenite/selenium nanoparticles (SeNPs) protect cardiomyoblasts and zebrafish embryos against ethanol induced oxidative stress.

    Science.gov (United States)

    Kalishwaralal, Kalimuthu; Jeyabharathi, Subhaschandrabose; Sundar, Krishnan; Muthukumaran, Azhaguchamy

    2015-10-01

    Alcoholic cardiomyopathy is the damage caused to the heart muscles due to high level of alcohol consumption resulting in enlargement and inflammation of the heart. Selenium is an important trace element that is beneficial to human health. Selenium protects the cells by preventing the formation of free radicals in the body. In the present study, protein mediated synthesis of SeNPs was investigated. Two different sizes of SeNPs were synthesized using BSA and keratin. The synthesized SeNPs were characterized by scanning electron microscopy (SEM) with elemental composition analysis Energy Dispersive X-ray spectroscopy(EDX) and X-ray diffraction (XRD). This study demonstrates the in vitro and in vivo antioxidative effects of sodium selenite and SeNPs. Further selenium and SeNPs were evaluated for their ability to protect against 1% ethanol induced oxidative stress in H9C2 cell line. The selenium and SeNPs were found to reduce the 1% ethanol-induced oxidative damage through scavenging intracellular reactive oxygen species. The selenium and SeNPs could also prevent pericardial edema induced ethanol treatment and reduced apoptosis and cell death in zebrafish embryos. The results indicate that selenium and SeNPs could potentially be used as an additive in alcoholic beverage industry to control the cardiomyopathy. Copyright © 2015 Elsevier GmbH. All rights reserved.

  5. Phytochemical, antioxidant and protective effect of Rhus tripartitum root bark extract against ethanol-induced ulcer in rats.

    Science.gov (United States)

    Alimi, Hichem; Mbarki, Sakhria; Barka, Zeineb B; Feriani, Anwer; Bouoni, Zouhour; Hfaeidh, Najla; Sakly, Mohsen; Tebourbi, Olfa; Rhouma, Khémais B

    2013-03-01

    Rhus tripartitum (sumac) is an Anacardiaceae tree with a wide phytotherapeutic application including the use of its roots in the management of gastric ulcer. In the present study the Rhus tripartitum root barks extract (RTE) was phytochemical studied, in vitro tested for their potential antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power assay and in vivo evaluated for its ability to prevent ethanol-induced gastric ulcer in rats. The RTE was rich in phenolics, flavonoids, tannins and polysaccharide contents and exhibited a low but not weak in vitro antioxidant activity when compared with (+)-catechin. Pre-treatment with RTE at oral doses 50, 200 and 400 mg/kg body weight was found to provide a dose-dependent protection against ethanol-induced ulcer by averting the deep ulcer lesions of the gastric epithelium, by reducing gastric juice and acid output, by enhancing gastric mucus production by preserving normal antioxidant enzymes activities, and inhibiting the lipid peroxidation. The antiulcerogenic activity of RTE might be due to a possible synergistic antioxidant and antisecretory effects.

  6. Rutin upregulates neurotrophic factors resulting in attenuation of ethanol-induced oxidative stress in HT22 hippocampal neuronal cells.

    Science.gov (United States)

    Song, Kibbeum; Na, Ji-Young; Kim, Sokho; Kwon, Jungkee

    2015-08-15

    Alcoholism, which refers to the excessive consumption of alcohol, has deleterious effects on personal and social health worldwide. Oxidative stress evoked by ethanol plays an important role in the pathogenesis of neurodegenerative diseases. Rutin is a bioflavonoid that has been demonstrated to scavenge superoxide radicals. However, the effects of rutin on neuronal toxicity following ethanol-induced oxidative stress have not previously been investigated. Thus we investigated the antioxidant effect of rutin in hippocampal neuronal cells (HT22 cells) exposed to ethanol. We found that rutin pretreatment prevented the ethanol-induced decrease in protein level expression of nerve growth factor, glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in HT22 cells. Cell viability as analyzed by the MTT method revealed a significant increase in cell viability in the rutin-treated group compared with the ethanol-only treated group. Antioxidant effect of rutin was confirmed to be due to reduction of intracellular reactive oxidative species production in ethanol-treated HT22 cells. Moreover, rutin significantly increased the level of the antioxidant glutathione, and the activities of the antioxidant enzymes superoxide dismutase and catalase. These findings indicate that rutin has potential as a therapeutic agent to treat alcohol-related neurodegenerative disorders. © 2014 Society of Chemical Industry.

  7. [Associations between ALDH2 and ADH1B Genotypes and Ethanol-Induced Cutaneous Erythema in Young Japanese Women].

    Science.gov (United States)

    Hayashida, Mariko; Kamada, Yuka; Ota, Tomoko; Kojima, Sayuri; Iwao-Koizumi, Kyoko; Murata, Shigenori; Kinoshita, Kenji

    2015-01-01

    The purpose of this study was to identify associations between ALDH2 and ADH1B genotypes and ethanol-induced cutaneous erythema and assess the accuracy of an ethanol patch test in young Japanese women. The subjects were 942 female Japanese university students. They were given an ethanol patch test and examined for ethanol-induced cutaneous erythema both immediately after removing the patch and 10 minutes after removing the patch. A saliva sample was used to determine the ALDH2 and ADH1B genotype of each subject by realtime PCR. The sensitivity and specificity of erythema immediately after removing the patch as the marker for the presence of inactive ALDH2 were 69.6% and 87.7%, respectively, and the sensitivity and specificity of erythema 10 minutes after removing the patch were 85.2% and 85.1%, respectively. The sensitivity of erythema after 10 minutes was markedly lower in the ADH1B*1/*1 carriers than in the ADH1B*2 carriers (8.3% vs. 89.7%, palcohol. This is a valuable tool for improving the health literacy of younger generation subjects.

  8. Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo.

    Science.gov (United States)

    Sidahmed, Heyam M A; Hashim, Najihah Mohd; Amir, Junaidah; Abdulla, Mahmood Ameen; Hadi, A Hamid A; Abdelwahab, Siddig Ibrahim; Taha, Manal Mohamed Elhassan; Hassandarvish, Pouya; Teh, Xinsheng; Loke, Mun Fai; Vadivelu, Jamuna; Rahmani, Mawardi; Mohan, Syam

    2013-07-15

    Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia. In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats. The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol. The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo. The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro. The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions. PA pretreatment significantly (pulcerated tissue. In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition. It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium. The efficacy of PA was accomplished safely without the presence of any toxicological parameters. The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori. Copyright © 2013 Elsevier GmbH. All rights reserved.

  9. Simultaneously measuring gait and cognitive performance in cognitively healthy and cognitively impaired older adults: the Basel motor-cognition dual-task paradigm.

    Science.gov (United States)

    Theill, Nathan; Martin, Mike; Schumacher, Vera; Bridenbaugh, Stephanie A; Kressig, Reto W

    2011-06-01

    To investigate dual-task performance of gait and cognition in cognitively healthy and cognitively impaired older adults using a motor-cognition dual-task paradigm. Cross-sectional retrospective study. The Basel Memory Clinic and the Basel Study on the Elderly (Project BASEL). Seven hundred eleven older adults (mean age 77.2±6.2, 350 (49.2%) female and 361 (50.8%) male). Gait velocity and cognitive task performance using a working memory (counting backward from 50 by 2s) and a semantic memory (enumerating animal names) task were measured during single- and dual-task conditions. Gait was assessed using the GAITRite electronic walkway system. Cognitive impairment was defined as a score less than 25 on the Mini-Mental State Examination. During dual tasks, participants reduced gait velocity (P.10). Cognitively impaired individuals had lower baseline gait velocity and a greater reduction in gait velocity but not cognitive performance during dual tasks than cognitively healthy participants (P<.01). Gait velocity was lower during both dual tasks, whereas decrease in cognitive performance depended on the cognitive ability needed in the dual-task condition. Cognitively impaired individuals generally have poorer baseline performance and greater dual task-related gait velocity reduction than those who are cognitively healthy. Future research should include different conditions for gait to determine adaptive potentials of older adults. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

  10. Lower Extremity Motor Impairments in Ambulatory Chronic Hemiparetic Stroke: Evidence for Lower Extremity Weakness and Abnormal Muscle and Joint Torque Coupling Patterns.

    Science.gov (United States)

    Sánchez, Natalia; Acosta, Ana Maria; Lopez-Rosado, Roberto; Stienen, Arno H A; Dewald, Julius P A

    2017-09-01

    Although global movement abnormalities in the lower extremity poststroke have been studied, the expression of specific motor impairments such as weakness and abnormal muscle and joint torque coupling patterns have received less attention. We characterized changes in strength, muscle coactivation and associated joint torque couples in the paretic and nonparetic extremity of 15 participants with chronic poststroke hemiparesis (age 59.6 ± 15.2 years) compared with 8 age-matched controls. Participants performed isometric maximum torques in hip abduction, adduction, flexion and extension, knee flexion and extension, ankle dorsi- and plantarflexion and submaximal torques in hip extension and ankle plantarflexion. Surface electromyograms (EMGs) of 10 lower extremity muscles were measured. Relative weakness (paretic extremity compared with the nonparetic extremity) was measured in poststroke participants. Differences in EMGs and joint torques associated with maximum voluntary torques were tested using linear mixed effects models. Results indicate significant poststroke torque weakness in all degrees of freedom except hip extension and adduction, adductor coactivation during extensor tasks, in addition to synergistic muscle coactivation patterns. This was more pronounced in the paretic extremity compared with the nonparetic extremity and with controls. Results also indicated significant interjoint torque couples during maximum and submaximal hip extension in both extremities of poststroke participants and in controls only during maximal hip extension. Additionally, significant interjoint torque couples were identified only in the paretic extremity during ankle plantarflexion. A better understanding of these motor impairments is expected to lead to more effective interventions for poststroke gait and posture.

  11. Combined transcranial direct current stimulation and home-based occupational therapy for upper limb motor impairment following intracerebral hemorrhage: a double-blind randomized controlled trial.

    Science.gov (United States)

    Mortensen, Jesper; Figlewski, Krystian; Andersen, Henning

    2016-01-01

    To investigate the combined effect of transcranial direct current stimulation (tDCS) and home-based occupational therapy on activities of daily living (ADL) and grip strength, in patients with upper limb motor impairment following intracerebral hemorrhage (ICH). A double-blind randomized controlled trial with one-week follow-up. Patients received five consecutive days of occupational therapy at home, combined with either anodal (n = 8) or sham (n = 7) tDCS. The primary outcome was ADL performance, which was assessed with the Jebsen-Taylor test (JTT). Both groups improved JTT over time (p occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is a promising add-on intervention regarding training of upper limb motor impairment. It is well tolerated by patients and can easily be applied for home-based training. Larger studies with long-term follow-up are needed to further explore possible effects of tDCS in patients with ICH. Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is well tolerated by patients and can easily be applied for home-based rehabilitation.

  12. Usability and Workload of Access Technology for People With Severe Motor Impairment: A Comparison of Brain-Computer Interfacing and Eye Tracking.

    Science.gov (United States)

    Pasqualotto, Emanuele; Matuz, Tamara; Federici, Stefano; Ruf, Carolin A; Bartl, Mathias; Olivetti Belardinelli, Marta; Birbaumer, Niels; Halder, Sebastian

    2015-01-01

    Eye trackers are widely used among people with amyotrophic lateral sclerosis, and their benefits to quality of life have been previously shown. On the contrary, Brain-computer interfaces (BCIs) are still quite a novel technology, which also serves as an access technology for people with severe motor impairment. To compare a visual P300-based BCI and an eye tracker in terms of information transfer rate (ITR), usability, and cognitive workload in users with motor impairments. Each participant performed 3 spelling tasks, over 4 total sessions, using an Internet browser, which was controlled by a spelling interface that was suitable for use with either the BCI or the eye tracker. At the end of each session, participants evaluated usability and cognitive workload of the system. ITR and System Usability Scale (SUS) score were higher for the eye tracker (Wilcoxon signed-rank test: ITR T = 9, P = .016; SUS T = 12.50, P = .035). Cognitive workload was higher for the BCI (T = 4; P = .003). Although BCIs could be potentially useful for people with severe physical disabilities, we showed that the usability of BCIs based on the visual P300 remains inferior to eye tracking. We suggest that future research on visual BCIs should use eye tracking-based control as a comparison to evaluate performance or focus on nonvisual paradigms for persons who have lost gaze control. © The Author(s) 2015.

  13. Rethinking stimulation of the brain in stroke rehabilitation: why higher motor areas might be better alternatives for patients with greater impairments.

    Science.gov (United States)

    Plow, Ela B; Cunningham, David A; Varnerin, Nicole; Machado, Andre

    2015-06-01

    Stimulating the brain to drive its adaptive plastic potential is promising to accelerate rehabilitative outcomes in stroke. The ipsilesional primary motor cortex (M1) is invariably facilitated. However, evidence supporting its efficacy is divided, indicating that we may have overgeneralized its potential. Since the M1 and its corticospinal output are frequently damaged in patients with serious lesions and impairments, ipsilesional premotor areas (PMAs) could be useful alternates instead. We base our premise on their higher probability of survival, greater descending projections, and adaptive potential, which is causal for recovery across the seriously impaired. Using a conceptual model, we describe how chronically stimulating PMAs would strongly affect key mechanisms of stroke motor recovery, such as facilitating the plasticity of alternate descending output, restoring interhemispheric balance, and establishing widespread connectivity. Although at this time it is difficult to predict whether PMAs would be "better," it is important to at least investigate whether they are reasonable substitutes for the M1. Even if the stimulation of the M1 may benefit those with maximum recovery potential, while that of PMAs may only help the more disadvantaged, it may still be reasonable to achieve some recovery across the majority rather than stimulate a single locus fated to be inconsistently effective across all. © The Author(s) 2014.

  14. Prediction of Neurocognitive Deficits by Parkinsonian Motor Impairment in Schizophrenia: A Study in Neuroleptic-Naïve Subjects, Unaffected First-Degree Relatives and Healthy Controls From an Indigenous Population.

    Science.gov (United States)

    Molina, Juan L; González Alemán, Gabriela; Florenzano, Néstor; Padilla, Eduardo; Calvó, María; Guerrero, Gonzalo; Kamis, Danielle; Stratton, Lee; Toranzo, Juan; Molina Rangeon, Beatriz; Hernández Cuervo, Helena; Bourdieu, Mercedes; Sedó, Manuel; Strejilevich, Sergio; Cloninger, Claude Robert; Escobar, Javier I; de Erausquin, Gabriel A

    2016-11-01

    Neurocognitive deficits are among the most debilitating and pervasive symptoms of schizophrenia, and are present also in unaffected first-degree relatives. Also, multiple reports reveal parkisonian motor deficits in untreated subjects with schizophrenia and in first-degree relatives of affected subjects. Yet, the relation between motor and cognitive impairment and its value as a classifier of endophenotypes has not been studied. To test the efficacy of midbrain hyperechogenicity (MHE) and parkinsonian motor impairment (PKM) as predictors of neurocognitive impairment in subjects with or at risk for schizophrenia, that could be used to segregate them from first-degree relatives and healthy controls. Seventy-six subjects with chronic schizophrenia never exposed to antipsychotic medication, 106 unaffected first-degree relatives, and 62 healthy controls were blindly assessed for cognitive and motor function, and transcranial ultrasound. Executive function, fluid intelligence, motor planning, and hand coordination showed group differences. PKM and MHE were significantly higher in untreated schizophrenia and unaffected relatives. Unaffected relatives showed milder impairment, but were different from controls. PKM and MHE predict cognitive impairment in neuroleptic-naive patients with schizophrenia and their unaffected first-degree relatives and may be used to segregate them from first-degree relatives and healthy controls. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model.

    Science.gov (United States)

    Millecamps, Magali; Czerminski, Jan T; Mathieu, Axel P; Stone, Laura S

    2015-12-01

    Chronic low back pain is debilitating and difficult to treat. Depending on the etiology, responses to treatments vary widely. Although chronic low back pain is frequently related to intervertebral disc degeneration, the relationship between disc degeneration severity and clinical symptoms are still poorly understood. In humans, studies investigating the relationship between disc degeneration severity and low back pain are limited by the difficulty of obtaining disc samples from well-characterized patients and pain-free controls. We have previously described the secreted protein, acidic, rich in cysteine (SPARC)-null mouse model of chronic low back pain. SPARC is a matricellular protein involved in regulating the assembly and composition of extracellular matrix. The SPARC-null mice develop age-dependent disc degeneration of increasing severity accompanied by behavioral signs suggestive of axial low back pain, radiating leg pain, and motor impairment. The existence of this model allows for examination of the relationships between clinical symptoms in vivo and pathological signs of disc degeneration ex vivo. The goal of this study was to explore the relationship between behavioral signs of pain and the severity of lumbar disc degeneration using the SPARC-null mouse model of disc degeneration-related low back pain. This study used a cross-sectional, multiple-cohort behavioral and histological study of disc degeneration and behavioral symptoms in a mouse model of low back pain associated with disc degeneration. SPARC-null and wild-type control mice ranging from 6 to 78 weeks of age were used in this study. The severity of disc degeneration was determined by ex vivo analysis of the lumbar spine using colorimetric histological staining and a scoring system adapted from the Pfirrmann scale. Behavioral signs of axial low back pain, radiating leg pain, and motor impairment were quantified as tolerance to axial stretching in the grip force assay, hypersensitivity to cold or

  16. Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome

    Directory of Open Access Journals (Sweden)

    Byron Chen

    2017-08-01

    Full Text Available Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established. Here, we used a mouse model of LS lacking Ndufs4, a mitochondrial complex I subunit, to confirm that loss of complex I, but not complex II, alters respiration in the striatum. To assess the role of striatal dysfunction in the pathology, we selectively inactivated Ndufs4 in the striatal medium spiny neurons (MSNs, which account for over 95% of striatal neurons. Our results show that lack of Ndufs4 in MSNs causes a non-fatal progressive motor impairment without affecting the cognitive function of mice. Furthermore, no inflammatory responses or neuronal loss were observed up to 6 months of age. Hence, complex I deficiency in MSNs contributes to the motor deficits observed in LS, but not to the neural degeneration, suggesting that other neuronal populations drive the plethora of clinical signs in LS.

  17. Genetic rescue of CB1 receptors on medium spiny neurons prevents loss of excitatory striatal synapses but not motor impairment in HD mice.

    Science.gov (United States)

    Naydenov, Alipi V; Sepers, Marja D; Swinney, Katie; Raymond, Lynn A; Palmiter, Richard D; Stella, Nephi

    2014-11-01

    Huntington's disease (HD) is caused by an expanded polyglutamine repeat in huntingtin protein that disrupts synaptic function in specific neuronal populations and results in characteristic motor, cognitive and affective deficits. Histopathological hallmarks observed in both HD patients and genetic mouse models include the reduced expression of synaptic proteins, reduced medium spiny neuron (MSN) dendritic spine density and decreased frequency of spontaneous excitatory post-synaptic currents (sEPSCs). Early down-regulation of cannabinoid CB1 receptor expression on MSN (CB1(MSN)) is thought to participate in HD pathogenesis. Here we present a cell-specific genetic rescue of CB1(MSN) in R6/2 mice and report that treatment prevents the reduction of excitatory synaptic markers in the striatum (synaptophysin, vGLUT1 and vGLUT2), of dendritic spine density on MSNs and of MSN sEPSCs, but does not prevent motor impairment. We conclude that loss of excitatory striatal synapses in HD mice is controlled by CB1(MSN) and can be uncoupled from the motor phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. An additive factor analysis of the effect of sub-anaesthetic doses of nitrous oxide on information processing: evidence for an impairment of the motor adjustment stage.

    Science.gov (United States)

    Courtière, Alain; Hardouin, Jeannine; Vidal, Franck; Possamaï, Camille-Aimé; Hasbroucq, Thierry

    2003-02-01

    Nitrous oxide (N(2)O) inhalation, at subanaesthetic concentrations, impairs choice reaction time (RT). However, the functional locus of this effect remains to be ascertained. In the present study, this issue was investigated by applying the additive factor logic to the RTs of rats performing a visuo-motor task. The task consisted of either a left-side or a right-side body displacement to a visual stimulus displayed in either the left or right hemispace. The experimental design involved the manipulation of two task factors (stimulus luminance and foreperiod duration) the effects of which are additive on RT. Inhaled N(2)O (from 0% to 60%) was varied as the third factor of the design. N(2)O prolonged RT in a dose-dependent manner and this effect was additive with that of stimulus luminance, whilst it interacted with that of foreperiod duration. Moreover, at low concentrations (10-20%), N(2)O abolished the effect of foreperiod, possibly through a disturbance of time estimation processes, whereas at higher concentrations (30-40%) N(2)O enhanced the effect of foreperiod, probably by slowing down motor processes. Movement time (MT) was decreased by N(2)O at 20-40%. The present data provide evidence that N(2)O impairs information processing by altering at least the stage of motor adjustment. In addition, N(2)O spares the sensory processes implemented during the stimulus preprocessing stage. A subsidiary result is that at some concentrations, N(2)O displays opposite effects on reaction time and movement time. These results demonstrate that the additive factor method constitutes a powerful new tool for studying the pharmacology of information processing in animal models.

  19. NADPH Oxidase Plays a Role on Ethanol-Induced Hypertension and Reactive Oxygen Species Generation in the Vasculature.

    Science.gov (United States)

    Marchi, Katia Colombo; Ceron, Carla Speroni; Muniz, Jaqueline J; De Martinis, Bruno S; Tanus-Santos, José E; Tirapelli, Carlos Renato

    2016-09-01

    Investigate the role of NADPH oxidase on ethanol-induced hypertension and vascular oxidative stress. Male Wistar rats were treated with ethanol (20% v/v). Apocynin (10 mg/kg/day, i.p.) prevented ethanol-induced hypertension. The increased contractility of endothelium-intact and endothelium-denuded aortic rings from ethanol-treated rats to phenylephrine was prevented by apocynin. Ethanol consumption increased superoxide anion (O2 (-)) generation and lipid peroxidation and apocynin prevented these responses. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was not prevented by apocynin. Treatment with ethanol did not affect aortic levels of hydrogen peroxide (H2O2) or reduced glutathione (GSH). Ethanol did not alter the activities of xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol increased the expression of Nox1, PKCδ, nNOS, SAPK/JNK and SOD2 in the rat aorta and apocynin prevented these responses. No difference on aortic expression of Nox2, Nox4, p47phox, Nox organizer 1 (Noxo1), eNOS and iNOS was detected after treatment with ethanol. Ethanol treatment did not alter the phosphorylation of SAPK/JNK, p38MAPK, c-Src, Rac1 or PKCδ. The major new finding of our study is that the increased vascular generation of reactive oxygen species (ROS) induced by ethanol is related to increased vascular Nox1/NADPH oxidase expression. This mechanism is involved in vascular dysfunction and hypertension induced by ethanol. Additionally, we conclude that ethanol consumption induces the expression of different proteins that regulate vascular contraction and growth and that NADPH oxidase-derived ROS play a role in such response. The key findings of our study are that ethanol-induced hypertension is mediated by NADPH oxidase. Moreover, increased vascular Nox1 expression is related to the generation of reactive oxygen species (ROS) by ethanol. Finally, ROS induced by ethanol increase the

  20. Effects of Pithecellobium Jiringa Ethanol Extract against Ethanol-Induced Gastric Mucosal Injuries in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Fouad Hussain AL-Bayaty

    2012-03-01

    Full Text Available Current anti-gastric ulcer agents have side effects, despite the progression and expansion of advances in treatment. This study aimed to investigate the gastroprotective mechanisms of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal ulcers in rats. For this purpose, Sprague Dawley rats were randomly divided into five groups: Group 1 (normal control rats were orally administered with vehicle (carboxymethyl cellulose, Group 2 (ulcer control rats were also orally administered with vehicle. Group 3 (positive control rats were orally administered with 20 mg/kg omeprazole, Groups 4 and 5 (experimental groups received ethanol extract of Pithecellobium jiringa ethanol extract at a concentration of 250 and 500 mg/kg, respectively. Sixty minutes later, vehicle was given orally to the normal control group, and absolute ethanol was given orally to the ulcer control, positive control and experimental groups to generate gastric mucosal injury. The rats were sacrificed an hour later. The effect of oral administration of plant extract on ethanol-induced gastric mucosal injury was studied grossly and histology. The level of lipid peroxidation (malondialdehyde—MDA, superoxide dismutase (SOD and gastric wall mucus were measured from gastric mucosal homogenate. The ulcer control group exhibited severe gastric mucosal injury, and this finding was also confirmed by histology of gastric mucosa which showed severe damage to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. Pre-treatment with plant extract significantly reduced the formation of ethanol-induced gastric lesions, and gastric wall mucus was significantly preserved. The study also indicated a significant increase in SOD activity in gastric mucosal homogenate, whereas a significant decrease in MDA was observed. Acute toxicity tests did not show any signs of toxicity and mortality up to 5 g/kg. The ulcer protective effect of this plant may

  1. Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models.

    Science.gov (United States)

    Yokoi, Fumiaki; Dang, Mai T; Yang, Guang; Li, Jindong; Doroodchi, Atbin; Zhou, Tong; Li, Yuqing

    2012-02-01

    Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ɛ-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ɛ-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ɛ-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ɛ-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ɛ-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Benefits of the use of ICT in school activities by students with motor, speech, visual, and hearing impairment: a literature review.

    Science.gov (United States)

    Lidström, Helene; Hemmingsson, Helena

    2014-07-01

    Information and communication technology (ICT) has the potential to enhance participation in educational activities for students with physical disabilities. Even though incorporating ICTs into teaching and learning in education has become an important issue, it is unclear what evidence research has provided. The aim of this study was to investigate types of ICT items and how ICT is being used by students with physical disabilities, and describe the benefits of ICT use in school activities. A systematic literature search, covering the period 2000-May 2012, was performed in the databases AMED, CINAHL, Eric, OTseeker, Psych Info, PubMed, and Scopus. Data analysis entailed extracting, editing, grouping, and abstracting findings. A total of 32 articles were included, 16 of which were intervention studies. More than half of the studies concerned students with motor impairments. Type of ICT used differed among impairment groups, and ICT seemed to be especially beneficial for writing, spelling, and communication. Even though the review found heterogeneity across the studies students seemed to benefit from ICT use regardless of the type. For future research it is important to highlight intervention studies, especially for students with visual, hearing, and communication impairments.

  3. Phosphatidylcholine reverses ethanol-induced increase in transepithelial endotoxin permeability and abolishes transepithelial leukocyte activation

    DEFF Research Database (Denmark)

    Mitscherling, K.; Volynets, V.; Parlesak, Alexandr

    2009-01-01

    disease (ALD). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent...

  4. Phosphatidylcholine Reverses Ethanol-Induced Increase in Transepithelial Endotoxin Permeability and Abolishes Transepithelial Leukocyte Activation

    DEFF Research Database (Denmark)

    Mitzscherling, Katja; Volynets, Valentina; Parlesak, Alexandr

    2009-01-01

    ). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent transepithelial...

  5. Therapeutic effect of low molecular weight chitosan containing sepia ink on ethanol-induced gastric ulcer in rats.

    Science.gov (United States)

    Zhang, Wei; Liu, Kang; Li, Lei; Li, Yingxin; Sui, Xianxian; Rao, Yinzhu; Wu, Jiahao; Wu, Qiuping

    2016-12-01

    To evaluate the role of low molecular chitosan containing sepia ink (LMCS) in ethanol-induced (5 ml/kg) gastric ulcer in rats. Animals were divided into four groups (n = 12): normal group (Normal), negative control group (Con), experiment group (LMCS) and positive control Omeprazole group (OMZ). Gastric empty rate was detected in the first 7 days. Rats were sacrificed at 7, 14 and 21 day for histology and ELISA detections. Gastric empty was no significant differences among the groups (P > 0.05). Histological observation showed gastric mucosal LMCS treated had better healing effect. Hydroxyproline (Hyp) was significantly increased from 7 day (P gastric mucosa tissue repair, exert significant influences on oxidative and antioxidant enzyme activities and neutrophil infiltration.

  6. L-Buthionine (S,R) sulfoximine depletes hepatic glutathione but protects against ethanol-induced liver injury.

    Science.gov (United States)

    Donohue, Terrence M; Curry-McCoy, Tiana V; Todero, Sandra L; White, Ronda L; Kharbanda, Kusum K; Nanji, Amin A; Osna, Natalia A

    2007-06-01

    L-Buthionine (S,R) sulfoximine (BSO) is an inhibitor of glutathione biosynthesis and has been used as an effective means of depleting glutathione from cells and tissues. Here we investigated whether treatment with BSO enhanced ethanol-induced liver injury in mice. Female C57Bl/6 mice were pair fed with control and ethanol-containing liquid diets in which ethanol was 29.2% of total calories. During the final 7 days of pair feeding, groups of control-fed and ethanol-fed mice were given 0, 5 or 7.6 mM BSO in the liquid diets. Compared with controls, ethanol given alone decreased total liver glutathione. This effect was exacerbated in mice given ethanol with 7.6 mM BSO, causing a 72% decline in hepatic glutathione. While ethanol alone caused no decrease in mitochondrial glutathione, inclusion of 7.6 mM BSO caused a 2-fold decline compared with untreated controls. L-Buthionine (S,R) sulfoximine did not affect ethanol consumption, but serum ethanol levels in BSO-treated mice were nearly 6-fold lower than in mice given ethanol alone. The latter decline in serum ethanol was associated with a significant elevation in the specific activities of cytochrome P450 2E1 and alcohol dehydrogenase in livers of BSO-treated animals. Ethanol consumption caused a 3.5-fold elevation in serum alanine aminotransferase levels but the enzyme fell to control levels when BSO was included in the diet. L-Buthionine (S,R) sulfoximine administration also attenuated ethanol-induced steatosis, prevented the leakage of lysosomal cathepsins into the cytosol, and prevented the ethanol-elicited decline in proteasome activity. L-Buthionine (S,R) sulfoximine, administered with ethanol, significantly depleted hepatic glutathione, compared with controls. However, despite the decrease in hepatic antioxidant levels, liver injury by ethanol was alleviated, due, in part, to a BSO-elicited acceleration of ethanol metabolism.

  7. Biochemical and immunological basis of silymarin effect, a milk thistle (Silybum marianum) against ethanol-induced oxidative damage.

    Science.gov (United States)

    Das, Subir Kumar; Mukherjee, Sukhes

    2012-06-01

    Ethanol metabolism induces generation of excessive amount of reactive oxygen species (ROS) which results in immune dysfunction. We examined the efficacy of silymarin on ethanol-induced oxidative stress, immunomodulatory activity, and vascular function in mice blood. Effectiveness of silymarin was compared with potent antioxidant ascorbic acid. In the present study, 8- to 10-week-old male BALB/c mice (20-30 g) were divided into the four groups of six each. One group were fed with ethanol (1.6 g/kg body weight), while second group were fed with ethanol (1.6 g/kg body weight) and silybin (250 mg/kg body weight), and the third group were exposed to ethanol (250 mg/kg body weight) and ascorbic acid (250 mg/kg body weight) per day for 12 weeks. The control group was fed with isocaloric glucose solution instead of ethanol. Ethanol exposure significantly increased thiobarbituric acid reactive substance (TBARS) and nitrite levels besides glutathione-S-transferase (GST) activity, and significantly decreased reduced glutathione (GSH) content and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in whole blood hemolyzate, while silymarin treatment significantly normalized these altered parameters. Silymarin significantly prevented ethanol-induced, elevated activities of interleukin (IL)-10, tumor necrosis factor (TNF)-α, γ interferon (IFN-γ), vascular endothelial growth factor (VEGF)-A, and transforming growth factor (TGF)-β1, as well as decreased IL-4 activity in mice blood. These results were comparable with the activity of ascorbic acid.

  8. Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis and steatosis

    Science.gov (United States)

    Barnes, Mark A.; McMullen, Megan R.; Roychowdhury, Sanjoy; Pisano, Sorana G.; Liu, Xiuli; Stavitsky, Abram B.; Bucala, Richard; Nagy, Laura E.

    2012-01-01

    MIF, a multi-potent protein that exhibits both cytokine and chemotactic properties, is expressed by many cell types, including hepatocytes and non-parenchymal cells. We hypothesized that MIF is a key contributor to liver injury after ethanol exposure. Female C57BL/6 or MIF−/− mice were fed an ethanol-containing liquid diet or pair-fed control diet for 4 (11% total kcal; early response) or 25 (32% kcal; chronic response) days. Expression of MIF mRNA was induced at both 4d and 25d of ethanol feeding. After chronic ethanol, hepatic triglycerides and plasma ALT and AST were increased in wild-type, but not MIF−/−, mice. In order to understand the role of MIF in chronic ethanol-induced liver injury, we investigated the early response of wild-type and MIF−/− to ethanol. Ethanol feeding for 4d increased apoptosis of hepatic macrophages and activated complement in both wild-type and MIF−/− mice. However, TNFα expression was increased only in wild-type mice. This attenuation of TNF-α expression was associated with fewer F4/80+ macrophages in liver of MIF−/− mice. After 25d of ethanol feeding, chemokine expression was increased in wild-type mice, but not MIF−/− mice. Again, this protection was associated with decreased F4/80+ cells in MIF−/− mice after ethanol feeding. Chronic ethanol feeding also sensitized wild-type, but not MIF−/−, mice to lipopolysaccharide, increasing chemokine expression and monocyte recruitment into the liver. Conclusion Taken together, these data indicate that MIF is an important mediator in the regulation of chemokine production and immune cell infiltration in the liver during ethanol feeding and promotes ethanol-induced steatosis and hepatocyte damage. PMID:23174952

  9. Protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice.

    Science.gov (United States)

    Etani, Reo; Kataoka, Takahiro; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Ishimori, Yuu; Mitsunobu, Fumihiro; Taguchi, Takehito; Yamaoka, Kiyonori

    2017-09-01

    Radon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  10. Autophagy protects gastric mucosal epithelial cells from ethanol-induced oxidative damage via mTOR signaling pathway.

    Science.gov (United States)

    Chang, Weilong; Bai, Jie; Tian, Shaobo; Ma, Muyuan; Li, Wei; Yin, Yuping; Deng, Rui; Cui, Jinyuan; Li, Jinjin; Wang, Guobin; Zhang, Peng; Tao, Kaixiong

    2017-05-01

    Alcohol abuse is an important cause of gastric mucosal epithelial cell injury and gastric ulcers. A number of studies have demonstrated that autophagy, an evolutionarily conserved cellular mechanism, has a protective effect on cell survival. However, it is not known whether autophagy can protect gastric mucosal epithelial cells against the toxic effects of ethanol. In the present study, gastric mucosal epithelial cells (GES-1 cells) and Wistar rats were treated with ethanol to detect the adaptive response of autophagy. Our results demonstrated that ethanol exposure induced gastric mucosal epithelial cell damage, which was accompanied by the downregulation of mTOR signaling pathway and activation of autophagy. Suppression of autophagy with pharmacological agents resulted in a significant increase of GES-1 cell apoptosis and gastric mucosa injury, suggesting that autophagy could protect cells from ethanol toxicity. Furthermore, we evaluated the cellular oxidative stress response following ethanol treatment and found that autophagy induced by ethanol inhibited generation of reactive oxygen species and degradation of antioxidant and lipid peroxidation. In conclusion, these findings provide evidence that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate oxidative damage induced by ethanol in gastric mucosal epithelial cells. Therefore, modifying autophagy may provide a therapeutic strategy against alcoholic gastric mucosa injury. Impact statement The effect and mechanism of autophagy on ethanol-induced cell damage remain controversial. In this manuscript, we report the results of our study demonstrating that autophagy can protect gastric mucosal epithelial cells against ethanol toxicity in vitro and in vivo. We have shown that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate ethanol-induced oxidative damage in

  11. Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

    Science.gov (United States)

    Alvarez-Suarez, José M.; Dekanski, Dragana; Ristić, Slavica; Radonjić, Nevena V.; Petronijević, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

    2011-01-01

    Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a

  12. Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Sandra A Acosta

    Full Text Available Traumatic brain injury (TBI is associated with neuro-inflammation, debilitating sensory-motor deficits, and learning and memory impairments. Cell-based therapies are currently being investigated in treating neurotrauma due to their ability to secrete neurotrophic factors and anti-inflammatory cytokines that can regulate the hostile milieu associated with chronic neuroinflammation found in TBI. In tandem, the stimulation and mobilization of endogenous stem/progenitor cells from the bone marrow through granulocyte colony stimulating factor (G-CSF poses as an attractive therapeutic intervention for chronic TBI. Here, we tested the potential of a combined therapy of human umbilical cord blood cells (hUCB and G-CSF at the acute stage of TBI to counteract the progressive secondary effects of chronic TBI using the controlled cortical impact model. Four different groups of adult Sprague Dawley rats were treated with saline alone, G-CSF+saline, hUCB+saline or hUCB+G-CSF, 7-days post CCI moderate TBI. Eight weeks after TBI, brains were harvested to analyze hippocampal cell loss, neuroinflammatory response, and neurogenesis by using immunohistochemical techniques. Results revealed that the rats exposed to TBI treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis in DG and SVZ, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized the neurogenesis, and reduced hippocampal cell loss compared to saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation in striatum, DG, SVZ, and corpus callosum and fornix, a modest neurogenesis, and a moderate reduction of hippocampal cells loss. On the other hand, combined therapy of hUCB+G-CSF displayed synergistic effects that robustly dampened neuroinflammation, while enhancing endogenous neurogenesis and reducing hippocampal cell loss. Vigorous and long-lasting recovery of

  13. Older Adults Show Preserved Equilibrium but Impaired Step Length Control in Motor-Equivalent Stabilization of Gait

    Science.gov (United States)

    Verrel, Julius; Lövdén, Martin; Lindenberger, Ulman

    2012-01-01

    Stable walking depends on the coordination of multiple biomechanical degrees of freedom to ensure the dynamic maintenance of whole-body equilibrium as well as continuous forward progression. We investigated adult age-related differences in whole-body coordination underlying stabilization of center of mass (CoM) position and step pattern during locomotion. Sixteen younger (20-30 years) and 16 healthy older men (65–80 years) walked on a motorized treadmill at 80%, 100% and 120% of their self-selected preferred speed. Preferred speeds did not differ between the age groups. Motor-equivalent stabilization of step parameters (step length and width) and CoM position relative to the support (back and front foot) was examined using a generalized covariation analysis. Across age groups, covariation indices were highest for CoM position relative to the front foot, the measure most directly related to body equilibrium. Compared to younger adults, older adults showed lower covariation indices with respect to step length, extending previous findings of age-related differences in motor-equivalent coordination. In contrast, no reliable age differences were found regarding stabilization of step width or any of the CoM parameters. The observed pattern of results may reflect robust prioritization of balance over step pattern regularity, which may be adaptive in the face of age-associated sensorimotor losses and decline of coordinative capacities. PMID:23272200

  14. Hepatoprotective effects of Solanum nigrum against ethanol-induced injury in primary hepatocytes and mice with analysis of glutathione S-transferase A1

    Directory of Open Access Journals (Sweden)

    Fang-Ping Liu

    2016-02-01

    Conclusion: These results suggested that S. nigrum has hepatoprotective effects against ethanol-induced injury both in vitro and in vivo, and can protect the integrity of hepatocytes and thus reduce the release of liver GSTA1, which contributes to improved liver detoxification.

  15. Protective Effects of Emodin and Chrysophanol Isolated from Marine Fungus Aspergillus sp. on Ethanol-Induced Toxicity in HepG2/CYP2E1 Cells

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    Zhong-Ji Qian

    2011-01-01

    Full Text Available Alcohol-induced liver injury progresses from fatty infiltration followed by a harmful cause of inflammation leading to an irreversible damage. In this study, two compounds (emodin and chrysophanol isolated from marine fungus Aspergillus sp. were examined for their protective effects against ethanol-induced toxicity in vitro. Ethanol-induced HepG2/CYP2E1 cells were treated with the compounds at various concentrations, and the results showed that there was a dose-dependent decrease of gamma-glutamyl transpeptidase (GGT activity and increase of glutathione (GSH in the culture media with an increase in cell viability. Furthermore, the protective effects of the compounds were evaluated by protein expression levels of GGT, GSH, and CYP2E1 using Western blot. Among the compounds, emodin addressed to the ethanol-induced cytotoxicity more effectively compared to the chrysophanol. It could be suggested that emodin isolated from this genus would be a potential candidate for attenuating ethanol induced liver damage for further industrial applications such as functional food and pharmaceutical developments.

  16. Understanding the relationship between brain and upper limb function in children with unilateral motor impairments: A multimodal approach.

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    Weinstein, Maya; Green, Dido; Rudisch, Julian; Zielinski, Ingar M; Benthem-Muñiz, Marta; Jongsma, Marijtje L A; McClelland, Verity; Steenbergen, Bert; Shiran, Shelly; Ben Bashat, Dafna; Barker, Gareth J

    2018-01-01

    Atypical brain development and early brain injury have profound and long lasting impact on the development, skill acquisition, and subsequent independence of a child. Heterogeneity is present at the brain level and at the motor level; particularly with respect to phenomena of bilateral activation and mirrored movements (MMs). In this multiple case study we consider the feasibility of using several modalities to explore the relationship between brain structure and/or activity and hand function: Electroencephalography (EEG), both structural and functional Magnetic Resonance Imaging (sMRI, fMRI), diffusion tensor imaging (DTI), transcranial magnetic stimulation (TMS), Electromyography (EMG) and hand function assessments. 15 children with unilateral CP (ages: 9.4 ± 2.5 years) undertook hand function assessments and at least two additional neuroimaging and/or neurophysiological procedures: MRI/DTI/fMRI (n = 13), TMS (n = 11), and/or EEG/EMG (n = 8). During the fMRI scans and EEG measurements, a motor task was performed to study cortical motor control activity during simple hand movements. DTI tractography analysis was used to study the corpus-callosum (CC) and cortico-spinal tracts (CST). TMS was used to study cortico-spinal connectivity pattern. Type and range of severity of brain injury was evident across all levels of manual ability with the highest radiological scores corresponded to children poorer manual ability. Evidence of MMs was found in 7 children, mostly detected when moving the affected hand, and not necessarily corresponding to bilateral brain activation. When moving the affected hand, bilateral brain activation was seen in 6/11 children while 3/11 demonstrated unilateral activation in the contralateral hemisphere, and one child demonstrated motor activation predominantly in the supplementary motor area (SMA). TMS revealed three types of connectivity patterns from the cortex to the affected hand: a contralateral (n = 3), an ipsilateral (n = 4

  17. Functional electrical stimulation mediated by iterative learning control and 3D robotics reduces motor impairment in chronic stroke

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    Meadmore Katie L

    2012-06-01

    Full Text Available Abstract Background Novel stroke rehabilitation techniques that employ electrical stimulation (ES and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients’ voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL, a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. Methods Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants’ arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl-Meyer, Action Research Arm Test at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. Results From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. Conclusions The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this.

  18. Chronic Ethanol Exposure during Adolescence in Rats Induces Motor Impairments and Cerebral Cortex Damage Associated with Oxidative Stress

    OpenAIRE

    Francisco Bruno Teixeira; Luana Nazaré da Silva Santana; Fernando Romualdo Bezerra; Sabrina De Carvalho; Enéas Andrade Fontes-Júnior; Rui Daniel Prediger; Maria Elena Crespo-López; Cristiane Socorro Ferraz Maia; Rafael Rodrigues Lima

    2014-01-01

    Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, in...

  19. Clonidine Reduces Nociceptive Responses in Mouse Orofacial Formalin Model: Potentiation by Sigma-1 Receptor Antagonist BD1047 without Impaired Motor Coordination.

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    Yoon, Seo-Yeon; Kang, Suk-Yun; Kim, Hyun-Woo; Kim, Hyung-Chan; Roh, Dae-Hyun

    2015-01-01

    Although the administration of clonidine, an alpha-2 adrenoceptor agonist, significantly attenuates nociception and hyperalgesia in several pain models, clinical trials of clonidine are limited by its side effects such as drowsiness, hypotension and sedation. Recently, we determined that the sigma-1 receptor antagonist BD1047 dose-dependently reduced nociceptive responses in a mouse orofacial formalin model. Here we examined whether intraperitoneal injection of clonidine suppressed the nociceptive responses in the orofacial formalin test, and whether co-administration with BD1047 enhances lower-dose clonidine-induced anti-nociceptive effects without the disruption of motor coordination and blood pressure. Formalin (5%, 10 µL) was subcutaneously injected into the right upper lip, and the rubbing responses with the ipsilateral fore- or hind-paw were counted for 45 min. Clonidine (10, 30 or 100 µg/kg) was intraperitoneally administered 30 min before formalin injection. Clonidine alone dose-dependently reduced nociceptive responses in both the first and second phases. Co-localization for alpha-2A adrenoceptors and sigma-1 receptors was determined in trigeminal ganglion cells. Interestingly, the sub-effective dose of BD1047 (3 mg/kg) significantly potentiated the anti-nociceptive effect of lower-dose clonidine (10 or 30 µg/kg) in the second phase. In particular, the middle dose of clonidine (30 µg/kg) in combination with BD1047 produced an anti-nociceptive effect similar to that of the high-dose clonidine, but without a significant motor dysfunction or hypotension. In contrast, mice treated with the high dose of clonidine developed severe impairment in motor coordination and blood pressure. These data suggest that a combination of low-dose clonidine with BD1047 may be a novel and safe therapeutic strategy for orofacial pain management.

  20. Motor cortex tRNS improves pain, affective and cognitive impairment in patients with fibromyalgia: preliminary results of a randomised sham-controlled trial.

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    Curatolo, Massimiliano; La Bianca, Giuseppe; Cosentino, Giuseppe; Baschi, Roberta; Salemi, Giuseppe; Talotta, Rossella; Romano, Marcello; Triolo, Giovanni; De Tommaso, Marina; Fierro, Brigida; Brighina, Filippo

    2017-01-01

    Fibromyalgia (FM) is a clinical syndrome characterised by widespread musculoskeletal pain, chronic fatigue, cognitive deficits, and sleep and mood disorders. The effectiveness of most pharmacological treatments is limited, and there is a need for new, effective and well-tolerated therapies. It has recently been shown that transcranial direct-current stimulation (tDCS) of the motor cortex reduces pain, and that tDCS of the dorso-lateral prefrontal cortex (DLPFC) improves anxiety, depression and cognitive impairment in FM patients. The new technique of transcranial random noise stimulation (tRNS) using randomly changing alternating currents has very recently been shown to improve working memory and pain in limited series of patients with FM or neuropathic pain. The aim of this study was to investigate the clinical effects of primary motor cortex (M1) tRNS in FM patients. Twenty female FM patients aged 26-67 years were randomised to undergo active (real) or placebo (sham) tRNS sessions on five days a week (Monday-Friday) for two weeks. Each patient was evaluated before and after treatment using a visual analogue scale (VAS), the Fibromyalgia Impact Questionnaire (FIQ), the Hospital Anxiety and Depression Scale (HADS), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT), the Forward and Backward Digit Span test, and the FAS verbal fluency test. In comparison with sham treatment, active tRNS of M1 induced a general improvement in the clinical picture of FM, with a significant reduction in pain, depression, anxiety and FIQ scores and a significant improvement in TMT (A), RAVLT and FAS scores. These findings suggest that tRNS of M1 can be very effective in relieving FM symptoms. Unlike motor cortex tDCS, it seems to counteract both pain and cognitive disturbances, possibly because the invoked mechanism of stochastic resonance synchronises neural firing and thus leads to more widespread and lasting effects.

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

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    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.

  2. Lack of impairment due to confirmed codeine use prior to a motor vehicle accident: role of pharmacogenomics.

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    Wu, Alan H B; Kearney, Thomas

    2013-11-01

    We examined forensic serum toxicology and pharmacogenomics data from a woman on codeine shortly before she caused a motor vehicle accident. A woman driving erratically collided with a parked car of a highway seriously injuring 2 men working to repair the parked vehicle. The woman tested positive for codeine, acetaminophen and barbital. She had been taking these medications for 20 years due to migraine headache. Serum toxicology and genotype analysis for cytochrome P450, UDP glucuronosyltransferase, and other metabolizing enzymes were measured. The woman was tried and convicted of driving under the influence resulting in bodily harm and was sentenced to 6 years. Toxicology results on peripheral blood showed a total and free codeine of 840 and 348 μg/L, respectively, and total morphine of 20 μg/L (17, 3, and 0 μg/L for morphine-3-glucuronide, morphine-6-glucuronide, and free morphine, respectively). She was heterozygous for CYP 2D6 *2/*4 (extensive/poor metabolism) and heterozygous for UGT 2B7 *1/*2 (extensive/ultra-rapid metabolism). The woman was also taking fluoxetine and bupropion which are strong inhibitors of CYP 2D6. Based on her genotype and phenotype and reports by the arresting officer, we suggest that the subject in question was not intoxicated by opiates at the time of her motor vehicle accident and may have been falsely incarcerated. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  3. Imbalanced mechanistic target of rapamycin C1 and C2 activity in the cerebellum of Angelman syndrome mice impairs motor function.

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    Sun, Jiandong; Liu, Yan; Moreno, Stephanie; Baudry, Michel; Bi, Xiaoning

    2015-03-18

    Angelman syndrome (AS) is a neurogenetic disorder caused by deficiency of maternally expressed ubiquitin-protein ligase E3A (UBE3A), an E3 ligase that targets specific proteins for proteasomal degradation. Although motor function impairment occurs in all patients with AS, very little research has been done to understand and treat it. The present study focuses on Ube3A deficiency-induced alterations in signaling through the mechanistic target of rapamycin (mTOR) pathway in the cerebellum of the AS mouse model and on potential therapeutic applications of rapamycin. Levels of tuberous sclerosis complex 2 (TSC2), a negative regulator of mTOR, were increased in AS mice compared with wild-type mice; however, TSC2 inhibitory phosphorylation was also increased. Correspondingly, levels of phosphorylated/active mTOR were increased. Phosphorylation of the mTORC1 substrates S6 kinase 1 (S6K1) and S6 was elevated, whereas that of the mTORC2 substrates AKT and N-myc downstream regulated 1 was decreased, suggesting enhanced mTORC1 but inhibited mTORC2 signaling. Semi-chronic treatment of AS mice with rapamycin not only improved their motor performance but also normalized mTORC1 and mTORC2 signaling. Furthermore, inhibitory phosphorylation of rictor, a key regulatory/structural subunit of the mTORC2 complex, was increased in AS mice and decreased after rapamycin treatment. These results indicate that Ube3A deficiency leads to overactivation of the mTORC1-S6K1 pathway, which in turn inhibits rictor, resulting in decreased mTORC2 signaling in Purkinje neurons of AS mice. Finally, rapamycin treatment also improved dendritic spine morphology in AS mice, through inhibiting mTORC1 and possibly enhancing mTORC2-mediated regulation of synaptic cytoskeletal elements. Collectively, our results indicate that the imbalance between mTORC1 and mTORC2 activity may contribute to synaptic pathology and motor impairment in AS. Copyright © 2015 the authors 0270-6474/15/354706-13$15.00/0.

  4. Caffeine has greater potency and efficacy than theophylline to reverse the motor impairment caused by chronic but not acute interruption of striatal dopaminergic transmission in rats.

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    Acuña-Lizama, Miguel M; Bata-García, José L; Alvarez-Cervera, Fernando J; Góngora-Alfaro, José L

    2013-07-01

    In order to assess whether caffeine and theophylline have the same potency and efficacy to reverse the impairment of motor function caused by acute or chronic interruption of striatal dopamine transmission, a comparison of their dose-response relationship was made in the acute model of haloperidol-induced catalepsy, and the chronic model of unilateral lesion of the dopamine nigrostriatal pathway with 6-hydroxydopamine. At equimolar doses, both drugs reduced catalepsy intensity and increased its onset latency in a dose-dependent fashion, showing comparable potencies and attaining the maximal effect at similar doses. Catalepsy intensity: caffeine ED₅₀ = 24.1 μmol/kg [95% CI, 18.4-31.5]; theophylline ED₅₀ = 22.0 μmol/kg [95% CI, 17.0-28.4]. Catalepsy latency: caffeine ED₅₀ = 27.0 μmol/kg [95% CI, 21.1-34.6]; theophylline ED₅₀ = 28.8 μmol/kg [95% CI, 22.5-36.7]. In one group of hemiparkinsonian rats (n = 5), caffeine caused a dose-dependent recovery of the contralateral forepaw stepping: ED₅₀ = 2.4 μmol/kg/day [95% CI, 1.9-3.1]), reaching its maximum at the dose of 5.15 μmol/kg/day. When the treatment of these same rats was switched to 5.15 μmol/kg/day of theophylline, the stepping recovery was only 51 ± 12% of that induced by caffeine. Assessing the dose-response relationship of theophylline in another group of hemiparkinsonian rats (n = 7) revealed that it caused stepping recovery in an all-or-none fashion. Thus, the three lower doses had no effect, but at the dose of 5.15 μmol/kg/day theophylline suddenly increased the stepping to 56 ± 5% of the maximal effect observed when the treatment of these same rats was switched to an equimolar dose of caffeine. Increasing the dose of theophylline up to 15.45 μmol/kg/day caused no further stepping improvement since it was only 41 ± 6% of the maximal effect produced by caffeine at the dose of 5.15 μmol/kg/day. Given that theophylline showed less potency and efficacy than caffeine to reverse the

  5. Role of microglia in ethanol-induced neurodegenerative disease: Pathological and behavioral dysfunction at different developmental stages.

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    Yang, Jing-Yu; Xue, Xue; Tian, Hua; Wang, Xiao-Xiao; Dong, Ying-Xu; Wang, Fang; Zhao, Ya-Nan; Yao, Xue-Chun; Cui, Wei; Wu, Chun-Fu

    2014-12-01

    Alcohol abuse can result in significant alterations to the structure of the brain and ultimately to behavioral dysfunctions. Epidemiological studies have shown that alcoholism is closely associated with impaired memory and judgment. However, the degree of deficit (brain injury) depends on factors such as the age of onset, duration of heavy drinking, continuous versus periodic (binge) drinking and the typical amount consumed per session. In recent years, neuroinflammation has been proposed as one of the alcoholism-induced neuropathological mechanisms, since increased levels of microglial markers are observed in the brains of both post-mortem human alcoholics and various alcohol-treated animals, from newborn or adolescent rodents to adult rodents. Many studies have investigated how microglia modulate alcohol-induced behavioral changes such as cognitive deficits, abnormal locomotor activity, motor impairment and mood disturbance. Importantly, we try to characterize and compare the distinct features in different ethanol (EtOH)-induced neurodegenerative disease (NDD) models. Moreover, mounting evidence indicates that in response to certain environmental toxins, microglia can become over-activated under oxidative stress, releasing pro-inflammatory mediators that cause central nervous system (CNS) disease. The molecular mechanisms involve free radical formation and the release of pro-inflammatory cytokines that are detrimental to neighboring neurons and interfere with the molecules regulating cell-cell interactions. The identification and understanding of the cellular and molecular mechanisms of microglial activation are described, as well as multiple downstream targets, in different alcohol-treated animal models. This review might contribute to the development of treatments and/or therapeutic agents that can reduce or eliminate the deleterious effects of alcohol-induced NDD. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Glutathione attenuates ethanol-induced alveolar macrophage oxidative stress and dysfunction by downregulating NADPH oxidases.

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    Yeligar, Samantha M; Harris, Frank L; Hart, C Michael; Brown, Lou Ann S

    2014-03-01

    Chronic alcohol abuse increases lung oxidative stress and susceptibility to respiratory infections by impairing alveolar macrophage (AM) function. NADPH oxidases (Nox) are major sources of reactive oxygen species in AMs. We hypothesized that treatment with the critical antioxidant glutathione (GSH) attenuates chronic alcohol-induced oxidative stress by downregulating Noxes and restores AM phagocytic function. Bronchoalveolar lavage (BAL) fluid and AMs were isolated from male C57BL/6J mice (8-10 wk) treated ± ethanol in drinking water (20% wt/vol, 12 wk) ± orally gavaged GSH in methylcellulose vehicle (300 mg x kg(-1) x day(-1), during week 12). MH-S cells, a mouse AM cell line, were treated ± ethanol (0.08%, 3 days) ± GSH (500 μM, 3 days or last 1 day of ethanol). BAL and AMs were also isolated from ethanol-fed and control mice ± inoculated airway Klebsiella pneumoniae (200 colony-forming units, 28 h) ± orally gavaged GSH (300 mg/kg, 24 h). GSH levels (HPLC), Nox mRNA (quantitative RT-PCR) and protein levels (Western blot and immunostaining), oxidative stress (2',7'-dichlorofluorescein-diacetate and Amplex Red), and phagocytosis (Staphylococcus aureus internalization) were measured. Chronic alcohol decreased GSH levels, increased Nox expression and activity, enhanced oxidative stress, impaired phagocytic function in AMs in vivo and in vitro, and exacerbated K. pneumonia-induced oxidative stress. Although how oral GSH restored GSH pools in ethanol-fed mice is unknown, oral GSH treatments abrogated the detrimental effects of chronic alcohol exposure and improved AM function. These studies provide GSH as a novel therapeutic approach for attenuating alcohol-induced derangements in AM Nox expression, oxidative stress, dysfunction, and risk for pneumonia.

  7. Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.

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    Carolina R den Hartog

    Full Text Available Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs. In this study, we determined how expression of a mutant GluN1 subunit (F639A that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p. increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg. In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.

  8. Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7.

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    Godin, Elizabeth A; O'Leary-Moore, Shonagh K; Khan, Amber A; Parnell, Scott E; Ament, Jacob J; Dehart, Deborah B; Johnson, Brice W; Allan Johnson, G; Styner, Martin A; Sulik, Kathleen K

    2010-01-01

    This magnetic resonance microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 microm isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute

  9. Cannabidiol ameliorates cognitive and motor impairments in bile-duct ligated mice via 5-HT1A receptor activation.

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    Magen, I; Avraham, Y; Ackerman, Z; Vorobiev, L; Mechoulam, R; Berry, E M

    2010-02-01

    We aimed to demonstrate the involvement of 5-HT(1A) receptors in the therapeutic effect of cannabidiol, a non-psychoactive constituent of Cannabis sativa, in a model of hepatic encephalopathy induced by bile-duct ligation (BDL) in mice. Cannabidiol (5 mg x kg(-1); i.p.) was administered over 4 weeks to BDL mice. Cognition and locomotion were evaluated using the eight-arm maze and the open field tests respectively. Hippocampi were analysed by RT-PCR for expression of the genes for tumour necrosis factor-alpha receptor 1, brain-derived neurotrophic factor (BDNF) and 5-HT(1A) receptor. N-(2-(4-(2-methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), a 5-HT(1A) receptor antagonist (0.5 mg x kg(-1)), was co-administered with cannabidiol. Liver function was evaluated by measuring plasma liver enzymes and bilirubin. Cannabidiol improved cognition and locomotion, which were impaired by BDL, and restored hippocampal expression of the tumour necrosis factor-alpha receptor 1 and the BDNF genes, which increased and decreased, respectively, following BDL. It did not affect reduced 5-HT(1A) expression in BDL mice. All the effects of cannabidiol, except for that on BDNF expression, were blocked by WAY-100635, indicating 5-HT(1A) receptor involvement in cannabidiol's effects. Cannabidiol did not affect the impaired liver function in BDL. The behavioural outcomes of BDL result from both 5-HT(1A) receptor down-regulation and neuroinflammation. Cannabidiol reverses these effects through a combination of anti-inflammatory activity and activation of this receptor, leading to improvement of the neurological deficits without affecting 5-HT(1A) receptor expression or liver function. BDNF up-regulation by cannabidiol does not seem to account for the cognitive improvement.

  10. Cannabidiol ameliorates cognitive and motor impairments in bile-duct ligated mice via 5-HT1A receptor activation

    Science.gov (United States)

    Magen, I; Avraham, Y; Ackerman, Z; Vorobiev, L; Mechoulam, R; Berry, EM

    2010-01-01

    Background and purpose: We aimed to demonstrate the involvement of 5-HT1A receptors in the therapeutic effect of cannabidiol, a non-psychoactive constituent of Cannabis sativa, in a model of hepatic encephalopathy induced by bile-duct ligation (BDL) in mice. Experimental approach: Cannabidiol (5 mg·kg−1; i.p.) was administered over 4 weeks to BDL mice. Cognition and locomotion were evaluated using the eight-arm maze and the open field tests respectively. Hippocampi were analysed by RT-PCR for expression of the genes for tumour necrosis factor-α receptor 1, brain-derived neurotrophic factor (BDNF) and 5-HT1A receptor. N-(2-(4-(2-methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), a 5-HT1A receptor antagonist (0.5 mg·kg−1), was co-administered with cannabidiol. Liver function was evaluated by measuring plasma liver enzymes and bilirubin. Key results: Cannabidiol improved cognition and locomotion, which were impaired by BDL, and restored hippocampal expression of the tumour necrosis factor-α receptor 1 and the BDNF genes, which increased and decreased, respectively, following BDL. It did not affect reduced 5-HT1A expression in BDL mice. All the effects of cannabidiol, except for that on BDNF expression, were blocked by WAY-100635, indicating 5-HT1A receptor involvement in cannabidiol's effects. Cannabidiol did not affect the impaired liver function in BDL. Conclusions and implications: The behavioural outcomes of BDL result from both 5-HT1A receptor down-regulation and neuroinflammation. Cannabidiol reverses these effects through a combination of anti-inflammatory activity and activation of this receptor, leading to improvement of the neurological deficits without affecting 5-HT1A receptor expression or liver function. BDNF up-regulation by cannabidiol does not seem to account for the cognitive improvement. PMID:20128798

  11. Antioxidant Properties and Gastroprotective Effects of 2-(EthylthioBenzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats.

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    Nafal Nazarbahjat

    Full Text Available A series of new 2-(ethylthiobenzohydrazone derivatives (1-6 were prepared and characterised by IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The newly prepared compounds were screened for their in vitro antioxidant activities using free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH and ferric reducing antioxidant power (FRAP assays. Among them, most powerful antioxidant, compound 1 has been selected in order to illustrate anti-ulcer effect on ethanol-induced gastric mucosal lesions in rats. Four groups of Sprague Dawley rats were respectively treated with 10% Tween 20 as ulcer control group, 20 mg/kg omeprazole as reference group, 50 mg/kg and 100 mg/kg compound 1 as experimental animals. Macroscopically, ulcer control group showed extensive hemorrhagic lesions of gastric mucosa compared with omeprazole or compound 1. Rats pre-treated with compound 1 showed increased in gastric pH and gastric mucus. Histologically, ulcer control group showed severe damage to gastric mucosa with edema and leucocytes infiltration of submucosal layer. In immunohistochemical analysis, rats which were pre-treated with compound 1 showed up-regulation of HSP70 and down-regulation of Bax proteins. In conclusion, the gastroprotective effect of compound 1 may be due to its antioxidant activity, and/or due to up-regulation of HSP70 and down-regulation of Bax protein in stained tissue section.

  12. Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats

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    Iza Farhana Ismail

    2012-01-01

    Full Text Available Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS stains, levels of lipid peroxidation, malondialdehyde (MDA, antioxidant enzymes, and superoxide dismutase (SOD were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer.

  13. The effect of calorie restriction on acute ethanol-induced oxidative and nitrosative liver injury in rats.

    Science.gov (United States)

    Mladenović, Dušan; Ninković, Milica; Aleksić, Vuk; Šljivančanin, Tamara; Vučević, Danijela; Todorović, Vera; Stanković, Milena; Stanojlović, Olivera; Radosavljević, Tatjana

    2013-09-01

    The aim of our study was to examine the effect of calorie restriction (CR) on oxidative and nitrosative liver injury in rats, induced by acute ethanol intoxication. Male Wistar rats were divided into groups: (1) control; (2) calorie-restricted groups with intake of 60-70% (CR60-70) and 40-50% of daily energy needs (CR40-50); (3) ethanol-treated group (E); (4) calorie-restricted, ethanol-treated groups (E+CR60-70 and E+CR40-50). Ethanol was administered in 5 doses of 2g/kg every 12h, and duration of CR was 5 weeks before ethanol treatment. Malondialdehyde and nitrite and nitrate level were significantly lower in E+CR60-70 and higher in E+CR40-50 vs. E group. Liver reduced glutathione content and activity of both superoxide dismutase izoenzymes were significantly higher in E+CR60-70 and lower in E+CR40-50 vs. E group. Oxidative stress may be a potential mechanism of hormetic effects of CR on acute ethanol-induced liver injury. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. α-Tocopherol mitigates ethanol induced malformations and cell damage in the eye and brain of the chick embryo

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    Reda A. Ali

    2012-05-01

    Full Text Available The goal of this study is to investigate the ability of vitamin E in the active form α-tocopherol to mitigate the ethanol induced damaging effects and malformations in the developing chick embryo. Fertilized eggs were divided into five groups; the control group, and treated groups. The experimental groups were injected, in the air sac, before incubation with a single dose of 100 μl saline solution, 100 μl of 10% ethanol in saline solution, a mixture of 100 μl of 10% ethanol and 200 ppm vitamin E or 10% ethanol and 400 ppm vitamin E. Treatment of developing chick embryos with 10% ethanol resulted in growth retardation and malformations in the eye, brain, limbs and other body parts. Ethanol exerted its degenerative effects probably via increasing membrane fluidity leading to membrane damage and significantly increased levels of lipid peroxidation. Ethanol also induced significant reduction in nitric oxide levels resulting in reduced body weight of the treated embryo probably due to restricted bold flow. Ethanol significantly increased glutathione level as a defense response. Vitamin C levels were significantly decreased after ethanol treatment due to oxidation or utilization. Vitamin E in the active form α-tocopherol partially mitigated the ethanol damaging effects either by exerting its antioxidant properties leading to a significant reduction of lipid peroxidation levels, retaining normal levels of nitric oxide or maintaining normal levels of endogenous antioxidants, glutathione and vitamin C.

  15. Efficacy of sardinelle protein hydrolysate to alleviate ethanol-induced oxidative stress in the heart of adult rats.

    Science.gov (United States)

    Kamoun, Zeineb; Kamoun, Alya Sellami; Bougatef, Ali; Chtourou, Yassine; Boudawara, Tahia; Nasri, Moncef; Zeghal, Najiba

    2012-08-01

    The present study was undertaken to examine the protective effects of sardinelle proteins hydrolysate (SPH) obtained from heads and viscera against ethanol toxicity in the heart of adult rats. Twenty-four male rats of Wistar strain, weighing at the beginning of the experiment 250 to 300 g, were used in this study. They were divided into 4 groups: group (C) served as controls, group (Eth) received 30% ethanol solution at 3 g/kg body weight, group (SPH) received only 7.27 mg of SPH/kg body weight, and group (Eth-SPH) received ethanol and sardinelle proteins hydrolysate simultaneously. All treatments were made by gavage during 15 d. Treatment with ethanol revealed a significant elevation of malondialdehyde and protein carbonyl levels in the heart and of aspartate transaminase and alanine transaminase activities in plasma. Nitric oxide levels and the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase decreased. Nonenzymatic antioxidant such as reduced glutathione did not significantly change and ascorbic acid was decreased. SPH intake concomitantly with ethanol restored these parameters to near control values. These modifications confirmed histopathological aspects of the heart. The results revealed that SPH could provide protection of the myocardium against ethanol-induced oxidative damages in rats. This may be due to the high antioxidant potential of SPH. © 2012 Institute of Food Technologists®

  16. Gastroprotective Mechanism and Ulcer Resolution Effect of Cyrtocarpa procera Methanolic Extract on Ethanol-Induced Gastric Injury

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    Wendy Itzel Escobedo-Hinojosa

    2018-01-01

    Full Text Available Gastric ulcers are a worldwide health problem and their poor healing is one of the most important causes for their recurrence. We have previously reported the remarkable gastroprotective and anti-Helicobacter pylori activities of the methanolic extract (CpMet of Cyrtocarpa procera bark. This work investigates, in a murine model, the CpMet gastroprotective mechanism and establishes its preclinical efficacy in the resolution of ethanol-induced gastric ulcers. The results showed that the gastroprotective activity of CpMet is mainly associated with endogenous NO and prostaglandins, followed by sulfhydryl groups and KATP channels. Furthermore, CpMet (300 mg/kg, twice a day orally administered during 20 consecutive days promoted an ulcer area reduction of 62.65% at the 20th day of the treatment. The effect was confirmed macroscopically by the alleviation of gastric mucosal erosions and microscopically by an increase in mucin content and a reduction in the inflammatory infiltration at the site of the ulcer. No clinical symptoms or signs of toxicity were observed in the treated animals. The results indicate the safety and efficacy of CpMet in promoting high quality of ulcer healing by different mechanisms, but mostly through cytoprotective and anti-inflammatory effects, making it a promising phytodrug for ulcer treatment.

  17. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

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    Bahi, Amine

    2013-07-01

    Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

  18. Protective effect of N-acetylcysteine against ethanol-induced gastric ulcer: A pharmacological assessment in mice.

    Science.gov (United States)

    Jaccob, Ausama Ayoob

    2015-01-01

    Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-acetylcysteine (NAC) against ethanol-induced gastric ulcer models in mice. A total of 41 mice were allocated into six groups consisted of 7 mice each. Groups 1 (normal control) and 2 (ulcer control) received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6(th) group received ranitidine (50 mg/kg). All drugs administered orally once daily for 7 days, on the 8(th) day absolute ethanol (7 ml/kg) was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by anti-secretory, cytoprotective, histological and biochemical data, but the molecular mechanisms behind such protection are complex.

  19. Ultrastructural and biochemical aspects of liver mitochondria during recovery from ethanol-induced alterations. Experimental evidence of mitochondrial division.

    Science.gov (United States)

    Koch, O. R.; Roatta de Conti, L. L.; Bolaños, L. P.; Stoppani, A. O.

    1978-01-01

    To study the morphologic and biochemical changes occuring in liver mitochondria during recovery from ethanol-induced injury, rats fed a 6-month high-alcohol regimen plus a nutritionally adequate diet which did not induce fatty liver were compared with isocalorically fed controls. After this period the alcohol-fed animals displayed striking ultrastructural changes of liver mitochondria and a decreased respiratory activity with succinate or malate-glutamate as substrate. On the contrary, the respiratory rate with I-glycerophosphate was 50% increased. Regression changes were studied after alcohol was withdrawn from the diet. Enlarged mitochondria rapidly disappeared (in 24 hours), although a few megamitochondria were still present after 8 days of abstinence. A similar recovery was observed for the functional alterations. At the end of the experimental period, only a slight decrease of the maximal respiratory rate using malate-glutamate as a substrate was noted. The ultrastructural findings and the morphometric data suggest that the way in which mitochondrial normalization takes place is based on partition of these organelles. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 1 Figure 2 Figure 13 PMID:623205

  20. Gastro-protective effect of Ziziphus abyssinica root extracts in ethanol-induced acute ulcer in Wistar rats

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    Salahuddin Yau

    2017-02-01

    Full Text Available Objective: To evaluate the gastro-protective effect of the aqueous, methanol and hexane root extracts of Ziziphus abyssinica on ethanol induced gastric ulcer in Wistar rats as models. Methods: Seventy rats were divided into seven groups of ten rats each: control group, ulcer control group, standard control group (cimetidine 100 mg/kg body weight, aqueous, methanol, ethyl acetate and hexane extract groups. They were administered the extracts at 300 and 600 mg/kg for two weeks before ulcer was induced, and the protective effect of all extracts determined. Results: Histological changes in gastric tissue were evaluated. Pretreatment with Ziziphus abyssinica extracts showed significant (P < 0.05 gastro-protective effect with aqueous extract having the highest gastro-protective effect (95% and 93% at 300 and 600 mg/kg extract respectively. Methanol extract had 66.6% and 65.5% protection at 300 and 600 mg/ kg respectively. The percentage protection in ethyl acetate extract treated group was 51% and 45% respectively. The group treated with hexane had 23.8% and 28.6% protection at 300 and 600 mg/kg, respectively. Histological study showed that pretreatment with aqueous extract resulted in the preservation of the functional cyto-architecture of the entire mucosa with little pathological changes, compared to other extracts. Conclusions: The results of this study indicated that aqueous extract is effective against induced gastric ulcer.

  1. Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome

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    Kusum K. Kharbanda

    2012-01-01

    Full Text Available Introduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Methods. Male Wister rats were pair-fed control or ethanol-containing liquid diets supplemented with or without betaine (10 mg/mL for 4-5 wks. Liver was examined for triglyceride accumulation, levels of methionine cycle metabolites, and alterations in mitochondrial proteins. Results. Chronic ethanol ingestion resulted in triglyceride accumulation which was attenuated in the ethanol plus betaine group. Blue native gel electrophoresis (BN-PAGE revealed significant decreases in the content of the intact oxidative phosphorylation complexes in mitochondria from ethanol-fed animals. The alcohol-dependent loss in many of the low molecular weight oxidative phosphorylation proteins was prevented by betaine supplementation. This protection by betaine was associated with normalization of SAM : S-adenosylhomocysteine (SAH ratios and the attenuation of the ethanol-induced increase in inducible nitric oxide synthase and nitric oxide generation in the liver. Discussion/Conclusion. In summary, betaine attenuates alcoholic steatosis and alterations to the oxidative phosphorylation system. Therefore, preservation of mitochondrial function may be another key molecular mechanism responsible for betaine hepatoprotection.

  2. Ethanol-induced alcohol dehydrogenase E (AdhE) potentiates pneumolysin in Streptococcus pneumoniae.

    Science.gov (United States)

    Luong, Truc Thanh; Kim, Eun-Hye; Bak, Jong Phil; Nguyen, Cuong Thach; Choi, Sangdun; Briles, David E; Pyo, Suhkneung; Rhee, Dong-Kwon

    2015-01-01

    Alcohol impairs the host immune system, rendering the host more vulnerable to infection. Therefore, alcoholics are at increased risk of acquiring serious bacterial infections caused by Streptococcus pneumoniae, including pneumonia. Nevertheless, how alcohol affects pneumococcal virulence remains unclear. Here, we showed that the S. pneumoniae type 2 D39 strain is ethanol tolerant and that alcohol upregulates alcohol dehydrogenase E (AdhE) and potentiates pneumolysin (Ply). Hemolytic activity, colonization, and virulence of S. pneumoniae, as well as host cell myeloperoxidase activity, proinflammatory cytokine secretion, and inflammation, were significantly attenuated in adhE mutant bacteria (ΔadhE strain) compared to D39 wild-type bacteria. Therefore, AdhE might act as a pneumococcal virulence factor. Moreover, in the presence of ethanol, S. pneumoniae AdhE produced acetaldehyde and NADH, which subsequently led Rex (redox-sensing transcriptional repressor) to dissociate from the adhE promoter. An increase in AdhE level under the ethanol condition conferred an increase in Ply and H2O2 levels. Consistently, S. pneumoniae D39 caused higher cytotoxicity to RAW 264.7 cells than the ΔadhE strain under the ethanol stress condition, and ethanol-fed mice (alcoholic mice) were more susceptible to infection with the D39 wild-type bacteria than with the ΔadhE strain. Taken together, these data indicate that AdhE increases Ply under the ethanol stress condition, thus potentiating pneumococcal virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Lead Intoxication Synergies of the Ethanol-Induced Toxic Responses in Neuronal Cells--PC12.

    Science.gov (United States)

    Kumar, V; Tripathi, V K; Jahan, S; Agrawal, M; Pandey, A; Khanna, V K; Pant, A B

    2015-12-01

    Lead (Pb)-induced neurodegeneration and its link with widespread neurobehavioral changes are well documented. Experimental evidences suggest that ethanol could enhance the absorption of metals in the body, and alcohol consumption may increase the susceptibility to metal intoxication in the brain. However, the underlying mechanism of ethanol action in affecting metal toxicity in brain cells is poorly understood. Thus, an attempt was made to investigate the modulatory effect of ethanol on Pb intoxication in PC12 cells, a rat pheochromocytoma. Cells were co-exposed to biological safe doses of Pb (10 μM) and ethanol (200 mM), and data were compared to the response of cells which received independent exposure to these chemicals at similar doses. Ethanol (200 mM) exposure significantly aggravated the Pb-induced alterations in the end points associated with oxidative stress and apoptosis. The finding confirms the involvement of reactive oxygen species (ROS)-mediated oxidative stress, and impairment of mitochondrial membrane potential, which subsequently facilitate the translocation of triggering proteins between cytoplasm and mitochondria. We further confirmed the apoptotic changes due to induction of mitochondria-mediated caspase cascade. These cellular changes were found to recover significantly, if the cells are exposed to N-acetyl cysteine (NAC), a known antioxidant. Our data suggest that ethanol may potentiate Pb-induced cellular damage in brain cells, but such damaging effects could be recovered by inhibition of ROS generation. These results open up further possibilities for the design of new therapeutics based on antioxidants to prevent neurodegeneration and associated health problems.

  4. Neurobehavioral phenotyping of Gaq knockout mice reveals impairments in motor functions and spatial working memory without changes in anxiety or behavioral despair

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    Aliya L Frederick

    2012-06-01

    Full Text Available Many neurotransmitters, hormones and sensory stimuli elicit their cellular responses through the targeted activation of receptors coupled to Gq family heterotrimeric G proteins. Nevertheless, we still understand little about the consequences of loss of this signaling activity on brain function. We therefore examined the effects of genetic inactivation of Gnaq on responsiveness in a battery of behavioral tests in order to assess the contribution of Gaq signaling capacity in the brain circuits mediating expression of affective behaviors (anxiety and behavioral despair, spatial working memory and locomotor output (coordination, strength, spontaneous activity and drug-induced responses. First, we replicated and extended findings showing clear motor deficits in Gaq knockout mice as assessed on an accelerating rotarod and the inverted screen test. We then assessed the contribution of the basal ganglia motor loops to these impairments, using open field testing and analysis of drug-induced locomotor responses to the psychostimulant cocaine, the benzazepine D1 receptor agonists SKF83822 and SKF83959, and the NMDA receptor antagonist MK-801. We observed significant increases in drug-induced locomotor activity in Gaq knockout mice from the dopaminergic agonists but not MK-801, indicating that basal ganglia locomotor circuitry is largely intact in the absence of Gaq. Additionally, we observed normal phenotypes in both the elevated zero maze and the forced swim test indicating that anxiety and depression-related circuitry appears to be largely intact after loss of Gnaq expression. Lastly, use of the Y-maze revealed spatial memory deficits in Gaq knockout mice, indicating that receptors signaling through Gaq are necessary in these circuits for proficiency in this task.

  5. Neurobehavioral phenotyping of Gαq knockout mice reveals impairments in motor functions and spatial working memory without changes in anxiety or behavioral despair

    Science.gov (United States)

    Frederick, Aliya L.; Saborido, Tommy P.; Stanwood, Gregg D.

    2012-01-01

    Many neurotransmitters, hormones, and sensory stimuli elicit their cellular responses through the targeted activation of receptors coupled to the Gαq family of heterotrimeric G proteins. Nevertheless, we still understand little about the consequences of loss of this signaling activity on brain function. We therefore examined the effects of genetic inactivation of Gnaq, the gene that encode for Gαq, on responsiveness in a battery of behavioral tests in order to assess the contribution of Gαq signaling capacity in the brain circuits mediating expression of affective behaviors (anxiety and behavioral despair), spatial working memory, and locomotor output (coordination, strength, spontaneous activity, and drug-induced responses). First, we replicated and extended findings showing clear motor deficits in Gαq knockout mice as assessed on an accelerating rotarod and the inverted screen test. We then assessed the contribution of the basal ganglia motor loops to these impairments, using open field testing and analysis of drug-induced locomotor responses to the psychostimulant cocaine, the benzazepine D1 receptor agonists SKF83822 and SKF83959, and the NMDA receptor antagonist MK-801. We observed significant increases in drug-induced locomotor activity in Gαq knockout mice from the dopaminergic agonists but not MK-801, indicating that basal ganglia locomotor circuitry is largely intact in the absence of Gαq. Additionally, we observed normal phenotypes in both the elevated zero maze and the forced swim test indicating that anxiety and depression-related circuitry appears to be largely intact after loss of Gnaq expression. Lastly, use of the Y-maze revealed spatial memory deficits in Gαq knockout mice, indicating that receptors signaling through Gαq are necessary in these circuits for proficiency in this task. PMID:22723772

  6. Neurobehavioral phenotyping of G(αq) knockout mice reveals impairments in motor functions and spatial working memory without changes in anxiety or behavioral despair.

    Science.gov (United States)

    Frederick, Aliya L; Saborido, Tommy P; Stanwood, Gregg D

    2012-01-01

    Many neurotransmitters, hormones, and sensory stimuli elicit their cellular responses through the targeted activation of receptors coupled to the G(αq) family of heterotrimeric G proteins. Nevertheless, we still understand little about the consequences of loss of this signaling activity on brain function. We therefore examined the effects of genetic inactivation of Gnaq, the gene that encode for G(αq), on responsiveness in a battery of behavioral tests in order to assess the contribution of G(αq) signaling capacity in the brain circuits mediating expression of affective behaviors (anxiety and behavioral despair), spatial working memory, and locomotor output (coordination, strength, spontaneous activity, and drug-induced responses). First, we replicated and extended findings showing clear motor deficits in G(αq) knockout mice as assessed on an accelerating rotarod and the inverted screen test. We then assessed the contribution of the basal ganglia motor loops to these impairments, using open field testing and analysis of drug-induced locomotor responses to the psychostimulant cocaine, the benzazepine D(1) receptor agonists SKF83822 and SKF83959, and the NMDA receptor antagonist MK-801. We observed significant increases in drug-induced locomotor activity in G(αq) knockout mice from the dopaminergic agonists but not MK-801, indicating that basal ganglia locomotor circuitry is largely intact in the absence of G(αq). Additionally, we observed normal phenotypes in both the elevated zero maze and the forced swim test indicating that anxiety and depression-related circuitry appears to be largely intact after loss of Gnaq expression. Lastly, use of the Y-maze revealed spatial memory deficits in G(αq) knockout mice, indicating that receptors signaling through G(αq) are necessary in these circuits for proficiency in this task.

  7. Negative Influence of Motor Impairments on Upper Limb Movement Patterns in Children with Unilateral Cerebral Palsy. A Statistical Parametric Mapping Study

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    Cristina Simon-Martinez

    2017-10-01

    Full Text Available Upper limb three-dimensional movement analysis (UL-3DMA offers a reliable and valid tool to evaluate movement patterns in children with unilateral cerebral palsy (uCP. However, it remains unknown to what extent the underlying motor impairments explain deviant movement patterns. Such understanding is key to develop efficient rehabilitation programs. Although UL-3DMA has been shown to be a useful tool to assess movement patterns, it results in a multitude of data, challenging the clinical interpretation and consequently its implementation. UL-3DMA reports are often reduced to summary metrics, such as average or peak values per joint. However, these metrics do not take into account the continuous nature of the data or the interdependency between UL joints, and do not provide phase-specific information of the movement pattern. Moreover, summary metrics may not be sensitive enough to estimate the impact of motor impairments. Recently, Statistical Parametric Mapping (SPM was proposed to overcome these problems. We collected UL-3DMA of 60 children with uCP and 60 typically developing children during eight functional tasks and evaluated the impact of spasticity and muscle weakness on UL movement patterns. SPM vector field analysis was used to analyze movement patterns at the level of five joints (wrist, elbow, shoulder, scapula, and trunk. Children with uCP showed deviant movement patterns in all joints during a large percentage of the movement cycle. Spasticity and muscle weakness negatively impacted on UL movement patterns during all tasks, which resulted in increased wrist flexion, elbow pronation and flexion, increased shoulder external rotation, decreased shoulder elevation with a preference for movement in the frontal plane and increased trunk internal rotation. Scapular position was altered during movement initiation, although scapular movements were not affected by muscle weakness or spasticity. In conclusion, we identified pathological movement

  8. Correlation between Motor Cortex Excitability Changes and Cognitive Impairment in Vascular Depression: Pathophysiological Insights from a Longitudinal TMS Study

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    Manuela Pennisi

    2016-01-01

    Full Text Available Background. Transcranial magnetic stimulation (TMS highlighted functional changes in dementia, whereas there are few data in patients with vascular cognitive impairment-no dementia (VCI-ND. Similarly, little is known about the neurophysiological impact of vascular depression (VD on deterioration of cognitive functions. We test whether depression might affect not only cognition but also specific cortical circuits in subcortical vascular disease. Methods. Sixteen VCI-ND and 11 VD patients, age-matched with 15 controls, underwent a clinical-cognitive, neuroimaging, and TMS assessment. After approximately two years, all participants were prospectively reevaluated. Results. At baseline, a significant more pronounced intracortical facilitation (ICF was found in VCI-ND patients. Reevaluation revealed an increase of the global excitability in both VCI-ND and VD subjects. At follow-up, the ICF of VCI-ND becomes similar to the other groups. Only VD patients showed cognitive deterioration. Conclusions. Unlike VD, the hyperfacilitation found at baseline in VCI-ND patients suggests enhanced glutamatergic neurotransmission that might contribute to the preservation of cognitive functioning. The hyperexcitability observed at follow-up in both groups of patients also indicates functional changes in glutamatergic neurotransmission. The mechanisms enhancing the risk of dementia in VD might be related either to subcortical vascular lesions or to the lack of compensatory functional cortical changes.

  9. Correlation between Motor Cortex Excitability Changes and Cognitive Impairment in Vascular Depression: Pathophysiological Insights from a Longitudinal TMS Study.

    Science.gov (United States)

    Pennisi, Manuela; Lanza, Giuseppe; Cantone, Mariagiovanna; Ricceri, Riccardo; Spampinato, Concetto; Pennisi, Giovanni; Di Lazzaro, Vincenzo; Bella, Rita

    2016-01-01

    Background. Transcranial magnetic stimulation (TMS) highlighted functional changes in dementia, whereas there are few data in patients with vascular cognitive impairment-no dementia (VCI-ND). Similarly, little is known about the neurophysiological impact of vascular depression (VD) on deterioration of cognitive functions. We test whether depression might affect not only cognition but also specific cortical circuits in subcortical vascular disease. Methods. Sixteen VCI-ND and 11 VD patients, age-matched with 15 controls, underwent a clinical-cognitive, neuroimaging, and TMS assessment. After approximately two years, all participants were prospectively reevaluated. Results. At baseline, a significant more pronounced intracortical facilitation (ICF) was found in VCI-ND patients. Reevaluation revealed an increase of the global excitability in both VCI-ND and VD subjects. At follow-up, the ICF of VCI-ND becomes similar to the other groups. Only VD patients showed cognitive deterioration. Conclusions. Unlike VD, the hyperfacilitation found at baseline in VCI-ND patients suggests enhanced glutamatergic neurotransmission that might contribute to the preservation of cognitive functioning. The hyperexcitability observed at follow-up in both groups of patients also indicates functional changes in glutamatergic neurotransmission. The mechanisms enhancing the risk of dementia in VD might be related either to subcortical vascular lesions or to the lack of compensatory functional cortical changes.

  10. Gastroprotective Effects of Lion’s Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats

    OpenAIRE

    Jing-Yang Wong; Mahmood Ameen Abdulla; Jegadeesh Raman; Chia-Wei Phan; Umah Rani Kuppusamy; Shahram Golbabapour; Vikineswary Sabaratnam

    2013-01-01

    Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Sprague Dawley rats were investigated. The possible involvements of lipid peroxidation, superoxide dismutase, and catalase were also investigated. Acute toxicity study was performed. The effects of aqueous extract of H. erinaceus on the ulcer areas, ulcer inhibition, gastric wall mucus, gross and histological gastric lesions, antioxidant ...

  11. Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress.

    Science.gov (United States)

    Kim, Jung Wha; Yang, Heejung; Kim, Hyeon Woo; Kim, Hong Pyo; Sung, Sang Hyun

    2017-01-01

    Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the isolates, furofuran lignans 4-6, significantly protected rat hepatocytes against ethanol-induced oxidative stress by reducing intracellular reactive oxygen species levels, preserving antioxidative defense enzyme activities, and maintaining the glutathione content. Moreover, 4 dose-dependently induced the heme oxygenase-1 expression in HepG2 cells.

  12. Gastroprotection of Suaveolol, Isolated from Hyptis suaveolens, against Ethanol-Induced Gastric Lesions in Wistar Rats: Role of Prostaglandins, Nitric Oxide and Sulfhydryls

    OpenAIRE

    Vera-Arzave, Carlos; Antonio, Leticia Cruz; Arrieta, Jesús; Cruz-Hernández, Gerardo; Velázquez-Méndez, Antonio Magdiel; Reyes-Ramírez, Adelfo; Sánchez-Mendoza, María Elena

    2012-01-01

    Hyptis suaveolens is a medicinal plant that is, according to traditional medicine, considered useful in the treatment of gastric ulcers. Although its gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim of the present study was to identify at least one active compound potentially responsible for the gastroprotective activity of H. suaveolens by using a bioassay guided study with an ethanol-induced g...

  13. The guggulsterone derivative GG-52 inhibits NF-κB signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice.

    Science.gov (United States)

    Kim, Jung Mogg; Kim, Su Hyun; Ko, Su Hyuk; Jung, Jireh; Chun, Jaeyoung; Kim, Nayoung; Jung, Hyun Chae; Kim, Joo Sung

    2013-01-15

    Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.

  14. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

    Science.gov (United States)

    Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

    2017-12-01

    Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Evaluation of protective effects of costunolide and dehydrocostuslactone on ethanol-induced gastric ulcer in mice based on multi-pathway regulation.

    Science.gov (United States)

    Zheng, Hong; Chen, Yuling; Zhang, Jingze; Wang, Lei; Jin, Zhaoxiang; Huang, Hanhan; Man, Shuli; Gao, Wenyuan

    2016-04-25

    The aim of the present study was to evaluate the anti-ulcerogenic activity of costunolide (Co) and dehydrocostuslactone (De) on ethanol-induced gastric ulcer in mice and to elucidate the potential mechanisms of the action involved. Mice were pretreated orally with Co (5 or 20 mg/kg), De (5 or 20 mg/kg) and omeprazole (OME, 20 mg/kg) for 7 consecutive days, followed by ulcer induction using absolute ethanol (0.2 mL/20 g body weight). Treatment with Co had a remarkable gastroprotection compared to the ethanol-ulcerated mice that significantly reduced the ulcerative lesion index (ULI) and histopathological damage. Daily intragastric administration of Co exerted a powerful anti-inflammatory activity as evidenced by the suppression of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, as well as increased interleukin (IL)-10. Also, pretreatment with Co effectively inhibited ethanol-induced malondialdehyde (MDA) overproduction, increased the depleted superoxide dismutase (SOD) and promoted gastric mucosa epithelial cell proliferation by up-regulating proliferating cell nuclear antigen (PCNA) expression. Similarly, De had a protective effect on ethanol-induced ulcer, which was dependent on the inhibition of inflammatory cytokines and MDA generation, but independent of IL-10, SOD and PCNA improvement. Conclusively, the results have clearly demonstrated the anti-ulcerogenic potential of Co and De on ethanol-induced gastric ulcer; nevertheless, the gastroprotective activity of Co was superior to De due to more multi-pathway regulation than De. These findings suggested that Co or De could be a new useful natural gastroprotective tool against gastric ulcer, which provided a scientific basis for the gastroprotection of sesquiterpene lactones. Copyright © 2016. Published by Elsevier Ireland Ltd.

  16. Protection of hepatotoxicity using Spondias pinnata by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers in Wistar rats.

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    Iqbal, Shoaib Shadab; Mujahid, Md; Kashif, Sayed Mohammad; Khalid, Mohammad; Badruddeen; Arif, Muhammad; Bagga, Paramdeep; Akhtar, Juber; Rahman, Md Azizur

    2016-12-01

    Traditional systems of medicine use herbal drugs for hepatoprotection. Thus, the study was designed to evaluate the hepatoprotective and antioxidant effects of Spondias pinnata bark extracts against ethanol-induced liver injury in Wistar rats. Group I animals were treated with 1 mL/kg 0.3% carboxymethyl cellulose and Group II with 12 mL/kg 50% ethanol for 8 consecutive days. Groups III-VII animals were first treated with 400 mg/kg petroleum ether extract, chloroform extract, acetone extract (AE), ethanol extract (EE), and 100 mg/kg silymarin, and then 12 mL/kg 50% ethanol orally after 2 hours pretreatment each day for 8 consecutive days. Six hours after the last dose, blood was withdrawn. The hepatoprotective activity was assessed by several biochemical and antioxidant parameters. It was accomplished by the histopathology and DNA fragmentation study of liver tissues. Treatment with S. pinnata extracts, mainly AE and EE significantly (p extract was less than that of standard drug silymarin. Results of the study were well supported by the histopathological observations. S. pinnata extracts AE and EE possess a potent hepatoprotective effect against ethanol-induced liver injury in Wistar rats, and protect them from hepatotoxicity by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers.

  17. High Intrinsic Aerobic Capacity Protects against Ethanol-Induced Hepatic Injury and Metabolic Dysfunction: Study Using High Capacity Runner Rat Model.

    Science.gov (United States)

    Szary, Nicholas; Rector, R Scott; Uptergrove, Grace M; Ridenhour, Suzanne E; Shukla, Shivendra D; Thyfault, John P; Koch, Lauren G; Britton, Steven L; Ibdah, Jamal A

    2015-11-20

    Rats artificially selected over several generations for high intrinsic endurance/aerobic capacity resulting in high capacity runners (HCR) has been developed to study the links between high aerobic fitness and protection from metabolic diseases (Wisloff et al., Science, 2005). We have previously shown that the HCR strain have elevated hepatic mitochondrial content and oxidative capacity. In this study, we tested if the elevated hepatic mitochondrial content in the HCR rat would provide "metabolic protection" from chronic ethanol-induced hepatic steatosis and injury. The Leiber-Decarli liquid diet with ethanol (7% v/v; HCR-E) and without (HCR-C) was given to HCR rats (n = 8 per group) from 14 to 20 weeks of age that were weight matched and pair-fed to assure isocaloric intake. Hepatic triglyceride (TG) content and macro- and microvesicular steatosis were significantly greater in HCR-E compared with HCR-C (p High intrinsic aerobic fitness did not reduce ethanol-induced hepatic steatosis, but protected against ethanol-induced hepatic injury and systemic metabolic dysfunction in a high aerobic capacity rat model.

  18. A hot water extract of turmeric (Curcuma longa) suppresses acute ethanol-induced liver injury in mice by inhibiting hepatic oxidative stress and inflammatory cytokine production.

    Science.gov (United States)

    Uchio, Ryusei; Higashi, Yohei; Kohama, Yusuke; Kawasaki, Kengo; Hirao, Takashi; Muroyama, Koutarou; Murosaki, Shinji

    2017-01-01

    Turmeric (Curcuma longa) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.

  19. Occupation and communication programs for post-coma persons with or without consciousness disorders who show extensive motor impairment and lack of speech.

    Science.gov (United States)

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Buonocunto, Francesca; D'Amico, Fiora; Navarro, Jorge; Lanzilotti, Crocifissa; Megna, Marisa

    2014-05-01

    These two studies were aimed at extending the assessment of technology-aided programs for post-coma persons with extensive motor impairment and lack of speech. Specifically, Study I assessed a new program arrangement, in which stimulation access and caregiver attention could be obtained with variations of the same response (i.e., single- versus double-hand closure) by three participants who were diagnosed at the upper level of the minimally conscious state at the start of the study. Study II was aimed at enabling two persons who had emerged from a minimally conscious state to engage in leisure activities, listen to audio-recordings of family members, and send and receive messages. The responses selected for these participants were hand pressure and eyelid closure, respectively. The results of both studies were positive. The participants of Study I increased their responding to increase their stimulation input and caregiver interaction. The participants of Study II managed to successfully select all the options the program included (i.e., the leisure options, as well as the family and communication options). General implications of the programs and the related technology packages for intervention with post-coma persons with multiple disabilities are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats

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    Ibrahim IAA

    2015-12-01

    Full Text Available Ibrahim Abdel Aziz Ibrahim,1 Mahmood Ameen Abdulla,2 Maryam Hajrezaie,2 Ammar Bader,3 Naiyer Shahzad,1 Saeed S Al-Ghamdi,1 Ahmad S Gushash,4 Mohadeseh Hasanpourghadi5 1Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 4College of Arts and Science in Baljurashi, Albaha University, Baljurashi, Saudi Arabia; 5Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Abstract: Monolluma quadrangula (Forssk. Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid–Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the

  1. Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats.

    Science.gov (United States)

    Omar, Hanita; Nordin, Noraziah; Hassandarvish, Pouya; Hajrezaie, Maryam; Azizan, Ainnul Hamidah Syahadah; Fadaeinasab, Mehran; Abdul Majid, Nazia; Abdulla, Mahmood Ameen; Mohd Hashim, Najihah; Mohd Ali, Hapipah

    2017-01-01

    gastroprotective potential in rats' stomach against ethanol-induced ulcer.

  2. Anti-ulcerogenic effect of cavidine against ethanol-induced acute gastric ulcer in mice and possible underlying mechanism.

    Science.gov (United States)

    Li, Weifeng; Wang, Xiumei; Zhang, Hailin; He, Zehong; Zhi, Wenbing; Liu, Fang; Wang, Yu; Niu, Xiaofeng

    2016-09-01

    Cavidine, a major alkaloid compound isolated from Corydalis impatiens, has various pharmacological effects but its effect on gastric ulcer has not been previously explored. The current study aimed to investigate the possible anti-ulcerogenic potential of cavidine in the model of ethanol-induced gastric ulcer. Mice received cavidine (1, 5 or 10mg/kg, ig), cimetidine (CMD, 100mg/kg, ig) or vehicle at 12h and 1h before absolute ethanol administration (0.5mL/100g), and animals were euthanized 3h after ethanol ingestion. Gross and histological gastric lesions, biochemical, immunological and Western blot parameters were taken into consideration. The results showed that ethanol administration produced apparent mucosal injuries with morphological and histological damage, whereas cavidine pre-treatment reduced the gastric injuries. Cavidine pre-treatment also ameliorated the contents of malonaldehyde (MDA) and myeloperoxidase (MPO) activity, and increased the mucosa levels of glutathione (GSH), superoxide dismutase (SOD) and prostaglandin E2 (PGE2), relative to the model group. Also cavidine was able to decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), inhibit the up-regulation of cyclo-oxygenase-2 (COX-2) expression and activation of Nuclear factor-kappa B (NF-κB) pathway. Taken together, these results indicated that cavidine exerts a gastroprotective effect against gastric ulceration, and the underlying mechanism might be associated with the stimulation of PGE2, reduction of oxidative stress, suppression of NF-κB expression and subsequent reduced COX-2 and pro-inflammatory cytokines. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. In vivo antioxidant and antiulcer activity of Parkia speciosa ethanolic leaf extract against ethanol-induced gastric ulcer in rats.

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    Rami Al Batran

    Full Text Available BACKGROUND: The current study was carried out to examine the gastroprotective effects of Parkia speciosa against ethanol-induced gastric mucosa injury in rats. METHODOLOGY/PRINCIPAL FINDINGS: Sprague Dawley rats were separated into 7 groups. Groups 1-2 were orally challenged with carboxymethylcellulose (CMC; group 3 received 20 mg/kg omeprazole and groups 4-7 received 50, 100, 200 and 400 mg/kg of ethanolic leaf extract, respectively. After 1 h, CMC or absolute ethanol was given orally to groups 2-7. The rats were sacrificed after 1 h. Then, the injuries to the gastric mucosa were estimated through assessment of the gastric wall mucus, the gross appearance of ulcer areas, histology, immunohistochemistry and enzymatic assays. Group 2 exhibited significant mucosal injuries, with reduced gastric wall mucus and severe damage to the gastric mucosa, whereas reductions in mucosal injury were observed for groups 4-7. Groups 3-7 demonstrated a reversal in the decrease in Periodic acid-Schiff (PAS staining induced by ethanol. No symptoms of toxicity or death were observed during the acute toxicity tests. CONCLUSION: Treatment with the extract led to the upregulation of heat-shock protein 70 (HSP70 and the downregulation of the pro-apoptotic protein BAX. Significant increases in the levels of the antioxidant defense enzymes glutathione (GSH and superoxide dismutase (SOD in the gastric mucosal homogenate were observed, whereas that of a lipid peroxidation marker (MDA was significantly decreased. Significance was defined as p<0.05 compared to the ulcer control group (Group 2.

  4. Antioxidant Mechanism is Involved in the Gastroprotective Effects of Ozonized Sunflower Oil in Ethanol-Induced Ulcers in Rats

    Directory of Open Access Journals (Sweden)

    Siegfried Schulz

    2007-01-01

    Full Text Available This research was performed in order to determine the potential protective effects of ozonized sunflower oil (OSO in the injury of rat gastric mucosa induced by absolute ethanol and as well as to elucidate the role of reactive oxygen species (ROS, lipid peroxidation, and some important constituents of antioxidant defense such as superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, and catalase (CAT in these effects. OSO was administered to rats intragastrically by a cannula and it was applied during four days to animals. The doses of OSO administered daily to each group of rats were 4, 12, and 24 mg/kg, respectively, and one hour after the last treatment, absolute ethanol (1 mL/200 mg body weight was administered. Our results showed that gastric ulcer index was significantly reduced in rats pretreated with OSO as compared with ethanol-treated controls. However, in rats pretreated with OSO, no significant reduction of TBARS content in gastric mucosa was found as compared to those rats treated with ethanol alone. In contrast, SOD and GSH-Px activities were significantly increased in gastric mucosa of OSO-pretreated rats with respect to those treated with ethanol alone. In summary, our results demonstrate that OSO pretreatment exerts protective effects in ethanol-induced gastric ulcers in rats. Furthermore, these results provide evidence that these protective effects of OSO are mediated at least partially by stimulation of some important antioxidant enzymes such as SOD and GSH-Px, which are scavengers of ROS and therefore prevent gastric injury induced by them.

  5. Antioxidant mechanism is involved in the gastroprotective effects of ozonized sunflower oil in ethanol-induced ulcers in rats.

    Science.gov (United States)

    Zamora Rodríguez, Zullyt B; González Alvarez, Ricardo; Guanche, Dailén; Merino, Nelson; Hernández Rosales, Frank; Menéndez Cepero, Silvia; Alonso González, Yaima; Schulz, Siegfried

    2007-01-01

    This research was performed in order to determine the potential protective effects of ozonized sunflower oil (OSO) in the injury of rat gastric mucosa induced by absolute ethanol and as well as to elucidate the role of reactive oxygen species (ROS), lipid peroxidation, and some important constituents of antioxidant defense such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in these effects. OSO was administered to rats intragastrically by a cannula and it was applied during four days to animals. The doses of OSO administered daily to each group of rats were 4, 12, and 24 mg/kg, respectively, and one hour after the last treatment, absolute ethanol (1 mL/200 mg body weight) was administered. Our results showed that gastric ulcer index was significantly reduced in rats pretreated with OSO as compared with ethanol-treated controls. However, in rats pretreated with OSO, no significant reduction of TBARS content in gastric mucosa was found as compared to those rats treated with ethanol alone. In contrast, SOD and GSH-Px activities were significantly increased in gastric mucosa of OSO-pretreated rats with respect to those treated with ethanol alone. In summary, our results demonstrate that OSO pretreatment exerts protective effects in ethanol-induced gastric ulcers in rats. Furthermore, these results provide evidence that these protective effects of OSO are mediated at least partially by stimulation of some important antioxidant enzymes such as SOD and GSH-Px, which are scavengers of ROS and therefore prevent gastric injury induced by them.

  6. Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.

    Science.gov (United States)

    Farshori, Nida Nayyar; Al-Sheddi, Ebtsam S; Al-Oqail, Mai M; Hassan, Wafaa H B; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Siddiqui, Maqsood A

    2015-08-01

    The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 μg/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia. © The Author(s) 2013.

  7. Ghrelin gene expression in rats with ethanol-induced gastric ulcers: a role of melatonin.

    Science.gov (United States)

    Abdelraheim, S R; Okasha, A M; Ghany, H M; Ibrahim, H M

    2015-01-01

    The aim of the present work was to reveal the mechanisms of melatonin treatment on ethanol-induced gastric mucosal lesions in rats, including its role in the induction of ghrelin biosynthesis. Sixty male Wistar rats were divided into 3 groups (20 in each group): a) control group, b) ulcer group (100% ethanol was given intragastrically (i.g.) in a dose of 1 ml/100 g of body weight), and 3) melatonin-treated group, which received a single dose (25 mg/kg) of melatonin (Biovea) i.g. 30 min before ulcer induction with ethanol. Reduced glutathione (GSH) and malondialdehyde (MDA) were measured in tissues and ghrelin levels determined in the serum. RNA isolation and RT-PCR expression of ghrelin were performed. Both macroscopic and microscopic examinations of gastric mucosa were done in all groups. Significant decrease in ghrelin levels and mRNA expression and reduced levels of GSH were observed in ulcer group of rats in comparison with controls. All parameters studied were significantly increased after treatment with melatonin in comparison with ulcer bearing group of rats. On the other hand, the tissue levels of MDA were significantly increased in ulcer group of rats in comparison with controls and significantly decreased after melatonin treatment in comparison with the ulcer group of rats. Histological examinations revealed severe mucosal lesions induced by ethanol which were significantly improved by melatonin administration. The present data indicate that melatonin may have a potential impact in the treatment of peptic ulcer not only via its known antioxidant effect but also via induction of the ghrelin biosynthesis, as it was documented by significant increase in ghrelin mRNA expression.

  8. Synergistic effect of Se-methylselenocysteine and vitamin E in ameliorating the acute ethanol-induced oxidative damage in rat.

    Science.gov (United States)

    Yao, Zhao; Zhang, Yunlong; Li, Hongyan; Deng, Zeyuan; Zhang, Xiaoping

    2015-01-01

    The present study was conduced to investigate the synergistic effects of combined treatments with Se-methylselenocysteine (SeMSC) and vitamin E (Vit E) in reversing oxidative stress induced by ethanol in serum and different tissues of rats. Sixty female rats were randomly divided into six groups for 30 days' consecutive pretreatments as followed: control (I), physiological saline (II), 2.8μgkg(-1) Se as SeMSC (III), 2.8μgkg(-1) Se as sodium selenite (Na2SeO3, IV), 5mgkg(-1) α-tocopherol as α-tocopherol acetate (Vit E, V), 5mgkg(-1) α-tocopherol as α-tocopherol acetate and 2.8μgkg(-1) Se as SeMSC (VI). All animals in groups II-VI were treated by ethanol treatment to cause oxidative stress. After 6h of ethanol treatment, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), the contents of total antioxidant capacity (T-AOC), malondialdehyde (MDA), glutathione (GSH) and carbonyl protein (CP) in the serum, liver, heart and kidney were measured. The result showed that the individual SeSMC, Na2SeO3 and vitamin E could effectively increase the SOD, T-AOC, GSH-Px and GSH contents as well as significantly decrease the MDA and CP concentrations in the tissues of ethanol-induced rats. At the same dose on different forms of Se, SeMSC showed greater antioxidant activity than Na2SeO3. Moreover, group VI (SeMSC and α-tocopherol acetate) showed much better antioxidant activity than individual group III (SeMSC) and V (α-tocopherol acetate) due to the synergistic effect. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement.

    Science.gov (United States)

    Moghadamtousi, Soheil Zorofchian; Rouhollahi, Elham; Karimian, Hamed; Fadaeinasab, Mehran; Abdulla, Mahmood Ameen; Kadir, Habsah Abdul

    2014-01-01

    The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and graviola, is a widely distributed plant in Central and South America and tropical countries. Leaves of A. muricata have been reported to possess antioxidant and anti-inflammatory activities. In this study, the gastroprotective effects of ethyl acetate extract of A. muricata leaves (EEAM) were investigated against ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological features showed the antiulcerogenic characterizations of EEAM. There was significant suppression on the ulcer lesion index of rats pretreated with EEAM, which was comparable to the omeprazole effect in the omeprazole control group. Oral administration of EEAM to rats caused a significant increase in the level of nitric oxide and antioxidant activities, including catalase, glutathione, and superoxide dismutase associated with attenuation in gastric acidity, and compensatory effect on the loss of gastric wall mucus. In addition, pretreatment of rats with EEAM caused significant reduction in the level of malondialdehyde, as a marker for oxidative stress, associated with an increase in prostaglandin E2 activity. Immunohistochemical staining also demonstrated that EEAM induced the downregulation of Bax and upregulation of Hsp70 proteins after pretreatment. Collectively, the present results suggest that EEAM has a promising antiulcer potential, which could be attributed to its suppressive effect against oxidative damage and preservative effect toward gastric wall mucus.

  10. Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice.

    Science.gov (United States)

    Khan, Yasmin; Pandy, Vijayapandi

    2016-01-01

    Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

  11. Methanolic extract of Morinda citrifolia L. (noni unripe fruit attenuates ethanol-induced conditioned place preferences in mice

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    Yasmin Khan

    2016-09-01

    Full Text Available Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC, on compulsive ethanol-seeking behaviour using the mouse conditioned place preference (CPP test. CPP was established by injections of ethanol (2g/kg, i.p. in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM, on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3 and 5g/kg and ACAM (300 mg/kg 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction, during which the treatment groups received MMC (1, 3 and 5g/kg, p.o. or ACAM (300 mg/kg, p.o.. Finally, a priming injection of a low dose of ethanol (0.4g/kg, i.p. in the home cage (Reinstatement was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5g/kg, p.o and ACAM (300 mg/kg, p.o. significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

  12. Inhibition of vascular endothelial growth factor signaling facilitates liver repair from acute ethanol-induced injury in zebrafish

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    Changwen Zhang

    2016-11-01

    Full Text Available Alcoholic liver disease (ALD results from alcohol overconsumption and is among the leading causes of liver-related morbidity and mortality worldwide. Elevated expression of vascular endothelial growth factor (VEGF and its receptors has been observed in ALD, but how it contributes to ALD pathophysiology is unclear. Here, we investigated the impact of VEGF signaling inhibition on an established zebrafish model of acute alcoholic liver injury. Kdrl activity was blocked by chemical inhibitor treatment or by genetic mutation. Exposing 4-day-old zebrafish larvae to 2% ethanol for 24 h induced hepatic steatosis, angiogenesis and fibrogenesis. The liver started self-repair once ethanol was removed. Although inhibiting Kdrl did not block the initial activation of hepatic stellate cells during ethanol treatment, it suppressed their proliferation, extracellular matrix protein deposition and fibrogenic gene expression after ethanol exposure, thus enhancing the liver repair. It also ameliorated hepatic steatosis and attenuated hepatic angiogenesis that accelerated after the ethanol treatment. qPCR showed that hepatic stellate cells are the first liver cell type to increase the expression of VEGF ligand and receptor genes in response to ethanol exposure. Both hepatic stellate cells and endothelial cells, but not hepatic parenchymal cells, expressed kdrl upon ethanol exposure and were likely the direct targets of Kdrl inhibition.