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Sample records for brain damage chronic

  1. Late damage to brain microvasculature after chronic irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lyubimova, N. [Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Moscow (Russian Federation)

    1997-03-01

    The effects on mouse brain microvasculature were examined 12 months after exposure to chronic {gamma}- irradiation at 3 cGy/day for three months. Animals were injected i.p. with 100 mg/kg iproniazid, an inhibitor of mono-amine-oxidase. Six hours later and 15 min before animal sacrifice, 100 mg/kg L-DOPA was also injected. This procedure resulted in the accumulation of catecholamines (CA) in the endothelial cells, a process which otherwise would be prevented by mono-amine-oxidase activity. Animals were killed by decapitation under nembutal anesthesia at various times post irradiation. Dissected pieces of brain were immediately frozen in liquid nitrogen and lyophilized at -20 deg C under vacuum to avoid CA diffusion from the endothelial cell. The reaction between CA and paraformaldehyde gas at 70 % humidity and 80 deg C was used to generate fluorophores which act as endothelial cell markers. Histological specimens were embedded in paraffin was under vacuum and serial section cut. These were assessed under fluorescent microscopy. These studies indicate that in some ways repair of chronic radiation damage may be less complete than repair of damage caused by a single acute exposure. The dystrophic changes seen in the endothelium also suggest the possibility that chronic exposure may be more likely to lead to late functional impairment of brain microcirculation. (author)

  2. Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion

    National Research Council Canada - National Science Library

    Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

    2014-01-01

    .... Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage...

  3. Brain maturation and damage in infants dying from chronic pulmonary insufficiency in the postneonatal period

    Science.gov (United States)

    Smith, J. F.; Reynolds, E. O. R.; Taghizadeh, A.

    1974-01-01

    The changes in the brains of 11 infants who survived from 29 days to 13 months after severe chronic pulmonary insufficiency are described. Brain maturation as assessed by myelination and gyral formation was within normal limits. In 5 infants the brain weight was less than normal if age was used in the comparison, but greater than normal if body weight was used. In addition to hypoxic or ischaemic damage, which was found in some degree in all cases except one, there were several other local lesions. These included periventricular leucomalacia 7, periventricular haemorrhage 1, hydrocephalus 2, and cystic encephalomalacia 3. Though the last is almost certainly due to vascular occlusion, this could not be shown. The possibility of cerebral embolism after umbilical vein catheterization is considered but not proven. ImagesFIG. 1FIG. 3FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7 PMID:4834015

  4. Cigarette smoking exacerbates chronic alcohol-induced brain damage: a preliminary metabolite imaging study.

    Science.gov (United States)

    Durazzo, Timothy C; Gazdzinski, Stefan; Banys, Peter; Meyerhoff, Dieter J

    2004-12-01

    Cigarette smoking is common among alcohol-dependent individuals. Nevertheless, previous research has typically not accounted for the potential independent or compounding effects of cigarette smoking on alcohol-induced brain injury and neurocognition. Twenty-four 1-week-abstinent recovering alcoholics (RAs; 14 smokers and 10 nonsmokers) in treatment and 26 light-drinking controls (7 smokers and 19 nonsmokers) were compared on measures of common brain metabolites in gray matter and white matter of the major lobes, basal ganglia, midbrain, and cerebellar vermis, obtained via multislice short-echo time proton magnetic resonance spectroscopic imaging. Smoking and nonsmoking RAs were also contrasted on measures of neurocognitive functioning, as well as laboratory markers of drinking severity and nutritional status. Chronic alcohol dependence, independent of smoking, was associated with lower concentrations of frontal N-acetylaspartate (NAA) and frontal choline-containing compounds, as well as lower parietal and thalamic choline. Smoking RAs had lower NAA concentrations in frontal white matter and midbrain and lower midbrain choline than nonsmoking RAs. A four-group analysis of covariance also demonstrated that chronic cigarette smoking was associated with lower midbrain NAA and choline and with lower vermian choline. In smoking RAs, heavier drinking was associated with heavier smoking, which correlated with numerous subcortical metabolite abnormalities. The 1-week-abstinent smoking and nonsmoking RAs did not differ significantly on a brief neurocognitive battery. In smoking RAs, lower cerebellar vermis NAA was associated with poorer visuomotor scanning speed and incidental learning, and in nonsmoking RAs lower vermis NAA was related to poorer visuospatial learning and memory. These human in vivo proton magnetic resonance spectroscopic imaging findings indicate that chronic cigarette smoking exacerbates chronic alcohol-induced neuronal injury and cell membrane damage in

  5. Damage to Myelin and Oligodendrocytes: A Role in Chronic Outcomes Following Traumatic Brain Injury?

    Science.gov (United States)

    Maxwell, William L.

    2013-01-01

    There is increasing evidence in the experimental and clinical traumatic brain injury (TBI) literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s) of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1–2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter. PMID:24961533

  6. Damage to myelin and oligodendrocytes: a role in chronic outcomes following traumatic brain injury?

    Science.gov (United States)

    Maxwell, William L

    2013-09-16

    There is increasing evidence in the experimental and clinical traumatic brain injury (TBI) literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s) of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1-2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

  7. Damage to Myelin and Oligodendrocytes: A Role in Chronic Outcomes Following Traumatic Brain Injury?

    Directory of Open Access Journals (Sweden)

    William L. Maxwell

    2013-09-01

    Full Text Available There is increasing evidence in the experimental and clinical traumatic brain injury (TBI literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1–2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

  8. Structural brain changes in chronic pain reflect probably neither damage nor atrophy.

    Directory of Open Access Journals (Sweden)

    Rea Rodriguez-Raecke

    Full Text Available Chronic pain appears to be associated with brain gray matter reduction in areas ascribable to the transmission of pain. The morphological processes underlying these structural changes, probably following functional reorganisation and central plasticity in the brain, remain unclear. The pain in hip osteoarthritis is one of the few chronic pain syndromes which are principally curable. We investigated 20 patients with chronic pain due to unilateral coxarthrosis (mean age 63.25±9.46 (SD years, 10 female before hip joint endoprosthetic surgery (pain state and monitored brain structural changes up to 1 year after surgery: 6-8 weeks, 12-18 weeks and 10-14 month when completely pain free. Patients with chronic pain due to unilateral coxarthrosis had significantly less gray matter compared to controls in the anterior cingulate cortex (ACC, insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC and orbitofrontal cortex. These regions function as multi-integrative structures during the experience and the anticipation of pain. When the patients were pain free after recovery from endoprosthetic surgery, a gray matter increase in nearly the same areas was found. We also found a progressive increase of brain gray matter in the premotor cortex and the supplementary motor area (SMA. We conclude that gray matter abnormalities in chronic pain are not the cause, but secondary to the disease and are at least in part due to changes in motor function and bodily integration.

  9. Is There Chronic Brain Damage in Retired NFL Players? Neuroradiology, Neuropsychology, and Neurology Examinations of 45 Retired Players

    OpenAIRE

    Casson, Ira R.; Viano, David C.; Haacke, E. Mark; Kou, Zhifeng; LeStrange, Danielle G.

    2014-01-01

    Background: Neuropathology and surveys of retired National Football League (NFL) players suggest that chronic brain damage is a frequent result of a career in football. There is limited information on the neurological statuses of living retired players. This study aimed to fill the gap in knowledge by conducting in-depth neurological examinations of 30- to 60-year-old retired NFL players. Hypothesis: In-depth neurological examinations of 30- to 60-year-old retired players are unlikely to dete...

  10. Hepatoprotective and neuroprotective activity of liposomal quercetin in combating chronic arsenic induced oxidative damage in liver and brain of rats.

    Science.gov (United States)

    Ghosh, Aparajita; Mandal, Ardhendu K; Sarkar, Sibani; Das, Nirmalendu

    2011-08-01

    Arsenic is a naturally occurring toxicant that causes acute and chronic adverse health effects, including cancer. The study was performed to evaluate the therapeutic efficacy of liposome entrapped flavonoidal quercetin in combating arsenic toxicity mediated oxidative damage in hepatocytes and brain cells in rat model. Hepatic and neuronal cell damage in rats was made by daily arsenic (6 mg/kg b wt, 9 mg/kg b wt and 12 mg/kg b wt) treatment via oral route for four consecutive months. Liposomal quercetin (2.71 mg QC/kg b. wt) were injected s.c. on rats treated with 12 mg/kg b. wt. NaAsO(2) twice a week for four months. Inorganic arsenic deposition was found to be most significant in hepatic (9.32 ± 0.100 µg/g tissue) and neuronal (6.21 ± 0.090 µg/g tissue) cells of rats treated with 12 mg/kg b wt of arsenite. Antioxidant levels in hepatic and neuronal cells were reduced significantly by the induction of arsenic. Liposomal quercetin was found most potent for a complete prevention of arsenite-induced reduction in antioxidant levels in the liver and brain of rats. Arsenic induced a substantial increase in hepatic hydroxyproline (HP) and Liposomal quercetin treatment resulted in complete replenishment of the HP level to normal. Liposomal quercetin completely prevented the arsenite-induced upregulation of cytochrome c expression in liver and brain significantly suggesting that the protective effect of Liposomal quercetin could be related to the reduction of arsenic deposition in both the organs. Thus, Liposomal quercetin might prove to be of therapeutic potential against arsenite-induced hepatic and neuronal cell damage in rats.

  11. Is There Chronic Brain Damage in Retired NFL Players? Neuroradiology, Neuropsychology, and Neurology Examinations of 45 Retired Players

    Science.gov (United States)

    Casson, Ira R.; Viano, David C.; Haacke, E. Mark; Kou, Zhifeng; LeStrange, Danielle G.

    2014-01-01

    Background: Neuropathology and surveys of retired National Football League (NFL) players suggest that chronic brain damage is a frequent result of a career in football. There is limited information on the neurological statuses of living retired players. This study aimed to fill the gap in knowledge by conducting in-depth neurological examinations of 30- to 60-year-old retired NFL players. Hypothesis: In-depth neurological examinations of 30- to 60-year-old retired players are unlikely to detect objective clinical abnormalities in the majority of subjects. Study Design: A day-long medical examination was conducted on 45 retired NFL players, including state-of-the-art magnetic resonance imaging (MRI; susceptibility weighted imaging [SWI], diffusion tensor imaging [DTI]), comprehensive neuropsychological and neurological examinations, interviews, blood tests, and APOE (apolipoprotein E) genotyping. Level of Evidence: Level 3. Methods: Participants’ histories focused on neurological and depression symptoms, exposure to football, and other factors that could affect brain function. The neurological examination included Mini-Mental State Examination (MMSE) evaluation of cognitive function and a comprehensive search for signs of dysarthria, pyramidal system dysfunction, extrapyramidal system dysfunction, and cerebellar dysfunction. The Beck Depression Inventory (BDI) and Patient Health Questionnaire (PHQ) measured depression. Neuropsychological tests included pen-and-paper and ImPACT evaluation of cognitive function. Anatomical examination SWI and DTI MRI searched for brain injuries. The results were statistically analyzed for associations with markers of exposure to football and related factors, such as body mass index (BMI), ethanol use, and APOE4 status. Results: The retired players’ ages averaged 45.6 ± 8.9 years (range, 30-60 years), and they had 6.8 ± 3.2 years (maximum, 14 years) of NFL play. They reported 6.9 ± 6.2 concussions (maximum, 25) in the NFL. The

  12. Is There Chronic Brain Damage in Retired NFL Players? Neuroradiology, Neuropsychology, and Neurology Examinations of 45 Retired Players.

    Science.gov (United States)

    Casson, Ira R; Viano, David C; Haacke, E Mark; Kou, Zhifeng; LeStrange, Danielle G

    2014-09-01

    Neuropathology and surveys of retired National Football League (NFL) players suggest that chronic brain damage is a frequent result of a career in football. There is limited information on the neurological statuses of living retired players. This study aimed to fill the gap in knowledge by conducting in-depth neurological examinations of 30- to 60-year-old retired NFL players. In-depth neurological examinations of 30- to 60-year-old retired players are unlikely to detect objective clinical abnormalities in the majority of subjects. A day-long medical examination was conducted on 45 retired NFL players, including state-of-the-art magnetic resonance imaging (MRI; susceptibility weighted imaging [SWI], diffusion tensor imaging [DTI]), comprehensive neuropsychological and neurological examinations, interviews, blood tests, and APOE (apolipoprotein E) genotyping. Level 3. Participants' histories focused on neurological and depression symptoms, exposure to football, and other factors that could affect brain function. The neurological examination included Mini-Mental State Examination (MMSE) evaluation of cognitive function and a comprehensive search for signs of dysarthria, pyramidal system dysfunction, extrapyramidal system dysfunction, and cerebellar dysfunction. The Beck Depression Inventory (BDI) and Patient Health Questionnaire (PHQ) measured depression. Neuropsychological tests included pen-and-paper and ImPACT evaluation of cognitive function. Anatomical examination SWI and DTI MRI searched for brain injuries. The results were statistically analyzed for associations with markers of exposure to football and related factors, such as body mass index (BMI), ethanol use, and APOE4 status. The retired players' ages averaged 45.6 ± 8.9 years (range, 30-60 years), and they had 6.8 ± 3.2 years (maximum, 14 years) of NFL play. They reported 6.9 ± 6.2 concussions (maximum, 25) in the NFL. The majority of retired players had normal clinical mental status and central

  13. Contextualizing aquired brain damage

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2014-01-01

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

  14. 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.

  15. Chronic brain damage in sickle cell disease and its relation with quality of life.

    Science.gov (United States)

    Cela, Elena; Vélez, Ana G; Aguado, Alejandra; Medín, Gabriela; Bellón, José M; Beléndez, Cristina

    2016-12-16

    Sickle cell anaemia causes progressive organ damage. The objective is to describe school performance of patients with sickle cell anaemia and their clinical parameters and quality of life that may have an influence. The hypothesis is that if school alterations occur without other objective data, additional factors must be present besides the disease itself. Transversal study performed in November 2015 considering analytical variables, complications and neuroradiological images of children with sickle cell anaemia, and family survey on school performance and quality of life. Median age was 6.8 years and 78% were diagnosed at birth. Sixty patients were included. School performance was altered in 51% of cases and was related to nocturnal hypoxemia. Acute stroke incidence was 6.7%. Transcranial ultrasound was abnormal in 4% of cases and magnetic resonance imaging in 16% of cases. Quality of life showed pathological findings in all areas and the low values increased proportionally in older ages. The stroke affected the physical and social sphere, and lung disease affected the physical and emotional spheres. Poor school performance affects half of the patients and it is related to nocturnal hypoxemia, although other socio-cultural factors may have an influence. Quality of life is affected in most of these cases independently of academic results. The absence of alterations in neuroimaging or the apparent lack of severe clinical parameters do not mean that quality of life and schooling are normal. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  16. DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Maronpot, Robert R; Torres-Jardon, Ricardo; Henríquez-Roldán, Carlos; Schoonhoven, Robert; Acuña-Ayala, Hilda; Villarreal-Calderón, Anna; Nakamura, Jun; Fernando, Reshan; Reed, William; Azzarelli, Biagio; Swenberg, James A

    2003-01-01

    Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant gases affect people in urban areas and those exposed to fires, disasters, and wars. Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NFkappaB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid(1-42) in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days-10 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex. Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer

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

    Science.gov (United States)

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

    2011-01-01

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

  18. Unpredictable Chronic Mild Stress Paradigm Established Effects of Pro- and Anti-inflammatory Cytokine on Neurodegeneration-Linked Depressive States in Hamsters with Brain Endothelial Damages.

    Science.gov (United States)

    Avolio, Ennio; Fazzari, Gilda; Mele, Maria; Alò, Raffaella; Zizza, Merylin; Jiao, Wei; Di Vito, Anna; Barni, Tullio; Mandalà, Maurizio; Canonaco, Marcello

    2017-10-01

    The mechanisms by which inflammation affects the different emotional moods are only partially known. Previous works have pointed to stress hormones like glucocorticoids plus the vascular factor endothelin-1 as key factors evoking stressful states especially in relation to endothelial dysfunctions. With this work, it was our intention to establish the role of pro- and anti-inflammatory cytokine expression variations towards depression-like behaviors and consequently the development of neurodegeneration events caused by endothelial damages in the hamster (Mesocricetus auratus). Such a rodent, which is considered a valuable animal model to test depression and anxiety states, exhibited a variety of depression-like behaviors including reduction in sucrose consumption, locomotion, and exploration (p < 0.01) following exposure to unpredictable chronic mild stress. Contextually, a tight correlation between unpredictable chronic mild stress-induced depressive states and expression of the pro-inflammatory cytokines was detected as shown by marked expression levels (p < 0.01) of IL-1β and NF-kB in the hippocampus, amygdala, and prefrontal cortex. Even the anti-inflammatory cytokine IL-10 supplied notably significant (p < 0.001) expression levels in the same areas of resilient hamsters. Application of hemodynamic and endothelial functional studies pointed to altered arterial endothelial activities in depressed with respect to resilient animals. Moreover, evident damaged neuronal fields in the above areas of depressed hamsters allowed us to correlate such a behavioral phenomenon to the upregulation of IL-1β and NF-κB. Overall, the differing roles of pro- and anti-inflammatory cytokines on depressive states, especially in view of brain endothelial damages, may provide novel therapeutic measures against mood disorders linked to neurodegenerative diseases.

  19. Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Fatimeh Khodabandehloo

    2013-05-01

    Full Text Available In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p≪0.01 and p≪0.001. In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p≪0.05 and p≪0.001. In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA concentrations were higher than in the Sham and OVX groups (p≪0.05 and p≪0.001. It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.

  20. Role of Caspase-3-Mediated Apoptosis in Chronic Caspase-3-Cleaved Tau Accumulation and Blood-Brain Barrier Damage in the Corpus Callosum after Traumatic Brain Injury in Rats.

    Science.gov (United States)

    Glushakova, Olena Y; Glushakov, Andriy O; Borlongan, Cesar V; Valadka, Alex B; Hayes, Ronald L; Glushakov, Alexander V

    2017-07-21

    Traumatic brain injury (TBI) may be a significant risk factor for development of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE), post-traumatic epilepsy (PTE), and Alzheimer's (AD) and Parkinson's (PD) diseases. Chronic TBI is associated with several pathological features that are also characteristic of neurodegenerative diseases, including tau pathologies, caspase-3-mediated apoptosis, neuroinflammation, and microvascular alterations. The goal of this study was to evaluate changes following TBI in cleaved-caspase-3 and caspase-3-cleaved tau truncated at Asp421, and their relationships to cellular markers potentially associated with inflammation and blood-brain (BBB) barrier damage. We studied astrocytes (glial fibrillary acidic protein [GFAP]), microglia (ionized calcium-binding adapter molecule 1 [Iba1]), BBB (endothelial barrier antigen [EBA]), and activated microglia/macrophages (cluster of differentiation 68 [CD68]). We employed immunohistochemistry at different time points from 24 h to 3 months after controlled cortical impact (CCI) injury in rats, with particular interest in white matter. The study demonstrated that CCI caused chronic upregulation of cleaved-caspase-3 in the white matter of the corpus callosum. Increases in cleaved-caspase-3 in the corpus callosum were accompanied by accumulation of caspase-3-cleaved tau, with increasing perivascular aggregation 3 months after CCI. Immunofluorescence experiments further showed cellular co-localization of cleaved-caspase-3 with GFAP and CD68 and its adjacent localization with EBA, suggesting involvement of apoptosis and neuroinflammation in mechanisms of delayed BBB and microvascular damage that could contribute to white matter changes. This study also provides the first evidence that evolving upregulation of cleaved-caspase-3 is associated with accumulation of caspase-3-cleaved tau following experimental TBI, thus providing new insights into potential common mechanisms mediated

  1. PREDICTING APHASIA TYPE FROM BRAIN DAMAGE MEASURED WITH STRUCTURAL MRI

    OpenAIRE

    Yourganov, Grigori; Smith, Kimberly G.; Fridriksson, Julius; Rorden, Chris

    2015-01-01

    Chronic aphasia is a common consequence of a left-hemisphere stroke. Since the early insights by Broca and Wernicke, studying the relationship between the loci of cortical damage and patterns of language impairment has been one of the concerns of aphasiology. We utilized multivariate classification in a cross-validation framework to predict the type of chronic aphasia from the spatial pattern of brain damage. Our sample consisted of 98 patients with five types of aphasia (Broca’s, Wernicke’s,...

  2. Air pollution and brain damage.

    Science.gov (United States)

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

    2002-01-01

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

  3. Variation in chronic nicotinamide treatment after traumatic brain injury can alter components of functional recovery independent of histological damage.

    Science.gov (United States)

    Hoane, Michael R; Pierce, Jeremy L; Kaufman, Nicholas A; Beare, Jason E

    2008-01-01

    Previously, we have shown that the window of opportunity for nicotinamide (NAM) therapy (50 mg/kg) following cortical contusion injuries (CCI) extended to 4-8 hrs post-CCI when administered over a six day post-CCI interval. The purpose of the present study was to determine if a more chronic NAM treatment protocol administered following CCI would extend the current window of opportunity for effective treatment onset. Groups of rats received either unilateral CCI's or sham procedures. Initiation of NAM therapy (50 mg/kg, ip) began at either 15-min, 4-hrs, 8-hrs or 24-hrs post-injury. All groups received daily systemic treatments for 12 days post-CCI at 24 hr intervals. Behavioral assessments were conducted for 28 days post injury and included: vibrissae forelimb placing, bilateral tactile adhesive removal, forelimb asymmetry task and locomotor placing testing. Behavioral analysis on both the tactile removal and locomotor placing tests showed that all NAM-treated groups facilitated recovery of function compared to saline treatment. However, on the vibrissae-forelimb placing and forelimb asymmetry tests only the 4-hr and 8-hr NAM-treated groups were significantly different from the saline-treated group. The lesion analysis showed that treatment with NAM out to 8 hrs post-CCI significantly reduced the size of the injury cavity. The window of opportunity for NAM treatment is task-dependent and in some situations can extend to 24 hrs post-CCI. These results suggest that a long term treatment regimen of 50 mg/kg of NAM starting at the clinically relevant time points may prove efficacious in human TBI.

  4. Variation in Chronic Nicotinamide Treatment after Traumatic Brain Injury Can Alter Components of Functional Recovery Independent of Histological Damage

    Directory of Open Access Journals (Sweden)

    Michael R Hoane

    2008-01-01

    Full Text Available Previously, we have shown that the window of opportunity for nicotinamide (NAM therapy (50 mg/kg following cortical contusion injuries (CCI extended to 4–8 hrs post-CCI when administered over a six day post-CCI interval. The purpose of the present study was to determine if a more chronic NAM treatment protocol administered following CCI would extend the current window of opportunity for effective treatment onset. Groups of rats received either unilateral CCI's or sham procedures. Initiation of NAM therapy (50 mg/kg, ip began at either 15-min, 4-hrs, 8-hrs or 24-hrs post-injury. All groups received daily systemic treatments for 12 days post-CCI at 24 hr intervals. Behavioral assessments were conducted for 28 days post injury and included: vibrissae forelimb placing, bilateral tactile adhesive removal, forelimb asymmetry task and locomotor placing testing. Behavioral analysis on both the tactile removal and locomotor placing tests showed that all NAM-treated groups facilitated recovery of function compared to saline treatment. However, on the vibrissae-forelimb placing and forelimb asymmetry tests only the 4-hr and 8-hr NAM-treated groups were significantly different from the saline-treated group. The lesion analysis showed that treatment with NAM out to 8 hrs post-CCI significantly reduced the size of the injury cavity. The window of opportunity for NAM treatment is task-dependent and in some situations can extend to 24 hrs post-CCI. These results suggest that a long term treatment regimen of 50 mg/kg of NAM starting at the clinically relevant time points may prove efficacious in human TBI.

  5. Predicting aphasia type from brain damage measured with structural MRI.

    Science.gov (United States)

    Yourganov, Grigori; Smith, Kimberly G; Fridriksson, Julius; Rorden, Chris

    2015-12-01

    Chronic aphasia is a common consequence of a left-hemisphere stroke. Since the early insights by Broca and Wernicke, studying the relationship between the loci of cortical damage and patterns of language impairment has been one of the concerns of aphasiology. We utilized multivariate classification in a cross-validation framework to predict the type of chronic aphasia from the spatial pattern of brain damage. Our sample consisted of 98 patients with five types of aphasia (Broca's, Wernicke's, global, conduction, and anomic), classified based on scores on the Western Aphasia Battery (WAB). Binary lesion maps were obtained from structural MRI scans (obtained at least 6 months poststroke, and within 2 days of behavioural assessment); after spatial normalization, the lesions were parcellated into a disjoint set of brain areas. The proportion of damage to the brain areas was used to classify patients' aphasia type. To create this parcellation, we relied on five brain atlases; our classifier (support vector machine - SVM) could differentiate between different kinds of aphasia using any of the five parcellations. In our sample, the best classification accuracy was obtained when using a novel parcellation that combined two previously published brain atlases, with the first atlas providing the segmentation of grey matter, and the second atlas used to segment the white matter. For each aphasia type, we computed the relative importance of different brain areas for distinguishing it from other aphasia types; our findings were consistent with previously published reports of lesion locations implicated in different types of aphasia. Overall, our results revealed that automated multivariate classification could distinguish between aphasia types based on damage to atlas-defined brain areas. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. PREDICTING APHASIA TYPE FROM BRAIN DAMAGE MEASURED WITH STRUCTURAL MRI

    Science.gov (United States)

    Yourganov, Grigori; Smith, Kimberly G.; Fridriksson, Julius; Rorden, Chris

    2015-01-01

    Chronic aphasia is a common consequence of a left-hemisphere stroke. Since the early insights by Broca and Wernicke, studying the relationship between the loci of cortical damage and patterns of language impairment has been one of the concerns of aphasiology. We utilized multivariate classification in a cross-validation framework to predict the type of chronic aphasia from the spatial pattern of brain damage. Our sample consisted of 98 patients with five types of aphasia (Broca’s, Wernicke’s, global, conduction, and anomic), classified based on scores on the Western Aphasia Battery. Binary lesion maps were obtained from structural MRI scans (obtained at least 6 months poststroke, and within 2 days of behavioural assessment); after spatial normalization, the lesions were parcellated into a disjoint set of brain areas. The proportion of damage to the brain areas was used to classify patients’ aphasia type. To create this parcellation, we relied on five brain atlases; our classifier (support vector machine) could differentiate between different kinds of aphasia using any of the five parcellations. In our sample, the best classification accuracy was obtained when using a novel parcellation that combined two previously published brain atlases, with the first atlas providing the segmentation of grey matter, and the second atlas used to segment the white matter. For each aphasia type, we computed the relative importance of different brain areas for distinguishing it from other aphasia types; our findings were consistent with previously published reports of lesion locations implicated in different types of aphasia. Overall, our results revealed that automated multivariate classification could distinguish between aphasia types based on damage to atlas-defined brain areas. PMID:26465238

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

    Science.gov (United States)

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

    1977-08-01

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

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

    NARCIS (Netherlands)

    VanderWerf, YD; DeJongste, MJL; terHorst, GJ

    1995-01-01

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

  9. Respiratory mechanics in brain-damaged patients.

    Science.gov (United States)

    Koutsoukou, Antonia; Perraki, Helen; Raftopoulou, Asimina; Koulouris, Nikolaos; Sotiropoulou, Christina; Kotanidou, Anastasia; Orfanos, Stylianos; Roussos, Charis

    2006-12-01

    To assess respiratory mechanics on the 1st and 5th days of mechanical ventilation in a cohort of brain-damaged patients on positive end-expiratory pressure (PEEP) of 8 cmH(2)O or zero PEEP (ZEEP). Physiological study with randomized control trial design in a multidisciplinary intensive care unit of a university hospital. Twenty-one consecutive mechanically ventilated patients with severe brain damage and no acute lung injury were randomly assigned to be ventilated with ZEEP (n = 10) or with 8 cmH(2)O of PEEP (n = 11). Respiratory mechanics and arterial blood gases were assessed on days 1 and day 5 of mechanical ventilation. In the ZEEP group on day 1 static elastance and minimal resistance were above normal limits (18.9 +/- 3.8 cmH(2)O/l and 5.6 +/- 2.2 cmH(2)O/l per second, respectively); on day 5 static elastance and iso-CO(2) minimal resistance values were higher than on day 1 (21.2 +/- 4.1 cmH(2)O/l; 7.0 +/- 1.9 cmH(2)O/l per second, respectively). In the PEEP group these parameters did not change significantly. One of the ten patients on ZEEP developed acute lung injury. On day 5 there was a significant decrease in PaO(2)/FIO(2) in both groups. On day 1 of mechanical ventilation patients with brain damage exhibit abnormal respiratory mechanics. After 5 days of mechanical ventilation on ZEEP static elastance and minimal resistance increased significantly, perhaps reflecting "low lung volume" injury. Both could be prevented by administration of moderate levels of PEEP.

  10. Chronic Broca's Aphasia Is Caused by Damage to Broca's and Wernicke's Areas

    OpenAIRE

    Fridriksson, Julius; Fillmore, Paul; Guo, Dazhou; Rorden, Chris

    2014-01-01

    Despite being perhaps the most studied form of aphasia, the critical lesion location for Broca's aphasia has long been debated, and in chronic patients, cortical damage often extends far beyond Broca's area. In a group of 70 patients, we examined brain damage associated with Broca's aphasia using voxel-wise lesion-symptom mapping (VLSM). We found that damage to the posterior portion of Broca's area, the pars opercularis, is associated with Broca's aphasia. However, several individuals with ot...

  11. Right hemisphere brain damage impairs strategy updating.

    Science.gov (United States)

    Danckert, James; Stöttinger, Elisabeth; Quehl, Nadine; Anderson, Britt

    2012-12-01

    Our behavior is predicated on mental models of the environment that must be updated to accommodate incoming information. We had 13 right-brain-damaged (RBD) patients and 10 left-brain-damaged (LBD) patients play the children's game "rock, paper, scissors" against a computer opponent that covertly altered its strategy. Healthy age-matched controls and LBD patients quickly detected extreme departures from uniform play ("paper" chosen on 80% of trials), but the RBD patient group did not. Seven RBD patients presented with neglect and although this was associated with greater impairment in strategy updating, there were exceptions: 2 of 7 neglect patients performed above the median of the patient group and 1 of the 6 nonneglect participants was severely impaired. Although speculative, lesion analyses contrasting high and low performing patients showed that severe impairments were associated with insula and putamen lesions. Interestingly, relative to the controls, the LBD group tended to "maximize" choices in the strongly biased condition (i.e., optimal strategy chosen on 100% of the trials), whereas controls "matched" the computer's strategy (i.e., optimal strategy chosen on 80% of the trials). We conclude that RBD leads to impaired updating of mental models to exploit environmental changes.

  12. Gender differences in alcohol-induced neurotoxicity and brain damage.

    Science.gov (United States)

    Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

    2013-09-06

    Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Blood-brain barrier damage in vascular dementia.

    Science.gov (United States)

    Ueno, Masaki; Chiba, Yoichi; Matsumoto, Koichi; Murakami, Ryuta; Fujihara, Ryuji; Kawauchi, Machi; Miyanaka, Hiroshi; Nakagawa, Toshitaka

    2016-04-01

    New findings on flow or drainage pathways of brain interstitial fluid and cerebrospinal fluid have been made. The interstitial fluid flow has an effect on the passage of blood-borne substances in the brain parenchyma, especially in areas near blood-brain barrier (BBB)-free regions. Actually, blood-borne substances can be transferred in areas with intact BBB function, such as the hippocampus, the corpus callosum, periventricular areas, and medial portions of the amygdala, presumably through leaky vessels in the subfornical organs or the choroid plexus. Increasing evidence indicates that dysfunction of the BBB function may play a significant role in the pathogenesis of vascular dementia. Accordingly, we have examined which insults seen in patients suffering from vascular dementia have an effect on the BBB using experimental animal models exhibiting some phenotypes of vascular dementia. The BBB in the hippocampus was clearly deteriorated in Mongolian gerbils exposed to acute ischemia followed by reperfusion and also in stroke-prone spontaneously hypertensive rats (SHRSP) showing hypertension. The BBB in the corpus callosum was clearly deteriorated in Wistar rats with permanent ligation of the bilateral common carotid arteries showing chronic hypoperfusion. The BBB in the hippocampus and the olfactory bulb was mildly deteriorated in aged senescence accelerated prone mice (SAMP8) showing cognitive dysfunction. The BBB in the hippocampus was mildly deteriorated in aged animals with hydrocephalus. Mild endothelial damage was seen in hyperglycemic db/db mice. In addition, mRNA expression of osteopontin, matrix metalloproteinase-13 (MMP-13), and CD36 was increased in vessels showing BBB damage in hypertensive SHRSP. As osteopontin, MMP-13 and CD36 are known to be related to brain injury and amyloid β accumulation or clearance, BBB damage followed by increased gene expression of these molecules not only contributes to the pathogenesis of vascular dementia, but also bridges

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

    Science.gov (United States)

    Pellicer, Begoña; Herraiz, Sonia; Leal, Antonio; Simón, Carlos; Pellicer, Antonio

    2011-01-01

    Cerebral palsy is a major neonatal handicap with unknown aetiology. There is evidence that prenatal brain injury is the leading cause of CP. Severe placental pathology accounts for a high percentage of cases. Several factors predispose to prenatal brain damage but when and how they act is unclear. The aim of this paper was to determine if hypoxia during pregnancy leads to damage in fetal brain and to evaluate the localization of this injury. An animal model of chronic hypoxia produced by chronic administration of a nitric oxide synthase inhibitor (L-NAME) was used to evaluate apoptotic activity in fetal brains and to localize the most sensitive areas. L-NAME reproduces a preeclamptic-like condition with increased blood pressure, proteinuria, growth restriction and intrauterine mortality. Apoptotic activity was increased in L-NAME brains and the most sensitive areas were the subventricular and pallidum zone. These results may explain the clinical features of CP. Further studies are needed. PMID:21490794

  15. Chronic inflammatory cells and damaged limbal cells in pterygium ...

    African Journals Online (AJOL)

    Background: Chronic inflammation in pterygium occurrence has not been explained. Whether damaged limbal basal epithelial cells are associated with pterygium occurrence in black Africans is not clear. Objective: To explain chronic inflammation in pterygium, and to clarify whether damaged limbal basal epithelial cells ...

  16. TOOL USE DISORDERS AFTER LEFT BRAIN DAMAGE

    Directory of Open Access Journals (Sweden)

    Josselin eBaumard

    2014-05-01

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

  17. Rehabilitation of damage to the visual brain.

    Science.gov (United States)

    Ajina, S; Kennard, C

    2012-10-01

    Homonymous visual field loss is a common consequence of stroke and traumatic brain injury. It is associated with an adverse functional prognosis and has implications on day-to-day activities such as driving, reading, and safe navigation. Early recovery is expected in around half of cases, and may be associated with a return in V1 activity. In stable disease, recovery is unlikely beyond 3 and certainly 6 months. Rehabilitative approaches generally target three main areas, encompassing a range of techniques with variable success: visual aids aim to expand or relocate the affected visual field; eye movement training builds upon compensatory strategies to improve explorative saccades; visual field restitution aims to improve visual processing within the damaged field itself. All these approaches seem to offer modest improvements with repeated practice, with none clearly superior to the rest. However, a number of areas are demonstrating particular promise currently, including simple web-based training initiatives, and work on neuroimaging and learning. The research interest in this area is encouraging, and it is to be hoped that future trials can better untangle and control for the number of complicated confounds, so that we will be in a much better position to evaluate and select the most appropriate therapy for patients. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  18. Relating brain damage to brain plasticity in patients with multiple sclerosis.

    Science.gov (United States)

    Tomassini, Valentina; Johansen-Berg, Heidi; Jbabdi, Saad; Wise, Richard G; Pozzilli, Carlo; Palace, Jacqueline; Matthews, Paul M

    2012-01-01

    Failure of adaptive plasticity with increasing pathology is suggested to contribute to progression of disability in multiple sclerosis (MS). However, functional impairments can be reduced with practice, suggesting that brain plasticity is preserved even in patients with substantial damage. . Here, functional magnetic resonance imaging (fMRI) was used to probe systems-level mechanisms of brain plasticity associated with improvements in visuomotor performance in MS patients and related to measures of microstructural damage. 23 MS patients and 12 healthy controls underwent brain fMRI during the first practice session of a visuomotor task (short-term practice) and after 2 weeks of daily practice with the same task (longer-term practice). Participants also underwent a structural brain MRI scan. Patients performed more poorly than controls at baseline. Nonetheless, with practice, patients showed performance improvements similar to controls and independent of the extent of MRI measures of brain pathology. Different relationships between performance improvements and activations were found between groups: greater short-term improvements were associated with lower activation in the sensorimotor, posterior cingulate, and parahippocampal cortices for patients, whereas greater long-term improvements correlated with smaller activation reductions in the visual cortex of controls. Brain plasticity for visuomotor practice is preserved in MS patients despite a high burden of cerebral pathology. Cognitive systems different from those acting in controls contribute to this plasticity in patients. These findings challenge the notion that increasing pathology is accompanied by an outright failure of adaptive plasticity, supporting a neuroscientific rationale for recovery-oriented strategies even in chronically disabled patients.

  19. Damage of hippocampal neurons in rats with chronic alcoholism

    OpenAIRE

    Du, Ailin; Jiang, Hongbo; Xu, Lei; An, Na; Liu, Hui; Li, Yinsheng; Zhang, Ruiling

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deficits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were significantly increased, while F-actin expression was decreased. Hippocampal neurons i...

  20. Protection of the Blood-Brain Barrier as a Therapeutic Strategy for Brain Damage.

    Science.gov (United States)

    Michinaga, Shotaro; Koyama, Yutaka

    2017-01-01

    Severe brain damage by trauma, ischemia, and hemorrhage lead to fatal conditions including sudden death, subsequent complications of the extremities and cognitive dysfunctions. Despite the urgent need for treatments for these complications, currently available therapeutic drugs are limited. Blood-brain barrier (BBB) disruption is a common pathogenic feature in many types of brain damage. The characteristic pathophysiological conditions caused by BBB disruption are brain edema resulting from an excessive increase of brain water content, inflammatory damage caused by infiltrating immune cells, and hemorrhage caused by the breakdown of microvessel structures. Because these pathogenic features induced by BBB disruption cause fatal conditions, their improvement is a desirable strategy. Many studies using experimental animal models have focused on molecules involved in BBB disruption, including vascular endothelial growth factors (VEGFs), matrix metalloproteinases (MMPs) and endothelins (ETs). The inhibition of these factors in several experimental animals was protective against BBB disruption caused by several types of brain damage, and ameliorated brain edema, inflammatory damage, and hemorrhagic transformation. In patients with brain damage, the up-regulation of these factors was observed and was related to brain damage severity. Thus, BBB protection by targeting VEGFs, MMPs, and ETs might be a novel strategy for the treatment of brain damage.

  1. Pathology of perinatal brain damage: background and oxidative stress markers.

    Science.gov (United States)

    Tonni, Gabriele; Leoncini, Silvia; Signorini, Cinzia; Ciccoli, Lucia; De Felice, Claudio

    2014-07-01

    To review historical scientific background and new perspective on the pathology of perinatal brain damage. The relationship between birth asphyxia and subsequent cerebral palsy has been extensively investigated. The role of new and promising clinical markers of oxidative stress (OS) is presented. Electronic search of PubMed-Medline/EMBASE database has been performed. Laboratory and clinical data involving case series from the research group are reported. The neuropathology of birth asphyxia and subsequent perinatal brain damage as well as the role of electronic fetal monitoring are reported following a review of the medical literature. This review focuses on OS mechanisms underlying the neonatal brain damage and provides different perspective on the most reliable OS markers during the perinatal period. In particular, prior research work on neurodevelopmental diseases, such as Rett syndrome, suggests the measurement of oxidized fatty acid molecules (i.e., F4-Neuroprostanes and F2-Dihomo-Isoprostanes) closely related to brain white and gray matter oxidative damage.

  2. Spinal cord injury drives chronic brain changes

    Directory of Open Access Journals (Sweden)

    Ignacio Jure

    2017-01-01

    Full Text Available Only a few studies have considered changes in brain structures other than sensory and motor cortex after spinal cord injury, although cognitive impairments have been reported in these patients. Spinal cord injury results in chronic brain neuroinflammation with consequent neurodegeneration and cognitive decline in rodents. Regarding the hippocampus, neurogenesis is reduced and reactive gliosis increased. These long-term abnormalities could explain behavioral impairments exhibited in humans patients suffering from spinal cord trauma.

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

    Directory of Open Access Journals (Sweden)

    Chunmei eWang

    2013-07-01

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

  4. Neglect severity after left and right brain damage.

    Science.gov (United States)

    Suchan, Julia; Rorden, Chris; Karnath, Hans-Otto

    2012-05-01

    While unilateral spatial neglect after left brain damage is undoubtedly less common than spatial neglect after a right hemisphere lesion, it is also assumed to be less severe. Here we directly test this latter hypothesis using a continuous measure of neglect severity: the so-called Center of Cancellation (CoC). Rorden and Karnath (2010) recently validated this index for right brain damaged neglect patients. A first aim of the present study was to evaluate this new measure for spatial neglect after left brain damage. In a group of 48 left-sided stroke patients with and without neglect, a score greater than -0.086 on the Bells Test and greater than -0.024 on the Letter Cancellation Task turned out to indicate neglect behavior for acute left brain damaged patients. A second aim was to directly compare the severity of spatial neglect after left versus right brain injury by using the new CoC measure. While neglect is less frequent following left than right hemisphere injury, we found that when this symptom occurs it is of similar severity in acute left brain injury as in patients after acute right brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Damage and repair of irradiated mammalian brain

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-07-01

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

  6. Visceral adipose tissue is associated with microstructural brain tissue damage.

    Science.gov (United States)

    Widya, Ralph L; Kroft, Lucia J M; Altmann-Schneider, Irmhild; van den Berg-Huysmans, Annette A; van der Bijl, Noortje; de Roos, Albert; Lamb, Hildo J; van Buchem, Mark A; Slagboom, P Eline; van Heemst, Diana; van der Grond, Jeroen

    2015-05-01

    Obesity has been associated with microstructural brain tissue damage. Different fat compartments demonstrate different metabolic and endocrine behaviors. The aim was to investigate the individual associations between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and microstructural integrity in the brain. This study comprised 243 subjects aged 65.4 ± 6.7 years. The associations between abdominal VAT and SAT, assessed by CT, and magnetization transfer imaging markers of brain microstructure for gray and white matter were analyzed and adjusted for confounding factors. VAT was associated with normalized MTR peak height in gray (β -0.216) and white matter (β -0.240) (both P  0.05). Stepwise linear regression analysis showed that only VAT was associated with normalized MTR peak height in gray and white matter (both P VAT rather than SAT is associated with microstructural brain tissue damage in elderly individuals. © 2015 The Obesity Society.

  7. Dynamics and heterogeneity of brain damage in multiple sclerosis

    KAUST Repository

    Kotelnikova, Ekaterina

    2017-10-26

    Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less severely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a long-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an unsupervised clustering analysis. We found that by adjusting certain parameters, albeit within their biological range, the mathematical model reproduced the different disease courses, supporting the dynamic CNS damage hypothesis to explain MS heterogeneity. Our analysis suggests that the irreversible axon degeneration produced in the early stages of progressive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capacity for remyelination. However, and in agreement with recent pathological studies, degeneration of chronically demyelinated axons is not a key feature that distinguishes this phenotype. Moreover, the model reveals that lower rates of axon degeneration and more rapid remyelination make relapsing MS more resilient than the

  8. Functionality predictors in acquired brain damage.

    Science.gov (United States)

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

    2015-01-01

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

  9. Brain damage in commercial breath-hold divers.

    Directory of Open Access Journals (Sweden)

    Kiyotaka Kohshi

    Full Text Available Acute decompression illness (DCI involving the brain (Cerebral DCI is one of the most serious forms of diving-related injuries which may leave residual brain damage. Cerebral DCI occurs in compressed air and in breath-hold divers, likewise. We conducted this study to investigate whether long-term breath-hold divers who may be exposed to repeated symptomatic and asymptomatic brain injuries, show brain damage on magnetic resonance imaging (MRI.Our study subjects were 12 commercial breath-hold divers (Ama with long histories of diving work in a district of Japan. We obtained information on their diving practices and the presence or absence of medical problems, especially DCI events. All participants were examined with MRI to determine the prevalence of brain lesions.Out of 12 Ama divers (mean age: 54.9±5.1 years, four had histories of cerebral DCI events, and 11 divers demonstrated ischemic lesions of the brain on MRI studies. The lesions were situated in the cortical and/or subcortical area (9 cases, white matters (4 cases, the basal ganglia (4 cases, and the thalamus (1 case. Subdural fluid collections were seen in 2 cases.These results suggest that commercial breath-hold divers are at a risk of clinical or subclinical brain injury which may affect the long-term neuropsychological health of divers.

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

    Directory of Open Access Journals (Sweden)

    Begoña Pellicer

    2011-01-01

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

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

    African Journals Online (AJOL)

    This study was undertaken to determine the protective effect of propolis against the hepatotoxicity and brain damage of chlorpyrifos (CPF) in male rats. Animals were assigned to one of four groups. The first group was used as control. Groups 2, 3 and 4 were treated with 6.8 mg CPF /kg BW (1/20 LD50); 50 mg propolis/kg ...

  12. Clinical Relevance of Discourse Characteristics after Right Hemisphere Brain Damage

    Science.gov (United States)

    Blake, Margaret Lehman

    2006-01-01

    Purpose: Discourse characteristics of adults with right hemisphere brain damage are similar to those reported for healthy older adults, prompting the question of whether changes are due to neurological lesions or normal aging processes. The clinical relevance of potential differences across groups was examined through ratings by speech-language…

  13. Discourse Impairments Following Right Hemisphere Brain Damage: A Critical Review.

    Science.gov (United States)

    Johns, Clinton L; Tooley, Kristen M; Traxler, Matthew J

    2008-11-01

    Right hemisphere brain damage (RHD) rarely causes aphasias marked by clear and widespread failures of comprehension or extreme difficulty producing fluent speech. Nonetheless, subtle language comprehension deficits can occur following unilateral RHD. In this article, we review the empirical record on discourse function following right hemisphere damage, as well as relevant work on non-brain damaged individuals that focuses on right hemisphere function. The review is divided into four sections that focus on discourse processing, inferencing, humor, and non-literal language. While the exact role that the right hemisphere plays in language processing, and the exact way that the two cerebral hemispheres coordinate their linguistic processes are still open to debate, our review suggests that the right hemisphere plays a critical role in managing inferred or implied information by maintaining relevant information and/or suppressing irrelevant information. Deficits in one or both of these mechanisms may account for discourse deficits following RHD.

  14. Chronic neurodegenerative consequences of traumatic brain injury.

    Science.gov (United States)

    Chauhan, Neelima B

    2014-01-01

    Traumatic brain injury (TBI) is a serious public health concern and a major cause of death and disability worldwide. Each year, an estimated 1.7 million Americans sustain TBI of which ~52,000 people die, ~275,000 people are hospitalized and 1,365,000 people are treated as emergency outpatients. Currently there are ~5.3 million Americans living with TBI. TBI is more of a disease process than of an event that is associated with immediate and long-term sensomotor, psychological and cognitive impairments. TBI is the best known established epigenetic risk factor for later development of neurodegenerative diseases and dementia. People sustaining TBI are ~4 times more likely to develop dementia at a later stage than people without TBI. Single brain injury is linked to later development of symptoms resembling Alzheimer's disease while repetitive brain injuries are linked to later development of chronic traumatic encephalopathy (CTE) and/or Dementia Pugilistica (DP). Furthermore, genetic background of ß-amyloid precursor protein (APP), Apolipoprotein E (ApoE), presenilin (PS) and neprilysin (NEP) genes is associated with exacerbation of neurodegenerative process after TBI. This review encompasses acute effects and chronic neurodegenerative consequences after TBI.

  15. Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain.

    Science.gov (United States)

    Rump, Travis J; Abdul Muneer, P M; Szlachetka, Adam M; Lamb, Allyson; Haorei, Catherine; Alikunju, Saleena; Xiong, Huangui; Keblesh, James; Liu, Jianuo; Zimmerman, Matthew C; Jones, Jocelyn; Donohue, Terrence M; Persidsky, Yuri; Haorah, James

    2010-11-30

    The studies presented here demonstrate the protective effect of acetyl-L-carnitine (ALC) against alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission. Our findings reveal the cellular and biochemical mechanisms of alcohol-induced oxidative damage in various types of brain cells. Chronic ethanol administration to mice caused an increase in inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine adduct formation in frontal cortical neurons but not in astrocytes from brains of these animals. Interestingly, alcohol administration caused a rather selective activation of NADPH oxidase (NOX), which, in turn, enhanced levels of reactive oxygen species (ROS) and 4-hydroxynonenal, but these were predominantly localized in astrocytes and microglia. Oxidative damage in glial cells was accompanied by their pronounced activation (astrogliosis) and coincident neuronal loss, suggesting that inflammation in glial cells caused neuronal degeneration. Immunohistochemistry studies indicated that alcohol consumption induced different oxidative mediators in different brain cell types. Thus, nitric oxide was mostly detected in iNOS-expressing neurons, whereas ROS were predominantly generated in NOX-expressing glial cells after alcohol ingestion. Assessment of neuronal activity in ex vivo frontal cortical brain tissue slices from ethanol-fed mice showed a reduction in long-term potentiation synaptic transmission compared with slices from controls. Coadministration of ALC with alcohol showed a significant reduction in oxidative damage and neuronal loss and a restoration of synaptic neurotransmission in this brain region, suggesting that ALC protects brain cells from ethanol-induced oxidative injury. These findings suggest the potential clinical utility of ALC as a neuroprotective agent that prevents alcohol-induced brain damage and development of neurological disorders. Published by Elsevier Inc.

  16. Vascular damage after fractionated whole-brain irradiation in rats.

    Science.gov (United States)

    Brown, William R; Thore, Clara R; Moody, Dixon M; Robbins, Michael E; Wheeler, Kenneth T

    2005-11-01

    Whole-brain irradiation of animals and humans has been reported to lead to late delayed structural (vascular damage, demyelination, white matter necrosis) and functional (cognitive impairment) alterations. However, most of the experimental data on late delayed radiation-induced brain injury have been generated with large single doses or short fractionation schemes that may provide a less accurate indication of the events that occur after clinical whole-brain radiotherapy. The pilot study reported here investigates cerebral vascular pathology in male Fischer 344 rats after whole-brain irradiation with a fractionated total dose of 137Cs gamma rays that is expected to be biologically similar to that given to brain tumor patients. The brains of young adult rats (4 months old) were irradiated with a total dose of 40 Gy, given as eight 5-Gy fractions twice per week for 4 weeks. Brain capillary and arteriole pathology was studied using an alkaline phosphatase enzyme histochemistry method; vessel density and length were quantified using a stereology method with computerized image processing and analysis. Vessel density and length were unchanged 24 h after the last dose, but at 10 weeks postirradiation, both were substantially decreased. After 20 weeks, the rate of decline in the vessel density and length in irradiated rats was similar to that in unirradiated age-matched controls. No gross gliosis or demyelination was observed 12 months postirradiation using conventional histopathology techniques. We suggest that the early (10-week) and persistent vascular damage that occurs after a prolonged whole-brain irradiation fractionation scheme may play an important role in the development of late delayed radiation-induced brain injury.

  17. Patterns of damage in the mature neonatal brain

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-15

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

  18. Post-stroke acquired amusia: A comparison between right- and left-brain hemispheric damages.

    Science.gov (United States)

    Jafari, Zahra; Esmaili, Mahdiye; Delbari, Ahmad; Mehrpour, Masoud; Mohajerani, Majid H

    2017-01-01

    Although extensive research has been published about the emotional consequences of stroke, most studies have focused on emotional words, speech prosody, voices, or facial expressions. The emotional processing of musical excerpts following stroke has been relatively unexplored. The present study was conducted to investigate the effects of chronic stroke on the recognition of basic emotions in music. Seventy persons, including 25 normal controls (NC), 25 persons with right brain damage (RBD) from stroke, and 20 persons with left brain damage (LBD) from stroke between the ages of 31-71 years were studied. The Musical Emotional Bursts (MEB) test, which consists of a set of short musical pieces expressing basic emotional states (happiness, sadness, and fear) and neutrality, was used to test musical emotional perception. Both stroke groups were significantly poorer than normal controls for the MEB total score and its subtests (p right hemisphere dominance in processing negative emotions.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Josefina Ricardo-Garcell

    2012-01-01

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

  1. Brain damage and the moral significance of consciousness.

    Science.gov (United States)

    Kahane, Guy; Savulescu, Julian

    2009-02-01

    Neuroimaging studies of brain-damaged patients diagnosed as in the vegetative state suggest that the patients might be conscious. This might seem to raise no new ethical questions given that in related disputes both sides agree that evidence for consciousness gives strong reason to preserve life. We question this assumption. We clarify the widely held but obscure principle that consciousness is morally significant. It is hard to apply this principle to difficult cases given that philosophers of mind distinguish between a range of notions of consciousness and that is unclear which of these is assumed by the principle. We suggest that the morally relevant notion is that of phenomenal consciousness and then use our analysis to interpret cases of brain damage. We argue that enjoyment of consciousness might actually give stronger moral reasons not to preserve a patient's life and, indeed, that these might be stronger when patients retain significant cognitive function.

  2. A chronic increase of corticosterone age-dependently reduces systemic DNA damage from oxidation in rats

    DEFF Research Database (Denmark)

    Jorgensen, Anders; Kalliokoski, Otto; Forsberg, Kristin

    2017-01-01

    differences. In old animals, CORT caused a borderline significant reduction of RNA oxidation in CNS, which was paralleled by a normalization of performance in an object location memory test. To our knowledge, this is the first demonstration that chronic stress-associated levels of CORT can reduce nucleic acid......Stress and depression are associated with an acceleration of brain and bodily aging; effects which have been attributed to chronic elevations of glucocorticoids. We tested the hypothesis that a three week administration of stress-associated levels of corticosterone (CORT, the principal rodent...... glucocorticoid) would increase systemic and CNS DNA and RNA damage from oxidation; a phenomenon known to be centrally involved in the aging process. We also hypothesized that older individuals would be more sensitive to this effect and that the chronic CORT administration would exacerbate age-related memory...

  3. [Risk factors for cardiovascular system damage in chronic kidney disease].

    Science.gov (United States)

    Kutyrina, I M; Rudenko, T E; Savel'eva, S A; Shvetsov, M Iu; Vasil'eva, M P

    2013-01-01

    To study the prevalence of and risk factors (RF) associated with cardiovascular system damage in patients with predialysis diabetic and nondiabetic chronic kidney disease (CKD). The investigation enrolled 317 patients with CKD of various etiologies. In Group 1 (165 patients with CKD: 54% of men, 46% of women; mean age 46 +/- 15 years), the glomerular filtration rate (GFR) was 37.2 ml/min; the serum creatinine level was 2.9 mg/dl. Group 2 included 152 (41%) patients with type 2 diabetes mellitus (DM) (41% of men and 59% of women; mean age 57.3 +/- 7.1 years). The duration of DM averaged 10.4 +/- 7.1 years. All the patients underwent physical examination; the levels of glycated hemoglobin and adipose tissue hormones, urinary albumin excretion were additionally determined in the diabetic patients. Echocardiography was performed in 172 patients. The influence of populationwide and renal failure-associated RFs on the cardiovascular system was evaluated in CKD. Clinical and instrumental examinations of 165 patients with Stages II-IV nondiabetic CKD revealed atherosclerosis of the aorta and the vessels of the heart, brain, kidney, and lower extremities in 60 (37%), 35 (24%), 30 (18%), 23 (14%), and 8 (5%), respectively. As atherosclerotic vascular lesion progressed, the incidence of cardiovascular events (CVE) increased. Left ventricular hypertrophy (LVH) was diagnosed in 37.3% of the patients with nondiabetic CKD. Along with traditional cardiovascular RFs (age, smoking, gender, arterial hypertension), the renal dysfunction-related factors (anemia, diminished glomerular filtration rate, elevated creatitine levels, and abnormal phosphorus and calcium metabolism) are of importance. An association was found between LVH, atherosclerotic vascular lesion, and heart valve calcification. According to EchoCG data, 36% of the patients with type 2 DM were diagnosed as having LVH. The RFs of the latter were albuminuria, obesity, and abnormal carbohydrate and purine metabolisms. There

  4. Let thy left brain know what thy right brain doeth: Inter-hemispheric compensation of functional deficits after brain damage.

    Science.gov (United States)

    Bartolomeo, Paolo; Thiebaut de Schotten, Michel

    2016-12-01

    Recent evidence revealed the importance of inter-hemispheric communication for the compensation of functional deficits after brain damage. This review summarises the biological consequences observed using histology as well as the longitudinal findings measured with magnetic resonance imaging methods in brain damaged animals and patients. In particular, we discuss the impact of post-stroke brain hyperactivity on functional recovery in relation to time. The reviewed evidence also suggests that the proportion of the preserved functional network both in the lesioned and in the intact hemispheres, rather than the simple lesion location, determines the extent of functional recovery. Hence, future research exploring longitudinal changes in patients with brain damage may unveil potential biomarkers underlying functional recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Chronic Traumatic Brain Injury in Amateur Boxers

    Directory of Open Access Journals (Sweden)

    M. Rahmati

    2008-04-01

    Full Text Available Introduction & objective: Despite of young and adolescence intent to the boxing sport, because of dominant aggression and direct blows contact to head, face and central nervous system, it is continuously criticize by different groups. The groups of sporting and physician conventions are distinguished boxing with physical and neuropsychological disorders and some groups believe that side effects of this sport are not more than other sports. For this base the aim of this study was to determine the chronic traumatic brain injury in a group amateur boxers.Materials & Methods: In a case-control study, three groups of sport men were considered, each group contained 20 randomly selected cases. The first group were amateur boxers with 4 years minimal activity(directly has been presented to the head blows, second group were amateur soccer players with 4 years minimal activity(has been presented to the not very severe head blows, third group were non athlete subjects .The groups were matched in weight, height, age and education .To understand brain disorder interview by medicine method has been used, then Wiskancin, Bonardele, Bender geshtalt, Kim karad visual memory, Benton and wechler memory (Alef type tests has been performed and EEG has got in the same hour and condition.Results: The homogeneity of between group variances was gained by the statistical method. Also between structural–visual abilities neuropsychological aspect in groups, significant difference has been gained (p= 0.000. In Kim karad visual memory test at the mild and long term visual memory deficit, significant differences between three groups was observed (P= 0.000, P=0.009 that least score has been belonged to the boxers. Also in boxers 6 abnormal EEGs is observed.Conclusion: It can be said that of four years amateur boxing can affect on boxers visual and memory perception and their spatial orientation. Additionally our study have showed that amateur boxing has a significant

  7. Cortical and subcortical anatomy of chronic spatial neglect following vascular damage

    Directory of Open Access Journals (Sweden)

    Schnider Armin

    2008-09-01

    Full Text Available Abstract Background The role of the inferior parietal lobule (IPL and superior temporal gyrus (STG or subcortical pathways as possible anatomical correlates of spatial neglect is currently intensely discussed. Some of the conflicting results might have arisen because patients were examined in the acute stage of disease. Methods We examined the anatomical basis of spatial neglect in a sample of patients examined in the post-acute stage following right-hemispheric vascular brain damage. Lesions of 28 patients with chronic spatial neglect were contrasted to lesions of 22 control patients without neglect using lesion subtraction techniques and voxel-wise comparisons. Results The comparisons identified the temporo-parietal junction (TPJ with underlying white matter, the supramarginal gyrus, the posterior STG, and the insula as brain regions damaged significantly more often in neglect compared to non-neglect patients. In a subgroup of neglect patients showing particularly large cancellation bias together with small errors on line bisection damage was prevalent deep in the frontal lobe while damage of patients with the reverse pattern was located in the white matter of the TPJ. Conclusion Considering our results and the findings of previous studies, spatial neglect appears to be associated with a network of regions involving the TPJ, inferior IPL, posterior STG, the insular cortex, and posterior-frontal projections. Frontal structures or projections may be of particular relevance for spatial exploration, while the IPL may be important for object-based attention as required for line bisection.

  8. Autobiographical memory and structural brain changes in chronic phase TBI.

    Science.gov (United States)

    Esopenko, Carrie; Levine, Brian

    2017-04-01

    Traumatic brain injury (TBI) is associated with a range of neuropsychological deficits, including attention, memory, and executive functioning attributable to diffuse axonal injury (DAI) with accompanying focal frontal and temporal damage. Although the memory deficit of TBI has been well characterized with laboratory tests, comparatively little research has examined retrograde autobiographical memory (AM) at the chronic phase of TBI, with no prior studies of unselected patients drawn directly from hospital admissions for trauma. Moreover, little is known about the effects of TBI on canonical episodic and non-episodic (e.g., semantic) AM processes. In the present study, we assessed the effects of chronic-phase TBI on AM in patients with focal and DAI spanning the range of TBI severity. Patients and socioeconomic- and age-matched controls were administered the Autobiographical Interview (AI) (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) a widely used method for dissociating episodic and semantic elements of AM, along with tests of neuropsychological and functional outcome. Measures of episodic and non-episodic AM were compared with regional brain volumes derived from high-resolution structural magnetic resonance imaging (MRI). Severe TBI (but not mild or moderate TBI) was associated with reduced recall of episodic autobiographical details and increased recall of non-episodic details relative to healthy comparison participants. There were no significant associations between AM performance and neuropsychological or functional outcome measures. Within the full TBI sample, autobiographical episodic memory was associated with reduced volume distributed across temporal, parietal, and prefrontal regions considered to be part of the brain's AM network. These results suggest that TBI-related distributed volume loss affects episodic autobiographical recollection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Measuring and Inducing Brain Plasticity in Chronic Aphasia

    Science.gov (United States)

    Fridriksson, Julius

    2011-01-01

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

  10. DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers

    Directory of Open Access Journals (Sweden)

    Nicole Schupp

    2016-01-01

    Full Text Available Patients with chronic kidney disease (CKD exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients’ burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis-block micronucleus assay, the comet assay, and the quantification of 8-oxo-7,8-dihydro-2′-deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker’s potential to predict clinical outcomes.

  11. Free radical scavenging by brain homogenate: implication to free radical damage and antioxidant defense in brain.

    Science.gov (United States)

    Mori, A; Liu, J; Wang, X; Kawai, M

    1994-03-01

    To study the mechanisms of free radical-induced brain damage and the antioxidant defense in the brain, we quantified the superoxide and hydroxyl radical scavenging effects of brain homogenate using electron spin resonance spectrometry. Brain homogenate was found to scavenge both superoxide and hydroxyl radicals in concentration-dependent fashion. Heat denaturation significantly decreased these scavenging effects. The ability of brain homogenate to scavenge free radicals implies that brain damage can be induced by free radicals since they are known to react virtually with any type of molecule such as nucleic acids, membrane lipids, and proteins in the brain. On the other hand, some molecules which can be regenerated or repaired after free radical scavenging are considered to be antioxidants which include both enzymatic and non-enzymatic antioxidants. Measurement of the decrease in antioxidant activity following heat denaturation suggests that the contribution of enzymatic antioxidants is about 20-40% in scavenging superoxide radicals and about 10-20% in scavenging hydroxyl radicals.

  12. Vestibular damage in chronic ototoxicity: a mini-review.

    Science.gov (United States)

    Sedó-Cabezón, Lara; Boadas-Vaello, Pere; Soler-Martín, Carla; Llorens, Jordi

    2014-07-01

    Ototoxicity is a major cause of the loss of hearing and balance in humans. Ototoxic compounds include pharmaceuticals such as aminoglycoside antibiotics, anti-malarial drugs, loop diuretics and chemotherapeutic platinum agents, and industrial chemicals including several solvents and nitriles. Human and rodent data indicate that the main target of toxicity is hair cells (HCs), which are the mechanosensory cells responsible for sensory transduction in both the auditory and the vestibular system. Nevertheless, the compounds may also affect the auditory and vestibular ganglion neurons. Exposure to ototoxic compounds has been found to cause HC apoptosis, HC necrosis, and damage to the afferent terminals, of differing severity depending on the ototoxicity model. One major pathway frequently involved in HC apoptosis is the c-jun N-terminal kinase (JNK) signaling pathway activated by reactive oxygen species, but other apoptotic pathways can also play a role in ototoxicity. Moreover, little is known about the effects of chronic low-dose exposure. In rodent vestibular epithelia, extrusion of live HCs from the sensory epithelium may be the predominant form of cell demise during chronic ototoxicity. In addition, greater involvement of the afferent terminals may occur, particularly the calyx units contacting type I vestibular HCs. As glutamate is the neurotransmitter in this synapse, excitotoxic phenomena may participate in afferent and ganglion neuron damage. Better knowledge of the events that take place in chronic ototoxicity is of great interest, as it will increase understanding of the sensory loss associated with chronic exposure and aging. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Protective effects of carnosine on white matter damage induced by chronic cerebral hypoperfusion

    Directory of Open Access Journals (Sweden)

    Jing Ma

    2016-01-01

    Full Text Available Carnosine is a dipeptide that scavenges free radicals, inhibits inflammation in the central nervous system, and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions. Therefore, we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury. White matter damage was induced by right unilateral common carotid artery occlusion in mice. The animals were treated with 200, 500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury. Then, 37 days later, Klüver-Barrera staining, toluidine blue staining and immunofluorescence staining were performed. Carnosine (200, 500 mg/kg substantially reduced damage to the white matter in the corpus callosum, internal capsule and optic tract, and it rescued expression of myelin basic protein, and alleviated the loss of oligodendrocytes. However, carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses. These findings show that carnosine, at a particular dose range, protects against white matter damage caused by chronic cerebral ischemia in mice, likely by reducing oligodendroglial cell loss.

  14. Mechanism of Chronic Pain in Rodent Brain Imaging

    Science.gov (United States)

    Chang, Pei-Ching

    Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

  15. Study Suggests Brain Is Hard-Wired for Chronic Pain

    Science.gov (United States)

    ... News Release Tuesday, September 17, 2013 NIH-funded study suggests brain is hard-wired for chronic pain ... Apkarian, Ph.D., a senior author of the study and professor of physiology at Northwestern University Feinberg ...

  16. Reversing brain damage in former NFL players: implications for traumatic brain injury and substance abuse rehabilitation.

    Science.gov (United States)

    Amen, Daniel G; Wu, Joseph C; Taylor, Derek; Willeumier, Kristen

    2011-01-01

    Brain injuries are common in professional American football players. Finding effective rehabilitation strategies can have widespread implications not only for retired players but also for patients with traumatic brain injury and substance abuse problems. An open label pragmatic clinical intervention was conducted in an outpatient neuropsychiatric clinic with 30 retired NFL players who demonstrated brain damage and cognitive impairment. The study included weight loss (if appropriate); fish oil (5.6 grams a day); a high-potency multiple vitamin; and a formulated brain enhancement supplement that included nutrients to enhance blood flow (ginkgo and vinpocetine), acetylcholine (acetyl-l-carnitine and huperzine A), and antioxidant activity (alpha-lipoic acid and n-acetyl-cysteine). The trial average was six months. Outcome measures were Microcog Assessment of Cognitive Functioning and brain SPECT imaging. In the retest situation, corrected for practice effect, there were statistically significant increases in scores of attention, memory, reasoning, information processing speed and accuracy on the Microcog. The brain SPECT scans, as a group, showed increased brain perfusion, especially in the prefrontal cortex, parietal lobes, occipital lobes, anterior cingulate gyrus and cerebellum. This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions.

  17. Using MRI for the assessment of paraoxon-induced brain damage and efficacy of antidotal treatment.

    Science.gov (United States)

    Rosman, Yossi; Eisenkraft, Arik; Krivoy, Amir; Schein, Ophir; Makarovski, Igor; Shrot, Shai; Ramaty, Erez; Shilderman, Eugenia Bloch; Kapon, Joseph; Gilat, Eran; Kadar, Tamar; Maier, Stephan; Daniels, Dianne; Shneor, Ran; Salomon, Sharona; Tamar, Gregori; Last, David; Mardor, Yael

    2012-06-01

    Organophosphate intoxication induces neural toxicity as demonstrated in histological analysis of poisoned animals. Diffusion-weighted magnetic resonance imaging (DWMRI) enables early noninvasive characterization of biological tissues based on their water diffusion characteristics. Our objectives were to study the application of MRI for assessment of paraoxon-induced brain damage and the efficacy of antidotal treatments. Seventy-six rats were poisoned with paraoxon followed by treatment with atropine and obidoxime. The rats were then divided into five treatment groups consisting of midazolam after 1 or 30 min, scopolamine after 1 or 30 min and a no anticonvulsant treatment group. Five untreated rats served as controls. Animals underwent MRI on days 1, 8, 15, 29 and 50 post poisoning. Histological evaluation was performed on representative rat brains. Acute DWMRI effects, such as enhancement of temporal brain regions, and chronic effects such as ventricular enlargement and brain atrophy, depicted on T₂-weighted MRI, were significantly more prominent in late anticonvulsant treatment groups. There was no significant difference between the neuroprotective effects of midazolam and scopolamine as shown by DWMRI. Early MRI abnormalities were found to correlate significantly with histological analysis of samples obtained 15 days post treatment. In conclusion, our results demonstrate the feasibility of using DWMRI for depiction of early cytotoxic response to paraoxon and T₂-weighted MRI for later changes, thus enabling assessment of early/late brain damage as well as treatment efficacy in rats. The ability to depict these changes early and noninvasively may be applied clinically in the acute phase of organophosphate poisoning. Copyright © 2011 John Wiley & Sons, Ltd.

  18. Chronic brain ischemia in patients with arterial hypertension and hypothyroidism

    Directory of Open Access Journals (Sweden)

    O.Ye. Kovalenko

    2017-04-01

    Full Text Available The questions of the pathogenesis of chronic brain ischemia in patients with hypertension and hypothyroidism are studied. Examples of some results of authors’ research are listed. According to the research, patients with hypertensive dyscirculatory encephalopathy and hypothyroidism have deterioration of blood supply to the brain by reducing the reactivity of the vascular wall, decrease in the functional activity of the brain, impairement of cognitive function and increase in the anxiety and depression.

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

    Directory of Open Access Journals (Sweden)

    George E. Barreto

    2015-04-01

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

  20. Acetylcholine facilitates recovery of episodic memory after brain damage.

    Science.gov (United States)

    Croxson, Paula L; Browning, Philip G F; Gaffan, David; Baxter, Mark G

    2012-10-03

    Episodic memory depends on a network of interconnected brain structures including the inferior temporal cortex, hippocampus, fornix, and mammillary bodies. We have previously shown that a moderate episodic memory impairment in monkeys with transection of the fornix is exacerbated by prior depletion of acetylcholine from inferotemporal cortex, despite the fact that depletion of acetylcholine from inferotemporal cortex on its own has no effect on episodic memory. Here we show that this effect occurs because inferotemporal acetylcholine facilitates recovery of function following structural damage within the neural circuit for episodic memory. Episodic memory impairment caused by lesions of the mammillary bodies, like fornix transection, was exacerbated by prior removal of temporal cortical acetylcholine. However, removing temporal cortical acetylcholine after the lesion of the fornix or mammillary bodies did not increase the severity of the impairment. This lesion order effect suggests that acetylcholine within the inferior temporal cortex ordinarily facilitates functional recovery after structural lesions that impair episodic memory. In the absence of acetylcholine innervation to inferotemporal cortex, this recovery is impaired and the amnesia caused by the structural lesion is more severe. These results suggest that humans with loss of cortical acetylcholine function, for example in Alzheimer's disease, may be less able to adapt to memory impairments caused by structural neuronal damage to areas in the network important for episodic memory.

  1. Environmental enrichment reduces brain damage in hydrocephalic immature rats.

    Science.gov (United States)

    Catalão, Carlos Henrique Rocha; Shimizu, Glaucia Yuri; Tida, Jacqueline Atsuko; Garcia, Camila Araújo Bernardino; Dos Santos, Antonio Carlos; Salmon, Carlos Ernesto Garrido; Rocha, Maria José Alves; da Silva Lopes, Luiza

    2017-06-01

    We investigate the effects of environmental enrichment (EE) on morphological alterations in different brain structures of pup rats submitted to hydrocephalus condition. Hydrocephalus was induced in 7-day-old pup rats by injection of 20% kaolin into the cisterna magna. Ventricular dilatation and magnetization transfer to analyze myelin were assessed by magnetic resonance. Hydrocephalic and control rats exposed to EE (n = 10 per group) were housed in cages with a tunnel, ramp, and colored plastic balls that would emit sound when touched. The walls of the housing were decorated with colored adhesive tape. Moreover, tactile and auditory stimulation was performed daily throughout the experiment. Hydrocephalic and control rats not exposed to EE (n = 10 per group) were allocated singly in standard cages. All animals were weighed daily and exposed to open-field conditions every 2 days until the end of the experiment when they were sacrificed and the brains removed for histology and immunohistochemistry. Solochrome cyanine staining was performed to assess the thickness of the corpus callosum. The glial fibrillary acidic protein method was used to evaluate reactive astrocytes, and the Ki67 method to assess cellular proliferation in the subventricular zone. The hydrocephalic animals exposed to EE showed better performance in Open Field tests (p magnetization transfer (p < 0.05). Finally, the EE group showed a reduction in reactive astrocytes by means of glial fibrillary acidic protein immunostaining and preservation of the proliferation potential of progenitor cells. The results suggest that EE can protect the developing brain against damaging effects caused by hydrocephalus.

  2. A chronic increase of corticosterone age-dependently reduces systemic DNA damage from oxidation in rats.

    Science.gov (United States)

    Jorgensen, Anders; Kalliokoski, Otto; Forsberg, Kristin; Breitenstein, Katrine; Weimann, Allan; Henriksen, Trine; Hau, Jann; Wörtwein, Gitta; Poulsen, Henrik Enghusen; Jorgensen, Martin Balslev

    2017-03-01

    Stress and depression are associated with an acceleration of brain and bodily aging; effects which have been attributed to chronic elevations of glucocorticoids. We tested the hypothesis that a three week administration of stress-associated levels of corticosterone (CORT, the principal rodent glucocorticoid) would increase systemic and CNS DNA and RNA damage from oxidation; a phenomenon known to be centrally involved in the aging process. We also hypothesized that older individuals would be more sensitive to this effect and that the chronic CORT administration would exacerbate age-related memory decline. Young and old male Sprague-Dawley rats were non-invasively administered CORT by voluntary ingestion of nut paste containing either CORT (25mg/kg) or vehicle for a total of 22 days. CORT increased the 24h urinary excretion of the hormone to the levels previously observed after experimental psychological stress and caused a downregulation of the glucocorticoid receptor in the CA1 area of the hippocampus. Contrary to our hypothesis, 24h excretion of 8-oxodG/8-oxoGuo (markers of DNA/RNA damage from oxidation) was reduced in CORT-treated young animals, whereas old animals showed no significant differences. In old animals, CORT caused a borderline significant reduction of RNA oxidation in CNS, which was paralleled by a normalization of performance in an object location memory test. To our knowledge, this is the first demonstration that chronic stress-associated levels of CORT can reduce nucleic acid damage from oxidation. These findings contradict the notion of elevated CORT as a mediator of the accelerated aging observed in stress and depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Is brain gliosis a characteristic of chronic methamphetamine use in the human?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul; Furukawa, Yoshiaki; Schmunk, Gregory A; Wickham, Dennis J; Ang, Lee-Cyn; Sherwin, Allan; McCluskey, Tina; Boileau, Isabelle; Kish, Stephen J

    2014-07-01

    Animal data show that high doses of the stimulant drug methamphetamine can damage brain dopamine neurones; however, it is still uncertain whether methamphetamine, at any dose, is neurotoxic to human brain. Since gliosis is typically associated with brain damage and is observed in animal models of methamphetamine exposure, we measured protein levels (intact protein and fragments, if any) of markers of microgliosis (glucose transporter-5, human leukocyte antigens HLA-DRα [TAL.1B5] and HLA-DR/DQ/DPβ [CR3/43]) and astrogliosis (glial fibrillary acidic protein, vimentin, and heat shock protein-27) in homogenates of autopsied brain of chronic methamphetamine users (n=20) and matched controls (n=23). Intact protein levels of all markers were, as expected, elevated (+28%-1270%, Phuman recreational methamphetamine users who used the drug chronically and shortly before death. However, a logistically more difficult quantitative histopathological study is needed to confirm whether glial changes occur or do not occur in brain of human methamphetamine (and amphetamine) users. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia

    Science.gov (United States)

    Gjedde, Albert; Crone, Christian

    1981-10-01

    Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

  5. Sex Differences in the Effects of Unilateral Brain Damage on Intelligence.

    Science.gov (United States)

    Inglis, James; Lawson, J. S.

    1981-01-01

    A sexual dimorphism in the functional asymmetry of the damaged human brain is reflected in a test-specific laterality effect in male patients, explaining some contradictions concerning the effects of unilateral brain damage on intelligence in studies in which the influence of sex was overlooked. (Author/SK)

  6. Neuroinflammation in traumatic brain injury: A chronic response to an acute injury

    Directory of Open Access Journals (Sweden)

    Samantha J Schimmel

    2017-01-01

    Full Text Available Every year, approximately 1.4 million US citizens visit emergency rooms for traumatic brain injuries. Formerly known as an acute injury, chronic neurodegenerative symptoms such as compromised motor skills, decreased cognitive abilities, and emotional and behavioral changes have caused the scientific community to consider chronic aspects of the disorder. The injury causing impact prompts multiple cell death processes, starting with neuronal necrosis, and progressing to various secondary cell death mechanisms. Secondary cell death mechanisms, including excitotoxicity, oxidative stress, mitochondrial dysfunction, blood–brain barrier disruption, and inflammation accompany chronic traumatic brain injury (TBI and often contribute to long-term disabilities. One hallmark of both acute and chronic TBI is neuroinflammation. In acute stages, neuroinflammation is beneficial and stimulates an anti-inflammatory response to the damage. Conversely, in chronic TBI, excessive inflammation stimulates the aforementioned secondary cell death. Converting inflammatory cells from pro-inflammatory to anti-inflammatory may expand the therapeutic window for treating TBI, as inflammation plays a role in all stages of the injury. By expanding current research on the role of inflammation in TBI, treatment options and clinical outcomes for afflicted individuals may improve. This paper is a review article. Referred literature in this paper has been listed in the references section. The data sets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

  7. Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury.

    Science.gov (United States)

    Hay, Jennifer; Johnson, Victoria E; Smith, Douglas H; Stewart, William

    2016-05-23

    Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of nonboxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article.

  8. The Sensitization Model to Explain How Chronic Pain Exists Without Tissue Damage

    NARCIS (Netherlands)

    van Wilgen, C. Paul; Keizer, Doeke

    The interaction of nurses with chronic pain patients is often difficult. One of the reasons is that chronic pain is difficult to explain, because no obvious anatomic defect or tissue damage is present. There is now enough evidence available indicating that chronic pain syndromes such as low back

  9. Induction of chronic Fos-related antigens in rat brain by chronic morphine administration.

    Science.gov (United States)

    Nye, H E; Nestler, E J

    1996-04-01

    Previous studies have shown that repeated exposure to cocaine or to several other stimuli induces novel 35-37 kDa Fos-related antigens (chronic Fras) in specific brain regions. Induction of these proteins is associated with prolonged increases in AP-1 DNA binding activity that parallel the long half-life of the chronic Fras in brain. In the current study, we characterized regulation of the chronic Fras in response to prolonged exposure to morphine. After 5 days of morphine treatment, we observed increased levels of the chronic Fras and of AP-1 binding activity in rat striatum and nucleus accumbens, effects that were not seen in most other brain regions that we studied. Concomitant administration of naltrexone, an opioid receptor antagonist, prevented the induction of these proteins. Two-dimensional gel analysis showed that the chronic Fras induced by chronic morphine administration are identical to those induced after chronic cocaine and other treatments. A time course study indicated that chronic Fra induction was first apparent after 3 days of morphine treatment and peaked between 5 and 7 days of treatment in both the striatum and nucleus accumbens. Withdrawal studies demonstrated robust induction of several known acute Fras, including c-Fos, FosB, Fra-1, Fra-2, and delta FosB, at 6 hr after naltrexone precipitation of withdrawal in the striatum, nucleus accumbens, and several other brain regions. Levels of these proteins returned to basal values by 72 hr. In contrast, no further induction of the chronic Fras was evident after 6 hr of withdrawal in the striatum and nucleus accumbens, but levels of the proteins increased beyond their already elevated chronic morphine values after longer periods (72 hr) of withdrawal, even though physical withdrawal symptoms had resolved at this time point. Chronic Fras were also induced after these prolonged withdrawal periods in several other brain regions, where the proteins were not induced by chronic morphine alone. We discuss

  10. Role of microvascular disruption in brain damage from traumatic brain injury

    Science.gov (United States)

    Logsdon, Aric F.; Lucke-Wold, Brandon P.; Turner, Ryan C.; Huber, Jason D.; Rosen, Charles L.; Simpkins, James W.

    2015-01-01

    Traumatic brain injury (TBI) is acquired from an external force, which can inflict devastating effects to the brain vasculature and neighboring neuronal cells. Disruption of vasculature is a primary effect that can lead to a host of secondary injury cascades. The primary effects of TBI are rapidly occurring while secondary effects can be activated at later time points and may be more amenable to targeting. Primary effects of TBI include diffuse axonal shearing, changes in blood brain barrier (BBB) permeability, and brain contusions. These mechanical events, especially changes to the BBB, can induce calcium perturbations within brain cells producing secondary effects, which include cellular stress, inflammation, and apoptosis. These secondary effects can be potentially targeted to preserve the tissue surviving the initial impact of TBI. In the past, TBI research had focused on neurons without any regard for glial cells and the cerebrovasculature. Now a greater emphasis is being placed on the vasculature and the neurovascular unit following TBI. A paradigm shift in the importance of the vascular response to injury has opened new avenues of drug treatment strategies for TBI. However, a connection between the vascular response to TBI and the development of chronic disease has yet to be elucidated. Long-term cognitive deficits are common amongst those sustaining severe or multiple mild TBIs. Understanding the mechanisms of cellular responses following TBI is important to prevent the development of neuropsychiatric symptoms. With appropriate intervention following TBI, the vascular network can perhaps be maintained and the cellular repair process possibly improved to aid in the recovery of cellular homeostasis. PMID:26140712

  11. Localized cortical chronic traumatic encephalopathy pathology after single, severe axonal injury in human brain.

    Science.gov (United States)

    Shively, Sharon B; Edgerton, Sarah L; Iacono, Diego; Purohit, Dushyant P; Qu, Bao-Xi; Haroutunian, Vahram; Davis, Kenneth L; Diaz-Arrastia, Ramon; Perl, Daniel P

    2017-03-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical β-amyloid plaques. In this study, we analyzed postmortem brain tissues from five institutionalized patients with schizophrenia and history of surgical leucotomy with subsequent survival of at least another 40 years. Because leucotomy involves severing axons bilaterally in prefrontal cortex, this surgical procedure represents a human model of single traumatic brain injury with severe axonal damage and no external impact. We examined cortical tissues at the leucotomy site and at both prefrontal cortex rostral and frontal cortex caudal to the leucotomy site. For comparison, we analyzed brain tissues at equivalent neuroanatomical sites from non-leucotomized patients with schizophrenia, matched in age and gender. All five leucotomy cases revealed severe white matter damage with dense astrogliosis at the axotomy site and also neurofibrillary tangles and p-tau immunoreactive neurites in the overlying gray matter. Four cases displayed p-tau immunoreactivity in neurons, astrocytes and cell processes encompassing blood vessels at cortical sulcal depths in irregular patterns, similar to CTE. The three cases with apolipoprotein E ε4 haplotype showed scattered β-amyloid plaques in the overlying gray matter, but not the two cases with apolipoprotein E ε3/3 genotype. Brain tissue samples from prefrontal cortex rostral and frontal cortex caudal to the leucotomy site, and all cortical samples from the non-leucotomized patients

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

    Directory of Open Access Journals (Sweden)

    Natanael Antonio Dos Santos

    2013-04-01

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

  13. Brain MRI changes in chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Skehan, S. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Norris, S. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Hegarty, J. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Owens, A. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); MacErlaine, D. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland)

    1997-08-01

    Cirrhotic patients are known to have abnormally high signal principally in the globus pallidus on non-contrast T1-weighted MRI. The purpose of this study was to relate MR changes to clinical and pathological features of chronic liver disease. We confirmed abnormally high signal in the globus pallidus on T1-weighted images in 25 of 28 patients with chronic liver disease, showing that it also occurs in patients who have not yet progressed to cirrhosis. Changes were seen in patients both with and without clinical portosystemic shunting. This abnormality is not responsible for hepatic encephalopathy. Cholestatic disease was more likely to produce marked changes than non-cholestatic disease. No statistically significant correlation was demonstrated between the severity of liver disease and the degree of MR abnormality. However, marked improvement in MR appearances was seen after successful liver transplantation. (orig.). With 3 figs., 4 tabs.

  14. Neuronal over-expression of ACE2 protects brain from ischemia-induced damage.

    Science.gov (United States)

    Chen, Ji; Zhao, Yuhui; Chen, Shuzhen; Wang, Jinju; Xiao, Xiang; Ma, Xiaotang; Penchikala, Madhuri; Xia, Huijing; Lazartigues, Eric; Zhao, Bin; Chen, Yanfang

    2014-04-01

    Angiotensin (Ang) II exaggerates cerebral injury in ischemic damage. Angiotensin-converting enzyme type 2 (ACE2) converts Ang II into Ang (1-7) and thus, may protect against the effects of Ang II. We hypothesized that neuronal ACE2 over-expression decreases ischemic stroke in mice with Ang II overproduction. Human renin and angiotensinogen double transgenic (RA) mice and RA mice with neuronal over-expression of ACE2 (SARA) were used for the study. The mean arterial pressure (MAP) was calculated from telemetry-recorded blood pressure (BP). SARA mice were infused peripherally with Norepinephrine to "clamp" the BP, or intracerebroventricularly-infused with a Mas receptor antagonist (A-779). Middle cerebral artery occlusion (MCAO) surgery was performed to induce permanent focal ischemic stroke. Cerebral blood flow (CBF) and neurological function were determined. Two days after surgery, brain samples were collected for various analyses. Results showed: 1) When compared to chronically hypertensive RA mice, SARA mice had lower basal MAP, less MCAO-induced infarct volume, and increased CBF, neurological function and cerebral microvascular density in the peri-infarct area; 2) These changes in SARA mice were not altered after MAP "clamping", but partially reversed by brain infusion of A-779; 3) Ang (1-7)/Ang II ratio, angiogenic factors, endothelial nitric oxide synthase (eNOS) expression and nitric oxide production were increased, whereas, NADPH oxidase subunits and reactive oxygen species were decreased in the brain of SARA mice. ACE2 protects brain from ischemic injury via the regulation of NADPH oxidase/eNOS pathways by changing Ang (1-7)/Ang II ratio, independently of MAP changes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Chronic Broca's Aphasia Is Caused by Damage to Broca's and Wernicke's Areas

    National Research Council Canada - National Science Library

    Fridriksson, Julius; Fillmore, Paul; Guo, Dazhou; Rorden, Chris

    2015-01-01

    Despite being perhaps the most studied form of aphasia, the critical lesion location for Broca's aphasia has long been debated, and in chronic patients, cortical damage often extends far beyond Broca's area...

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

    Science.gov (United States)

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

    1979-03-01

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

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  18. Attenuating brain inflammation, ischemia, and oxidative damage by hyperbaric oxygen in diabetic rats after heat stroke

    Directory of Open Access Journals (Sweden)

    Kai-Li Lee

    2013-08-01

    Conclusion: Our results suggest that, in diabetic animals, HBO2 therapy may improve outcomes of HS in part by reducing heat-induced activated inflammation and ischemic and oxidative damage in the hypothalamus and other brain regions.

  19. Unilateral Brain Damage Effects on Processing Homonymous and Polysemous Words

    Science.gov (United States)

    Klepousniotou, E.; Baum, S.R.

    2005-01-01

    Using an auditory semantic priming paradigm, the present study investigated the abilities of left-hemisphere-damaged (LHD) non-fluent aphasic, right-hemisphere-damaged (RHD) and normal control individuals to access, out of context, the multiple meanings of three types of ambiguous words, namely homonyms (e.g., ''punch''), metonymies (e.g.,…

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

    NARCIS (Netherlands)

    D.C. Engel (Doortje Caroline)

    2008-01-01

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

  1. Evidence for zolpidem efficacy in brain damage | Clauss | South ...

    African Journals Online (AJOL)

    Previous reports have shown that zolpidem could reverse semi-coma and improve cerebral perfusion after brain injury. Studies in animals have implicated omega 1 GABAergic action as reason for this improvement. Evidence for the efficacy of zolpidem in a wide range of brain pathology is reviewed here and the mechanism ...

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

    Science.gov (United States)

    ... Psychiatry contradicted each other on the question of gender–related vulnerability to brain shrinkage in alcoholism (12,13). Clearly, more research ... E.; and Rawlings, R.R. Evidence for a gender–related effect of alcoholism on brain volumes. American Journal of Psychiatry 158:198–204, ...

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

    Science.gov (United States)

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

    2011-01-01

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

  4. Shared Immune and Repair Markers During Experimental Toxoplasma Chronic Brain Infection and Schizophrenia.

    Science.gov (United States)

    Tomasik, Jakub; Schultz, Tracey L; Kluge, Wolfgang; Yolken, Robert H; Bahn, Sabine; Carruthers, Vern B

    2016-03-01

    Chronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse model of chronic T gondii infection to identify protein biomarkers that are altered in serum and brain samples at 2 time points during chronic infection. Furthermore, we compare the identified biomarkers to those differing between "postmortem" brain samples from 35 schizophrenia patients and 33 healthy controls. Our findings suggest that T gondii infection causes substantial and widespread immune activation indicative of neural damage and reactive tissue repair in the animal model that partly overlaps with changes observed in the brains of schizophrenia patients. The overlapping changes include increases in C-reactive protein (CRP), interleukin-1 beta (IL-1β), interferon gamma (IFNγ), plasminogen activator inhibitor 1 (PAI-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular cell adhesion molecule 1 (VCAM-1). Potential roles of these factors in the pathogenesis of schizophrenia and toxoplasmosis are discussed. Identifying a defined set of markers shared within the pathophysiological landscape of these diseases could be a key step towards understanding their specific contributions to pathogenesis. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Differentiation of Brain Damage Among Low IQ Subjects with Three Projective Techniques

    Science.gov (United States)

    Wagner, Edwin E.; And Others

    1978-01-01

    The Rorschach, Hand, and Bender-Gestalt tests discriminated slightly between low IQ subjects classified as brain damaged or not. Substantial discrimination was observed between the same subjects classified by intelligence level. Brain impairment may underlie most or all retardation. The efficacy of projective techniques for diagnosing organicity…

  6. In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.

    Science.gov (United States)

    Barrio, Jorge R; Small, Gary W; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A; Giza, Christopher C; Fitzsimmons, Robert P; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir

    2015-04-21

    Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.

  7. Investigation of Chronic Pain Following Traumatic Brain Injury

    Science.gov (United States)

    2013-01-01

    Brain Injury: Non-invasive Imaging Approaches", Presented at 3rd Federal Interagency TBI Meeting, June 2011. Robin, DA, Parkinson , A, Manes J. Using...trials of cogniti ve behavioral therapy strate- gies have have found clinically significalll effects on pain and associated symptoms. such as. fatigue...111o rriss. R. K .. Dickens. C.. el al. (20 II ). Road lrJftic accidems. bmno1 01her physically 1raummic e1ems. predic1 1he o nset of chronic

  8. Disrupted Brain Functional Network Architecture in Chronic Tinnitus Patients.

    Science.gov (United States)

    Chen, Yu-Chen; Feng, Yuan; Xu, Jin-Jing; Mao, Cun-Nan; Xia, Wenqing; Ren, Jun; Yin, Xindao

    2016-01-01

    Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated the disruptions of multiple brain networks in tinnitus patients. Nonetheless, several studies found no differences in network processing between tinnitus patients and healthy controls (HCs). Its neural bases are poorly understood. To identify aberrant brain network architecture involved in chronic tinnitus, we compared the resting-state fMRI (rs-fMRI) patterns of tinnitus patients and HCs. Chronic tinnitus patients (n = 24) with normal hearing thresholds and age-, sex-, education- and hearing threshold-matched HCs (n = 22) participated in the current study and underwent the rs-fMRI scanning. We used degree centrality (DC) to investigate functional connectivity (FC) strength of the whole-brain network and Granger causality to analyze effective connectivity in order to explore directional aspects involved in tinnitus. Compared to HCs, we found significantly increased network centrality in bilateral superior frontal gyrus (SFG). Unidirectionally, the left SFG revealed increased effective connectivity to the left middle orbitofrontal cortex (OFC), left posterior lobe of cerebellum (PLC), left postcentral gyrus, and right middle occipital gyrus (MOG) while the right SFG exhibited enhanced effective connectivity to the right supplementary motor area (SMA). In addition, the effective connectivity from the bilateral SFG to the OFC and SMA showed positive correlations with tinnitus distress. Rs-fMRI provides a new and novel method for identifying aberrant brain network architecture. Chronic tinnitus patients have disrupted FC strength and causal connectivity mostly in non-auditory regions, especially the prefrontal cortex (PFC). The current findings will provide a new perspective for understanding the neuropathophysiological mechanisms in chronic tinnitus.

  9. Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury

    Science.gov (United States)

    Hay, Jennifer; Johnson, Victoria E.; Smith, Douglas H.; Stewart, William

    2017-01-01

    Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of non-boxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article. PMID:26772317

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

    NARCIS (Netherlands)

    Prenen, Gerardus Hyacinthus Maria

    1992-01-01

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

  11. Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

    Science.gov (United States)

    Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

    2017-12-01

    Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [15O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

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

    DEFF Research Database (Denmark)

    Reinstrup, Peter; Nordström, Carl-Henrik

    2011-01-01

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

  13. MRI-based quantification of brain damage in cerebrovascular disorders

    NARCIS (Netherlands)

    de Bresser, J.H.J.M.

    2011-01-01

    Brain diseases can lead to diverse structural abnormalities that can be assessed on magnetic resonance imaging (MRI) scans. These abnormalities can be quantified by (semi-)automated techniques. The studies described in this thesis aimed to optimize and apply cerebral quantification techniques in

  14. Neurotrophic Substances and Behavioral Recovery from Brain Damage.

    Science.gov (United States)

    1983-07-01

    NAME ,ND ADQRESS 0. PROGRAM ELEMENT QOJECT, TASK ar unversity, Psycology ept. AREA &*ORK UNIT NUMBERS nand G. Stein, grini. Investigator Brain Research...investigator adhered to the "Guide for the Care and Use of Laboratory Animals," prepared by the Committee on Care and Use of Laboratory Animals of the

  15. Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology

    Science.gov (United States)

    Fu, Tian-Ming; Hong, Guosong; Viveros, Robert D.; Zhou, Tao

    2017-01-01

    Implantable electrical probes have led to advances in neuroscience, brain−machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution of these neurons over the entire course of study. Silicon probes based on microfabrication can yield large-scale, high-density recording but face challenges of chronic gliosis and instability due to mechanical and structural mismatch with the brain. Ultraflexible mesh electronics, on the other hand, have demonstrated negligible chronic immune response and stable long-term brain monitoring at single-neuron level, although, to date, it has been limited to 16 channels. Here, we present a scalable scheme for highly multiplexed mesh electronics probes to bridge the gap between scalability and flexibility, where 32 to 128 channels per probe were implemented while the crucial brain-like structure and mechanics were maintained. Combining this mesh design with multisite injection, we demonstrate stable 128-channel local field potential and single-unit recordings from multiple brain regions in awake restrained mice over 4 mo. In addition, the newly integrated mesh is used to validate stable chronic recordings in freely behaving mice. This scalable scheme for mesh electronics together with demonstrated long-term stability represent important progress toward the realization of ideal implantable electrical probes allowing for mapping and tracking single-neuron level circuit changes associated with learning, aging, and neurodegenerative diseases. PMID:29109247

  16. An introduction to alcohol-induced brain damage and its causes.

    Science.gov (United States)

    Harper, C; Kril, J

    1994-01-01

    The aim of the symposium on alcohol-induced brain damage is to review current opinion and recent advances concerning factors which are thought to play a significant role in this disorder. The three principal factors are: alcohol specific neurotoxicity, associated vitamin B1 (thiamine) deficiency (the Wernicke-Korsakoff syndrome) and liver failure secondary to alcoholic cirrhosis. There is a complex interaction of these and other factors and it is difficult to dissect out the relative importance of each in the pathogenesis of alcohol-related brain damage. Moreover recent molecular and biochemical studies suggest that several of these factors may have pathogenetic mechanisms in common-for example, excitotoxicity, mitric oxide and free radicals. The application of new technologies in neuropathological studies of carefully selected groups of alcoholic cases is beginning to reveal a far more complex pattern of damage than current view holds. Quantitative morphometry and immunohistochemistry can be combined to create three dimensional images of various anatomical regions of the brain together with detailed analyses of neuronal counts, sizes and neurochemical type. In the Wernicke-Korsakoff syndrome (WKS) there is good evidence (in support of neuropsychological and neuroradiological data) to suggest that specific populations of neurons are damaged in cortical and subcortical regions. In those cases with the WKS there is also evidence of pathological damage in cortical and subcortical regions other than the well described periventricular distributions. These more detailed studies provide us with a more comprehensive understanding of alcohol-related brain damage.

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

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2011-01-01

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

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

    Science.gov (United States)

    Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

    2011-01-01

    Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

  19. Increased oxidative phosphorylation in response to acute and chronic DNA damage.

    Science.gov (United States)

    Brace, Lear E; Vose, Sarah C; Stanya, Kristopher; Gathungu, Rose M; Marur, Vasant R; Longchamp, Alban; Treviño-Villarreal, Humberto; Mejia, Pedro; Vargas, Dorathy; Inouye, Karen; Bronson, Roderick T; Lee, Chih-Hao; Neilan, Edward; Kristal, Bruce S; Mitchell, James R

    2016-01-01

    Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient Csa -/- |Xpa -/- mouse model of CS. Exogenous genotoxic stress was modeled in mice in vivo and primary cells in vitro treated with different genotoxins giving rise to diverse spectrums of lesions, including ultraviolet radiation, intrastrand crosslinking agents and ionizing radiation. Both chronic endogenous and acute exogenous genotoxic stress increased mitochondrial fatty acid oxidation (FAO) on the organismal level, manifested by increased oxygen consumption, reduced respiratory exchange ratio, progressive adipose loss and increased FAO in tissues ex vivo . In multiple primary cell types, the metabolic response to different genotoxins manifested as a cell-autonomous increase in oxidative phosphorylation (OXPHOS) subsequent to a transient decline in steady-state NAD+ and ATP levels, and required the DNA damage sensor PARP-1 and energy-sensing kinase AMPK. We conclude that increased FAO/OXPHOS is a general, beneficial, adaptive response to DNA damage on cellular and organismal levels, illustrating a fundamental link between genotoxic stress and energy metabolism driven by the energetic cost of DNA damage. Our study points to therapeutic opportunities to mitigate detrimental effects of DNA damage on primary cells in the context of radio/chemotherapy or progeroid syndromes.

  20. Brain Metal Distribution and Neuro-Inflammatory Profiles after Chronic Vanadium Administration and Withdrawal in Mice

    Directory of Open Access Journals (Sweden)

    Oluwabusayo R. Folarin

    2017-07-01

    Full Text Available Vanadium is a potentially toxic environmental pollutant and induces oxidative damage in biological systems including the central nervous system (CNS. Its deposition in brain tissue may be involved in the pathogenesis of certain neurological disorders which after prolonged exposure can culminate into more severe pathology. Most studies on vanadium neurotoxicity have been done after acute exposure but in reality some populations are exposed for a lifetime. This work was designed to ascertain neurodegenerative consequences of chronic vanadium administration and to investigate the progressive changes in the brain after withdrawal from vanadium treatment. A total of 85 male BALB/c mice were used for the experiment and divided into three major groups of vanadium treated (intraperitoneally (i.p. injected with 3 mg/kg body weight of sodium metavanadate and sacrificed every 3 months till 18 months; matched controls; and animals that were exposed to vanadium for 3 months and thereafter the metal was withdrawn. Brain tissues were obtained after animal sacrifice. Sagittal cut sections of paraffin embedded tissue (5 μm were analyzed by the Laser ablation-inductively coupled plasma-mass spectrometry (LA–ICP–MS to show the absorption and distribution of vanadium metal. Also, Haematoxylin and Eosin (H&E staining of brain sections, and immunohistochemistry for Microglia (Iba-1, Astrocytes (GFAP, Neurons (Neu-N and Neu-N + 4′,6-diamidine-2′-pheynylindole dihydrochloride (Dapi Immunofluorescent labeling were observed for morphological and morphometric parameters. The LA–ICP–MS results showed progressive increase in vanadium uptake with time in different brain regions with prediction for regions like the olfactory bulb, brain stem and cerebellum. The withdrawal brains still show presence of vanadium metal in the brain slightly more than the controls. There were morphological alterations (of the layering profile, nuclear shrinkage in the prefrontal

  1. Overweight worsens apoptosis, neuroinflammation and blood-brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation

    Directory of Open Access Journals (Sweden)

    Wu Hsin-Chieh

    2011-04-01

    Full Text Available Abstract Background Apoptosis, neuroinflammation and blood-brain barrier (BBB damage affect the susceptibility of the developing brain to hypoxic-ischemic (HI insults. c-Jun N-terminal kinase (JNK is an important mediator of insulin resistance in obesity. We hypothesized that neonatal overweight aggravates HI brain damage through JNK hyperactivation-mediated upregulation of neuronal apoptosis, neuroinflammation and BBB leakage in rat pups. Methods Overweight (OF pups were established by reducing the litter size to 6, and control (NF pups by keeping the litter size at 12 from postnatal (P day 1 before HI on P7. Immunohistochemistry and immunoblotting were used to determine the TUNEL-(+ cells and BBB damage, cleaved caspase-3 and poly (ADP-ribose polymerase (PARP, and phospho-JNK and phospho-BimEL levels. Immunofluorescence was performed to determine the cellular distribution of phospho-JNK. Results Compared with NF pups, OF pups had a significantly heavier body-weight and greater fat deposition on P7. Compared with the NF-HI group, the OF-HI group showed significant increases of TUNEL-(+ cells, cleaved levels of caspase-3 and PARP, and ED1-(+ activated microglia and BBB damage in the cortex 24 hours post-HI. Immunofluorescence of the OF-HI pups showed that activated-caspase 3 expression was found mainly in NeuN-(+ neurons and RECA1-(+ vascular endothelial cells 24 hours post-HI. The OF-HI group also had prolonged escape latency in the Morris water maze test and greater brain-volume loss compared with the NF-HI group when assessed at adulthood. Phospho-JNK and phospho-BimEL levels were higher in OF-HI pups than in NF-HI pups immediately post-HI. JNK activation in OF-HI pups was mainly expressed in neurons, microglia and vascular endothelial cells. Inhibiting JNK activity by AS601245 caused more attenuation of cleaved caspase-3 and PARP, a greater reduction of microglial activation and BBB damage post-HI, and significantly reduced brain damage in

  2. A chronic generalized bi-directional brain-machine interface.

    Science.gov (United States)

    Rouse, A G; Stanslaski, S R; Cong, P; Jensen, R M; Afshar, P; Ullestad, D; Gupta, R; Molnar, G F; Moran, D W; Denison, T J

    2011-06-01

    A bi-directional neural interface (NI) system was designed and prototyped by incorporating a novel neural recording and processing subsystem into a commercial neural stimulator architecture. The NI system prototype leverages the system infrastructure from an existing neurostimulator to ensure reliable operation in a chronic implantation environment. In addition to providing predicate therapy capabilities, the device adds key elements to facilitate chronic research, such as four channels of electrocortigram/local field potential amplification and spectral analysis, a three-axis accelerometer, algorithm processing, event-based data logging, and wireless telemetry for data uploads and algorithm/configuration updates. The custom-integrated micropower sensor and interface circuits facilitate extended operation in a power-limited device. The prototype underwent significant verification testing to ensure reliability, and meets the requirements for a class CF instrument per IEC-60601 protocols. The ability of the device system to process and aid in classifying brain states was preclinically validated using an in vivo non-human primate model for brain control of a computer cursor (i.e. brain-machine interface or BMI). The primate BMI model was chosen for its ability to quantitatively measure signal decoding performance from brain activity that is similar in both amplitude and spectral content to other biomarkers used to detect disease states (e.g. Parkinson's disease). A key goal of this research prototype is to help broaden the clinical scope and acceptance of NI techniques, particularly real-time brain state detection. These techniques have the potential to be generalized beyond motor prosthesis, and are being explored for unmet needs in other neurological conditions such as movement disorders, stroke and epilepsy.

  3. A chronic generalized bi-directional brain-machine interface

    Science.gov (United States)

    Rouse, A. G.; Stanslaski, S. R.; Cong, P.; Jensen, R. M.; Afshar, P.; Ullestad, D.; Gupta, R.; Molnar, G. F.; Moran, D. W.; Denison, T. J.

    2011-06-01

    A bi-directional neural interface (NI) system was designed and prototyped by incorporating a novel neural recording and processing subsystem into a commercial neural stimulator architecture. The NI system prototype leverages the system infrastructure from an existing neurostimulator to ensure reliable operation in a chronic implantation environment. In addition to providing predicate therapy capabilities, the device adds key elements to facilitate chronic research, such as four channels of electrocortigram/local field potential amplification and spectral analysis, a three-axis accelerometer, algorithm processing, event-based data logging, and wireless telemetry for data uploads and algorithm/configuration updates. The custom-integrated micropower sensor and interface circuits facilitate extended operation in a power-limited device. The prototype underwent significant verification testing to ensure reliability, and meets the requirements for a class CF instrument per IEC-60601 protocols. The ability of the device system to process and aid in classifying brain states was preclinically validated using an in vivo non-human primate model for brain control of a computer cursor (i.e. brain-machine interface or BMI). The primate BMI model was chosen for its ability to quantitatively measure signal decoding performance from brain activity that is similar in both amplitude and spectral content to other biomarkers used to detect disease states (e.g. Parkinson's disease). A key goal of this research prototype is to help broaden the clinical scope and acceptance of NI techniques, particularly real-time brain state detection. These techniques have the potential to be generalized beyond motor prosthesis, and are being explored for unmet needs in other neurological conditions such as movement disorders, stroke and epilepsy.

  4. Brain Gray Matter Deficits in Patients with Chronic Primary Insomnia.

    Science.gov (United States)

    Joo, Eun Yeon; Noh, Hyun Jin; Kim, Jeong-Sik; Koo, Dae Lim; Kim, Daeyoung; Hwang, Kyoung Jin; Kim, Ji Young; Kim, Sung Tae; Kim, Mi Rim; Hong, Seung Bong

    2013-07-01

    To investigate the structural changes in patients with chronic primary insomnia and the relationships with clinical features of insomnia. Statistical parametric mapping 8-based voxel-based morphometry was used to identify differences in regional gray and white matter between patients with chronic primary insomnia and normal controls. University hospital. Twenty-seven patients and 27 age/sex-matched controls. Regional differences were compared using two-sample t-tests with age, sex, and intracranial volume as covariates. The patients were a mean age of 52.3 y and had a mean history of insomnia of 7.6 y. Patients displayed cognitive deficits in attention, frontal/executive function, and nonverbal memory. Patients also displayed significantly reduced gray matter concentrations (GMCs) in dorsolateral prefrontal and pericentral cortices, superior temporal gyrus, and cerebellum and decreased gray matter volumes in medial frontal and middle temporal gyri compared with control patients with the cluster threshold ≥ 50 voxels at the level of uncorrected P matter deficits in multiple brain regions including bilateral frontal lobes in patients with psychophysiologic insomnia. Gray matter deficit of the pericentral and lateral temporal areas may be associated with the difficulties in sleep initiation and maintenance. It is still unclear whether gray matter reductions are a preexisting abnormality or a consequence of insomnia. Joo EY; Noh HJ; Kim JS; Koo DL; Kim D; Hwang KJ; Kim JY; Kim ST; Kim MR; Hong SB. Brain gray matter deficits in patients with chronic primary insomnia. SLEEP 2013;36(7):999-1007.

  5. Iris Freckles a Potential Biomarker for Chronic Sun Damage.

    Science.gov (United States)

    Schwab, Christoph; Mayer, Christoph; Zalaudek, Iris; Riedl, Regina; Richtig, Markus; Wackernagel, Werner; Hofmann-Wellenhof, Rainer; Richtig, Georg; Langmann, Gerald; Tarmann, Lisa; Wedrich, Andreas; Richtig, Erika

    2017-05-01

    To investigate the role of sunlight exposure in iris freckles formation. We prospectively examined volunteers attending a skin cancer screening program conducted by ophthalmologists and dermatologists. Frequency and topographical variability of iris freckles were noted and associated with behavioral and dermatologic characteristics indicating high sun exposure. Six hundred thirty-two participants (n = 360; 57% female) were examined. Mean age of all participants was 38.4 ± 18.4 years (range, 4-84 years). Of all individuals, 76.1% (n = 481) exhibited at least one iris freckle. Most freckles were observed in the inferior temporal quadrant. The presence of iris freckles was associated with higher age (participants with iris freckles: 41.8 ± 16.8 years versus participants without iris freckles: 27.6 ± 19.2 years), a high number of sunburns during lifetime (>10: 31% vs. 19%), sunlight-damaged skin (26% vs. 11%), presence of actinic lentigines (72% vs. 45%), and a high total nevus body count (>10; 78% vs. 67%). The association of iris freckles, behavioral factors, and dermatologic findings, as well as the topographical distribution, indicate that sunlight exposure may trigger the formation of iris freckles. The evaluation of iris freckles offers an easily accessible potential biomarker, which might be helpful in indicating sun damage on the skin associated with cutaneous malignancies. Furthermore, the evaluation of iris freckles could also be helpful in understanding the role of sunlight in several ophthalmologic diseases.

  6. Impact of Cardiovascular Organ Damage on Cortical Renal Perfusion in Patients with Chronic Renal Failure

    OpenAIRE

    Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Smoszna, Jerzy; Niemczyk, Stanis?aw

    2013-01-01

    Introduction. Properly preserved renal perfusion is the basic determinant of oxygenation, vitality, nutrition, and organ function and its structure. Perfusion disorders are functional changes and are ahead of the appearance of biochemical markers of organ damage. The aim of this study was to evaluate a relationship between the renal cortex perfusion and markers of cardiovascular organ damage in patients with stable chronic renal failure (CKD). Methods. Seventeen patients (2?F; 15?M; age 47 ? ...

  7. Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats Dano oxidativo ao tecido cerebral como possível mecanismo de efeito deletério da alta dose crônica de estradiol no aprendizado e memória de ratas ooforectomizadas

    Directory of Open Access Journals (Sweden)

    Fatimeh Khodabandehloo

    2013-05-01

    Full Text Available In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p≪0.01 and p≪0.001. In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p≪0.05 and p≪0.001. In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA concentrations were higher than in the Sham and OVX groups (p≪0.05 and p≪0.001. It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.Além dos efeitos antioxidantes, os estrógenos também têm ação pró-oxidativa. Foi investigado o efeito da administração crônica de alta dose de valereato de estradiol no desempenho do labirinto aquático de Morris e o dano oxidativo ao tecido cerebral. Os grupos Sham-Est e OVX-Est foram tratados com valereato de estradiol (4 mg/kg por 12 semanas. O tempo de latência para escapada e o caminho percorrido foram significativamente maiores nos grupos Sham-Est e OVX-Est em relação aos grupos Sham e OVX (p≪0,01 e p≪0,001. No estudo probe, os animais dos grupos Sham-Est e OVX-Est levaram menos tempo no Q1 em comparação aos grupos Sham e OVX (p≪0,05 e p≪0,001. Nos grupos Sham-Est e OVX-Est, a concentração total de tiol foi significativamente menor, enquanto a concentração de malondialdehydo (MDA for maior do que aquela dos grupos Sham e OVX (p≪0,05 e p≪0,001. Concluiu-se que a administração de altas doses de estradiol exógeno compromete o desempenho e aumenta o estresse oxidativo

  8. Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning.

    Science.gov (United States)

    Zakharov, Sergey; Kotikova, Katerina; Nurieva, Olga; Hlusicka, Jiri; Kacer, Petr; Urban, Pavel; Vaneckova, Manuela; Seidl, Zdenek; Diblik, Pavel; Kuthan, Pavel; Navratil, Tomas; Pelclova, Daniela

    2017-04-01

    The role of neuroinflammation in methanol-induced toxic brain damage has not been studied. We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors. Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge. The acute maximum (Cmax) LT concentrations were higher than concentrations in survivors: Cmax for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p  0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4. Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.

  9. Vascular damage: a persisting pathology common to Alzheimer's disease and traumatic brain injury.

    Science.gov (United States)

    Franzblau, Max; Gonzales-Portillo, Chiara; Gonzales-Portillo, Gabriel S; Diamandis, Theo; Borlongan, Mia C; Tajiri, Naoki; Borlongan, Cesar V

    2013-11-01

    Alzheimer's disease (AD) and traumatic brain injury (TBI) are both significant clinical problems characterized by debilitating symptoms with limited available treatments. Interestingly, both neurological diseases are characterized by neurovascular damage. This impaired brain vasculature correlates with the onset of dementia, a symptom associated with hippocampal degeneration seen in both diseases. We posit that vascular damage is a major pathological link between TBI and AD, in that TBI victims are predisposed to AD symptoms due to altered brain vasculature; vice versa, the progression of AD pathology may be accelerated by TBI especially when the brain insult worsens hippocampal degeneration. Our hypothesis is supported by recent data reporting expedited AD pathology in presymptomatic transgenic AD mice subjected to TBI. If our hypothesis is correct, treatments targeted at repairing the vasculature may prove effective at treating both diseases and preventing the evolution of AD symptoms in TBI victims. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-15

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

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

    Science.gov (United States)

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

    2014-08-01

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

  12. External ventricular drain causes brain tissue damage: an imaging study.

    Science.gov (United States)

    Ortolano, Fabrizio; Carbonara, Marco; Stanco, Antonella; Civelli, Vittorio; Carrabba, Giorgio; Zoerle, Tommaso; Stocchetti, Nino

    2017-10-01

    An external ventricular drain (EVD) is used to measure intracranial pressure (ICP) and to drain cerebrospinal fluid (CSF). The procedure is generally safe, but parenchymal sequelae are reported as a possible side effect, with variable incidence. We investigated the mechanical sequelae of EVD insertion and their clinical significance in acute brain-injured patients, with a special focus on hemorrhagic lesions. Mechanical sequelae of EVD insertion were detected in patients by computed tomography (CT) and magnetic resonance imaging (MRI), performed for clinical purposes. In 155 patients we studied the brain tissue surrounding the EVD by CT scan (all patients) and MRI (16 patients); 53 patients were studied at three time points (day 1-2, day 3-10, >10 days after EVD placement) to document the lesion time course. Small hemorrhages, with a hyperdense core surrounded by a hypodense area, were identified by CT scan in 33 patients. The initial average (hyper- + hypodense) lesion volume was 8.16 ml, increasing up to 15 ml by >10 days after EVD insertion. These lesions were not accompanied by neurologic deterioration or ICP elevation. History of arterial hypertension, coagulation abnormalities and multiple EVD insertions were significantly associated with hemorrhages. In 122 non-hemorrhagic patients, we detected very small hypodense areas (average volume 0.38 ml) surrounding the catheter. At later times these hypodensities slightly increased. MRI studies in 16 patients identified both intra- and extracellular edema around the catheters. The extracellular component increased with time. EVD insertion, even when there are no clinically important complications, causes a tissue reaction with minimal bleedings and small areas of brain edema.

  13. The Brain Tourniquet: Physiological Isolation of Brain Regions Damaged by Traumatic Head Injury

    Science.gov (United States)

    2008-06-19

    brain slices were treated after injury with either a nootropic agent (aniracetam, cyclothiazide, IDRA 21, or 1-BCP) or the antiepileptic drug...pharmacological approach. 15. SUBJECT TERMS traumatic brain injury, cell necrosis, neuroprotection, nootropics , epilepsy, long-term potentiation...render their use problematic in an effective brain tourniquet system. We chose to focus our investigations on the nootropic (cognition enhancing) drugs

  14. Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow.

    Directory of Open Access Journals (Sweden)

    Clas Linnman

    Full Text Available Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1 receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis were selected out of a larger (n = 120 randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis. These ten subjects were examined by positron emission tomography (PET with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA, was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.

  15. Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation?

    Science.gov (United States)

    Faden, Alan I; Loane, David J

    2015-01-01

    It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support. There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a "specific" entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).

  16. Glymphatic system disruption as a mediator of brain trauma and chronic traumatic encephalopathy.

    Science.gov (United States)

    Sullan, Molly J; Asken, Breton M; Jaffee, Michael S; DeKosky, Steven T; Bauer, Russell M

    2017-08-30

    Traumatic brain injury (TBI) is an increasingly important issue among veterans, athletes and the general public. Difficulties with sleep onset and maintenance are among the most commonly reported symptoms following injury, and sleep debt is associated with increased accumulation of beta amyloid (Aβ) and phosphorylated tau (p-tau) in the interstitial space. Recent research into the glymphatic system, a lymphatic-like metabolic clearance mechanism in the central nervous system (CNS) which relies on cerebrospinal fluid (CSF), interstitial fluid (ISF), and astrocytic processes, shows that clearance is potentiated during sleep. This system is damaged in the acute phase following mTBI, in part due to re-localization of aquaporin-4 channels away from astrocytic end feet, resulting in reduced potential for waste removal. Long-term consequences of chronic dysfunction within this system in the context of repetitive brain trauma and insomnia have not been established, but potentially provide one link in the explanatory chain connecting repetitive TBI with later neurodegeneration. Current research has shown p-tau deposition in perivascular spaces and along interstitial pathways in chronic traumatic encephalopathy (CTE), pathways related to glymphatic flow; these are the main channels by which metabolic waste is cleared. This review addresses possible links between mTBI-related damage to glymphatic functioning and physiological changes found in CTE, and proposes a model for the mediating role of sleep disruption in increasing the risk for developing CTE-related pathology and subsequent clinical symptoms following repetitive brain trauma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Story processing in right-hemisphere brain-damaged patients.

    Science.gov (United States)

    Rehak, A; Kaplan, J A; Weylman, S T; Kelly, B; Brownell, H H; Gardner, H

    1992-04-01

    The understanding of stories requires sensitivity to structural aspects of narrative, the emotional content conveyed by the narrative, and the interaction between structural and emotional facets of the story. Right-hemisphere-damaged (RHD) and normal control subjects performed a number of different analytic tasks which probed their competence at story comprehension. Results revealed that RHD subjects perform at a level comparable to that of normal controls with stories that follow a canonical form and that they show few difficulties with structural aspects of narrative. Contrary to expectation, they are strongly influenced by the "interest" level of a story and by other factors that tap emotional sensitivity. Findings are discussed in terms of the processing and arousal mechanisms which may give rise to the observed pattern of difficulties in RHD patients.

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

    Science.gov (United States)

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

    2013-01-01

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

  19. Chronic kidney disease aggravates arteriovenous fistula damage in rats.

    Science.gov (United States)

    Langer, Stephan; Kokozidou, Maria; Heiss, Christian; Kranz, Jennifer; Kessler, Tina; Paulus, Niklas; Krüger, Thilo; Jacobs, Michael J; Lente, Christina; Koeppel, Thomas A

    2010-12-01

    Neointimal hyperplasia (NIH) and impaired dilatation are important contributors to arteriovenous fistula (AVF) failure. It is unclear whether chronic kidney disease (CKD) itself causes adverse remodeling in arterialized veins. Here we determined if CKD specifically triggers adverse effects on vascular remodeling and assessed whether these changes affect the function of AVFs. For this purpose, we used rats on a normal diet or on an adenine-rich diet to induce CKD and created a fistula between the right femoral artery and vein. Fistula maturation was followed noninvasively by high-resolution ultrasound (US), and groups of rats were killed on 42 and 84 days after surgery for histological and immunohistochemical analyses of the AVFs and contralateral femoral vessels. In vivo US and ex vivo morphometric analyses confirmed a significant increase in NIH in the AVFs of both groups with CKD compared to those receiving a normal diet. Furthermore, we found using histological evaluation of the fistula veins in the rats with CKD that the media shrank and their calcification increased significantly. Afferent artery dilatation was significantly impaired in CKD and the downstream fistula vein had delayed dilation after surgery. These changes were accompanied by significantly increased peak systolic velocity at the site of the anastomosis, implying stenosis. Thus, CKD triggers adverse effects on vascular remodeling in AVFs, all of which contribute to anatomical and/or functional stenosis.

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

    NARCIS (Netherlands)

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

    1995-01-01

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

  1. Principles of Experience-Dependent Neural Plasticity: Implications for Rehabilitation after Brain Damage

    Science.gov (United States)

    Kleim, Jeffrey A.; Jones, Theresa A.

    2008-01-01

    Purpose: This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. Method: Neuroscience research using a variety of models of learning, neurological disease, and trauma are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the…

  2. Map-following skills in left and right brain-damaged patients with and without hemineglect.

    Science.gov (United States)

    Palermo, Liana; Ranieri, Giulia; Boccia, Maddalena; Piccardi, Laura; Nemmi, Federico; Guariglia, Cecilia

    2012-01-01

    Map-following tasks require a "semantic interpretation" of the map, which could be affected by left brain damage, and "superimposition of the map upon the space," which could be compromised by right lesions and particularly by the presence of hemineglect. Participants followed a pathway depicted on a map of a real environment. The pathway included four left and four right turns. A legend explained the meaning of each symbol that appeared on the map. Our results showed no deficits in left brain-damaged patients, but poor performance in right brain-damaged patients affected by hemineglect. This deficit can be ascribed to their impaired egocentric frame of reference, but we cannot exclude a prevalent role of the right hemisphere in their use of the allocentric information on the map despite the presence of hemineglect. Indeed, three right brain-damaged patients without hemineglect showed a specific deficit in performing the task. We discuss the results in light of the possible impairment of the parietomedial temporal pathway, which supports spatial navigation and could be responsible for the patients' deficit.

  3. Automated detection of unfilled pauses in speech of healthy and brain-damaged individuals

    NARCIS (Netherlands)

    Ossewaarde, Roelant; Jonkers, Roel; Jalvingh, Fedor; Bastiaanse, Yvonne

    Automated detection of un lled pauses in speech of healthy and brain-damaged individuals Roelant Ossewaardea,b, Roel Jonkersa, Fedor Jalvingha,c, Roelien Bastiaansea aCenter for Language and Cognition, University of Groningen; bInstitute for ICT, HU University of Applied Science, Utrecht; cSt.

  4. An Evidence-Based Systematic Review on Communication Treatments for Individuals with Right Hemisphere Brain Damage

    Science.gov (United States)

    Blake, Margaret Lehman; Frymark, Tobi; Venedictov, Rebecca

    2013-01-01

    Purpose: The purpose of this review is to evaluate and summarize the research evidence related to the treatment of individuals with right hemisphere communication disorders. Method: A comprehensive search of the literature using key words related to right hemisphere brain damage and communication treatment was conducted in 27 databases (e.g.,…

  5. The access and processing of familiar idioms by brain-damaged and normally aging adults.

    Science.gov (United States)

    Tompkins, C A; Boada, R; McGarry, K

    1992-06-01

    Idiom interpretation tasks are routinely used in the clinical evaluation of adults with brain damage, and idiom processing has received increasing attention in the psycholinguistic literature. Clinical evidence suggests that adults with unilateral right-hemisphere damage (RHD) are insensitive to nonliteral meanings conveyed by idiomatic expressions and other figurative forms. However, this portrayal is derived from their terminal responses to tasks that reflect multiple aspects of mental operations (off-line measures), obscuring the source of poor performance. This study used an on-line word-monitoring task to assess RHD, left-hemisphere-damaged, and normally aging adults' implicit knowledge of familiar idiomatic expressions. Brain-damaged subjects performed similarly to normal controls on this task, even though the clinical subjects fared poorly by comparison on an off-line idiom definition measure. These results suggest that adults with unilateral brain damage can activate and retrieve familiar idiomatic forms, and that their idiom-interpretation deficits most likely reflect impairment at some later stage of information processing. Further, error analysis of idiom-definition performance did not support the customary characterization of RHD adults as excessively literal responders. The paper discusses clinical implications of the nature and use of idiom interpretation tasks.

  6. Modafinil Effects on Behavior and Oxidative Damage Parameters in Brain of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Felipe Ornell

    2014-01-01

    Full Text Available The effects of modafinil (MD on behavioral and oxidative damage to protein and lipid in the brain of rats were evaluated. Wistar rats were given a single administration by gavage of water or MD (75, 150, or 300 mg/kg. Behavioral parameters were evaluated in open-field apparatus 1, 2, and 3 h after drug administration. Thiobarbituric acid reactive substances (TBARS and protein carbonyl formation were measured in the brain. MD increased locomotor activity at the highest dose 1 and 3 h after administration. MD administration at the dose of 300 mg/kg increased visits to the center of open-field 1 h after administration; however, 3 h after administration, all administered doses of MD increased visits to the open-field center. MD 300 mg/kg increased lipid damage in the amygdala, hippocampus, and striatum. Besides, MD increased protein damage in the prefrontal cortex, amygdala, and hippocampus; however, this effect varies depending on the dose administered. In contrast, the administration of MD 75 and 300 mg/kg decreased the protein damage in the striatum. This study demonstrated that the MD administration induces behavioral changes, which was depending on the dose used. In addition, the effects of MD on oxidative damage parameters seemed to be in specific brain region and doses.

  7. Immunomodulation by poly-YE reduces organophosphate-induced brain damage.

    Science.gov (United States)

    Finkelstein, Arseny; Kunis, Gilad; Berkutzki, Tamara; Ronen, Ayal; Krivoy, Amir; Yoles, Eti; Last, David; Mardor, Yael; Van Shura, Kerry; McFarland, Emylee; Capacio, Benedict A; Eisner, Claire; Gonzales, Mary; Gregorowicz, Danise; Eisenkraft, Arik; McDonough, John H; Schwartz, Michal

    2012-01-01

    Accidental organophosphate poisoning resulting from environmental or occupational exposure, as well as the deliberate use of nerve agents on the battlefield or by terrorists, remain major threats for multi-casualty events, with no effective therapies yet available. Even transient exposure to organophosphorous compounds may lead to brain damage associated with microglial activation and to long-lasting neurological and psychological deficits. Regulation of the microglial response by adaptive immunity was previously shown to reduce the consequences of acute insult to the central nervous system (CNS). Here, we tested whether an immunization-based treatment that affects the properties of T regulatory cells (Tregs) can reduce brain damage following organophosphate intoxication, as a supplement to the standard antidotal protocol. Rats were intoxicated by acute exposure to the nerve agent soman, or the organophosphate pesticide, paraoxon, and after 24 h were treated with the immunomodulator, poly-YE. A single injection of poly-YE resulted in a significant increase in neuronal survival and tissue preservation. The beneficial effect of poly-YE treatment was associated with specific recruitment of CD4(+) T cells into the brain, reduced microglial activation, and an increase in the levels of brain derived neurotrophic factor (BDNF) in the piriform cortex. These results suggest therapeutic intervention with poly-YE as an immunomodulatory supplementary approach against consequences of organophosphate-induced brain damage. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Neuroanatomical abnormalities in chronic tinnitus in the human brain

    Science.gov (United States)

    Adjamian, Peyman; Hall, Deborah A.; Palmer, Alan R.; Allan, Thomas W.; Langers, Dave R.M.

    2014-01-01

    In this paper, we review studies that have investigated brain morphology in chronic tinnitus in order to better understand the underlying pathophysiology of the disorder. Current consensus is that tinnitus is a disorder involving a distributed network of peripheral and central pathways in the nervous system. However, the precise mechanism remains elusive and it is unclear which structures are involved. Given that brain structure and function are highly related, identification of anatomical differences may shed light upon the mechanism of tinnitus generation and maintenance. We discuss anatomical changes in the auditory cortex, the limbic system, and prefrontal cortex, among others. Specifically, we discuss the gating mechanism of tinnitus and evaluate the evidence in support of the model from studies of brain anatomy. Although individual studies claim significant effects related to tinnitus, outcomes are divergent and even contradictory across studies. Moreover, results are often confounded by the presence of hearing loss. We conclude that, at present, the overall evidence for structural abnormalities specifically related to tinnitus is poor. As this area of research is expanding, we identify some key considerations for research design and propose strategies for future research. PMID:24892904

  9. The chronic and evolving neurological consequences of traumatic brain injury.

    Science.gov (United States)

    Wilson, Lindsay; Stewart, William; Dams-O'Connor, Kristen; Diaz-Arrastia, Ramon; Horton, Lindsay; Menon, David K; Polinder, Suzanne

    2017-10-01

    Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Melatonin attenuated brain death tissue extract-induced cardiac damage by suppressing DAMP signaling.

    Science.gov (United States)

    Sung, Pei-Hsun; Lee, Fan-Yen; Lin, Ling-Chun; Chen, Kuan-Hung; Lin, Hung-Sheng; Shao, Pei-Lin; Li, Yi-Chen; Chen, Yi-Ling; Lin, Kun-Chen; Yuen, Chun-Man; Chang, Hsueh-Wen; Lee, Mel S; Yip, Hon-Kan

    2018-01-09

    We tested the hypothesis that melatonin prevents brain death (BD) tissue extract (BDEX)-induced cardiac damage by suppressing inflammatory damage-associated molecular pattern (DAMP) signaling in rats. Six hours after BD induction, levels of a DAMP component (HMGB1) and inflammatory markers (TLR-2, TLR-4, MYD88, IκB, NF-κB, IL-1β, IFN-γ, TNF-α and IL-6) were higher in brain tissue from BD animals than controls. Levels of HMGB1 and inflammatory markers were higher in BDEX-treated H9C2 cardiac myoblasts than in cells treated with healthy brain tissue extract. These increases were attenuated by melatonin but re-induced with luzindole (all P DAMP inflammatory axis.

  11. Macroscopic networks in the human brain: mapping connectivity in healthy and damaged brains

    NARCIS (Netherlands)

    Nijhuis, E.H.J.

    2013-01-01

    The human brain contains a network of interconnected neurons. Recent advances in functional and structural in-vivo magnetic resonance neuroimaging (MRI) techniques have provided opportunities to model the networks of the human brain on a macroscopic scale. This dissertation investigates the

  12. Chronic lithium treatment has antioxidant properties but does not prevent oxidative damage induced by chronic variate stress.

    Science.gov (United States)

    de Vasconcellos, Ana Paula Santana; Nieto, Fabiane Battistela; Crema, Leonardo Machado; Diehl, Luisa Amália; de Almeida, Lúcia Maria; Prediger, Martha Elisa; da Rocha, Elizabete Rocha; Dalmaz, Carla

    2006-09-01

    This study evaluated the effects of chronic stress and lithium treatments on oxidative stress parameters in hippocampus, hypothalamus, and frontal cortex. Adult male Wistar rats were divided into two groups: control and submitted to chronic variate stress, and subdivided into treated or not with LiCl. After 40 days, rats were killed, and lipoperoxidation, production free radicals, total antioxidant reactivity (TAR) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were evaluated. The results showed that stress increased lipoperoxidation and that lithium decreased free radicals production in hippocampus; both treatments increased TAR. In hypothalamus, lithium increased TAR and no effect was observed in the frontal cortex. Stress increased SOD activity in hippocampus; while lithium increased GPx in hippocampus and SOD in hypothalamus. We concluded that lithium presented antioxidant properties, but is not able to prevent oxidative damage induced by chronic variate stress.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  14. Protective effect of curcumin against chronic alcohol-induced cognitive deficits and neuroinflammation in the adult rat brain.

    Science.gov (United States)

    Tiwari, V; Chopra, K

    2013-08-06

    Chronic alcohol intake is known to induce the selective neuronal damage associated with increase oxidative-nitrosative stress and activation of inflammatory cascade finally resulting in cognitive deficits. In the present study, we investigated the protective effect of curcumin, a potent natural anti-oxidant and anti-inflammatory molecule against chronic alcohol-induced cognitive dysfunction and nuclear factor kappa beta (NF-κβ) mediated inflammatory signaling in the brain of rats chronically administered ethanol. Male Wistar rats were given ethanol (10 g/kg; oral gavage) for 10 weeks, and treated with curcumin (15, 30 and 60 mg/kg) for the same duration. Ethanol-exposed rats showed impaired spatial navigation in the Morris water maze test and poor retention in the elevated plus maze task which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)), NF-kβ and caspase-3 levels in different brain regions (cerebral cortex and hippocampus) of ethanol-treated rats. Co-administration with curcumin significantly and dose-dependently prevented all the behavioral, biochemical and molecular alterations in rats chronically administered ethanol. Thus, findings from the current study demonstrates the possible involvement of oxidative-nitrosative stress mediated cytokine release and inflammatory signaling in chronic alcohol-induced cognitive dysfunction and also suggests the effectiveness of curcumin in preventing cognitive deficits associated with chronic alcohol consumption. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Alcohol consumption during adolescence: A link between mitochondrial damage and ethanol brain intoxication.

    Science.gov (United States)

    Tapia-Rojas, Cheril; Mira, Rodrigo G; Torres, Angie K; Jara, Claudia; Pérez, María José; Vergara, Erick H; Cerpa, Waldo; Quintanilla, Rodrigo A

    2017-12-01

    Adolescence is a period of multiple changes where social behaviors influence interpersonal-relations. Adolescents live new experiences, including alcohol consumption which has become an increasing health problem. The age of onset for consumption has declined in the last decades, and additionally, the adolescents now uptake greater amounts of alcohol per occasion. Alcohol consumption is a risk factor for accidents, mental illnesses or other pathologies, as well as for the appearance of addictions, including alcoholism. An interesting topic to study is the damage that alcohol induces on the central nervous system (CNS) in the young population. The brain undergoes substantial modifications during adolescence, making brain cells more vulnerable to the ethanol toxicity. Over the last years, the brain mitochondria have emerged as a cell organelle which is particularly susceptible to alcohol. Mitochondria suffer severe alterations which can be exacerbated if the amount of alcohol or the exposure time is increased. In this review, we focus on the changes that the adolescent brain undergoes after drinking, placing particular emphasis on mitochondrial damage and their consequences against brain function. Finally, we propose the mitochondria as an important mediator in alcohol toxicity and a potential therapeutic target to reduce or treat brain conditions associated with excessive alcohol consumption. © 2017 Wiley Periodicals, Inc.

  16. L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD.

    Science.gov (United States)

    Mescka, Caroline Paula; Rosa, Andrea Pereira; Schirmbeck, Gabriel; da Rosa, Thales Hein; Catarino, Felipe; de Souza, Laila Oliveira; Guerreiro, Gilian; Sitta, Angela; Vargas, Carmen Regla; Dutra-Filho, Carlos Severo

    2016-11-01

    Maple syrup urine disease (MSUD), or branched-chain α-keto aciduria, is an inherited disorder that is caused by a deficiency in branched-chain α-keto acid dehydrogenase complex (BCKAD) activity. Blockade of this pathway leads to the accumulation of the branched-chain amino acids (BCAAs), leucine, isoleucine, and valine, and their respective ketoacids in tissues. The main clinical symptoms presented by MSUD patients include ketoacidosis, hypoglycemia, opisthotonos, poor feeding, apnea, ataxia, convulsions, coma, psychomotor delay, and mental retardation. Although increasing evidence indicates that oxidative stress is involved in the pathophysiology of this disease, the mechanisms of the brain damage caused by this disorder remain poorly understood. In the present study, we investigated the effect of BCAAs on some oxidative stress parameters and evaluated the efficacy of L-carnitine (L-car), an efficient antioxidant that may be involved in the reduction of oxidative damage observed in some inherited neurometabolic diseases, against these possible pro-oxidant effects of a chronic MSUD model in the cerebral cortex and cerebellum of rats. Our results showed that chronic BCAA administration was able to promote both lipid and protein oxidation, impair brain antioxidant defenses, and increase reactive species production, particularly in the cerebral cortex, and that L-car was able to prevent these effects. Taken together, the present data indicate that chronic BCAA administration significantly increased oxidative damage in the brains of rats subjected to a chronic model of MSUD and that L-car may be an efficient antioxidant in this disorder.

  17. An implantable device for neuropsychiatric rehabilitation by chronic deep brain stimulation in freely moving rats.

    Science.gov (United States)

    Liu, Hongyu; Wang, Chenguang; Zhang, Fuqiang; Jia, Hong

    2017-02-08

    Successful practice of clinical deep brain stimulation (DBS) calls for basic research on the mechanisms and explorations of new indications in animals. In the article, a new implantable, single-channel, low-power miniature device is proposed, which may transmit pulses chronically into the brain nucleus of freely moving rats. The DBS system consists of an implantable pulse generator (IPG), a bipolar electrode, and an external programmer. The IPG circuit module is assembled as a 20-mm diameter circular board and fixed on a rat's skull together with an electrode and battery. The rigid electrode may make its fabrication and implantation more easy. The external programmer is designed for bidirectional communication with the IPG by a telecontrol transceiver and adjusts stimulation parameters. A biological validation was performed in which the effects of electrical stimulation in brain nucleus accumbens were detected. The programmed parameters were accurate, implant steady, and power sufficient to allow stimulation for more than 3 months. The larger area of the electrode tip provided a moderate current or charge density and minimized the damage from electrochemistry and pyroelectricity. The rats implanted with the device showed a reduction in morphine-induced conditioned place preference after high-frequency stimulation. In conclusion, the DBS device is based on the criteria of simple technology, minimal invasion, low cost, small in size, light-weight, and wireless controlled. This shows that our DBS device is appropriate and can be used for preclinical studies, indicating its potential utility in the therapy and rehabilitation of neuropsychiatric disorders.

  18. Internal distribution of uranium and associated genotoxic damages in the chronically exposed bivalve Corbicula fluminea

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Olivier, E-mail: olivier.simon@irsn.fr [Laboratoire de Radioecologie et Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat, 186 BP3, 13115 Saint Paul-Lez-Durance Cedex (France); Floriani, Magali; Cavalie, Isabelle; Camilleri, Virginie; Adam, Christelle; Gilbin, Rodolphe; Garnier-Laplace, Jacqueline [Laboratoire de Radioecologie et Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat, 186 BP3, 13115 Saint Paul-Lez-Durance Cedex (France)

    2011-08-15

    Uranium (U) internal distribution and involved effects in the bivalve Corbicula fluminea have been studied after direct chronic exposure (90 d, 10 {mu}g.L-1). U distribution was assessed at the subcellular level (Metal Rich Granules -MRG-, pellets and cytosol fractions) in two main organs of the bivalve (gills and visceral mass). Micro-localisation was investigated by TEM-EDX analysis in the gills epithelium. DNA damage in gill and hemolymph samples was measured by the Comet assay. The 90-d exposure period led to a significant increase of U concentration in gills over time (x5) and a large U quantity in subcellular granules in gills. Finally, a significant increase (x2) in DNA damage was noted in exposed gills and haemocytes. This study shows that the accumulation levels and consequently the potential toxicity cannot be successfully predicted only on the basis of concentration in water or in tissues and subcellular fractions after chronic exposure. - Highlights: > Relevant information concerning the chronic impact of uranium on biota is scarce. > We study its biological speciation to explain bioavailability, accumulation, toxicity. > 80% of U accumulated was measured in the pellet fraction (organelles + granules/MRG). > Chronic exposure to U induced genetic damage in gill and haemolymph cells of the bivalve.

  19. Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

    Directory of Open Access Journals (Sweden)

    Yu-Chen Chen

    2014-01-01

    Conclusions: The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients.

  20. Subtle alterations in brain anatomy may change an individual's personality in chronic pain.

    Directory of Open Access Journals (Sweden)

    Sylvia M Gustin

    Full Text Available It is well established that gross prefrontal cortex damage can affect an individual's personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual's personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual's personality.

  1. Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

    Science.gov (United States)

    Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

    2014-01-01

    It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

  2. Correlation between brain damage, associated biomarkers, and medication in psychiatric inpatients: A cross-sectional study.

    Science.gov (United States)

    Yoshida, Madoka; Kanzaki, Tetsuto; Mizoi, Mutsumi; Nakamura, Mizuho; Uemura, Takeshi; Mimori, Seisuke; Uju, Yoriyasu; Sekine, Keisuke; Ishii, Yukihiro; Yoshimi, Taro; Yasui, Reiko; Yasukawa, Asuka; Sato, Mamoru; Okamoto, Seiko; Hisaoka, Tetsuya; Miura, Masafumi; Kusanishi, Shun; Murakami, Kanako; Nakano, Chieko; Mizuta, Yasuhiko; Mishima, Shunichi; Hayakawa, Tatsuro; Tsukada, Kazumi; Kashiwagi, Keiko; Igarashi, Kazuei

    2017-01-01

    We clarified the correlation between brain damage, associated biomarkers and medication in psychiatric patients, because patients with schizophrenia have an increased risk of stroke. The cross-sectional study was performed from January 2013 to December 2015. Study participants were 96 hospitalized patients (41 men and 55 women) in the Department of Psychiatry at Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan. Patients were classified into schizophrenia (n=70) and mood disorders (n=26) by psychiatric diagnoses with DSM-IV-TR criteria. The incidence of brain damage [symptomatic and silent brain infarctions (SBIs) and white matter hyperintensity (WMH)] was correlated more with mood disorders than with schizophrenia. It has been previously shown that the concentrations of protein-conjugated acrolein (PC-Acro) and interleukin-6 (IL-6) increased in plasma of brain infarction patients together with C-reactive protein (CRP). The concentration of PC-Acro was significantly higher in patients with mood disorders than in those with schizophrenia. The concentration of IL-6 in both groups was nearly equal to that in the control group, but that of CRP in both groups, especially in mood disorders, was higher than that in the control group. Accordingly, the relative risk value for brain infarction was higher in patients with mood disorders than with schizophrenia. Medication with atypical antipsychotics reduced PC-Acro significantly in all psychiatric patients and reduced IL-6 in mood disorder patients. Measurement of 3 biomarkers (CRP, PC-Acro and IL-6) are probably useful for judgement of severity of brain damage and effectiveness of medication in psychiatric patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Mesenchymal stem cells as a treatment for neonatal ischemic brain damage.

    Science.gov (United States)

    van Velthoven, Cindy T J; Kavelaars, Annemieke; Heijnen, Cobi J

    2012-04-01

    Mesenchymal stem cell (MSC)-based therapies have been proven effective in experimental models of numerous disorders. Treatment of ischemic brain injury by transplantation of MSCs in neonatal animal models has been shown to be effective in reducing lesion volume and improving functional outcome. The beneficial effect of MSC transplantation to treat neonatal brain injury might be explained by the great plasticity of the neonatal brain. The neonatal brain is still in a developmentally active phase, leading to a better efficiency of MSC transplantation than that observed in experiments using adult models of stroke. Enhanced neurogenesis and axonal remodeling likely underlie the improved functional outcome following MSC treatment after neonatal hypoxic-ischemic (HI) brain injury. With respect to the mechanism of repair by MSCs, MSCs do not survive long term and replace damaged tissue themselves. We propose that MSCs react to the needs of the ischemic cerebral environment by secretion of several growth factors, cytokines, and other bioactive molecules to regulate damage and repair processes. Parenchymal cells react to the secretome of the MSCs and contribute to stimulate repair processes. These intrinsic adaptive properties of MSCs make them excellent candidates for a novel therapy to treat the devastating effects of HI encephalopathy in the human neonate.

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

    Directory of Open Access Journals (Sweden)

    Carolin Wippel

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

  5. Molecular pathophysiology of impaired glucose metabolism, mitochondrial dysfunction, and oxidative DNA damage in Alzheimer's disease brain.

    Science.gov (United States)

    Abolhassani, Nona; Leon, Julio; Sheng, Zijing; Oka, Sugako; Hamasaki, Hideomi; Iwaki, Toru; Nakabeppu, Yusaku

    2017-01-01

    In normal brain, neurons in the cortex and hippocampus produce insulin, which modulates glucose metabolism and cognitive functions. It has been shown that insulin resistance impairs glucose metabolism and mitochondrial function, thus increasing production of reactive oxygen species. Recent progress in Alzheimer's disease (AD) research revealed that insulin production and signaling are severely impaired in AD brain, thereby resulting in mitochondrial dysfunction and increased oxidative stress. Among possible oxidative DNA lesions, 8-oxoguanine (8-oxoG) is highly accumulated in the brain of AD patients. Previously we have shown that incorporating 8-oxoG in nuclear and mitochondrial DNA promotes MUTYH (adenine DNA glycosylase) dependent neurodegeneration. Moreover, cortical neurons prepared from MTH1 (8-oxo-dGTPase)/OGG1 (8-oxoG DNA glycosylase)-double deficient adult mouse brains is shown to exhibit significantly poor neuritogenesis in vitro with increased 8-oxoG accumulation in mitochondrial DNA in the absence of antioxidants. Therefore, 8-oxoG can be considered involved in the neurodegenerative process in AD brain. In mild cognitive impairment, mitochondrial dysfunction and oxidative damage may induce synaptic dysfunction due to energy failures in neurons thus resulting in impaired cognitive function. If such abnormality lasts long, it can lead to vicious cycles of oxidative damage, which may then trigger the neurodegenerative process seen in Alzheimer type dementia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology.

    Science.gov (United States)

    Kulbe, Jacqueline R; Hall, Edward D

    2017-11-01

    In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, American football, Australian football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy have been confirmed to have deposits of hyperphosphorylated tau in locations that make its anatomical distribution distinct for other tauopathies. The fact that these individuals experienced repetitive TBI episodes during their athletic or military careers suggests that the secondary injury mechanisms that have been extensively characterized in acute TBI preclinical models, and in TBI patients, including glutamate excitotoxicity, intracellular calcium overload, mitochondrial dysfunction, free radical-induced oxidative damage and neuroinflammation, may contribute to the brain damage associated with CTE. Thus, the current review begins with an in depth analysis of what is known about the tau protein and its functions and dysfunctions followed by a discussion of the major TBI secondary injury mechanisms, and how the latter have been shown to contribute to tau pathology. The value of this review is that it might lead to improved neuroprotective strategies for either prophylactically attenuating the development of CTE or slowing its progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Quantitation of heavy ion damage to the mammalian brain - Some preliminary findings

    Science.gov (United States)

    Cox, A. B.; Kraft, L. M.

    1984-01-01

    For several years, studies have been conducted regarding late effects of particulate radiations in mammalian tissues, taking into account the brains of rodents and lagomorphs. Recently, it has become feasible to quantify pathological damage and morpho-physiologic alterations accurately in large numbers of histological specimens. New investigative procedures make use of computer-assisted automated image analysis systems. Details regarding the employed methodology are discussed along with the results of the information. The radiations of high linear energy transfer (LET) cause apparently earlier and more dramatic shrinkage of olfactory glomeruli in exposed rabbit brains than comparable doses of Co-60 gamma photons.

  8. Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure.

    Science.gov (United States)

    Wang, Jie; Du, Hongying; Jiang, Lihong; Ma, Xiaoxian; de Graaf, Robin A; Behar, Kevin L; Mason, Graeme F

    2013-08-27

    It has been reported that chronic and acute alcohol exposure decreases cerebral glucose metabolism and increases acetate oxidation. However, it remains unknown how much ethanol the living brain can oxidize directly and whether such a process would be affected by alcohol exposure. The questions have implications for reward, oxidative damage, and long-term adaptation to drinking. One group of adult male Sprague-Dawley rats was treated with ethanol vapor and the other given room air. After 3 wk the rats received i.v. [2-(13)C]ethanol and [1, 2-(13)C2]acetate for 2 h, and then the brain was fixed, removed, and divided into neocortex and subcortical tissues for measurement of (13)C isotopic labeling of glutamate and glutamine by magnetic resonance spectroscopy. Ethanol oxidation was seen to occur both in the cortex and the subcortex. In ethanol-naïve rats, cortical oxidation of ethanol occurred at rates of 0.017 ± 0.002 µmol/min/g in astroglia and 0.014 ± 0.003 µmol/min/g in neurons, and chronic alcohol exposure increased the astroglial ethanol oxidation to 0.028 ± 0.002 µmol/min/g (P = 0.001) with an insignificant effect on neuronal ethanol oxidation. Compared with published rates of overall oxidative metabolism in astroglia and neurons, ethanol provided 12.3 ± 1.4% of cortical astroglial oxidation in ethanol-naïve rats and 20.2 ± 1.5% in ethanol-treated rats. For cortical astroglia and neurons combined, the ethanol oxidation for naïve and treated rats was 3.2 ± 0.3% and 3.8 ± 0.2% of total oxidation, respectively. (13)C labeling from subcortical oxidation of ethanol was similar to that seen in cortex but was not affected by chronic ethanol exposure.

  9. Patterns of poststroke brain damage that predict speech production errors in apraxia of speech and aphasia dissociate.

    Science.gov (United States)

    Basilakos, Alexandra; Rorden, Chris; Bonilha, Leonardo; Moser, Dana; Fridriksson, Julius

    2015-06-01

    Acquired apraxia of speech (AOS) is a motor speech disorder caused by brain damage. AOS often co-occurs with aphasia, a language disorder in which patients may also demonstrate speech production errors. The overlap of speech production deficits in both disorders has raised questions on whether AOS emerges from a unique pattern of brain damage or as a subelement of the aphasic syndrome. The purpose of this study was to determine whether speech production errors in AOS and aphasia are associated with distinctive patterns of brain injury. Forty-three patients with history of a single left-hemisphere stroke underwent comprehensive speech and language testing. The AOS Rating Scale was used to rate speech errors specific to AOS versus speech errors that can also be associated with both AOS and aphasia. Localized brain damage was identified using structural magnetic resonance imaging, and voxel-based lesion-impairment mapping was used to evaluate the relationship between speech errors specific to AOS, those that can occur in AOS or aphasia, and brain damage. The pattern of brain damage associated with AOS was most strongly associated with damage to cortical motor regions, with additional involvement of somatosensory areas. Speech production deficits that could be attributed to AOS or aphasia were associated with damage to the temporal lobe and the inferior precentral frontal regions. AOS likely occurs in conjunction with aphasia because of the proximity of the brain areas supporting speech and language, but the neurobiological substrate for each disorder differs. © 2015 American Heart Association, Inc.

  10. The impact of unilateral brain damage on weight perception, sensorimotor anticipation, and fingertip force adaptation.

    Science.gov (United States)

    Buckingham, Gavin; Bieńkiewicz, Marta; Rohrbach, Nina; Hermsdörfer, Joachim

    2015-10-01

    Damage to the left parietal cortex can lead to apraxia - a selective deficit in tool use and action planning. There is conflicting evidence as to whether this disorder affects more fundamental motor parameters, such as applying the appropriate forces to lift objects based upon how heavy they look. Here we examined how individuals with left and right-lateralized brain damage lift and perceive the weight of objects of the same mass which vary in their size and material properties. No clear differences emerged between the groups in terms of how visual material properties affected their perceptions of object weight or their initial application of grip and load forces. There was, however, some evidence that unilateral brain injury impaired the use of size cues for the parameterization of grip forces. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Prism adaptation reduces the disengage deficit in right brain damage patients.

    Science.gov (United States)

    Striemer, Christopher; Danckert, James

    2007-01-08

    Recent research has shown that prism adaptation alleviates some of the symptoms of neglect. Although prism adaptation can aid patients with neglect, the mechanisms underlying these benefits remain largely unknown. One way in which prisms may work is by altering attentional orienting mechanisms known to be impaired in neglect. To investigate this hypothesis, we tested four right brain damaged patients (two with neglect) on a reflexive covert attention task before and after rightward prism adaptation and compared them with a group of healthy controls who underwent sham prism adaptation. Results demonstrated that rightward prism adaptation reduced both the rightward attentional bias, and the disengage deficit in patients with right brain damage irrespective of the presence of neglect.

  12. Visual acceleration and spatial distortion in right brain-damaged patients.

    Science.gov (United States)

    Latini Corazzini, Luca; Geminiani, Giuliano; Stucchi, Natale; Gindri, Patrizia; Cremasco, Luigi

    2005-03-01

    A subset of right brain-damaged patients shows leftward overextension in the line extension task. It has been argued that this deficit can be attributed to a distortion of the metric structure of perceived space (spatial anisometry). We investigated whether spatial distortion of static stimuli is associated with a corresponding misperception of perceived acceleration of moving stimuli. Seven right brain-damaged patients with spatial anisometry and two control groups were presented with stimuli moving leftwards or rightwards along the horizontal axis at different rates of acceleration. They were asked to estimate whether the target accelerated or decelerated. The anisometric group judged the perceived acceleration of leftward motions as less than that of rightward motions. The magnitude of the misperception of acceleration correlated positively with relative left overextension in the line extension task and with rightward displacement error in the line bisection task. This directional difference is in line with the predictions of the spatial anisometry hypothesis.

  13. Binge ethanol treatment causes greater brain damage in alcohol-preferring P rats than in alcohol-nonpreferring NP rats.

    Science.gov (United States)

    Crews, Fulton T; Braun, Christopher J

    2003-07-01

    Genetics is a known risk factor for alcoholism, and human alcoholics are known to suffer from a loss of brain function and mass. A 4 day rat binge drinking model is known to cause brain region-specific damage. To investigate the role of genetics in binge-drinking-induced brain damage, we studied bidirectionally selected rat lines, the alcohol-preferring P and the alcohol-nonpreferring NP rat lines. P and NP rats were treated with a 4 day binge ethanol protocol. Animals were killed, transcardially perfused, and fixed, and their brains were removed, sectioned, and stained by using the amino cupric silver stain of de Olmos or by using immunohistochemistry for phospho-extracellular signal regulated kinases and other antigens. Significant brain damage was found in the olfactory bulbs, posterior perirhinal cortex, and entorhinal cortex in both P and NP rats. P rats were found to have significantly greater brain damage, compared with NP rats, in the posterior perirhinal and posterior entorhinal cortexes, 239% +/- 50% (p p P rat line, a genetic model of alcoholism, shows greater region-specific brain damage due to binge ethanol treatment than its genetic counterpart, the NP rat line. These findings suggest that genetics contribute to susceptibility for binge-induced brain damage.

  14. Bottom-up and top-down processes in body representation: a study of brain-damaged and amputee patients.

    Science.gov (United States)

    Palermo, Liana; Di Vita, Antonella; Piccardi, Laura; Traballesi, Marco; Guariglia, Cecilia

    2014-09-01

    Body representation is a complex process involving different sources of top-down and bottom-up information. Processing the position and the relations among different body parts is necessary to build up a specific body representation, that is, the visuospatial body map (or topological map of the body). Here we aimed to investigate how the loss of peripheral or central information affects this representation by testing amputee and brain-damaged patients. Thirty-two unilateral brain-damaged patients (i.e., left-brain-damaged patients and right-brain-damaged patients who were or were not affected by personal neglect), 18 lower limb amputees and 15 healthy controls took part in the study. The topological body map was assessed by means of the "Frontal body-evocation subtest" (Daurat-Hmeljiak, Stambak, & Berges, 1978), in which participants have to put tiles (each representing a body part) on a small wooden board on which a head is depicted. Group statistical analysis showed that in amputee patients the loss of peripheral information about the right lower limb affects the ability to represent relations among different body parts as much as the loss of top-down information in brain-damaged patients with personal neglect. Single case analysis of brain-damaged patients without personal neglect showed that the topological map of the body was deficient in 1 right-brain-damaged and 2 left-brain-damaged patients. Studying amputee and brain-damaged patients together allowed us to highlight the importance of visuospatial information about one's own limbs and the role of both hemispheres (not only the left one) in creating an efficient topological body representation. (c) 2014 APA, all rights reserved.

  15. Involvement of MIF in basement membrane damage in chronically UVB-exposed skin in mice.

    Directory of Open Access Journals (Sweden)

    Yoko Yoshihisa

    Full Text Available Solar ultraviolet (UV B radiation is known to induce matrix metalloproteinases (MMPs that degrade collagen in the basement membrane. Macrophage migration inhibitory factor (MIF is a pluripotent cytokine that plays an essential role in the pathophysiology of skin inflammation induced by UV irradiation. This study examined the effects of MIF on basement membrane damage following chronic UVB irradiation in mice. The back skin of MIF transgenic (Tg and wild-type (WT mice was exposed to UVB three times a week for 10 weeks. There was a decrease in intact protein levels of type IV collagen and increased basement membrane damage in the exposed skin of the MIF Tg mice compared to that observed in the WT mice. Moreover, the skin of the MIF Tg mice exhibited higher MIF, MMP-2 and MMP-9 expression and protein levels than those observed in the WT mice. We also found that chronic UVB exposure in MIF Tg mice resulted in higher levels of neutrophil infiltration in the dermis compared with that observed in the WT mice. In vitro experiments revealed that MIF induced increases in the MMPs expression, including that of MMP-9 in keratinocytes and MMP-2 in fibroblasts. Cultured neutrophils also secreted MMP-9 stimulated by MIF. Therefore, MIF-mediated basement membrane damage occurs primarily through MMPs activation and neutrophil influx in murine skin following chronic UVB irradiation.

  16. Mouse model of diffuse brain damage following anoxia, evaluated by a new assay of generalized arousal

    OpenAIRE

    Arrieta-Cruz, Isabel; Pfaff, Donald W.; Shelley, Deborah N.

    2007-01-01

    Diffuse brain damage following anoxia due to cardiac failure, drowning, carbon monoxide exposure or other accidents constitutes a major medical problem. We have created a novel mouse model using the breathing of pure nitrogen, followed by a recently developed assay that reflects an operational definition of generalized arousal. The operational definition is precise, complete, and leads to quantitative, physical measures in a genetically tractable animal. Exposure to pure nitrogen for controll...

  17. Microcavitation as a neuronal damage mechanism in blast -traumatic brain injury

    OpenAIRE

    Estrada, Jon; Franck, Christian

    2014-01-01

    Traumatic brain injury (TBI), usually the result of impact or blast to the head, affects about 1.5 million Americans annually. Diffuse axonal injury, the hallmark feature of blunt TBI, has been investigated in direct mechanical loading conditions. However, recent evidence suggests inertial cavitation as a possible bTBI mechanism, particularly in the case of armed forces exposed to concussive blasts. Cavitation damage to free surfaces has been well-studied in the field of fluid dynamics, but b...

  18. Interfacing brain with computer to improve communication and rehabilitation after brain damage.

    Science.gov (United States)

    Riccio, A; Pichiorri, F; Schettini, F; Toppi, J; Risetti, M; Formisano, R; Molinari, M; Astolfi, L; Cincotti, F; Mattia, D

    2016-01-01

    Communication and control of the external environment can be provided via brain-computer interfaces (BCIs) to replace a lost function in persons with severe diseases and little or no chance of recovery of motor abilities (ie, amyotrophic lateral sclerosis, brainstem stroke). BCIs allow to intentionally modulate brain activity, to train specific brain functions, and to control prosthetic devices, and thus, this technology can also improve the outcome of rehabilitation programs in persons who have suffered from a central nervous system injury (ie, stroke leading to motor or cognitive impairment). Overall, the BCI researcher is challenged to interact with people with severe disabilities and professionals in the field of neurorehabilitation. This implies a deep understanding of the disabled condition on the one hand, and it requires extensive knowledge on the physiology and function of the human brain on the other. For these reasons, a multidisciplinary approach and the continuous involvement of BCI users in the design, development, and testing of new systems are desirable. In this chapter, we will focus on noninvasive EEG-based systems and their clinical applications, highlighting crucial issues to foster BCI translation outside laboratories to eventually become a technology usable in real-life realm. © 2016 Elsevier B.V. All rights reserved.

  19. Protective Effects of Carvacrol against Oxidative Stress Induced by Chronic Stress in Rat’s Brain, Liver, and Kidney

    Directory of Open Access Journals (Sweden)

    Saeed Samarghandian

    2016-01-01

    Full Text Available Restraint stress may be associated with elevated free radicals, and thus, chronic exposure to oxidative stress may cause tissue damage. Several studies have reported that carvacrol (CAR has a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CAR on restraint stress induced oxidative stress damage in the brain, liver, and kidney. For chronic restraint stress, rats were kept in the restrainers for 6 h every day, for 21 consecutive days. The animals received systemic administrations of CAR daily for 21 days. To evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA, reduced glutathione (GSH, superoxide dismutase (SOD, glutathione peroxidase (GPx, glutathione reductase (GR, and catalase (CAT activities were measured in the brain, liver, and kidney. In the stressed animals that received vehicle, the MDA level was significantly higher (P<0.001 and the levels of GSH and antioxidant enzymes were significantly lower than the nonstressed animals (P<0.001. CAR ameliorated the changes in the stressed animals as compared with the control group (P<0.001. This study indicates that CAR can prevent restraint stress induced oxidative damage.

  20. [Differential Diagnosis of Immune-Mediated Encephalopathies: "Neurological Symptoms of Diffuse Brain Damage": A New Concept].

    Science.gov (United States)

    Maki, Yoshimitsu; Takashima, Hiroshi

    2017-10-01

    In recent years, incidence of autoimmune encephalopathies has increased. The diagnosis of the severe form of autoimmune encephalopathy is not difficult; however, milder forms can be misdiagnosed as general encephalopathies. We often treat Hashimoto's encephalopathy, which has diverse clinical symptoms and is often misdiagnosed as a psychosomatic disease. We have found that the neurological findings and symptoms of patients with Hashimoto's encephalopathy are similar to those of psychogenic diseases, such as giveway weakness and atypical sensory disorder. To understand the mechanism underlying these symptoms, we propose a new concept: neurological symptoms of diffuse brain damage. This theory is based on the premise that etiologically, symptoms observed were caused by diffuse, spotty, and shaded brain damage due to autoimmune encephalopathies. We also found similar neurological conditions in patients with anti-ganglionic acetylcholine receptor antibody-related encephalopathy, encephalopathies that developed after injection of the cervical cancer vaccine, and encephalopathies associated with Stiff person syndrome. In conclusion, the clinical features of autoimmune encephalopathy include the "neurological symptoms of diffuse brain damage" as well as the presence of antibodies. We could diagnose autoimmune encephalopathy more easily, using this new diagnostic concept.

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Yu-Feng Tian

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fleming RL

    2015-12-01

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

  4. Vanadyl sulfate administration protects the streptozotocin-induced oxidative damage to brain tissue in rats.

    Science.gov (United States)

    Yanardag, Refiye; Tunali, Sevim

    2006-06-01

    Diabetes mellitus manifests itself in a wide variety of complications and the symptoms of the disease are multifactorial. The present study was carried out to investigate the effects of vanadyl sulfate on biochemical parameters, enzyme activities and brain lipid peroxidation, glutathione and nonenzymatic glycosylation of normal- and streptozotocin-diabetic rats. Streptozotocin (STZ) was administered as a single dose (65 mg/kg) to induce diabetes. A dose of 100 mg/kg vanadyl sulfate was orally administered daily to STZ-diabetic and normal rats, separately until the end of the experiment, at day 60. In STZ-diabetic group, blood glucose, serum sialic and uric acid levels, serum catalase (CAT) and lactate dehydrogenase (LDH) activities, brain lipid peroxidation (LPO) and nonenzymatic glycosylation (NEG) increased, while brain glutathione (GSH) level and body weight decreased. In the diabetic group given vanadyl sulfate, blood glucose, serum sialic and uric acid levels, serum CAT and LDH activities and brain LPO and NEG levels decreased, but brain GSH and body weight increased. The present study showed that vanadyl sulfate exerted antioxidant effects and consequently may prevent brain damage caused by streptozotocin-induced diabetes.

  5. Chronic gliosis and behavioral deficits in mice following repetitive mild traumatic brain injury.

    Science.gov (United States)

    Mannix, Rebekah; Berglass, Jacqueline; Berkner, Justin; Moleus, Philippe; Qiu, Jianhua; Andrews, Nick; Gunner, Georgia; Berglass, Laura; Jantzie, Lauren L; Robinson, Shenandoah; Meehan, William P

    2014-12-01

    With the recent increasing interest in outcomes after repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions), several models of rmTBI have been established. Characterizing these models in terms of behavioral and histopathological outcomes is vital to assess their clinical translatability. The purpose of this study is to provide an in-depth behavioral and histopathological phenotype of a clinically relevant model of rmTBI. The authors used a previously published weight-drop model of rmTBI (7 injuries in 9 days) in 2- to 3-month-old mice that produces cognitive deficits without persistent loss of consciousness, seizures, gross structural imaging findings, or microscopic evidence of structural brain damage. Injured and sham-injured (anesthesia only) mice were subjected to a battery of behavioral testing, including tests of balance (rotarod), spatial memory (Morris water maze), anxiety (open field plus maze), and exploratory behavior (hole-board test). After behavioral testing, brains were assessed for histopathological outcomes, including brain volume and microglial and astrocyte immunolabeling. Compared with sham-injured mice, mice subjected to rmTBI showed increased exploratory behavior and had impaired balance and worse spatial memory that persisted up to 3 months after injury. Long-term behavioral deficits were associated with chronic increased astrocytosis and microgliosis but no volume changes. The authors demonstrate that their rmTBI model results in a characteristic behavioral phenotype that correlates with the clinical syndrome of concussion and repetitive concussion. This model offers a platform from which to study therapeutic interventions for rmTBI.

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

    OpenAIRE

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

    2001-01-01

    Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillaries. The present study describes ultrastructural alterations of the cerebrocortical capillary wall, such as thickening and collagen accumulation in the basement membrane of aging spontaneously hype...

  7. Non-invasive brain stimulation techniques for chronic pain.

    Science.gov (United States)

    O'Connell, Neil E; Wand, Benedict M; Marston, Louise; Spencer, Sally; Desouza, Lorraine H

    2014-04-11

    This is an updated version of the original Cochrane review published in 2010, Issue 9. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS) and reduced impedance non-invasive cortical electrostimulation (RINCE). To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain. We searched CENTRAL (2013, Issue 6), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS and clinical trials registers. The original search for the review was run in November 2009 and searched all databases from their inception. To identify studies for inclusion in this update we searched from 2009 to July 2013. Randomised and quasi-randomised studies of rTMS, CES, tDCS or RINCE if they employed a sham stimulation control group, recruited patients over the age of 18 with pain of three months duration or more and measured pain as a primary outcome. Two authors independently extracted and verified data. Where possible we entered data into meta-analyses. We excluded studies judged as being at high risk of bias from the analysis. We used the GRADE system to summarise the quality of evidence for core comparisons. We included an additional 23 trials (involving 773 participants randomised) in this update, making a total of 56 trials in the review (involving 1710 participants randomised). This update included a total of 30 rTMS studies, 11 CES, 14 tDCS and one study of RINCE(the original review included 19 rTMS, eight CES and six tDCS studies). We judged only three studies as being at low risk of bias across all criteria.Meta-analysis of studies of rTMS (involving 528 participants) demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective (low

  8. Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank.

    Science.gov (United States)

    Bieniek, Kevin F; Ross, Owen A; Cormier, Kerry A; Walton, Ronald L; Soto-Ortolaza, Alexandra; Johnston, Amelia E; DeSaro, Pamela; Boylan, Kevin B; Graff-Radford, Neill R; Wszolek, Zbigniew K; Rademakers, Rosa; Boeve, Bradley F; McKee, Ann C; Dickson, Dennis W

    2015-12-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future

  9. Chronic deep brain stimulation in mesial temporal lobe epilepsy.

    Science.gov (United States)

    Boëx, Colette; Seeck, Margitta; Vulliémoz, Serge; Rossetti, Andrea O; Staedler, Claudio; Spinelli, Laurent; Pegna, Alan J; Pralong, Etienne; Villemure, Jean-Guy; Foletti, Giovanni; Pollo, Claudio

    2011-07-01

    The objective of this study was to evaluate the efficiency and the effects of changes in parameters of chronic amygdala-hippocampal deep brain stimulation (AH-DBS) in mesial temporal lobe epilepsy (TLE). Eight pharmacoresistant patients, not candidates for ablative surgery, received chronic AH-DBS (130 Hz, follow-up 12-24 months): two patients with hippocampal sclerosis (HS) and six patients with non-lesional mesial TLE (NLES). The effects of stepwise increases in intensity (0-Off to 2 V) and stimulation configuration (quadripolar and bipolar), on seizure frequency and neuropsychological performance were studied. The two HS patients obtained a significant decrease (65-75%) in seizure frequency with high voltage bipolar DBS (≥1 V) or with quadripolar stimulation. Two out of six NLES patients became seizure-free, one of them without stimulation, suggesting a microlesional effect. Two NLES patients experienced reductions of seizure frequency (65-70%), whereas the remaining two showed no significant seizure reduction. Neuropsychological evaluations showed reversible memory impairments in two patients under strong stimulation only. AH-DBS showed long-term efficiency in most of the TLE patients. It is a valuable treatment option for patients who suffer from drug resistant epilepsy and who are not candidates for resective surgery. The effects of changes in the stimulation parameters suggest that a large zone of stimulation would be required in HS patients, while a limited zone of stimulation or even a microlesional effect could be sufficient in NLES patients, for whom the importance of the proximity of the electrode to the epileptogenic zone remains to be studied. Further studies are required to ascertain these latter observations. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Clara Luh

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

  11. What does it mean to call chronic pain a brain disease?

    Science.gov (United States)

    Sullivan, Mark D; Cahana, Alex; Derbyshire, Stuart; Loeser, John D

    2013-04-01

    Multiple investigators have recently asked whether neuroimaging has shown that chronic pain is a brain disease. We review the clinical implications of seeing chronic pain as a brain disease. Abnormalities noted on imaging of peripheral structures have previously misled the clinical care of patients with chronic pain. We also cannot assume that the changes associated with chronic pain on neuroimaging are causal. When considering the significance of neuroimaging results, it is important to remember that "disease" is a concept that arises out of clinical medicine, not laboratory science. Following Canguilhem, we believe that disease is best defined as a structural or functional change that causes disvalue to the whole organism. It is important to be cautious in our assertions about chronic pain as a brain disease because these may have negative effects on 1) the therapeutic dialogue between clinicians and patients; 2) the social dialogue about reimbursement for pain treatments and disability due to pain; and 3) the chronic pain research agenda. Considered scientifically, we may be looking for the cause of chronic pain through neuroimaging, but considered clinically, we are in fact often looking to validate pain complaints. We should not yield to the temptation to validate pain with the magnetic resonance imaging scanner (structural or functional). We should not see pain as caused by the brain alone. Pain is not felt by the brain, but by the person. Neuroimaging investigators have argued that brain imaging may demonstrate that chronic pain is a brain disease. We argue that "disease" is a clinical concept and that conceiving of chronic pain as a brain disease can have negative consequences for research and clinical care of patients with chronic pain. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  12. Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

    Science.gov (United States)

    2015-07-01

    chronic neuronal cell loss, glial activation, and chronic traumatic encephalopathy (CTE) measure of β-amyloid and hyper-phosphorylated tau protein...Award Number: W81XWH-14-1-0195 TITLE: Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury...30 Jun 2015 4. TITLE AND SUBTITLE Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After TBI 5a. CONTRACT NUMBER W81XWH-14-1

  13. Metric to quantify white matter damage on brain magnetic resonance images

    Energy Technology Data Exchange (ETDEWEB)

    Valdes Hernandez, Maria del C.; Munoz Maniega, Susana; Anblagan, Devasuda; Bastin, Mark E.; Wardlaw, Joanna M. [University of Edinburgh, Department of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh (United Kingdom); University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh (United Kingdom); UK Dementia Research Institute, Edinburgh Dementia Research Centre, London (United Kingdom); Chappell, Francesca M.; Morris, Zoe; Sakka, Eleni [University of Edinburgh, Department of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh (United Kingdom); UK Dementia Research Institute, Edinburgh Dementia Research Centre, London (United Kingdom); Dickie, David Alexander; Royle, Natalie A. [University of Edinburgh, Department of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh (United Kingdom); University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh (United Kingdom); Armitage, Paul A. [University of Sheffield, Department of Cardiovascular Sciences, Sheffield (United Kingdom); Deary, Ian J. [University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh (United Kingdom); University of Edinburgh, Department of Psychology, Edinburgh (United Kingdom)

    2017-10-15

    Quantitative assessment of white matter hyperintensities (WMH) on structural Magnetic Resonance Imaging (MRI) is challenging. It is important to harmonise results from different software tools considering not only the volume but also the signal intensity. Here we propose and evaluate a metric of white matter (WM) damage that addresses this need. We obtained WMH and normal-appearing white matter (NAWM) volumes from brain structural MRI from community dwelling older individuals and stroke patients enrolled in three different studies, using two automatic methods followed by manual editing by two to four observers blind to each other. We calculated the average intensity values on brain structural fluid-attenuation inversion recovery (FLAIR) MRI for the NAWM and WMH. The white matter damage metric is calculated as the proportion of WMH in brain tissue weighted by the relative image contrast of the WMH-to-NAWM. The new metric was evaluated using tissue microstructure parameters and visual ratings of small vessel disease burden and WMH: Fazekas score for WMH burden and Prins scale for WMH change. The correlation between the WM damage metric and the visual rating scores (Spearman ρ > =0.74, p < 0.0001) was slightly stronger than between the latter and WMH volumes (Spearman ρ > =0.72, p < 0.0001). The repeatability of the WM damage metric was better than WM volume (average median difference between measurements 3.26% (IQR 2.76%) and 5.88% (IQR 5.32%) respectively). The follow-up WM damage was highly related to total Prins score even when adjusted for baseline WM damage (ANCOVA, p < 0.0001), which was not always the case for WMH volume, as total Prins was highly associated with the change in the intense WMH volume (p = 0.0079, increase of 4.42 ml per unit change in total Prins, 95%CI [1.17 7.67]), but not with the change in less-intense, subtle WMH, which determined the volumetric change. The new metric is practical and simple to calculate. It is robust to variations in

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

    Science.gov (United States)

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

    2010-07-01

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

  15. Brain DNA damage and behavioral changes after repeated intermittent acute ethanol withdrawal by young rats.

    Science.gov (United States)

    Costa, Priscila A; Poli, Jefferson H Z; Sperotto, Nathalia D M; Moura, Dinara J; Saffi, Jenifer; Nin, Maurício S; Barros, Helena M T

    2015-10-01

    Alcohol addiction causes severe problems, and its deprivation may potentiate symptoms such as anxiety. Furthermore, ethanol is a neurotoxic agent that induces degeneration and the consequences underlying alcohol-mediated brain damage remain unclear. This study assessed the behavioral changes during acute ethanol withdrawal periods and determined the levels of DNA damage and reactive oxygen species (ROS) in multiple brain areas. Male Wistar rats were subjected to an oral ethanol self-administration procedure with a forced diet where they were offered 8% (v/v) ethanol solution for 21 days followed by five repeated 24-h cycles alternating between ethanol withdrawal and re-exposure. Control animals received an isocaloric control diet without ethanol. Behavioral changes were analyzed on ethanol withdrawal days in the open-field (OF) and elevated plus-maze (EPM) tests within the first 6 h of ethanol deprivation. The pre-frontal cortex, hypothalamus, striatum, hippocampus, and cerebellum were dissected for alkaline and neutral comet assays and for dichlorofluorescein ROS testing. The repeated intermittent ethanol access enhanced solution intake and alcohol-seeking behavior. Decreased exploratory activity was observed in the OF test, and the animals stretched less in the EPM test. DNA single-strand breaks and ROS production were significantly higher in all structures evaluated in the ethanol-treated rats compared with controls. The animal model of repeated intermittent ethanol access induced behavioral changes in rats, and this ethanol exposure model induced an increase in DNA single-strand breaks and ROS production in all brain areas. Our results suggest that these brain damages may influence future behaviors.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-07-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Brain-Derived Neurotrophic Factor in Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Jôice Dias Corrêa

    2014-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is a member of the neurotrophic factor family. Outside the nervous system, BDNF has been shown to be expressed in various nonneural tissues, such as periodontal ligament, dental pulp, and odontoblasts. Although a role for BDNF in periodontal regeneration has been suggested, a function for BDNF in periodontal disease has not yet been studied. The aim of this study was to analyze the BDNF levels in periodontal tissues of patients with chronic periodontitis (CP and periodontally healthy controls (HC. All subjects were genotyped for the rs4923463 and rs6265 BDNF polymorphisms. Periodontal tissues were collected for ELISA, myeloperoxidase (MPO, and microscopic analysis from 28 CP patients and 29 HC subjects. BDNF levels were increased in CP patients compared to HC subjects. A negative correlation was observed when analyzing concentration of BDNF and IL-10 in inflamed periodontium. No differences in frequencies of BDNF genotypes between CP and HC subjects were observed. However, BDNF genotype GG was associated with increased levels of BDNF, TNF-α, and CXCL10 in CP patients. In conclusion, BDNF seems to be associated with periodontal disease process, but the specific role of BDNF still needs to be clarified.

  20. Chronic Traumatic Encephalopathy: The cellular sequela to repetitive brain injury.

    Science.gov (United States)

    Vile, Alexander R; Atkinson, Leigh

    2017-07-01

    This review aims to integrate current literature on the pathogenic mechanisms of Chronic Traumatic Encephalopathy (CTE) to create a multifactorial understanding of the disease. CTE is a progressive neurodegenerative disease, classed as a tauopathy, although it appears the pathogenic mechanisms are more complex than this. It affects those with a history of repetitive mild traumatic brain injury. Currently, there are no treatments for CTE and the disease can only be affirmatively diagnosed in post mortem. Understanding the pathogenesis of the disease will provide an avenue to explore possible treatment and diagnostic modalities. The pathological hallmarks of CTE have been well characterised and have been linked to the pathophysiologic mechanisms in this review. Human studies are limited due to ethical implications of exposing subjects to head trauma. Phosphorylation of tau, microglial activation, TAR DNA-binding protein 43 and diffuse axonal injury have all been implicated in the pathogenesis of CTE. The neuronal loss and axonal dysfunction mediated by these pathognomonic mechanisms lead to the broad psycho-cognitive symptoms seen in CTE. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Inhibition of myeloperoxidase oxidant production by N-acetyl lysyltyrosylcysteine amide reduces brain damage in a murine model of stroke

    OpenAIRE

    Yu, Guoliang; Liang, Ye; Huang, Ziming; Jones, Deron W.; Kirkwood A Pritchard; Zhang, Hao

    2016-01-01

    Background Oxidative stress plays an important and causal role in the mechanisms by which ischemia/reperfusion (I/R) injury increases brain damage after stroke. Accordingly, reducing oxidative stress has been proposed as a therapeutic strategy for limiting damage in the brain after stroke. Myeloperoxidase (MPO) is a highly potent oxidative enzyme that is capable of inducing both oxidative and nitrosative stress in vivo. Methods To determine if and the extent to which MPO-generated oxidants co...

  2. Chronic acrylamide exposure in male mice induces DNA damage to spermatozoa; Potential for amelioration by resveratrol.

    Science.gov (United States)

    Katen, Aimee L; Stanger, Simone J; Anderson, Amanda L; Nixon, Brett; Roman, Shaun D

    2016-08-01

    Humans are chronically exposed to acrylamide since carbohydrate rich foods contain the toxicant as a result of cooking at high temperatures. While acrylamide is unreactive with DNA, it is readily oxidised to glycidamide, which adducts with DNA. This metabolism occurs via the enzyme, cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1). Acrylamide was administered to male CD1 mice for three or six months at a dose of 0.18mg/kg bodyweight/day. DNA damage was detected in germ cells and mature spermatozoa of exposed mice without compromising their overall fertility. The use of resveratrol, an antioxidant and known CYP2E1 inhibitor, was found to ameliorate the DNA damage in both germ cells and spermatozoa. However, extended resveratrol treatment (six months, 10.0mg/kg bw/week) resulted in premature activation of these cells. Thus the DNA damage found in spermatozoa after chronic acrylamide administration can be alleviated but an alternative CYP2E1 inhibitor may be required. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  3. [Epidemiological and clinical profile of skin damages in black African patients on chronic hemodialysis].

    Science.gov (United States)

    Kouotou, Emmanuel Armand; Folefack, François Kaze; Tatsa, Joël Tameyi; Sieleunou, Isidore; Njingang, Jobert Richie Nansseu; Ashuntantang, Gloria; Bissek, Anne-Cécile Zoung-Kanyi

    2016-01-01

    Dermatologic manifestations are common among patients on chronic hemodialysis and may represent systemic involvement. Our study aims to determine the epidemiological and clinical profile of skin damages in black patients living in Yaounde, Cameroon. We conducted a cross sectional study including all patients receiving chronic haemodialysis treatment for at least 3 months in two hemodialysis centers in Yaounde from February to May 2014. Patients underwent an interview and a dermatological examination. Chi-squared tests and Student's t-test (or equivalents) were used for statistical analysis, with significance level at p patients (78 (69.9%) men) with an average age of 48.6 ± 13 years and a mean duration of dialysis of 46,3 ± 37 months were included in the study. Skin lesions were present in 94 (83.9%) patients. Xerosis (63.3%), pruritus (37.5%), melanoderma (34.8%), acne (12.5%) and half and half nails (10.7%) were the most common dermatologic manifestations. Xerosis was associated with anuria (p = 0.0001) and advanced age (p = 0.032); melanoderma was associated with anuria (p = 0.042) and time spent on dialysis (p = 0.027) while half and half nails were associated with young age (p = 0.018) and biweekly dialysis (p = 0.01 ). Skin damages are frequent and dominated by xerosis, pruritus and melanoderma in patients on chronic hemodialysis living in Yaounde. Biweekly dialysis, advanced age, anuria and time spent on dialysis were associated factors.

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

    Directory of Open Access Journals (Sweden)

    Denis N Silachev

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

  5. Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage.

    Science.gov (United States)

    Hadanny, A; Golan, H; Fishlev, G; Bechor, Y; Volkov, O; Suzin, G; Ben-Jacob, E; Efrati, S

    2015-01-01

    Cognitive impairment may occur in 42-50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury.The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest. Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging. The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5-7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging. Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event.

  6. Mouse model of diffuse brain damage following anoxia, evaluated by a new assay of generalized arousal.

    Science.gov (United States)

    Arrieta-Cruz, Isabel; Pfaff, Donald W; Shelley, Deborah N

    2007-06-01

    Diffuse brain damage following anoxia due to cardiac failure, drowning, carbon monoxide exposure or other accidents constitutes a major medical problem. We have created a novel mouse model using the breathing of pure nitrogen, followed by a recently developed assay that reflects an operational definition of generalized arousal. The operational definition is precise, complete, and leads to quantitative, physical measures in a genetically tractable animal. Exposure to pure nitrogen for controlled periods had a surprising bifurcate effect: about half the mice survived with neurological measures that were virtually normal while the other half died. The new assay detected behavioral deficits unrevealed by neurological screening. Two important features of the results were that (i) deficits were not equal across the circadian cycle, and (ii) deficits were not equal across all the measures within the operational definition of arousal. Specific voluntary motor measurements were decreased in a manner that depended on the phase of the circadian cycle. Sensory responses were also decreased, with an emphasis on vertical movement responses; but, interestingly, fear learning was not damaged. This study establishes the first useful approach to diffuse brain damage in a genetically tractable animal. The model and its outcome measurements will be useful during future attempts at amelioration of acquired neurological disabilities following hypoxic-ischemic injuries.

  7. Neuroplasticity-dependent and -independent mechanisms of chronic deep brain stimulation in stressed rats

    National Research Council Canada - National Science Library

    Bambico, F R; Bregman, T; Diwan, M; Li, J; Darvish-Ghane, S; Li, Z; Laver, B; Amorim, B O; Covolan, L; Nobrega, J N; Hamani, C

    2015-01-01

    ...) and elevated plus maze were countered by chronic vmPFC DBS. In addition, stressed rats receiving stimulation had significant increases in hippocampal neurogenesis, PFC and hippocampal brain-derived neurotrophic factor levels...

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

    NARCIS (Netherlands)

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

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

  9. Central cortico-subcortical involvement: a distinct pattern of brain damage caused by perinatal and postnatal asphyxia in term infants

    NARCIS (Netherlands)

    Rademakers, R. P.; van der Knaap, M. S.; Verbeeten, B.; Barth, P. G.; Valk, J.

    1995-01-01

    The MR findings in a characteristic pattern of hypoxic-ischemic brain damage in term infants are described. The MR images of seven patients with cerebral palsy and a specific pattern of central cortico-subcortical cerebral damage were studied retrospectively and correlated with clinical findings.

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

    Science.gov (United States)

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

    2016-04-15

    Preconditioning exercise can exert neuroprotective effects after stroke. However, the mechanism underlying these neuroprotective effects by preconditioning exercise remains unclear. We investigated the neuroprotective effects of preconditioning exercise on brain damage and the expression levels of the midkine (MK) and brain-derived neurotrophic factor (BDNF) after brain ischemia. Animals were assigned to one of 4 groups: exercise and ischemia (Ex), no exercise and ischemia (No-Ex), exercise and no ischemia (Ex-only), and no exercise and intact (Control). Rats ran on a treadmill for 30 min once a day at a speed of 25 m/min for 5 days a week for 3 weeks. After the exercise program, stroke was induced by a 60 min left middle cerebral artery occlusion using an intraluminal filament. The infarct volume, motor function, neurological deficits, and the cellular expressions levels of MK, BDNF, GFAP, PECAM-1, caspase 3, and nitrotyrosine (NT) were evaluated 48 h after the induction of ischemia. The infarct volume, neurological deficits and motor function in the Ex group were significantly improved compared to that of the No-Ex group. The expression levels of MK, BDNF, GFAP, and PECAM-1 were enhanced in the Ex group compared to the expression levels in the No-Ex group after brain ischemia, while the expression levels of activated caspase 3 and NT were reduced in the area surrounding the necrotic lesion. Our findings suggest that preconditioning exercise reduced the infract volume and ameliorated motor function, enhanced expression levels of MK and BDNF, increased astrocyte proliferation, increased angiogenesis, and reduced neuronal apoptosis and oxidative stress. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Reduction in brain serotonin synthesis rate following chronic methamphetamine administration in rats.

    Science.gov (United States)

    Trulson, M E; Trulson, V M

    1982-09-10

    Chronic administration of methamphetamine (20 mg/kg i.p., every 12 h for 6 days) produced significant decreased in brain 5-hydroxytryptophan accumulation following decarboxylase inhibition and 5-hydroxyindoleacetic acid accumulation following probenecid treatment in rats. Administration of fluoxetine prior to each methamphetamine injection prevented these neurochemical changes. Acute methamphetamine treatment produced no changes in these neurochemical measures. These data demonstrate that chronic, but not acute, methamphetamine treatment reduces brain serotonin synthesis rate.

  12. Telephone Delivered Cognitive Behavioral Therapy for Chronic Pain Following Traumatic Brain Injury

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-12-2-0109 TITLE: Telephone -Delivered Cognitive Behavioral Therapy for Chronic Pain Following Traumatic Brain Injury...2015 - 29 Sep 2016 4. TITLE AND SUBTITLE Telephone -Delivered Cognitive Behavioral Therapy for Chronic Pain 5a. CONTRACT NUMBER Following Traumatic...evaluate the efficacy of a telephone -delivered cognitive behavioral treatment (T-CBT) in Veterans with a history of traumatic brain injury (TBI) for the

  13. Elucidation of mechanism of blood-brain barrier damage for prevention and treatment of vascular dementia.

    Science.gov (United States)

    Ueno, Masaki

    2017-03-28

    . These clearance pathways may play a role in maintenance of the barrier in the entire brain. Obstruction of the passage of fluids through the perivascular drainage and glymphatic pathways as well as damage of the BBB and BCSFB may induce several kinds of brain disorders, such as vascular dementia. In this review, we focus on the relationship between damage of the barriers and the pathogenesis of vascular dementia and introduce recent findings including our experimental data using animal models.

  14. Multiple cystic and focal encephalomalacia in infancy and childhood with brain stem damage.

    Science.gov (United States)

    Smith, J F; Rodeck, C

    1975-07-01

    Two cases are described in which damage to the brain stem was associated with extensive necrosis of the cerebral hemisphere. In the first case--a monochorionic twin--there was clear evidence that injury of an ischaemic or hypoxic type had occurred during fetal life and some evidence that an inadequate share of the placental circulation was an important aetiological factor. In the second case death occurred 4 yr after an asphyxial episode at birth. The lesions in the hemispheres and brain stem were extensive, although less than in the first example. The lesions are discussed in the context of our knowledge of the anatomy and physiology of the developing nervous system. Although they cannot as yet be fitted into the concepts of "critical periods" and "vulnerable periods" of development, this is perhaps because observations on human cases are scanty in comparison with the extensive animal studies which have been reported. The lesions are contrasted and compared with those seen in animals.

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

    DEFF Research Database (Denmark)

    Krummheuer, Antonia Lina; Rehm, Matthias; Lund, Maja K. L.

    2018-01-01

    Special needs education is focusing on a complex interplay of cognitive (knowledge), physical (motor rehabilitation), and social (interaction) learning. There is a strong discrepancy between the institutional spaces in which learning takes place and the need for scaffolding these levels of learning....... In this paper we present a first part of an ongoing collaboration with a special needs education facility for adolescents with congenital and acquired brain damage, that is interested in exploring the transformation of the institutional space into a smart learning ecosystem. We exemplify our research approach...

  16. Recovery of running performance following muscle-damaging exercise: relationship to brain IL-1beta.

    Science.gov (United States)

    Carmichael, Martin D; Davis, J Mark; Murphy, E Angela; Brown, Adrienne S; Carson, James A; Mayer, Eugene; Ghaffar, Abdul

    2005-09-01

    Recovery following muscle-damaging downhill running is associated with increased muscle inflammatory cytokines. Various inflammatory challenges can also increase cytokines in the brain, which have been linked to sickness behaviors, including fatigue, but little is known about the brain cytokine response to stressful exercise. We used a downhill running model to determine the relationship between brain IL-1beta and recovery of running performance. Male C57BL/6 mice were assigned to: downhill (DH), uphill (UH), or non-running control (Con) groups and run on a treadmill at 22 m/min and -14% or 14% grade, for 150 min. Following the run, a subset of DH and UH was placed into activity wheel cages where voluntary running activity was measured for 7 days. A second subset was run to fatigue on a motorized treadmill at 36 m/min, 8% grade at 24, 48, and 96 h post-up/downhill run. A third subset of DH, UH, and Con mice had brains dissected and assayed for IL-1beta at 24 and 48 h. DH resulted in delayed recovery of both voluntary wheel-running and treadmill running to fatigue as compared to UH (p coordination, motivation, perception of effort, and pain.

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

    Science.gov (United States)

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

    2015-01-01

    Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

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

    Science.gov (United States)

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

    2014-02-05

    Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA). The current study was designed to investigate the protective effects of candesartan (0.15 mg/kg, orally) and glycyrrhizin (30 mg/kg, orally) experimentally-induced ischemic brain damage in C57BL/6 mice (middle cerebral artery occlusion, MCAO) in comparison to the effects of a standard neuroprotective drug (cerebrolysin, 7.5 mg/kg, IP). All drugs were administered 30 min before and 24h after MCAO. Both candesartan and glycyrrhizin ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in behaviour tests, reduction in brain infarction, neuronal degeneration, and leukocyte infiltration. In addition, MCAO induced a significant upregulation in the different elements of the TLR pathway including TLR-2 and TLR-4, Myd88, TRIF and IRF-3 and the downstream effectors TNF-α, IL-1β, IL-6 and NF-kB. All these changes were significantly ameliorated by treatment with candesartan and glycyrrhizin. The results of the current study represent a new indication for both candesartan and glycyrrhizin in the management of ischemic stroke with effects comparable to those of the standard neuroprotective drug cerebrolysin. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Maternal obesity increases inflammation and exacerbates damage following neonatal hypoxic-ischaemic brain injury in rats.

    Science.gov (United States)

    Teo, Jonathan D; Morris, Margaret J; Jones, Nicole M

    2017-07-01

    In humans, maternal obesity is associated with an increase in the incidence of birth related difficulties. However, the impact of maternal obesity on the severity of brain injury in offspring is not known. Recent studies have found evidence of increased glial response and inflammatory mediators in the brains as a result of obesity in humans and rodents. We hypothesised that hypoxic-ischaemic (HI) brain injury is greater in neonatal offspring from obese rat mothers compared to lean controls. Female Sprague Dawley rats were randomly allocated to high fat (HFD, n=8) or chow (n=4) diet and mated with lean male rats. On postnatal day 7 (P7), male and female pups were randomly assigned to HI injury or control (C) groups. HI injury was induced by occlusion of the right carotid artery followed by 3h exposure to 8% oxygen, at 37°C. Control pups were removed from the mother for the same duration under ambient conditions. Righting behaviour was measured on day 1 and 7 following HI. The extent of brain injury was quantified in brain sections from P14 pups using cresyl violet staining and the difference in volume between brain hemispheres was measured. Before mating, HFD mothers were 11% heavier than Chow mothers (pmaternal weight. Similar observations were made with neuronal staining showing a greater loss of neurons in the brain of offspring from HFD-mothers following HI compared to Chow. Astrocytes appeared to more hypertrophic and a greater number of microglia were present in the injured hemisphere in offspring from mothers on HFD. HI caused an increase in the proportion of amoeboid microglia and exposure to maternal HFD exacerbated this response. In the contralateral hemisphere, offspring exposed to maternal HFD displayed a reduced proportion of ramified microglia. Our data clearly demonstrate that maternal obesity can exacerbate the severity of brain damage caused by HI in neonatal offspring. Given that previous studies have shown enhanced inflammatory responses in

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

    Directory of Open Access Journals (Sweden)

    C. M. J. Braun

    2002-01-01

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

  1. Rehabilitation of executive functioning in patients with frontal lobe brain damage with Goal Management Training

    Directory of Open Access Journals (Sweden)

    Brian eLevine

    2011-02-01

    Full Text Available Executive functioning deficits due to brain disease affecting frontal lobe functions cause significant real-life disability, yet solid evidence in support of executive functioning interventions is lacking. Goal Management Training (GMT, an executive functioning intervention that draws upon theories concerning goal processing and sustained attention, has received empirical support in studies of patients with traumatic brain injury, normal aging, and case studies. GMT promotes a mindful approach to complex real-life tasks that pose problems for patients with executive functioning deficits, with a main goal of periodically stopping ongoing behavior to monitor and adjust goals. In this controlled trial, an expanded version of GMT was compared to an alternative intervention, Brain Health Workshop (BHW that was matched to GMT on non-specific characteristics that can affect intervention outcome. Participants included 19 individuals in the chronic phase of recovery from brain disease (predominantly stroke affecting frontal lobe function. Outcome data indicated specific effects of GMT on the Sustained Attention to Response Task (SART as well as the Tower Test, a visuospatial problem solving measure that reflected far transfer of training effects. There were no significant effects on self-report questionnaires, likely owing to the complexity of these measures in this heterogeneous patient sample. Overall, these data support the efficacy of GMT in the rehabilitation of executive functioning deficits.

  2. Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

    Science.gov (United States)

    2017-07-01

    Award Number: W81XWH-14-1-0195 TITLE: Novel Mechanism for Reducing Acute and Chronic Neurodegeneration after Traumatic Brain Injury...Purpose: The purpose of this project is to develop a radically different strategy to reduce brain glutamate excitotoxicity and treat TBI. We will...objective of reducing blood levels of glutamate. This will produce a brain -to-blood gradient of glutamate which will enhance the removal of excess

  3. Hippotherapy in Adult Patients with Chronic Brain Disorders: A Pilot Study

    OpenAIRE

    Sunwoo, Hyuk; Chang, Won Hyuk; Kwon, Jeong-Yi; Kim, Tae-Won; Lee, Ji-Young; Kim, Yun-Hee

    2012-01-01

    Objective To investigate the effects of hippotherapy for adult patients with brain disorders. Method Eight chronic brain disorder patients (7 males, mean age 42.4?16.6 years) were recruited. The mean duration from injury was 7.9?7.7 years. The diagnoses were stroke (n=5), traumatic brain disorder (n=2), and cerebral palsy (n=1). Hippotherapy sessions were conducted twice a week for eight consecutive weeks in an indoor riding arena. Each hippotherapy session lasted 30 minutes. All participants...

  4. Patterns of Post-Stroke Brain Damage that Predict Speech Production Errors in Apraxia of Speech and Aphasia Dissociate

    Science.gov (United States)

    Basilakos, Alexandra; Rorden, Chris; Bonilha, Leonardo; Moser, Dana; Fridriksson, Julius

    2015-01-01

    Background and Purpose Acquired apraxia of speech (AOS) is a motor speech disorder caused by brain damage. AOS often co-occurs with aphasia, a language disorder in which patients may also demonstrate speech production errors. The overlap of speech production deficits in both disorders has raised questions regarding if AOS emerges from a unique pattern of brain damage or as a sub-element of the aphasic syndrome. The purpose of this study was to determine whether speech production errors in AOS and aphasia are associated with distinctive patterns of brain injury. Methods Forty-three patients with history of a single left-hemisphere stroke underwent comprehensive speech and language testing. The Apraxia of Speech Rating Scale was used to rate speech errors specific to AOS versus speech errors that can also be associated with AOS and/or aphasia. Localized brain damage was identified using structural MRI, and voxel-based lesion-impairment mapping was used to evaluate the relationship between speech errors specific to AOS, those that can occur in AOS and/or aphasia, and brain damage. Results The pattern of brain damage associated with AOS was most strongly associated with damage to cortical motor regions, with additional involvement of somatosensory areas. Speech production deficits that could be attributed to AOS and/or aphasia were associated with damage to the temporal lobe and the inferior pre-central frontal regions. Conclusion AOS likely occurs in conjunction with aphasia due to the proximity of the brain areas supporting speech and language, but the neurobiological substrate for each disorder differs. PMID:25908457

  5. Neuropsychiatric diagnosis and management of chronic sequelae of war-related mild to moderate traumatic brain injury.

    Science.gov (United States)

    Halbauer, Joshua D; Ashford, J Wesson; Zeitzer, Jamie M; Adamson, Maheen M; Lew, Henry L; Yesavage, Jerome A

    2009-01-01

    Soldiers with a traumatic brain injury (TBI) present with an array of neuropsychiatric symptoms that can be grouped into nosological clusters: (1) cognitive dysfunctions: difficulties in memory, attention, language, visuospatial cognition, sensory-motor integration, affect recognition, and/or executive function typically associated with neocortical damage; (2) neurobehavioral disorders: mood, affect, anxiety, posttraumatic stress, and psychosis, as well as agitation, sleep problems, and libido loss, that may have been caused by damage to the cortex, limbic system, and/or brain stem monoaminergic projection systems; (3) somatosensory disruptions: impaired smell, vision, hearing, equilibrium, taste, and somatosensory perception frequently caused by trauma to the sensory organs or their projections through the brain stem to central processing systems; (4) somatic symptoms: headache and chronic pain; and (5) substance dependence. TBI-related cognitive impairment is common in veterans who have served in recent conflicts in the Middle East and is often related to blasts from improvised explosive devices. Although neurobehavioral disorders such as depression and posttraumatic stress disorder commonly occur after combat, the presentation of such disorders in those with head injury may pass undetected with use of current diagnostic criteria and neuropsychological instruments. With a multidimensional approach (such as the biopsychosocial model) applied to each symptom cluster, psychological, occupational, and social dysfunction can be delineated and managed.

  6. QRS slopes for assessment of myocardial damage in chronic chagasic patients

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    Pueyo, E [Instituto de Investigacion en Ingenieria de Aragon (13A), and CIBER-BBN, Universidad de Zaragoza (Spain); Laciar, E [Gabinete de TecnologIa Medica, Universidad Nacional de San Juan (Argentina); Anzuola, E [Instituto de Investigacion en Ingenieria de Aragon (13A), and CIBER-BBN, Universidad de Zaragoza (Spain); Laguna, P [Instituto de Investigacion en Ingenieria de Aragon (13A), and CIBER-BBN, Universidad de Zaragoza (Spain); Jane, R [Department ESAII, CREB, Universitat Politecnica de Catalunya, Barcelona (Spain)

    2007-11-15

    In this study the slopes of the QRS complex are evaluated for determination of the degree of myocardial damage in chronic chagasic patients. Previous studies have demonstrated the ability of the slope indices to reflect alterations in the conduction velocity of the cardiac impulse. Results obtained in the present study show that chronic chagasic patients have significantly flatter QRS slopes as compared to healthy subjects. Not only that but the extent of slope lessening turns out to be proportional to the degree of myocardial damage caused by the disease. Additionally, when incorporating the slope indices into a classification analysis together with other indices indicative of the presence of ventricular late potentials obtained from high resolution electrocardiography, results show that the percentages of correct classification increase up to 62.5%, which means eight points above the percentages obtained prior to incorporation of the slope indices. It can be concluded that QRS slopes have great potential for assessing the degree of severity associated with Chagas' disease.

  7. Internal distribution of uranium and associated genotoxic damages in the chronically exposed bivalve Corbicula fluminea.

    Science.gov (United States)

    Simon, Olivier; Floriani, Magali; Cavalie, Isabelle; Camilleri, Virginie; Adam, Christelle; Gilbin, Rodolphe; Garnier-Laplace, Jacqueline

    2011-08-01

    Uranium (U) internal distribution and involved effects in the bivalve Corbicula fluminea have been studied after direct chronic exposure (90 d, 10 μg.L-1). U distribution was assessed at the subcellular level (Metal Rich Granules -MRG-, pellets and cytosol fractions) in two main organs of the bivalve (gills and visceral mass). Micro-localisation was investigated by TEM-EDX analysis in the gills epithelium. DNA damage in gill and hemolymph samples was measured by the Comet assay. The 90-d exposure period led to a significant increase of U concentration in gills over time (× 5) and a large U quantity in subcellular granules in gills. Finally, a significant increase (× 2) in DNA damage was noted in exposed gills and haemocytes. This study shows that the accumulation levels and consequently the potential toxicity cannot be successfully predicted only on the basis of concentration in water or in tissues and subcellular fractions after chronic exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

    Directory of Open Access Journals (Sweden)

    Godwin Sokpor

    2012-05-01

    Full Text Available Background: Chronic ethanol ingestion causes hepatic damage imputable to an increasedoxidative stress engendered by alcoholic toxicity. Polyphenols in cocoa have antioxidant properties, and natural cocoa powder (NCP contains the highest levels of total antioxidant capacity when compared to all other kinds of edible cocoa products. This study tested the hypothesis that dietary supplementation with NCP mitigates hepatic injury resulting from chronic ethanol consumption. Three groups of eight randomized Sprague-Dawley rats were fed standardrat food and treated daily for 12 weeks as follows: (i the Ethanol-water group was given unrestricted access to 40% (v/v ethanol for 12 hours (at night followed by water for the remaining 12 hours (daytime, (ii the Ethanol-cocoa group had similarly unrestricted access to 40% ethanol for 12 hours followed by 2% (w/v NCP for 12 hours, and (iii the control group was not given alcohol and had unrestricted access to only water which was synchronously replenished every 12 hours as it was for the ethanol treated animals.Results: Qualitative structural liver damage evidenced by hepatocyte cytoplasmic fatty accumulation, nuclear alterations, and disruption of general liver micro-architecture, was severe in the ethanol-water group when compared with the ethanol-cocoa group of rats. Design-based stereologic assessment yielded a significantly greater volume (Tukey’s HSD, p = 0.0005 ofundamaged hepatocytes (9.61 ml, SD 2.18 ml in the ethanol-cocoa group as opposed to theethanol-water group of rats (2.34 ml, SD 1.21 ml. Control rats had 10.34 ml (SD 1.47 ml of undamaged hepatocytes, and that was not significantly greater (Tukey’s HSD, p=0.659 than the value for the ethanol-cocoa group of rats. Relative to controls, therefore, histomorphometryFunctional Foods in Health and Disease 2012, 2(5:166- 187 showed 93% hepatocyte preservation from alcoholic injury in rats that voluntarily imbibed NCP suspension compared with 23% in

  9. Exploring social cognition in patients with apathy following acquired brain damage

    Science.gov (United States)

    2014-01-01

    Background Research on cognition in apathy has largely focused on executive functions. To the best of our knowledge, no studies have investigated the relationship between apathy symptoms and processes involved in social cognition. Apathy symptoms include attenuated emotional behaviour, low social engagement and social withdrawal, all of which may be linked to underlying socio-cognitive deficits. Methods We compared patients with brain damage who also had apathy symptoms against similar patients with brain damage but without apathy symptoms. Both patient groups were also compared against normal controls on key socio-cognitive measures involving moral reasoning, social awareness related to making judgements between normative and non-normative behaviour, Theory of Mind processing, and the perception of facial expressions of emotion. We also controlled for the likely effects of executive deficits and depressive symptoms on these comparisons. Results Our results indicated that patients with apathy were distinctively impaired in making moral reasoning decisions and in judging the social appropriateness of behaviour. Deficits in Theory of Mind and perception of facial expressions of emotion did not distinguish patients with apathy from those without apathy. Conclusion Our findings point to a possible socio-cognitive profile for apathy symptoms and provide initial insights into how socio-cognitive deficits in patients with apathy may affect social functioning. PMID:24450311

  10. Defective pantomime of object use in left brain damage: apraxia or asymbolia?

    Science.gov (United States)

    Goldenberg, Georg; Hartmann, Karoline; Schlott, Isa

    2003-01-01

    Disturbance of pantomime of object use in patients with left brain damage (LBD) and aphasia has been firmly established but its nature remains controversial. It may be due to an inability to perform movements from memory without external support by objects (apraxia) or to an inability to produce signs referring to absent objects and actions (asymbolia). The need to perform movements without external support is shared with imitation of gestures, and the demand to designate absent objects with drawing from memory. Both of these tasks have been found to be impaired in LBD. We examined pantomime of object use, drawing objects from memory, imitation of meaningless gestures, and aphasia in 40 patients with LBD and aphasia and compared them to healthy controls and to patients with right brain damage (RBD). Whereas drawing showed comparable sensitivity to LBD and RBD, pantomime was distinctly more disturbed in LBD than in RBD patients. Pantomime was worse than drawing in LBD but better than drawing in RBD. In the LBD group scores on pantomime showed significant correlations of very similar strength to drawing, imitation, and all language tests. Multidimensional scaling of the correlational structure placed pantomime in an intermediate position between verbal and non-verbal tests. We conclude that neither apraxia nor asymbolia can satisfactorily explain our results. It seems as if pantomime of object use taps a central aspect of left hemisphere function which is compromised by any LBD. We propose that this may be the ability to select and combine distinctive features of objects and actions.

  11. Ultrasound-clinical correlations in the assessment of the newborn at risk for brain damage.

    Science.gov (United States)

    Ometto, A; Fazzi, E

    1986-04-01

    In the Pavia Neonatal Intensive Care Unit all newborns at risk for brain damage have, since 1983, undergone transfontanellar ultrasound scanning regularly for the early diagnosis of hemorrhage and/or anoxia-ischemia. They have also been assessed clinically by a child neuropsychiatrist during the hospital stay and every two months at outpatients' for the first year of life as a check on the prognostic value of ultrasound scanning. The results relating to a sample of 56 at risk newborns, with normal and abnormal ultrasound scans, who have now reached 12 months corrected age are reported. A normal ultrasound scan presupposes normal neuropsychic development in 87% of cases, as happens in the event of uncomplicated hemorrhage. Major sequelae occur in as many as 83% of cases of complicated hemorrhage. The diagnosis of severe anoxia-ischemia likewise argues for a pathological neuropsychic development. Our results convince us that transfontanellar ultrasound scanning is an indispensable tool not only for the early diagnosis of brain damage but also as a guide to prognosis in the newborn at risk.

  12. [Neuroinflammation in the Brain of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].

    Science.gov (United States)

    Nakatomi, Yasuhito; Kuratsune, Hirohiko; Watanabe, Yasuyoshi

    2018-01-01

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by chronic, profound, disabling, and unexplained fatigue; cognitive impairment; and chronic widespread pain. By using positron emission tomography, our study demonstrated neuroinflammation in the brain of patients with ME/CFS. Neuroinflammation was found to be widespread in the brain areas of the patients with ME/CFS and was associated with the severity of their neuropsychological symptoms. The ongoing research would lead to the establishment of objective diagnostic criteria and development of an appropriate therapy.

  13. Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

    Directory of Open Access Journals (Sweden)

    Najmeh Kabiri

    2016-09-01

    Full Text Available The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99. Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly higher than the Sham group, although right hemispheres in all of the treated groups illustrated higher brain water content than the left ones. Brain anti-oxidant capacity elevated in the ischemic rats treated with Kombucha and in the Sham group. Brain and plasma malondialdehyde concentrations significantly decreased in both of the ischemic groups injected with Kombucha. The findings suggest that Kombucha tea could be useful for the prevention of cerebral damage.

  14. [Effect of copper sulphate on the lung damage induced by chronic intermittent exposure to ozone].

    Science.gov (United States)

    Oyarzún G, Manuel J; Sánchez R, Susan A; Dussaubat D, Nelson; Miller A, María E; González B, Sergio

    2017-01-01

    Ozone exposure could increase lung damage induced by airborne particulate matter. Particulate matter lung toxicity has been attributed to its metallic content. To evaluate the acute effect of intratracheal administration of copper sulfate (CuSO4) on rat lungs previously damaged by a chronic intermittent ozone exposure. Two-months-old male Sprague-Dawley rats were exposed to 0.5 ppm ozone four h per day, five days a week, during two months. CuSO4 was intratracheally instilled 20 h after ozone exposure. Controls breathed filtered air or were instilled with 0.9% NaCl or with CuSO4 or were only exposed to ozone. We evaluated lung histopathology. F2 isoprostanes were determined in plasma. Cell count, total proteins, γ glutamyl-transpeptidase (GGT) and alkaline phosphatases (AP) were determined in bronchoalveolar lavage fluid (BALF). Ozone increased total cell count, macrophages, proteins and AP in BALF (p Ozone plus CuSO4 exposed animals showed a neutrophil inflammatory lung response and an increase in total cell count, proteins, GGT and AP in BALF (p ozone induces a neutrophil pulmonary inflammatory response and cytoplasmic damage in macrophages.

  15. Fractional excretion as a new marker of tubular damage in children with chronic kidney disease.

    Science.gov (United States)

    Musiał, Kinga; Zwolińska, Danuta

    2018-02-06

    Vitamin D-binding protein (VDBP), retinol-binding protein (RBP)4, and heat shock proteins (hsp) are markers of tubular function and apoptosis, accompanying chronic kidney disease (CKD) from its earliest stages. Fractional excretion of proteins with urine is a marker of tubular damage. The aim of study was to assess the usefulness of fractional excretion (FE) of VDBP, RBP4, HSF1 and Hsp27 as markers of tubular damage in the course of CKD. The study group consisted of 70 children with CKD stages 1-5, treated conservatively, and 12 age-matched controls with normal kidney function. The serum and urine concentrations of VDBP, RBP4, HSF1 and Hsp27 were assessed by ELISA. The fractional excretion of analyzed parameters was calculated according to the formula: ([parameter urine concentration] × [creatinine serum concentration]) / ([parameter serum concentration] × [creatinine urine concentration])×100%. The FE values of all parameters exceeded 1% in CKD stage 2. However, the values of FE have raised significantly versus control group no sooner than CKD stage 2 (RBP4 and HSF1), stage 3 (VDBP) or stage 4 (Hsp27). Fractional excretion of RBP4 and HSF1 with urine may become a valuable marker, assessing the damage of tubular cells in children with CKD. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Microstructural Abnormalities Were Found in Brain Gray Matter from Patients with Chronic Myofascial Pain

    Science.gov (United States)

    Xie, Peng; Qin, Bangyong; Song, Ganjun; Zhang, Yi; Cao, Song; Yu, Jin; Wu, Jianjiang; Wang, Jiang; Zhang, Tijiang; Zhang, Xiaoming; Yu, Tian; Zheng, Hong

    2016-01-01

    Myofascial pain, presented as myofascial trigger points (MTrPs)-related pain, is a common, chronic disease involving skeletal muscle, but its underlying mechanisms have been poorly understood. Previous studies have revealed that chronic pain can induce microstructural abnormalities in the cerebral gray matter. However, it remains unclear whether the brain gray matters of patients with chronic MTrPs-related pain undergo alteration. In this study, we employed the Diffusion Kurtosis Imaging (DKI) technique, which is particularly sensitive to brain microstructural perturbation, to monitor the MTrPs-related microstructural alterations in brain gray matter of patients with chronic pain. Our results revealed that, in comparison with the healthy controls, patients with chronic myofascial pain exhibited microstructural abnormalities in the cerebral gray matter and these lesions were mainly distributed in the limbic system and the brain areas involved in the pain matrix. In addition, we showed that microstructural abnormalities in the right anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) had a significant negative correlation with the course of disease and pain intensity. The results of this study demonstrated for the first time that there are microstructural abnormalities in the brain gray matter of patients with MTrPs-related chronic pain. Our findings may provide new insights into the future development of appropriate therapeutic strategies to this disease. PMID:28066193

  17. Therapeutic impact of eicosapentaenoic acid on ischemic brain damage following transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Ueda, Masayuki; Inaba, Toshiki; Nito, Chikako; Kamiya, Nobuo; Katayama, Yasuo

    2013-06-26

    Long-chain n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), have been shown to reduce ischemic neuronal injury. We investigated the effects of ethyl-EPA (EPA-E) on ischemic brain damage using a rat transient focal cerebral ischemia model. Male Sprague-Dawley rats (n=105) were subjected to 90 min of focal cerebral ischemia. EPA-E (100mg/kg/day) or vehicle was administered once a day for 3, 5 or 7 days prior to ischemia. Different withdrawal intervals of 3, 5, and 7 days prior to ischemia following 7-day pretreatment with EPA-E or vehicle were also examined. In addition, post-ischemic administration of EPA-E was investigated. Pretreatment with EPA-E for 7 and 5 days, but not 3 days, showed significant infarct volume reduction and neurological improvements when compared with vehicle pretreatment. In addition, withdrawal of EPA-E administration for 3 days, but not 5 and 7 days, also demonstrated significant infarct volume reduction and neurological improvements when compared with vehicle treatment. Post-ischemic treatment of EPA-E did not show any neuroprotection. Immunohistochemistry revealed that 7-day pretreatment with EPA-E significantly reduced cortical expression of 8-hydroxydeoxyguanosine (maker for oxidative DNA damage), 4-hydroxy-2-nonenal (maker for lipid peroxidation), phosphorylated adducin (marker for Rho-kinase activation) and von Willebrand factor (endothelial marker) when compared with vehicle pretreatment. In addition, phosphorylated adducin expression co-localized with von Willebrand factor immunoreactivity. The present study established the neuroprotective effect of EPA-E on ischemic brain damage following transient focal cerebral ischemia in rats, which may be involved in the suppression of oxidative stress and endothelial Rho-kinase activation. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. A cross-talk between brain-damage patients and infants on action and language.

    Science.gov (United States)

    Papeo, Liuba; Hochmann, Jean-Remy

    2012-06-01

    Sensorimotor representations in the brain encode the sensory and motor aspects of one's own bodily activity. It is highly debated whether sensorimotor representations are the core basis for the representation of action-related knowledge and, in particular, action words, such as verbs. In this review, we will address this question by bringing to bear insights from the study of brain-damaged patients exhibiting language disorders and from the study of the mechanisms for language acquisition in infants. Cognitive neuropsychology studies have assessed how damage to representations supporting action production impacts patients' ability to process action-related words. While correlations between verbal and nonverbal (motor) impairments are very common in patients, damage to the representations for action production can leave the ability to understand action-words unaffected; likewise, actions can still be produced successfully in cases of impaired action-word understanding. Studies with infants have evaluated the relevance of sensorimotor information when infants learn to map a novel word onto an action that they are performing or perceiving. These results demonstrate that sensorimotor information is insufficient to fully account for the complexity of verb learning: in this process, infants seem to privilege abstract constructs such as goal, intentionality and causality, as well as syntactic constraints, over the perceptual and motor dimensions of an action. Altogether, the empirical data suggest that, while not crucial for verb learning and understanding, sensorimotor processes can contribute to solving the problem of symbol grounding and/or serve as a primary mechanism in social cognition, to learn about others' goals and intentions. By assessing the relevance of sensorimotor representations in the way action-related words are acquired and represented, we aim to provide a useful set of criteria for testing specific predictions made by different theories of concepts

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

    Science.gov (United States)

    Farkas, E; De Jong, G I; Apró, E; Keuker, J I; Luiten, P G

    2001-01-01

    Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillaries. The present study describes ultrastructural alterations of the cerebrocortical capillary wall, such as thickening and collagen accumulation in the basement membrane of aging spontaneously hypertensive stroke-prone rats. The ratio of cortical capillaries with such vascular pathology occurred significantly more frequently in hypertensive animals. Nimodipine and nifedipine are potential drugs to decrease blood pressure in hypertension but their beneficial effects in experimental studies reach beyond the control of blood pressure. Nimodipine and nifedipine can alleviate ischemia-related symptoms and improve cognition. These drugs differ in that nifedipine, but not nimodipine reduces blood pressure at the here-used concentration while both drugs can penetrate the blood-brain barrier. Here we show that chronic treatment of aging hypertensive stroke-prone rats with nimodipine or nifedipine could preserve microvascular integrity in the cerebral cortex.

  20. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients

    Science.gov (United States)

    Vanhaudenhuyse, Audrey; Noirhomme, Quentin; Tshibanda, Luaba J.-F.; Bruno, Marie-Aurelie; Boveroux, Pierre; Schnakers, Caroline; Soddu, Andrea; Perlbarg, Vincent; Ledoux, Didier; Brichant, Jean-François; Moonen, Gustave; Maquet, Pierre; Greicius, Michael D.

    2010-01-01

    The ‘default network’ is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient’s default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. PMID:20034928

  1. Verbal fluency in right brain damage: dissociations among production criteria and duration.

    Science.gov (United States)

    Zimmermann, Nicolle; Branco, Laura; Ska, Bernadette; Gasparetto, Emerson Leandro; Joanette, Yves; Fonseca, Rochele

    2014-01-01

    This study aimed to verify dissociations in the performance of verbal fluency tasks with different production criteria and duration following vascular right-hemisphere damage. We tested the hypothesis that longer fluency tasks would be more sensitive in identifying deficits in the sample. The relationship between verbal fluency performance and sustained attention was also investigated. Forty adults with vascular right-hemisphere damage were assessed using verbal fluency tasks with three different production criteria (unconstrained, phonemic, and semantic fluencies from the Montreal Communication Evaluation Battery). Performance deficits in 1-min and 2-min fluency tasks were calculated (Z score) and compared (chi-square). Results did not suggest a difference in sensitivity between the task lengths in detecting cognitive impairment. However, double dissociations were found, highlighting the contribution of extended verbal fluency tasks to neuropsychological assessment. Analyses also showed that participants exhibited greater levels of impairment in the semantic fluency task. No relationship was identified between performance in sustained attention tasks and verbal fluency tasks, regardless of the latter's duration. The combined use of longer and shorter fluency tasks in the assessment of patients with right brain damage may contribute to the identification of different executive function impairments in this sample.

  2. Regional susceptibility to dose-dependent white matter damage after brain radiotherapy.

    Science.gov (United States)

    Connor, Michael; Karunamuni, Roshan; McDonald, Carrie; Seibert, Tyler; White, Nathan; Moiseenko, Vitali; Bartsch, Hauke; Farid, Nikdokht; Kuperman, Joshua; Krishnan, Anitha; Dale, Anders; Hattangadi-Gluth, Jona A

    2017-05-01

    Regional differences in sensitivity to white matter damage after brain radiotherapy (RT) are not well-described. We characterized the spatial heterogeneity of dose-response across white matter tracts using diffusion tensor imaging (DTI). Forty-nine patients with primary brain tumors underwent MRI with DTI before and 9-12months after partial-brain RT. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were generated. Atlas-based white matter tracts were identified. A secondary analysis using skeletonized tracts was also performed. Linear mixed-model analysis of the relationship between mean and max dose and percent change in DTI metrics was performed. Tracts with the strongest correlation of FA change with mean dose were the fornix (-0.46 percent/Gy), cingulum bundle (-0.44 percent/Gy), and body of corpus callosum (-0.23 percent/Gy), pchanges in MD and RD. In the skeletonized analysis, the fornix and cingulum bundle remained highly dose-sensitive. Maximum and mean dose were similarly predictive of DTI change. The corpus callosum, cingulum bundle, and fornix show the most prominent dose-dependent changes following RT. Future studies examining correlation with cognitive functioning and potential avoidance of critical white matter regions are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. KCC2 expression changes in Diazepam-treated neonatal rats with hypoxia-ischaemia brain damage.

    Science.gov (United States)

    Ma, Jun-Yuan; Zhang, Su-Pei; Guo, Liu-Bin; Li, Yong-Mei; Li, Qiang; Wang, Sai-Qi; Liu, Hong-Min; Wang, Cong

    2014-05-14

    Hypoxia-ischaemia brain damage (HIBD) is a major type of perinatal brain injury in newborns. In this study, we investigate the short- and long-term neuroprotective effects of Diazepam on neonatal rats with HIBD and the potential mechanisms underlying its protective effects. Seven-day-old Sprague-Dawley rats were subjected to left carotid artery ligation followed by a 2-h exposure to 8% oxygen and 92% nitrogen. Diazepam was administered immediately via intraperitoneal (i.p.) injection after inducing HIBD at a dose of 10 mg kg(-1)8h(-1) for three consecutive days. Three days after HIBD, rats were decapitated, and the extent of brain injury was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Additionally, the expression of Potassium-chloride cotransporter-2 (KCC2) was analysed using real-time PCR, Western blot analysis and immunohistochemistry. Three weeks after HIBD, rats were subjected to the Morris water maze (MWM) test and the locomotor activity test to determine the long-term therapeutic effects of Diazepam. We observed that the volume of infarction in the Diazepam group was significantly less (PDiazepam rats improved significantly compared with the untreated rats (PDiazepam appears to attenuate HIBD and can efficiently improve the long-term learning and memory capabilities of the animal. A potential mechanism underlying these effects may involve preventing the decrease in KCC2 expression. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Maladaptive change of body representation in the brain after damage to central or peripheral nervous system.

    Science.gov (United States)

    Oouchida, Yutaka; Sudo, Tamami; Inamura, Tetsunari; Tanaka, Naofumi; Ohki, Yukari; Izumi, Shin-ichi

    2016-03-01

    Our brain has great flexibility to cope with various changes in the environment. Use-dependent plasticity, a kind of functional plasticity, plays the most important role in this ability to cope. For example, the functional recovery of paretic limb motor movement during post-stroke rehabilitation depends mainly on how much it is used. Patients with hemiparesis, however, tend to gradually disuse the paretic limb because of its motor impairment. Decreased use of the paretic hand then leads to further functional decline brought by use-dependent plasticity. To break this negative loop, body representation, which is the conscious and unconscious information regarding body state stored in the brain, is key for using the paretic limb because it plays an important role in selecting an effector while a motor program is generated. In an attempt to understand body representation in the brain, we reviewed animal and human literature mainly on the alterations of the sensory maps in the primary somatosensory cortex corresponding to the changes in limb usage caused by peripheral or central nervous system damage. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  5. Neuroprotective effects of cactus polysaccharide on oxygen and glucose deprivation induced damage in rat brain slices.

    Science.gov (United States)

    Huang, Xianju; Li, Qin; Zhang, Yingpei; Lü, Qing; Guo, Lianjun; Huang, Lin; He, Zhi

    2008-06-01

    1. The neuroprotective effect of cactus polysaccharide (CP) on oxygen and glucose deprivation (OGD) and reoxygenation (REO)-induced damage in the cortical and hippocampal slices of rat brain was investigated. 2. Cell viability was evaluated by using the 2, 3, 5-triphenyl tetrazolium chloride (TTC) method. The fluorescence of propidium iodide (PI) staining was used for quantification of cellular survival, and lactate dehydrogenase (LDH) activity in incubation medium was assessed by LDH assay to evaluate the degree of injury. 3. The OGD ischemic condition significantly decreased cellular viability and increased LDH release in the incubation medium. CP (0.2 mg/l approximately 2 mg/l) protected brain slices from OGD injury in a dosage dependent manner as demonstrated by increased A 490 value of TTC, decreased PI intensity and LDH release. At the above concentration, CP also prevented the increase of nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity induced by OGD. 4. CP can protect the brain slices (cortical and hippocampus) against injury induced by OGD. Its neuroprotective effect may be partly mediated by the NO/iNOS system induced by OGD insult.

  6. Elevated global SUMOylation in Ubc9 transgenic mice protects their brains against focal cerebral ischemic damage.

    Directory of Open Access Journals (Sweden)

    Yang-Ja Lee

    Full Text Available We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects against ischemic brain damage, we have generated transgenic mice in which Ubc9 is expressed strongly in all tissues under the chicken β-actin promoter. Ubc9 expression levels in 10 founder lines ranged from 2 to 30 times the endogenous level, and lines that expressed Ubc9 at modestly increased levels showed robust resistance to brain ischemia compared to wild type mice. The infarction size was inversely correlated with the Ubc9 expression levels for up to five times the endogenous level. Although further increases showed no additional benefit, the Ubc9 expression level was highly correlated with global SUMO-1 conjugation levels (and SUMO-2,3 levels to a lesser extent up to a five-fold Ubc9 increase. Most importantly, there were striking reciprocal relationships between SUMO-1 (and SUMO-2,3 conjugation levels and cerebral infarction volumes among all tested animals, suggesting that the limit in cytoprotection by global SUMOylation remains undefined. These results support efforts to further augment global protein SUMOylation in brain ischemia.

  7. Elevated global SUMOylation in Ubc9 transgenic mice protects their brains against focal cerebral ischemic damage.

    Science.gov (United States)

    Lee, Yang-Ja; Mou, Yongshan; Maric, Dragan; Klimanis, Dace; Auh, Sungyoung; Hallenbeck, John M

    2011-01-01

    We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects against ischemic brain damage, we have generated transgenic mice in which Ubc9 is expressed strongly in all tissues under the chicken β-actin promoter. Ubc9 expression levels in 10 founder lines ranged from 2 to 30 times the endogenous level, and lines that expressed Ubc9 at modestly increased levels showed robust resistance to brain ischemia compared to wild type mice. The infarction size was inversely correlated with the Ubc9 expression levels for up to five times the endogenous level. Although further increases showed no additional benefit, the Ubc9 expression level was highly correlated with global SUMO-1 conjugation levels (and SUMO-2,3 levels to a lesser extent) up to a five-fold Ubc9 increase. Most importantly, there were striking reciprocal relationships between SUMO-1 (and SUMO-2,3) conjugation levels and cerebral infarction volumes among all tested animals, suggesting that the limit in cytoprotection by global SUMOylation remains undefined. These results support efforts to further augment global protein SUMOylation in brain ischemia.

  8. Organotins in Neuronal Damage, Brain Function, and Behavior: A Short Review

    Directory of Open Access Journals (Sweden)

    Igor Ferraz da Silva

    2018-01-01

    Full Text Available The consequences of exposure to environmental contaminants have shown significant effects on brain function and behavior in different experimental models. The endocrine-disrupting chemicals (EDC present various classes of pollutants with potential neurotoxic actions, such as organotins (OTs. OTs have received special attention due to their toxic effects on the central nervous system, leading to abnormal mammalian neuroendocrine axis function. OTs are organometallic pollutants with a tin atom bound to one or more carbon atoms. OT exposure may occur through the food chain and/or contaminated water, since they have multiple applications in industry and agriculture. In addition, OTs have been used with few legal restrictions in the last decades, despite being highly toxic. In addition to their action as EDC, OTs can also cross the blood–brain barrier and show relevant neurotoxic effects, as observed in several animal model studies specifically involving the development of neurodegenerative processes, neuroinflammation, and oxidative stress. Thus, the aim of this short review is to summarize the toxic effects of the most common OT compounds, such as trimethyltin, tributyltin, triethyltin, and triphenyltin, on the brain with a focus on neuronal damage as a result of oxidative stress and neuroinflammation. We also aim to present evidence for the disruption of behavioral functions, neurotransmitters, and neuroendocrine pathways caused by OTs.

  9. Lateral cord stimulation decreases spastic electromyographic spreading: responses in a brain-damaged pig preparation.

    Science.gov (United States)

    Andreani, Juan Carlos M; Guma, Cristina

    2008-07-01

    Objective.  The aim of our work was to investigate whether lateral stimulation of the spinal cord, lateral cord stimulation (LCS), results in inhibition of the spastic phenomena of upper motor lesions in an animal model. Methods.  This study was conducted using an animal model consisting of surgically brain damaged pigs subjected to unilateral cortical and subcortical brain lesions. A double laminectomy at cervical (C3-C4) and lumbar (L3-L6) was performed, and spastic thresholds of abnormal electromyographic responses, disseminated to adjacent segments, facilitated by spinal liberation, and produced by extradural electrical stimulation of the fourth lumbar root, were measured before and after cervical stimulation of the LCS. The variable studied was the minimal amount of current of LCS necessary to abolish electromyographic responses in the L7 myotome, away from the stimulated L4 nerve root. Results.  Experiments in 12 animals showed a significant increase of threshold after LCS, with a marked posteffect, signaling a less abnormal threshold. Conclusions.  This experiment demonstrated that LCS produces threshold increases to abolish abnormally propagated electromyographic evoked responses induced by the electrical stimulation of the fourth lumbar root in pigs with experimental cortical and subcortical brain lesions. © 2008 International Neuromodulation Society.

  10. Exacerbation of N-nitrosodiethylamine Induced Hepatotoxicity and DNA Damage in Mice Exposed to Chronic Unpredictable Stress

    Directory of Open Access Journals (Sweden)

    Nayeem Bilal

    2017-06-01

    Full Text Available Psychological stress contributes to increased susceptibility to a number of diseases including cancer. The present study was designed to assess the effect of chronic unpredictable stress on N-nitrosodiethylamine induced liver toxicity in terms of in vivo antioxidant status and DNA damage in Swiss albino mice. The animals used in this study were randomized into different groups based on the treatment with N-nitrosodiethylamine or chronic unpredictable stress alone and post-stress administration of N-nitrosodiethylamine. The mice were sacrificed after 12 weeks of treatment, and the status of major enzymatic and non-enzymatic antioxidants, liver function markers, lipid peroxidation and the extent of DNA damage were determined in circulation and liver tissues of all the groups. The N-nitrosodiethylamine treated group showed significantly compromised levels of the antioxidant enzymes, lipid peroxidation, and the liver function markers with enhanced DNA damage as compared to chronic unpredictable stress or control groups. A similar but less typical pattern observed in the chronic unpredictable stress treated mice. All the measured biochemical parameters were significantly altered in the group treated with the combination of chronic unpredictable stress and N-nitrosodiethylamine when compared to controls, or chronic unpredictable stress alone and/or N-nitrosodiethylamine alone treated groups. Thus, exposure to continuous, unpredictable stress conditions even in general life may significantly enhance the hepatotoxic potential of N-nitrosodiethylamine through an increase in the oxidative stress and DNA damage.

  11. Association between sleep quality and cardiovascular damage in pre-dialysis patients with chronic kidney disease.

    Science.gov (United States)

    Zhang, Jun; Wang, Cheng; Gong, Wenyu; Peng, Hui; Tang, Ying; Li, Cui Cui; Zhao, Wenbo; Ye, Zengchun; Lou, Tanqi

    2014-08-12

    Poor sleep quality, a novel risk factor of cardiovascular diseases (CVD), is highly prevalent in patients with chronic kidney disease (CKD). The association between poor sleep quality and cardiovascular damage in patients with CKD is unclear. This study is aimed to assess the prevalence and related risk factors of sleep disturbance and determine the relationship between sleep quality and cardiovascular damage in Chinese patients with pre-dialysis CKD. A total of 427 pre-dialysis CKD patients (mean age = 39 ± 15 years, 260 male/167 female) were recruited in this study. The demographics and clinical correlates were collected. The sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI), whereas the cardiovascular damage indicators (the Early/late diastolic peak flow velocity (E/A) ratio and left ventricular mass index (LVMI)) were determined by an echocardiographic examination. Of the CKD patients, 77.8% were poor sleepers as defined by a PSQI score > 5. Median estimated glomerular filtration rate (eGFR) was 69.4(15.8-110.9) ml/min/1.73 m(2). Logistic regression analysis revealed that left ventricular hypertrophy (LVH) was independently associated with the PSQI score (OR = 1.092, 95% CI = 1.011-1.179, p = 0.025), after adjustment for age, sex and clinical systolic blood pressure, diastolic blood pressure, Phosphate, Intact parathyroid hormone (iPTH), Hemoglobin and eGFR. The linear regression analysis showed that the E/A ratios were independently associated with the PSQI score (β = -0.115, P = 0.028) after adjustment for a series of potential confounding factors. Poor sleep quality, which is commonly found in pre-dialysis CKD patients, is an independent factor associated with cardiovascular damage in CKD patients. Our finding implies that the association between poor sleep and CVD might be mediated by cardiac remodeling.

  12. Sex-based differences in brain alterations across chronic pain conditions.

    Science.gov (United States)

    Gupta, Arpana; Mayer, Emeran A; Fling, Connor; Labus, Jennifer S; Naliboff, Bruce D; Hong, Jui-Yang; Kilpatrick, Lisa A

    2017-01-02

    Common brain mechanisms are thought to play a significant role across a multitude of chronic pain syndromes. In addition, there is strong evidence for the existence of sex differences in the prevalence of chronic pain and in the neurobiology of pain. Thus, it is important to consider sex when developing general principals of pain neurobiology. The goal of the current Mini-Review is to evaluate what is known about sex-specific brain alterations across multiple chronic pain populations. A total of 15 sex difference and 143 single-sex articles were identified from among 412 chronic pain neuroimaging articles. Results from sex difference studies indicate more prominent primary sensorimotor structural and functional alterations in female chronic pain patients compared with male chronic pain patients: differences in the nature and degree of insula alterations, with greater insula reactivity in male patients; differences in the degree of anterior cingulate structural alterations; and differences in emotional-arousal reactivity. Qualitative comparisons of male-specific and female-specific studies appear to be consistent with the results from sex difference studies. Given these differences, mixed-sex studies of chronic pain risk creating biased data or missing important information and single-sex studies have limited generalizability. The advent of large-scale neuroimaging databases will likely aid in building a more comprehensive understanding of sex differences and commonalities in brain mechanisms underlying chronic pain. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Effect of Pregabalin in Preventing Secondary Damage in Traumatic Brain Injury: An Experimental Study

    Science.gov (United States)

    Calikoglu, Cagatay; Aytekin, Hikmet; Akgül, Osman; Akgül, Mehmet Hüseyin; Gezen, Ahmet Ferruh; Akyuz, Feyzullah; Cakir, Murteza

    2015-01-01

    Background In this study we aimed to explore the effects of pregabalin on a traumatic brain injury model in rats. Material/Methods This study included 40 adult male Sprague-Dawley rats randomized into 4 groups, each of which contained equal numbers of animals. The control group had no head trauma and thus was not treated. The trauma group had head trauma but was not treated. The pregabalin group had no head trauma but was treated by pregabalin. The trauma + pregabalin group had head trauma treated with pregabalin. The biopsy samples taken from the study animals were histopathologically examined for the presence of edema, inflammation, and neuronal damage. Results All animals in the trauma group had edema, inflammation, and neuronal damage. Four subjects in the control group, 6 in the pregabalin group, and 4 in the trauma + pregabalin group had edema; inflammation was present in 1 subject in the control group, 3 subjects in the pregabalin group, and 3 subjects in the trauma + pregabalin group; neuronal damage existed in 1 subject in the control group, 1 subject in the pregabalin group, and 6 subjects in the trauma + pregabalin group. The trauma group had significantly higher edema and neuronal damage scores than the other groups. Similarly, inflammation was significantly more prevalent in the trauma group than the control and trauma + pregabalin groups. Conclusions The results of the present study indicated anti-edema, anti-inflammatory, and neuroprotective effects of pregabalin in an experimental head trauma model in rats. Pregabalin may thus be beneficial in humans with acute TBI by relieving concomitant edema and inflammation. PMID:25785578

  14. Presence of brain pathology in deceased subjects with and without chronic obstructive pulmonary disease.

    Science.gov (United States)

    Cleutjens, Fiona A H M; Spruit, Martijn A; Beckervordersandforth, Jan; Franssen, Frits M E; Dijkstra, Jeanette B; Ponds, Rudolf W H M; Wouters, Emiel F B; Janssen, Daisy J A

    2015-11-01

    Patients with chronic obstructive pulmonary disease (COPD) have extrapulmonary co-morbidities, such as cardiovascular disease, musculoskeletal wasting and neuropsychological conditions. To date, it remains unknown whether and to what extent COPD is associated with a higher prevalence of brain pathology. Therefore, the aim of this retrospective study was to compare the prevalence of neuropathological brain changes between deceased donors with and without COPD. Brain autopsy reports of age-matched donors with (n = 89) and without COPD (n = 89) from the Netherlands Brain Bank were assessed for demographics, cause of death, co-morbidities and brain pathology. The prevalence of degenerative brain changes was comparable for donors with and without COPD (50.6% vs. 61.8%, p > 0.05). Neoplastic brain changes were reported in a minority of the donors (5.6% vs. 10.1%, p > 0.05). After correction for cerebrovascular accident or cardiac cause of death and Charlson co-morbidity index score, the prevalence of vascular brain changes was higher among control versus COPD donors (27.0% vs. 11.2%, adjusted p = 0.013, odds ratio = 2.98). Brain autopsy reports of donors with and without COPD did not reveal differences in the presence of degenerative or neoplastic brain changes. Vascular brain changes were described more often in controls. Prospective studies including spirometry and structural and functional brain imaging should corroborate our findings. © The Author(s) 2015.

  15. No inherent left and right side in human 'mental number line': evidence from right brain damage.

    Science.gov (United States)

    Aiello, Marilena; Jacquin-Courtois, Sophie; Merola, Sheila; Ottaviani, Teresa; Tomaiuolo, Francesco; Bueti, Domenica; Rossetti, Yves; Doricchi, Fabrizio

    2012-08-01

    Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial

  16. HLA-DRB1*15 influences the development of brain tissue damage in early PPMS.

    Science.gov (United States)

    Tur, Carmen; Ramagopalan, Sreeram; Altmann, Daniel R; Bodini, Benedetta; Cercignani, Mara; Khaleeli, Zhaleh; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

    2014-11-04

    To investigate whether (1) there were differences between HLA-DRB1*15-positive and -negative patients at baseline, and (2) HLA-DRB1*15-positive patients showed a greater development of brain and spinal cord damage, as assessed by MRI, and greater progression of disability, during a 5-year follow-up, compared with HLA-DRB1*15-negative patients. HLA-DRB1*15 typing was performed in 41 patients with primary progressive multiple sclerosis (PPMS) who were recruited within 5 years of symptom onset. All patients and 18 healthy controls were studied clinically and with MRI at baseline, and every 6 months for 3 years, and then at 5 years. Magnetization transfer ratio parameters and volumes for brain gray matter and normal-appearing white matter, brain T2 lesion load, and spinal cord cross-sectional area were obtained. Patient disability was assessed at each visit using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite subscores. There were no significant differences between HLA-DRB1*15-positive and -negative patients at baseline. HLA-DRB1*15-positive patients showed a greater decline in brain magnetization transfer ratio for gray matter and normal-appearing white matter (both p = 0.005) than HLA-DRB1*15-negative patients over 5 years, while the same parameters did not change over time in healthy controls. HLA-DRB1*15-positive patients also showed a trend toward a faster increase in brain T2 lesion load than HLA-DRB1*15-negative patients (0.29 [95% confidence interval 0.20-0.38] vs 0.21 [0.13-0.30] mL/mo, p = 0.085) and higher T2 lesion volumes at all time points (average difference [95% confidence interval]: 10.58 mL [7.09-14.07], p < 0.001) during the follow-up, after adjusting for disease duration. These findings suggest that HLA-DRB1*15 influences the progression of brain pathology in PPMS. © 2014 American Academy of Neurology.

  17. Verb retrieval in brain-damaged subjects: 2. Analysis of errors.

    Science.gov (United States)

    Kemmerer, D; Tranel, D

    2000-07-01

    Verb retrieval for action naming was assessed in 53 brain-damaged subjects by administering a standardized test with 100 items. In a companion paper (Kemmerer & Tranel, 2000), it was shown that impaired and unimpaired subjects did not differ as groups in their sensitivity to a variety of stimulus, lexical, and conceptual factors relevant to the test. For this reason, the main goal of the present study was to determine whether the two groups of subjects manifested theoretically interesting differences in the kinds of errors that they made. All of the subjects' errors were classified according to an error coding system that contains 27 distinct types of errors belonging to five broad categories-verbs, phrases, nouns, adpositional words, and "other" responses. Errors involving the production of verbs that are semantically related to the target were especially prevalent for the unimpaired group, which is similar to the performance of normal control subjects. By contrast, the impaired group had a significantly smaller proportion of errors in the verb category and a significantly larger proportion of errors in each of the nonverb categories. This relationship between error rate and error type is consistent with previous research on both object and action naming errors, and it suggests that subjects with only mild damage to putative lexical systems retain an appreciation of most of the semantic, phonological, and grammatical category features of words, whereas subjects with more severe damage retain a much smaller set of features. At the level of individual subjects, a wide range of "predominant error types" were found, especially among the impaired subjects, which may reflect either different action naming strategies or perhaps different patterns of preservation and impairment of various lexical components. Overall, this study provides a novel addition to the existing literature on the analysis of naming errors made by brain-damaged subjects. Not only does the study

  18. Structural Brain Damage and Upper Limb Kinematics in Children with Unilateral Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Lisa Mailleux

    2017-12-01

    Full Text Available Background: In children with unilateral cerebral palsy (uCP virtually nothing is known on the relation between structural brain damage and upper limb (UL kinematics quantified with three-dimensional movement analysis (3DMA. This explorative study aimed to (1 investigate differences in UL kinematics between children with different lesion timings, i.e., periventricular white matter (PWM vs. cortical and deep gray matter (CDGM lesions and (2 to explore the relation between UL kinematics and lesion location and extent within each lesion timing group.Methods: Forty-eight children (age 10.4 ± 2.7 year; 29 boys; 21 right-sided; 33 PWM; 15 CDGM underwent an UL 3DMA during a reach-to-grasp task. Spatiotemporal parameters [movement duration, (timing of maximum velocity, trajectory straightness], the Arm Profile Score (APS and Arm Variable Scores (AVS were extracted. The APS and AVS refer to the total amount of movement pathology and movement deviations of the wrist, elbow, shoulder, scapula and trunk respectively. Brain lesion location and extent were scored based on FLAIR-images using a semi-quantitative MRI-scale.Results: Children with CDGM lesions showed more aberrant spatiotemporal parameters (p < 0.03 and more movement pathology (APS, p = 0.003 compared to the PWM group, mostly characterized by increased wrist flexion (p = 0.01. In the CDGM group, moderate to high correlations were found between lesion location and extent and duration, timing of maximum velocity and trajectory straightness (r = 0.53–0.90. Lesion location and extent were further moderately correlated with distal UL movement pathology (wrist flexion/extension, elbow pronation/supination, elbow flexion/extension; r = 0.50–0.65 and with the APS (r = 0.51–0.63. In the PWM group, only a few and low correlations were observed, mostly between damage to the PLIC and higher AVS of elbow flexion/extension, shoulder elevation and trunk rotation (r = 0.35–0.42. Regression analysis

  19. Elucidation of Inflammation Processes Exacerbating Neuronal Cell Damage to the Retina and Brain Visual Centers as Quest for Therapeutic Drug Targets in Rat Model of Blast Overpressure Wave Exposure

    Science.gov (United States)

    2016-10-01

    traumatic eye injuries to soldiers is exposure to blast shock waves; and it can involve cellular damage to the retina as well as brain visual centers...acid deficient diet , which promotes inflammation. Conversely, some are fed an omega-3 enriched diet by ocean fish oil supplementation. Up to one month...3 fatty acids showed slight if any ability to alleviate these acute injury events . Chronic events , however, maybe more amendable to other functions

  20. Processing of basic speech acts following localized brain damage: a new light on the neuroanatomy of language.

    Science.gov (United States)

    Soroker, Nachum; Kasher, Asa; Giora, Rachel; Batori, Gila; Corn, Cecilia; Gil, Mali; Zaidel, Eran

    2005-03-01

    We examined the effect of localized brain lesions on processing of the basic speech acts (BSAs) of question, assertion, request, and command. Both left and right cerebral damage produced significant deficits relative to normal controls, and left brain damaged patients performed worse than patients with right-sided lesions. This finding argues against the common conjecture that the right hemisphere of most right-handers plays a dominant role in natural language pragmatics. In right-hemisphere damaged patients, there was no correlation between location and extent of lesion in perisylvian cortex and performance on BSAs. By contrast, processing of the different BSAs by left hemisphere-damaged patients was strongly affected by perisylvian lesion location, with each BSA showing a distinct pattern of localization. This finding raises the possibility that the classical left perisylvian localization of language functions, as measured by clinical aphasia batteries, partly reflects the localization of the BSAs required to perform these functions.

  1. Co-speech hand movements during narrations: What is the impact of right vs. left hemisphere brain damage?

    Science.gov (United States)

    Hogrefe, Katharina; Rein, Robert; Skomroch, Harald; Lausberg, Hedda

    2016-12-01

    Persons with brain damage show deviant patterns of co-speech hand movement behaviour in comparison to healthy speakers. It has been claimed by several authors that gesture and speech rely on a single production mechanism that depends on the same neurological substrate while others claim that both modalities are closely related but separate production channels. Thus, findings so far are contradictory and there is a lack of studies that systematically analyse the full range of hand movements that accompany speech in the condition of brain damage. In the present study, we aimed to fill this gap by comparing hand movement behaviour in persons with unilateral brain damage to the left and the right hemisphere and a matched control group of healthy persons. For hand movement coding, we applied Module I of NEUROGES, an objective and reliable analysis system that enables to analyse the full repertoire of hand movements independent of speech, which makes it specifically suited for the examination of persons with aphasia. The main results of our study show a decreased use of communicative conceptual gestures in persons with damage to the right hemisphere and an increased use of these gestures in persons with left brain damage and aphasia. These results not only suggest that the production of gesture and speech do not rely on the same neurological substrate but also underline the important role of right hemisphere functioning for gesture production. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

    OpenAIRE

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-guo

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary ...

  3. Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

    OpenAIRE

    Yi, Yong-Hong; Guo, Wen-Chao; Sun, Wei-Wen; Su, Tao; Lin, Han; Chen, Sheng-Qiang; Deng, Wen-Yi; Zhou, Wei; Liao, Wei-Ping

    2008-01-01

    Lamotrigine (LTG), an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD) in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen). LTG was administered intra...

  4. Spirulina or dandelion-enriched diet of mothers alleviates lead-induced damages in brain and cerebellum of newborn rats.

    Science.gov (United States)

    Gargouri, Manel; Ghorbel-Koubaa, Fatma; Bonenfant-Magné, Michèle; Magné, Christian; Dauvergne, Xavier; Ksouri, Riadh; Krichen, Yousef; Abdelly, Chedly; El Feki, Abdelfattah

    2012-07-01

    This study was aimed at evaluating the toxic effects of a prenatal exposure to lead acetate on brain tissues of newborn rats, and potent protective effects of spirulina (Arthropira platensis) or dandelion (Taraxacum officinalis) added to rat diet. Female rats were given a normal diet (control) or a diet enriched with spirulina or dandelion. Additionally, lead acetate was administered to one half of these rats through drinking water from the 5th day of gestation, to day 14 postpartum. Lead toxicity was assessed by measuring blood lead levels, brain weight, tissue damage, as well as protein content, lipid peroxidation and activities of antioxidant enzymes in brain tissues of neonates. Lead poisoning of mothers caused lead deposition in the brain and cerebellum of newborns and cerebellum tissue damages. Moreover, a significant decrease in weight and protein content of these tissues was found. Oxidative stress and changes in antioxidant enzyme activities in brain tissues were also recorded. Conversely, no such damages or biochemical changes were found in neonates from plant fed lead-poisoned mothers. These results strongly suggest that beneficial effects of spirulina- or dandelion-added diet on lead-intoxicated rats proceeded through the reduction of the lead-induced oxidative stress and related damages. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Piano training in youths with hand motor impairments after damage to the developing brain

    Directory of Open Access Journals (Sweden)

    Lampe R

    2015-08-01

    Full Text Available Renée Lampe,1,* Anna Thienel,2 Jürgen Mitternacht,1 Tobias Blumenstein,1 Varvara Turova,1 Ana Alves-Pinto1,* 1Research Unit for Paediatric Neuroorthopaedics and Cerebral Palsy, Orthopaedics Department, Klinikum Rechts der Isar, Technische Universität München, 2Department Sonderpädagogik, Ludwig Maximilians-Universität München, Munich, Germany *These authors contributed equally to this work Abstract: Damage to the developing brain may lead to impairment of the hand motor function and negatively impact on patients’ quality of life. Development of manual dexterity and finger and hand motor function may be promoted by learning to play the piano. The latter brings together music with the intensive training of hand coordination and fine finger mobility. We investigated if learning to play the piano helped to improve hand motor skills in 18 youths with hand motor disorders resulting from damage during early brain development. Participants trained 35–40 minutes twice a week for 18 months with a professional piano teacher. With the use of a Musical Instrument Digital Interface piano, the uniformity of finger strokes could be objectively assessed from the timing of keystrokes. The analysis showed a significant improvement in the uniformity of keystrokes during the training. Furthermore, the youths showed strong motivation and engagement during the study. This is nevertheless an open study, and further studies remain needed to exclude effects of growth and concomitant therapies on the improvements observed and clarify which patients will more likely benefit from learning to play the piano. Keywords: manual skill, cerebral palsy, neurodevelopmental disorder, music, rehabilitation

  6. Reappraisal generation after acquired brain damage: The role of laterality and cognitive control

    Science.gov (United States)

    Salas, Christian E.; Gross, James J.; Turnbull, Oliver H.

    2014-01-01

    In the past decade, there has been growing interest in the neuroanatomical and neuropsychological bases of reappraisal. Findings suggest that reappraisal activates a set of areas in the left hemisphere (LH), which are commonly associated with language abilities and verbally mediated cognitive control. The main goal of this study was to investigate whether individuals with focal damage to the LH (n = 8) were more markedly impaired on a reappraisal generation task than individuals with right hemisphere lesions (RH, n = 8), and healthy controls (HC, n = 14). The reappraisal generation task consisted of a set of ten pictures from the IAPS, depicting negative events of different sorts. Participants were asked to quickly generate as many positive reinterpretations as possible for each picture. Two scores were derived from this task, namely difficulty and productivity. A second goal of this study was to explore which cognitive control processes were associated with performance on the reappraisal task. For this purpose, participants were assessed on several measures of cognitive control. Findings indicated that reappraisal difficulty – defined as the time taken to generate a first reappraisal – did not differ between LH and RH groups. However, differences were found between patients with brain injury (LH + RH) and HC, suggesting that brain damage in either hemisphere influences reappraisal difficulty. No differences in reappraisal productivity were found across groups, suggesting that neurological groups and HC are equally productive when time constraints are not considered. Finally, only two cognitive control processes inhibition and verbal fluency- were inversely associated with reappraisal difficulty. Implications for the neuroanatomical and neuropsychological bases of reappraisal generation are discussed, and implications for neuro-rehabilitation are considered. PMID:24711799

  7. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    Science.gov (United States)

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort.

    Science.gov (United States)

    Conti, F; Ceccarelli, F; Perricone, C; Leccese, I; Massaro, L; Pacucci, V A; Truglia, S; Miranda, F; Spinelli, F R; Alessandri, C; Valesini, G

    2016-06-01

    Literature data suggest a significantly higher mortality in patients affected by systemic lupus erythematosus (SLE) developing chronic damage. Therefore, damage prevention is a major goal in the management of SLE patients. In the present study, we assessed damage by means of the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI), in a large cohort of SLE patients. Additionally, we aimed at evaluating its association with demographic and clinical features as well as with disease activity and laboratory findings. We enrolled consecutive patients affected by SLE diagnosed according to the American College of Rheumatology (ACR) 1997 revised criteria. Chronic damage was determined by SDI calculated at the last examination in all patients with at least six months of follow-up. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); flare was defined as an increase of SLEDAI-2K ≥ 4 compared with the previous visit. We evaluated 349 SLE patients (M/F 25/324, mean age ± SD 42.7 ± 12.4 years, mean disease duration ± SD 164.9 ± 105.2 months). Among the enrolled patients, 125 (35.8%) showed a SDI ≥ 1 (mean SDI ± SD 1.7 ± 0.9, range 0-5). The musculo-skeletal was the most frequently involved organ/system in SDI score (41/349 patients, 11.7%), with deforming/erosive arthritis in 21/349 (6.0%). The presence of chronic damage was associated with age (P < 0.001), disease duration (P < 0.001), number of flares (P = 0.02) and with the use of glucocorticoids (P = 0.02). The logistic regression analysis revealed the association between neuropsychiatric damage and antiphospholipid syndrome (P = 0.01, OR = 3.9) and between the presence of cardiovascular damage and anti-β2GPI antibodies (P = 0.01, OR 6.2). In the present study chronic damage was identified in about one third of SLE patients. The

  9. Upregulation of Interferon-inducible and damage response pathways in chronic graft-versus-host disease

    Science.gov (United States)

    Hakim, Frances T.; Memon, Sarfraz; Jin, Ping; Imanguli, Matin M.; Wang, Huan; Rehman, Najibah; Yan, Xiao-Yi; Rose, Jeremy; Mays, Jacqueline W.; Dhamala, Susan; Kapoor, Veena; Telford, William; Dickinson, John; Davis, Sean; Halverson, David; Naik, Haley B.; Baird, Kristin; Fowler, Daniel; Stroncek, David; Cowen, Edward W.; Pavletic, Steven Z.; Gress, Ronald E.

    2016-01-01

    Although Chronic Graft-versus-Host Disease (CGVHD) is the primary non-relapse complication of allogeneic transplantation, understanding of its pathogenesis is limited. To identify the main operant pathways across the spectrum of CGVHD, we analyzed gene expression in circulating monocytes, chosen as in situ systemic reporter cells. Microarrays identified two interrelated pathways: (1) Interferon-inducible genes and (2) innate receptors for cellular damage. Corroborating these with multiplex RNA quantitation, we found that multiple IFN-inducible genes (affecting lymphocyte trafficking, differentiation and antigen presentation) were concurrently upregulated in CGVHD monocytes compared to normal and nonCGVHD controls. IFN-inducible chemokines were elevated in both lichenoid and sclerotic CGHVD plasma and linked to CXCR3+ lymphocyte trafficking. Furthermore, the IFN-inducible genes CXCL10 and TNFSF13B (BAFF) levels were correlated at both the gene and plasma levels, implicating IFN-induction as a factor in elevated BAFF levels in CGVHD. In the second pathway, DAMP/PAMP receptor genes capable of inducing Type I IFN were upregulated. Type I IFN-inducible MxA was expressed in proportion to CGVHD activity in skin, mucosa and glands, and expression of TLR and RIG-1 receptor genes correlated with upregulation of Type I IFN-inducible genes in monocytes. Finally, in serial analyses following transplant, IFN-inducible and damage-response genes were upregulated in monocytes at CGVHD onset and declined upon therapy and resolution in both lichenoid and sclerotic CGVHD patients. This interlocking analysis of IFN-inducible genes, plasma analytes and tissue immunohistochemistry strongly supports a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD. PMID:27694491

  10. Chronic vitamin C deficiency does not accelerate oxidative stress in ageing brains of guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Hasselholt, Stine; Miyashita, Namiyo

    2012-01-01

      Increased oxidative stress in the brain has consistently been implied in ageing and in several degenerative brain disorders. Acting as a pivotal antioxidant in the brain, vitamin C is preferentially retained during deficiency and may play an essential role in neuroprotection during ageing. Thus......, a lack of vitamin C could be associated with an increase in redox imbalance in the ageing brain. The present study compared oxidative stress of ageing to that of a long-term non-scorbutic vitamin C deficiency in guinea pigs. Adults (3-9 months old) were compared to old (36-42 months old) animals during...... a six-month dietary intervention by assessing vitamin C transport and redox homeostasis in the brain. In contrast to our hypothesis, chronic vitamin C deficiency did not affect the measured markers of oxidative stress in the brains of adult and aged animals. However, aged animals generally showed...

  11. Adipose Tissue-Derived Stem Cells Reduce Acute and Chronic Kidney Damage in Mice.

    Directory of Open Access Journals (Sweden)

    Marina Burgos-Silva

    Full Text Available Acute and chronic kidney injuries (AKI and CKI constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs in an experimental model of nephrotoxicity induced by folic acid (FA in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xiaojuan Qie

    2017-09-01

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

  14. Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD.

    Science.gov (United States)

    Borroni, Barbara; Alberici, Antonella; Cercignani, Mara; Premi, Enrico; Serra, Laura; Cerini, Carlo; Cosseddu, Maura; Pettenati, Carla; Turla, Marinella; Archetti, Silvana; Gasparotti, Roberto; Caltagirone, Carlo; Padovani, Alessandro; Bozzali, Marco

    2012-10-01

    Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degeneration (FTLD) by haploinsufficiency mechanism, although their effects on brain tissue dysfunction and damage still remain to be clarified. In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the DMN. Our findings suggest that compensatory mechanisms of brain plasticity are present in GRN-related FTLD, but with different patterns at a preclinical and symptomatic disease stage. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Dimethyl Fumarate Protects Brain From Damage Produced by Intracerebral Hemorrhage by Mechanism Involving Nrf2.

    Science.gov (United States)

    Zhao, Xiurong; Sun, Guanghua; Zhang, Jie; Ting, Shun-Ming; Gonzales, Nicole; Aronowski, Jaroslaw

    2015-07-01

    Intracerebral hemorrhage (ICH) represents a devastating form of stroke for which there is no effective treatment. This preclinical study was designed to evaluate dimethyl fumarate (DMF), a substance recently approved for the treatment of multiple sclerosis, as therapy for ICH. We hypothesized that DMF through activating the master regulator of cellular self-defense responses, transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), would act as effective treatment for ICH-mediated damage. Male rats and mice, including Nrf2 knockouts, were subjected to intracerebral injection of blood (to mimic ICH) and then treated with DMF. Neurological deficit, brain edema, gene induction profile and hematoma resolution were evaluated. Phagocytic functions of primary microglia in culture were used to study hematoma resolution. Treatment with DMF induced Nrf2-target genes, improved hematoma resolution, reduced brain edema, and ultimately enhanced neurological recovery in rats and wild-type, but not Nrf2 knockout, mice. Most importantly, the treatment of ICH with DMF showed a 24 h window of therapeutic opportunity. A clinically relevant dose of DMF demonstrates potent therapeutic efficacy and impressive 24 h therapeutic window of opportunity. This study merits further evaluation of this compound as potential treatment for ICH in humans. © 2015 American Heart Association, Inc.

  16. Clinical research on intelligence seven needle therapy treated infants with brain damage syndrome.

    Science.gov (United States)

    Liu, Zhen-Huan; Li, Ye-Rong; Lu, Yong-Lin; Chen, Jie-Kui

    2016-06-01

    To assess whether the intelligence seven needle therapy administered in infants with perinatal brain damage syndrome (BDS) as early intervention would improve patients' neural development. A randomized controlled trial was conducted. Sixty-four infants with BDS were randomly assigned to two groups: the comprehensive group and the control group. Both groups received routine early intervention; in addition, the comprehensive group received intelligence seven needle therapy. Before and after treatment, the Bayley Scale of Infant Development (BSID), Gesell Developmental Schedules, Gross Motor Function Measure (GMFM), transcranial doppler ultrasound (TCD), and cranial imaging examination were tested for contrast. After treatment, the comprehensive group showed significant difference in the Mental Development Index (MDI) scores of BSID compared with the control group (P0.05) was observed. The children's development quotients (DQ) of the comprehensive group exhibited a significant superiority in improving the social adaptation DQ of Gesell Developmental Schedules compared with the control group (Plinguistic and social intercourse (P0.05). The total scores of GMFM in the comprehensive group were higher than those in the control group (Pintelligence, motion function, linguistic competence and social intercourse can be promoted for infants with perinatal BDS by treating with the intelligence seven needle therapy. This approach can improve the brain blood supply and promote the growth of frontal and parietal lobes.

  17. Chronic alcohol consumption increases the expression of uncoupling protein-2 and -4 in the brain.

    Science.gov (United States)

    Graw, Jan A; von Haefen, Clarissa; Poyraz, Deniz; Möbius, Nadine; Sifringer, Marco; Spies, Claudia D

    2013-10-01

    Chronic alcohol consumption leads to oxidative stress in a variety of cells, especially in brain cells because they have a reduced oxidative metabolism of alcohol. Uncoupling proteins (UCPs) are anion channels of the inner mitochondrial membrane, which can decouple internal respiration. "Mild uncoupling" of the mitochondrial respiratory chain leads to a reduced production of free radicals (reactive oxygen species) and a reduction in oxidative cell stress. The extent to which chronic alcohol consumption regulates UCP-2 and -4 in the brain is still unknown. We examined the effects of a 12-week 5% alcohol diet in the brain of male Wistar rats (n = 34). Cerebral gene and protein expression of UCP-2, -4, as well as Bcl-2, and the release of cytochrome c out of the mitochondria were detected by real-time polymerase chain reaction and Western blot analysis. The percentage of degenerated cells was determined by Fluoro-Jade B staining of brain slices. Brains of rats with a chronic alcohol diet showed an increased gene and protein expression of UCP-2 and -4. The expression of the antiapoptotic protein Bcl-2 in the brain of the alcohol-treated animals was decreased significantly, whereas cytochrome c release from mitochondria was increased. In addition increased neurodegeneration could be demonstrated in the alcohol-treated animals. Chronic alcohol consumption leads to a cerebral induction of UCP-2 and -4 with a simultaneous decrease in the antiapoptotic protein Bcl-2, cytochrome c release from mitochondria and increased neurodegeneration. This study reveals a compensatory effect of UCP-2 and -4 in the brain during chronic alcohol consumption. Copyright © 2013 by the Research Society on Alcoholism.

  18. [Brain changes in patients on chronic hemodialysis recorded by computed axial tomography].

    Science.gov (United States)

    Todorov, V; Penkova, S; Boneva, R; Kiuchukov, G

    1988-01-01

    The brain changes in patients with chronic renal failure treated by chronic hemodialysis were studied with the help of computed tomography. The results showed the development of internal hydrocephalus in the patients in whose treatment "hard" water was used. In some of these patients the hydrocephalus was accompanied by clinical manifestations of the "disequilibrium" syndrome and the "hard water" syndrome. The patients dialyzed with "soft" water showed no brain changes and clinical signs. Hydrocephalus is probably the main pathogenetic factor for the development of the "hard water" syndrome which later develops in dialysis encephalopathy.

  19. Effect of taurine on chronic and acute liver injury: Focus on blood and brain ammonia

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-01-01

    Full Text Available Hyperammonemia is associated with chronic and acute liver injury. There is no promising therapeutic agent against ammonia-induced complications. Hence, finding therapeutic molecules with safe profile of administration has clinical value. The present study was conducted to evaluate the role of taurine (TA administration on plasma and brain ammonia and its consequent events in different models of chronic and acute liver injury and hyperammonemia. Bile duct ligated (BDL rats were used as a model of chronic liver injury. Thioacetamide and acetaminophen-induced acute liver failure were used as acute liver injury models. A high level of ammonia was detected in blood and brain of experimental groups. An increase in brain ammonia level coincided with a decreased total locomotor activity of animals and significant changes in the biochemistry of blood and also liver tissue. TA administration (500 and 1000 mg/kg, i.p, effectively alleviated liver injury and its consequent events including rise in plasma and brain ammonia and brain edema. The data suggested that TA is not only a useful and safe agent to preserve liver function, but also prevented hyperammonemia as a deleterious consequence of acute and chronic liver injury.

  20. Telephone-Delivered Cognitive Behavioral Therapy for Chronic Pain Following Traumatic Brain Injury

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-12-2-0109 TITLE: Telephone-Delivered Cognitive Behavioral Therapy for Chronic Pain Following Traumatic Brain Injury...2014-29 Sept 2015 4. TITLE AND SUBTITLE Telephone-Delivered Cognitive Behavioral Therapy for Chronic Pain 5a. CONTRACT NUMBER W81XWH-12-2-0109...included a Quad Chart for this particular study as requested by the CDMRP. Planned Recruitment Telephone-Delivered Cognitive Behavioral Therapy for

  1. Quantitative MRI analysis of the brain after twenty-two years of neuromyelitis optica indicates focal tissue damage

    DEFF Research Database (Denmark)

    Aradi, Mihaly; Koszegi, Edit; Orsi, Gergely

    2013-01-01

    BACKGROUND: The long-term effect of neuromyelitis optica (NMO) on the brain is not well established. METHODS: After 22 years of NMO, a patient's brain was examined by quantitative T1- and T2-weighted mono- and biexponential diffusion and proton spectroscopy. It was compared to 3 cases with short......, and they were also not quantitatively different from the controls. CONCLUSION: After NMO of 22-year duration, metabolic changes, altered diffusivity and magnetic resonance relaxation features of patchy brain areas may suggest tissue damage in NAWM that persist for at least 6 months....

  2. Systematic review of prediction of poor outcome in anoxic-ischaemic coma with biochemical markers of brain damage

    NARCIS (Netherlands)

    Zandbergen, E. G.; de Haan, R. J.; Hijdra, A.

    2001-01-01

    OBJECTIVE: To investigate whether accurate prognostic rules can be derived from the combined results of studies concerning prediction of poor prognosis in anoxic-ischaemic coma with biochemical markers of brain damage in cerebrospinal fluid (CSF) or serum. DESIGN: A meta-analysis of prognostic

  3. Metallic gold reduces TNFalpha expression, oxidative DNA damage and pro-apoptotic signals after experimental brain injury

    DEFF Research Database (Denmark)

    Pedersen, Mie Ostergaard; Larsen, Agnete; Pedersen, Dan Sonne

    2009-01-01

    -45 microm in size or the vehicle (placebo) were implanted in the cortical tissue followed by a cortical freeze-lesioning. At 1-2 weeks post-injury, brains were analyzed by using immunohistochemistry and markers of inflammation, oxidative stress and apoptosis. This study shows that gold treatment......Brain injury represents a major health problem and may result in chronic inflammation and neurodegeneration. Due to antiinflammatory effects of gold, we have investigated the cerebral effects of metallic gold particles following a focal brain injury (freeze-lesion) in mice. Gold particles 20...

  4. Bisecting or Not Bisecting: This Is the Neglect Question. Line Bisection Performance in the Diagnosis of Neglect in Right Brain-Damaged Patients

    Science.gov (United States)

    Guariglia, Paola; Matano, Alessandro; Piccardi, Laura

    2014-01-01

    In the present study we analysed the bisecting behaviour of 287 chronic right brain-damaged patients by taking into account the presence and severity of extrapersonal and/or personal neglect diagnosed with the hemineglect battery. We also analysed right brain-damaged patients who had (or did not have) neglect according to their line bisection performance. Our results showed that performance of the line bisection task correlates with performance of cancellation tasks, reading and perceptual tasks, but not with the presence of personal neglect. Personal neglect seems to be unrelated to line bisection behaviour. Indeed, patients affected by extrapersonal and personal neglect do not show more severe neglect in line bisection than patients with only extrapersonal neglect. Furthermore, we observed that 20.56% of the patients were considered affected or not by neglect on the line bisection task compared with the other spatial tasks of the hemineglect battery. We conclude that using a battery with multiple tests is the only way to guarantee a reliable diagnosis and effectively plan for rehabilitative training. PMID:24937472

  5. Cytogenetic Damages Induced by Chronic Exposure to Microwave Non-Ionizing Radiofrequency Fields

    Directory of Open Access Journals (Sweden)

    Boris Đinđić

    2013-12-01

    Full Text Available Non-ionizing radiation has a significant and positive impact on modern society through a number of uses. There is increasing public concern regarding the health risks of radio-frequency (RF radiation, particularly that produced by mobile phones. Concern regarding the potential risks of exposure to EMFs has led to many epidemiological investigations, but the effects of EMF exposure on human and other mammalian cells are still unclear. One of the most frequently asked questions about the effects of microwave radiation on biological systems is whether they produce genotoxic effects and could be there a possible link with oncogenic processes. It is most difficult to get accurate and reproducible results for the studies that tell us most about the effects of EMF on humans. Based on some “weak” evidence suggesting an association between exposure to radiofrequency fields (RF emitted from mobile phones and two types of brain cancer, glioma and acoustic neuroma, the International Agency for Research on Cancer has classified RF as ‘possibly carcinogenic to humans’ in group 2B. Literature results suggest that pulsed microwaves from working environment can be the cause of genetic and cell alterations. Taken together, the increased frequency of DNA damages, increased intensity of oxydative stress and production of reactive oxygen species as well as prolonged disruption in DNA repair mechanisms could be possible mechanisms for microwave induced cytogenetic damages even at low-level electromagnetic fields. Although there were contradictory results about harmful effects of electromagnetic fields we recommend that the mobile phone should be kept as far as possible from the body during conversations and also during usual daily activities to reduce the absorption of radiation by cells. In addition, the appropriate intake of antioxidant-rich food or drugs may be helpful for preventing the genotoxic effects that could be caused by mobile phone use.

  6. The Protective Effect of Selenium on Chronic Zearalenone-Induced Reproductive System Damage in Male Mice.

    Science.gov (United States)

    Long, Miao; Yang, Shuhua; Wang, Yuan; Li, Peng; Zhang, Yi; Dong, Shuang; Chen, Xinliang; Guo, Jiayi; He, Jianbin; Gao, Zenggui; Wang, Jun

    2016-12-07

    This study aims to explore the protective effect of selenium (Se) on chronic zearalenone (ZEN)-induced reproductive system damage in male mice and the possible protective molecular mechanism against this. The chronic ZEN-induced injury mouse model was established with the continuous intragastric administration of 40 mg/kg body mass (B.M.) ZEN for 28 days. Then, interventions with different doses (0.1, 0.2, and 0.4 mg/kg B.M.) of Se were conducted on mice to analyse the changes in organ indexes of epididymis and testis, antioxidant capability of testis, serum level of testosterone, sperm concentration and motility parameters, and the expression levels of apoptosis-associated genes and blood testis barrier- (BTB) related genes. Our results showed that Se could greatly improve the ZEN-induced decrease of epididymis indexes and testis indexes. Results also showed that the decrease in sperm concentration, sperm normality rate, and sperm motility parameters, including percentage of motile sperm (motile), tropism percentage (progressive) and sperm average path velocity (VAP), caused by ZEN were elevated upon administration of the higher dose (0.4 mg/kg) and intermediate dose (0.2 mg/kg) of Se. Selenium also significantly reduced the content of malondialdehyde (MDA) but enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the testis tissue. Further research demonstrated that ZEN increased the level of mRNA expression of BCL2-associated X protein (Bax) and caspase 3 (Casp3), decreased the level of mRNA expression of B cell leukemia/lymphoma 2 (Bcl2), vimentin (Vim) and cadherin 2 (Cdh2), whereas the co-administration of Se reversed these gene expression levels. Our results indicated that high levels of Se could protect against reproductive system damage in male mice caused by ZEN and the mechanism might such be that Se improved mice antioxidant ability, inhibited reproductive cell apoptosis, and increased the decrease

  7. The Protective Effect of Selenium on Chronic Zearalenone-Induced Reproductive System Damage in Male Mice

    Directory of Open Access Journals (Sweden)

    Miao Long

    2016-12-01

    Full Text Available This study aims to explore the protective effect of selenium (Se on chronic zearalenone (ZEN-induced reproductive system damage in male mice and the possible protective molecular mechanism against this. The chronic ZEN-induced injury mouse model was established with the continuous intragastric administration of 40 mg/kg body mass (B.M. ZEN for 28 days. Then, interventions with different doses (0.1, 0.2, and 0.4 mg/kg B.M. of Se were conducted on mice to analyse the changes in organ indexes of epididymis and testis, antioxidant capability of testis, serum level of testosterone, sperm concentration and motility parameters, and the expression levels of apoptosis-associated genes and blood testis barrier- (BTB related genes. Our results showed that Se could greatly improve the ZEN-induced decrease of epididymis indexes and testis indexes. Results also showed that the decrease in sperm concentration, sperm normality rate, and sperm motility parameters, including percentage of motile sperm (motile, tropism percentage (progressive and sperm average path velocity (VAP, caused by ZEN were elevated upon administration of the higher dose (0.4 mg/kg and intermediate dose (0.2 mg/kg of Se. Selenium also significantly reduced the content of malondialdehyde (MDA but enhanced the activities of antioxidant enzymes superoxide dismutase (SOD and glutathione peroxidase (GPx in the testis tissue. Further research demonstrated that ZEN increased the level of mRNA expression of BCL2-associated X protein (Bax and caspase 3 (Casp3, decreased the level of mRNA expression of B cell leukemia/lymphoma 2 (Bcl2, vimentin (Vim and cadherin 2 (Cdh2, whereas the co-administration of Se reversed these gene expression levels. Our results indicated that high levels of Se could protect against reproductive system damage in male mice caused by ZEN and the mechanism might such be that Se improved mice antioxidant ability, inhibited reproductive cell apoptosis, and increased the

  8. Imaging in Chronic Traumatic Encephalopathy and Traumatic Brain Injury.

    Science.gov (United States)

    Shetty, Teena; Raince, Avtar; Manning, Erin; Tsiouris, Apostolos John

    2016-01-01

    The diagnosis of chronic traumatic encephalopathy (CTE) can only be made pathologically, and there is no concordance of defined clinical criteria for premorbid diagnosis. The absence of established criteria and the insufficient imaging findings to detect this disease in a living athlete are of growing concern. The article is a review of the current literature on CTE. Databases searched include Medline, PubMed, JAMA evidence, and evidence-based medicine guidelines Cochrane Library, Hospital for Special Surgery, and Cornell Library databases. Clinical review. Level 4. Chronic traumatic encephalopathy cannot be diagnosed on imaging. Examples of imaging findings in common types of head trauma are discussed. Further study is necessary to correlate the clinical and imaging findings of repetitive head injuries with the pathologic diagnosis of CTE. © 2015 The Author(s).

  9. The Relation of Mild Traumatic Brain Injury to Chronic Lapses of Attention

    Science.gov (United States)

    Pontifex, Matthew B.; Broglio, Steven P.; Drollette, Eric S.; Scudder, Mark R.; Johnson, Chris R.; O'Connor, Phillip M.; Hillman, Charles H.

    2012-01-01

    We assessed the extent to which failures in sustained attention were associated with chronic mild traumatic brain injury (mTBI) deficits in cognitive control among college-age young adults with and without a history of sport-related concussion. Participants completed the ImPACT computer-based assessment and a modified flanker task. Results…

  10. Amateur boxing and risk of chronic traumatic brain injury: systematic review of observational studies

    Science.gov (United States)

    Knowles, Charles H; Whyte, Greg P

    2007-01-01

    Objective To evaluate the risk of chronic traumatic brain injury from amateur boxing. Setting Secondary research performed by combination of sport physicians and clinical academics. Design, data sources, and methods Systematic review of observational studies in which chronic traumatic brain injury was defined as any abnormality on clinical neurological examination, psychometric testing, neuroimaging studies, and electroencephalography. Studies were identified through database (1950 to date) and bibliographic searches without language restrictions. Two reviewers extracted study characteristics, quality, and data, with adherence to a protocol developed from a widely recommended method for systematic review of observational studies (MOOSE). Results 36 papers had relevant extractable data (from a detailed evaluation of 93 studies of 943 identified from the initial search). Quality of evidence was generally poor. The best quality studies were those with a cohort design and those that used psychometric tests. These yielded the most negative results: only four of 17 (24%) better quality studies found any indication of chronic traumatic brain injury in a minority of boxers studied. Conclusion There is no strong evidence to associate chronic traumatic brain injury with amateur boxing. PMID:17916811

  11. Systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury

    DEFF Research Database (Denmark)

    Godbolt, Alison K; Cancelliere, Carol; Hincapié, Cesar A

    2014-01-01

    OBJECTIVE: To synthesize the best available evidence regarding the risk of dementia and chronic cognitive impairment (CCI) after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001-2012) using a previously published search strategy and predefined...

  12. Brain-Machine Interface in chronic stroke rehabilitation: A controlled study

    NARCIS (Netherlands)

    Ramos-Murguialday, A.; Brötz, D.; Rea, M.; Laër, L.; Yilmaz, O.; Brasil, F.L.; Liberati, G.; Curado, M.R.; Garcia Cossio, E.; Vyziotis, A.; Cho, W.; Agostini, M.; Soares, E.; Soekadar, S.R.; Caria, A.; Cohen, L.G.; Birbaumer, N.

    2013-01-01

    Objective: Chronic stroke patients with severe hand weakness respond poorly to rehabilitation efforts. Here, we evaluated efficacy of daily brain-machine interface (BMI) training to increase the hypothesized beneficial effects of physiotherapy alone in patients with severe paresis in a double-blind

  13. Chronic traumatic encephalopathy: the neuropathological legacy of traumatic brain injury

    OpenAIRE

    Hay, Jennifer; Johnson, Victoria E.; Smith, Douglas H.; Stewart, W

    2016-01-01

    Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy st...

  14. The perception of peripersonal space in right and left brain damage hemiplegic patients

    Directory of Open Access Journals (Sweden)

    Angela eBartolo

    2014-01-01

    Full Text Available Peripersonal space, as opposed to extrapersonal space, is the space that contains reachable objects and in which multisensory and sensorimotor integration is enhanced. Thus, the perception of peripersonal space requires combining information on the spatial properties of the environment with information on the current capacity to act. In support of this, recent studies have provided converging evidences that perceiving objects in peripersonal space activates a neural network overlapping with that subtending voluntary motor action and motor imagery. Other studies have also underlined the dominant role of the right hemisphere in motor planning and of the left hemisphere in on-line motor guiding, respectively. In the present study, we investigated the effect of a right or left hemiplegia in the perception of peripersonal space. 16 hemiplegic patients with brain damage to the left (LH or right (RH hemisphere and 8 matched healthy controls (HC performed a colour discrimination, a motor imagery and a reachability judgment task. Analyses of response times and accuracy revealed no variation among the three groups in the colour discrimination task, suggesting the absence of any specific perceptual or decisional deficits in the patient groups. In contrast, the patient groups revealed longer response times in the motor imagery task when performed in reference to the hemiplegic arm (RH and LH or to the healthy arm (RH. Moreover, RH group showed longer response times in the reachability judgement task, but only for stimuli located at the boundary of peripersonal space, which was furthermore significantly reduced in size. Considered together, these results confirm the crucial role of the motor system in motor imagery task and the perception of peripersonal space. They also revealed that right hemisphere damage has a more detrimental effect on reachability estimates, suggesting that motor planning processes contribute specifically to the perception of

  15. The perception of peripersonal space in right and left brain damage hemiplegic patients.

    Science.gov (United States)

    Bartolo, Angela; Carlier, Mauraine; Hassaini, Sabrina; Martin, Yves; Coello, Yann

    2014-01-01

    Peripersonal space, as opposed to extrapersonal space, is the space that contains reachable objects and in which multisensory and sensorimotor integration is enhanced. Thus, the perception of peripersonal space requires combining information on the spatial properties of the environment with information on the current capacity to act. In support of this, recent studies have provided converging evidences that perceiving objects in peripersonal space activates a neural network overlapping with that subtending voluntary motor action and motor imagery. Other studies have also underlined the dominant role of the right hemisphere (RH) in motor planning and of the left hemisphere (LH) in on-line motor guiding, respectively. In the present study, we investigated the effect of a right or left hemiplegia in the perception of peripersonal space. 16 hemiplegic patients with brain damage to the left (LH) or right (RH) hemisphere and eight matched healthy controls performed a color discrimination, a motor imagery and a reachability judgment task. Analyses of response times and accuracy revealed no variation among the three groups in the color discrimination task, suggesting the absence of any specific perceptual or decisional deficits in the patient groups. In contrast, the patient groups revealed longer response times in the motor imagery task when performed in reference to the hemiplegic arm (RH and LH) or to the healthy arm (RH). Moreover, RH group showed longer response times in the reachability judgment task, but only for stimuli located at the boundary of peripersonal space, which was furthermore significantly reduced in size. Considered together, these results confirm the crucial role of the motor system in motor imagery task and the perception of peripersonal space. They also revealed that RH damage has a more detrimental effect on reachability estimates, suggesting that motor planning processes contribute specifically to the perception of peripersonal space.

  16. Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

    Science.gov (United States)

    Roll, Lars; Faissner, Andreas

    2014-01-01

    The limited regeneration capacity of the adult central nervous system (CNS) requires strategies to improve recovery of patients. In this context, the interaction of endogenous as well as transplanted stem cells with their environment is crucial. An understanding of the molecular mechanisms could help to improve regeneration by targeted manipulation. In the course of reactive gliosis, astrocytes upregulate Glial fibrillary acidic protein (GFAP) and start, in many cases, to proliferate. Beside GFAP, subpopulations of these astroglial cells coexpress neural progenitor markers like Nestin. Although cells express these markers, the proportion of cells that eventually give rise to neurons is limited in many cases in vivo compared to the situation in vitro. In the first section, we present the characteristics of endogenous progenitor-like cells and discuss the differences in their neurogenic potential in vitro and in vivo. As the environment plays an important role for survival, proliferation, migration, and other processes, the second section of the review describes changes in the extracellular matrix (ECM), a complex network that contains numerous signaling molecules. It appears that signals in the damaged CNS lead to an activation and de-differentiation of astrocytes, but do not effectively promote neuronal differentiation of these cells. Factors that influence stem cells during development are upregulated in the damaged brain as part of an environment resembling a stem cell niche. We give a general description of the ECM composition, with focus on stem cell-associated factors like the glycoprotein Tenascin-C (TN-C). Stem cell transplantation is considered as potential treatment strategy. Interaction of transplanted stem cells with the host environment is critical for the outcome of stem cell-based therapies. Possible mechanisms involving the ECM by which transplanted stem cells might improve recovery are discussed in the last section. PMID:25191223

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

    Science.gov (United States)

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

    2012-07-01

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

  18. A new method for evaluation of motor injury after acute brain ischemic damage.

    Science.gov (United States)

    Hu, Zeng-Chun; Ma, Hui; Fan, Qing; Yin, Jian; Wei, Ming-Hai; Lin, Yong-Zhong; Fan, Ming; Sun, Chang-Kai

    2015-04-01

    Motor impairment is an important index for assessing the extent of brain injury. The present study uses a new method, the movement capture analysis (MOCA) system, for assessing motor damage after acute ischemia. Forty rats were divided into four groups: standard ischemia, sham-operated, Dizocilpine (MK-801), and Ginkgo biloba extract (GBE) groups. Brain ischemia was induced using the temporary right middle cerebral artery occlusion model. Longa score and MOCA were used to assess motor injury one day after ischemia. Infarct volume was delineated with 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. The correlation of infarct volume with Longa score and MOCA data was calculated. Compared with the sham-operated group (0.10 ± 0.31), Longa scores of MK-801 (2.33 ± 0.73), GBE (1.80 ± 0.58), and standard (2.88 ± 0.83) groups showed a statistical difference (p 801 and standard groups. MOCA was able to clearly discern the differences in motor disparity among the four groups, standard (1.00 ± 0.19), sham-operated group (0.17 ± 0.02), MK-801 (0.79 ± 0.08), GBE (0.38 ± 0.05) (p 801 (18.03 ± 0.96%) and GBE (10.82 ± 1.93%) treatment reduced infarct size compared with the standard ischemia group (25.88 ± 1.16%) (p < 0.05). The MOCA data showed a more significant correlation with infarct size than Longa score (r = 0.85:0.53). MOCA system proved to be more sensitive than the Longa score. It may potentially be more accurate method for behavioral evaluation in clinical trials.

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

    Science.gov (United States)

    Nonato, L F; Rocha-Vieira, E; Tossige-Gomes, R; Soares, A A; Soares, B A; Freitas, D A; Oliveira, M X; Mendonça, V A; Lacerda, A C; Massensini, A R; Leite, H R

    2016-09-29

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

  20. Clozapine linked to nanocapsules minimizes tissue and oxidative damage to biomolecules lipids, proteins and DNA in brain of rats Wistar.

    Science.gov (United States)

    da Costa Güllich, Angélica Aparecida; Coelho, Ritiéle Pinto; Pilar, Bruna Cocco; Ströher, Deise Jaqueline; Galarça, Leandro Alex Sander Leal; Vieira, Simone Machado; da Costa Escobar Piccoli, Jacqueline; Haas, Sandra Elisa; Manfredini, Vanusa

    2015-06-01

    Clozapine, atypical antipsychotic, can change oxidative stress parameters. It is known that reactive species, in excess, can have a crucial role in the etiology of diseases, as well as, can potentiating adverse effects induce by drugs. The nanocapsules have attracted attention as carriers of several drugs, with consequent reduction of adverse effects. This study aimed to evaluate histopathology and oxidative damage of biomolecules lipids, proteins and DNA in the brain of Wistar rats after treatment with nanocapsules containing clozapine. The study consisted of eight groups of male Wistar rats (n = 6): saline (SAL), free clozapine (CZP) (25 mg/Kg i.p.), blank uncoated nanocapsules (BNC), clozapine-loaded uncoated nanocapsules (CNC) (25 mg/Kg i.p.), blank chitosan-coated nanocapsules (BCSN), clozapine-loaded chitosan-coated nanocapsules (CCSN) (25 mg/Kg i.p.), blank polyethyleneglycol-coated nanocapsules (BPEGN), clozapine-loaded polyethyleneglycol-coated nanocapsules (CPEGN) (25 mg/Kg i.p.). The animals received the formulation once a day for seven consecutive days and euthanized in the eighth day. After euthanasia, the brain was collected and homogenate was processed for further analysis. The histopathology showed less brain tissue damage in nanocapsules-treated groups. The lipid peroxidation and carbonylation of proteins showed a significant increase (p < 0.05) induced by CZP. CNC and CPEGN groups obtained a reduction membrane of lipids damage and nanocapsules-treated groups showed significant improvement protein damage. CZP was able to induce genetic oxidative damage, while the nanocapsules causing less damage to DNA. The findings show that different coatings can act protecting target tissues decreasing oxidative damage, suggesting that the drug when linked to different nanocapsules is able to mitigate the harmful effects of clozapine.

  1. Diversity of endurance training effects on antioxidant defenses and oxidative damage in different brain regions of adolescent male rats.

    Science.gov (United States)

    Chalimoniuk, M; Jagsz, S; Sadowska-Krepa, E; Chrapusta, S J; Klapcinska, B; Langfort, J

    2015-08-01

    Studies on the effect of physical activity on brain oxidative stress, performed mostly in adult rats, have shown that moderate aerobic activity increases resistance to oxidative stress and reduces cellular damage. These effects can greatly differ between various brain regions. The postnatal period of the highest brain sensitivity to various stimuli is adolescence. We hypothesized that endurance training will modify brain antioxidant barrier differently in various regions, depending on their role in locomotion. Therefore, we studied the effect of moderate intensity endurance training on the activities of selected antioxidant enzymes (superoxide dismutase, gluthathione peroxidase and catalase and the contents of thiobarbituric acid-reactive substances (the key index of lipid peroxidation) and glutathione in several brain regions with dissimilar relationship to locomotion, as well as in circulating blood. Additionally, we investigated the effect of the training on nitric oxide synthase activity that may be a major player in exercise-related oxidative stress in brain regions that are directly involved in the locomotion control and execution (the striatum, midbrain and cerebellum). The training significantly enhanced nitric oxide synthase activity only in the latter three regions. Surprisingly, it elevated the activities of all studied antioxidant enzymes (excepting gluthathione peroxidase) in the neocortex, while no appreciable change in these activities was found in either the cerebellum (except for elevated catalase activity), or the striatum, or the midbrain. The training also elevated total glutathione content (a key protector of brain proteins under the conditions of enhanced nitric oxide production) in the cerebellum and striatum, but not in the other regions. The observed brain changes greatly differed from those in circulating blood and did not prevent the training-related increases in oxidative damage as evidenced by elevations in cerebellar and striatal

  2. Up-regulation of heme oxygenase-1 protects against cold injury-induced brain damage: a laboratory-based study.

    Science.gov (United States)

    Shih, Ruey-Horng; Cheng, Shin-Ei; Tung, Wei-Hsuan; Yang, Chuen-Mao

    2010-08-01

    Heme oxygenase-1 (HO-1), a kind of stress protein, is critical for the protection against ischemic stroke and cerebrovascular endothelium damage. However, the effects of HO-1 on trauma-induced brain injury are still unknown. Hence, we attempted to use a cold injury-induced brain trauma (CIBT) model in mice, which provides for a well-established approach for assessing brain edema and blood-brain barrier breakdown. Additionally, we explored cultured mouse brain endothelial cells (bEnd.3) to investigate the protective effects of HO-1. HO-1 was induced by infection with a recombinant adenovirus carrying the human HO-1 gene or an inducer of HO-1 activity, cobalt protoporphyrin IX (CoPP). The recombinant adenovirus (3.5 x 10(7) PFU/mouse, i.v.) or CoPP (10 mg/kg, i.v.) significantly increased HO-1 protein expression and HO-1 enzyme activity in the cerebral cortex of the mice. We found that overexpression of HO-1 protected against cold injury-induced secondary damage and behavioral impairment. Up-regulation of HO-1 decreased brain edema and neutrophil infiltration induced by cold injury. These HO-1-dependent protecting effects were abrogated by pretreatment with the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP; 3 mg/kg, i.v.). HO-1 expression in the cerebral endothelium was observed by immunofluorescent staining. CoPP-induced (1 muM, 24 h) HO-1 protein expression was determined by western blotting in bEnd.3 cells. Enhanced HO-1 also protected against cold injury-induced cell loss and damage, which were respectively determined by GAPDH leakage into the cell medium and XTT assay in bEnd.3 cells. In summary, HO-1 overexpression appears to offer an effective neuroprotection against cold-induced secondary brain injury.

  3. The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy.

    Science.gov (United States)

    Petraglia, Anthony L; Plog, Benjamin A; Dayawansa, Samantha; Dashnaw, Matthew L; Czerniecka, Katarzyna; Walker, Corey T; Chen, Michael; Hyrien, Ollivier; Iliff, Jeffrey J; Deane, Rashid; Huang, Jason H; Nedergaard, Maiken

    2014-01-01

    An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury (mTBI) in mice that encapsulates the neurobehavioral spectrum characteristic of patients with CTE. We aimed to study the pathophysiological mechanisms underlying this animal model. Our previously described model allows for controlled, closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI mice received six concussive impacts daily, for 7 days. Mice were then subsequently sacrificed for macro- and micro-histopathologic analysis at 7 days, 1 month, and 6 months after the last TBI received. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for activated microglia, and AT8 for phosphorylated tau protein. Brains from single and repetitive mTBI mice lacked macroscopic tissue damage at all time-points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and increased phospho-tau immunoreactivity that was present acutely and at 1 month, but was not persistent at 6 months. Repetitive mTBI resulted in a more marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6-months. The neuropathological findings in this new model of repetitive mTBI resemble some of the histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation.

  4. Chronic noise stress-induced alterations of glutamate and gamma-aminobutyric acid and their metabolism in the rat brain

    OpenAIRE

    Amajad Iqbal Kazi; Anna Oommen

    2014-01-01

    Chronic stress induces neurochemical changes that include neurotransmitter imbalance in the brain. Noise is an environmental factor inducing stress. Chronic noise stress affects monoamine neurotransmitter systems in the central nervous system. The effect on other excitatory and inhibitory neurotransmitter systems is not known. The aim was to study the role of chronic noise stress on the glutamatergic and gamma-aminobutyric acid (GABA)ergic systems of the brain. Female Wistar rats (155 ± 5 g) ...

  5. Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy

    Science.gov (United States)

    Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K.; Bernick, Charles; Ghosh, Chaitali; Bazarian, Jeffrey J.; Janigro, Damir

    2016-01-01

    Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six post mortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. PMID:26556772

  6. Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.

    Science.gov (United States)

    Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K; Bernick, Charles; Ghosh, Chaitali; Rapp, Edward; Bazarian, Jeffrey J; Janigro, Damir

    2016-01-01

    Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (PCTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Chronic intoxication by methylmercury leads to oxidative damage and cell death in salivary glands of rats.

    Science.gov (United States)

    Farias-Junior, Paulo Mecenas Alves; Teixeira, Francisco Bruno; Fagundes, Nathalia Carolina Fernandes; Miranda, Giza Hellen Nonato; Oliveira Bittencourt, Leonardo; de Oliveira Paraense, Ricardo Sousa; Silva, Márcia Cristina Freitas; Sagica, Fernanda do Espírito Santo; de Oliveira, Edivaldo Herculano; Crespo-López, Maria Elena; Lima, Rafael Rodrigues

    2017-12-01

    Methylmercury (MeHg) is one of the most toxic species of mercury, causing several systemic damages; however, its effect on the salivary glands has rarely been explored to date. This study was aimed at analyzing the mercury deposit, oxidative stress markers, and cell viability in parotid and submandibular rat salivary glands after chronic methylmercury intoxication. Herein, forty male Wistar rats (40 days old) were used in the experiment. The animals of the experimental group were intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg per kg body weight per day for 35 days, whereas the control group received only corn oil, a diluent. After the period of intoxication, the glands were obtained for evaluation of total mercury deposit, cell viability, and the malondialdehyde (MDA) and the nitrite levels. Our results indicated mercury deposits in salivary glands, with a decrease in cell viability, higher levels of MDA in both glands of intoxicated animals, and a higher concentration of nitrite only in the submandibular gland of the mercury group. Thus, the intoxication by MeHg was able to generate deposits and oxidative stress in salivary glands that resulted in a decrease in cell viability in both types of glands.

  8. Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model.

    Directory of Open Access Journals (Sweden)

    Xu Li

    Full Text Available BACKGROUND: A reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL. The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2S has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2S in cochlear blood flow regulation and noise protection. METHODOLOGY/PRINCIPAL FINDINGS: The gene and protein expression of the H(2S synthetase cystathionine-γ-lyase (CSE in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP, NaHS or DL-propargylglycine (PPG were locally administered. Local sodium hydrosulfide (NaHS significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR, cochlear scanning electron microscope (SEM and outer hair cell (OHC count. The highest percentage of OHC loss occurred in the PPG group. CONCLUSIONS/SIGNIFICANCE: Our results suggest that H(2S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.

  9. Osteoprotegerin in Chronic Kidney Disease: Associations with Vascular Damage and Cardiovascular Events.

    Science.gov (United States)

    Yilmaz, Mahmut Ilker; Siriopol, Dimitrie; Saglam, Mutlu; Unal, Hilmi Umut; Karaman, Murat; Gezer, Mustafa; Kilinc, Ali; Eyileten, Tayfun; Guler, Ahmet Kerem; Aydin, İbrahim; Vural, Abdulgaffar; Oguz, Yusuf; Covic, Adrian; Ortiz, Alberto; Kanbay, Mehmet

    2016-08-01

    Vascular injury and dysfunction contribute to cardiovascular disease, the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily that has been linked to atherogenesis and endothelial dysfunction. Elevated circulating OPG levels predict future cardiovascular events (CVE). Our aim was to evaluate the determinants of circulating OPG levels, to investigate the relationship between OPG and markers of vascular damage and to test whether OPG improves risk stratification for future CVE beyond traditional and renal-specific risk factors in a CKD population. 291 patients with CKD stage 1-5 not on dialysis were included in the study. In the multivariate analysis, OPG was a significant predictor for flow-mediated dilatation, but not for carotid intima media thickness levels. During follow-up (median 36 months, IQR = 32-42 months), 87 patients had CVE. In the Cox survival analysis, OPG levels were independently associated with CVE even after adjustment for traditional and renal-specific cardiovascular risk factors. The addition of OPG to a model based on commonly used cardiovascular factors significantly improved the reclassification abilities of the model for predicting CVE. We show for the first time that OPG improves risk stratification for CVE in a non-dialysis CKD population, above and beyond a model with established traditional and renal-specific cardiovascular risk factors, including estimated glomerular filtration rate and fibroblast growth factor 23.

  10. Whole-Brain DTI Assessment of White Matter Damage in Children with Bilateral Cerebral Palsy: Evidence of Involvement beyond the Primary Target of the Anoxic Insult.

    Science.gov (United States)

    Arrigoni, F; Peruzzo, D; Gagliardi, C; Maghini, C; Colombo, P; Iammarrone, F Servodio; Pierpaoli, C; Triulzi, F; Turconi, A C

    2016-07-01

    Cerebral palsy is frequently associated with both motor and nonmotor symptoms. DTI can characterize the damage at the level of motor tracts but provides less consistent results in nonmotor areas. We used a standardized pipeline of analysis to describe and quantify the pattern of DTI white matter abnormalities of the whole brain in a group of children with chronic bilateral cerebral palsy and periventricular leukomalacia. We also explored potential correlations between DTI and clinical scale metrics. Twenty-five patients (mean age, 11.8 years) and 25 healthy children (mean age, 11.8 years) were studied at 3T with a 2-mm isotropic DTI sequence. Differences between patients and controls were assessed both voxelwise and in ROIs obtained from an existing DTI atlas. Clinical metrics included the Gross Motor Function Classification System, the Manual Ability Classification System, and intelligence quotient. The voxel-level and ROI-level analyses demonstrated highly significant (P < .001) modifications of DTI measurements in patients at several levels: cerebellar peduncles, corticospinal tracts and posterior thalamic radiations, posterior corpus callosum, external capsule, anterior thalamic radiation, superior longitudinal fasciculi and corona radiata, optic nerves, and chiasm. The reduction of fractional anisotropy values in significant tracts was between 8% and 30%. Statistically significant correlations were found between motor impairment and fractional anisotropy in corticospinal tracts and commissural and associative tracts of the supratentorial brain. We demonstrated the involvement of several motor and nonmotor areas in the chronic damage associated with periventricular leukomalacia and showed new correlations between motor skills and DTI metrics. © 2016 by American Journal of Neuroradiology.

  11. Prediction of perinatal brain damage by cord plasma vasopressin, erythropoietin, and hypoxanthine values.

    Science.gov (United States)

    Ruth, V; Autti-Rämö, I; Granström, M L; Korkman, M; Raivio, K O

    1988-11-01

    For an assessment of whether cord plasma arginine vasopressin, erythropoietin, and hypoxanthine concentrations are predictors of perinatal brain damage, these concentrations were measured in 62 infants born after preeclampsia of pregnancy, 31 acutely asphyxiated infants, and 38 control infants. Follow-up at 2 years included neurologic examination and the determination of a Bayley mental score. Clear abnormality (death, cerebral palsy, or developmental delay) was found in four infants in the preeclampsia group and five in the asphyxia group; slight abnormality was found in 12 and 6 infants, respectively; and no abnormality was found in the remainder. Neither arginine vasopressin values nor hypoxanthine values predicted adverse outcome in either study group. A high erythropoietin level was found in infants born after preeclampsia regardless of outcome: normal outcome (geometric mean (GM), 102; 95% confidence interval [CI], 69 to 153 mU/ml), slightly abnormal outcome (GM, 100; 95% CI, 37 to 270 mU/ml) or clearly abnormal outcome (GM, 84; 95% CI, 19 to 378 mU/ml). However, asphyxiated infants with clearly abnormal outcome had higher erythropoietin values (GM, 67; 95% CI, 33 to 137 mU/ml; p less than 0.05) than the normal infants (GM, 37; 95% CI, 23 to 59 mU/ml). We conclude that a high erythropoietin level after normal pregnancy, but not after preeclampsia, indicates an increased risk for cerebral palsy or death.

  12. The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats.

    Science.gov (United States)

    Matsuda, F; Sakakima, H; Yoshida, Y

    2011-02-01

    Exercise can be used to enhance neuroplasticity and facilitate motor recovery after a stroke in rats. We investigated whether treadmill running could reduce brain damage and enhance the expression of midkine (MK) and nerve growth factor (NGF), increase angiogenesis and decrease the expression of caspase-3. Seventy-seven Wistar rats were split into three experimental groups (ischaemia-control: 36, ischaemia-exercise: 36, sham-exercise: 5). Stroke was induced by 90-min left middle cerebral artery occlusion using an intraluminal filament. Beginning on the following day, the rats were made to run on a treadmill for 20 min once a day for a maximum of 28 consecutive days. Functional recovery after ischaemia was assessed using the beamwalking test and a neurological evaluation scale in all rats. Infarct volume, and the expression of MK, NGF, anti-platelet-endothelial cell adhesion molecule (PECAM-1), and caspase-3 were evaluated at 1, 3, 5, 7, 14 and 28 days after the induction of ischaemia. Over time motor coordination and neurological deficits improved more in the exercised group than in the non-exercised group. The infarct volume in the exercised group (12.4 ± 0.8%) subjected to treadmill running for 28 days was significantly decreased compared with that in the control group (19.8 ± 4.2%, P exercised rats. Our findings show that treadmill exercise improves motor behaviour and reduces neurological deficits and infarct volume, suggesting that it may aid recovery from central nervous system injury.

  13. Magnesium sulfate and nimesulide have synergistic effects on rescuing brain damage after transient focal ischemia.

    Science.gov (United States)

    Wang, Liang-Chao; Huang, Chih-Yuan; Wang, Hao-Kuang; Wu, Ming-Hsiu; Tsai, Kuen-Jer

    2012-05-01

    Magnesium sulfate and nimesulide are commonly used drugs with reported neuroprotective effects. Their combination as stroke treatment has the potential benefits of decreasing individual drug dosage and fewer adverse effects. This study evaluated their synergistic effects and compared a low-dose combination with individual drug alone and placebo. Sprague-Dawley rats underwent 90 min of focal ischemia with intraluminal suture occlusion of the middle cerebral artery followed by reperfusion. The rats were randomly assigned to receive one of the following treatments: placebo, magnesium sulfate (MgSO₄; 45 mg/kg) intravenously immediately after the induction of middle cerebral artery occlusion, nimesulide (6 mg/kg) intraperitoneally before reperfusion, and combined therapy. Three days after the ischemia-reperfusion insult, therapeutic outcome was assessed by 2,3,5-triphenyltetrazolium chloride staining and a 28-point neurological severity scoring system. Cyclooxygenase-2, prostaglandin E₂, myeloperoxidase, and caspase-3 expression after treatment were evaluated using Western blot analyses and immunohistochemical staining, followed by immunoreactive cell analysis using tissue cytometry. Only the combination treatment group showed a significant decrease in infarction volume (10.93±6.54% versus 26.43±7.08%, peffects of each individual drug. MgSO₄ and nimesulide have synergistic effects on ischemia-reperfusion insults. Their combination helps decrease drug dosage and adverse effects. Combined treatment strategies may help to combat stroke-induced brain damage in the future.

  14. The 2100MHz radiofrequency radiation of a 3G-mobile phone and the DNA oxidative damage in brain.

    Science.gov (United States)

    Sahin, Duygu; Ozgur, Elcin; Guler, Goknur; Tomruk, Arın; Unlu, Ilhan; Sepici-Dinçel, Aylin; Seyhan, Nesrin

    2016-09-01

    We aimed to evaluate the effect of 2100MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone on the brain of rats during 10 and 40 days of exposure. The female rats were randomly divided into four groups. Group I; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 2 weeks, group II; control 10 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 2 weeks, group III; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 8 weeks and group IV; control 40 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 8 weeks. After the genomic DNA content of brain was extracted, oxidative DNA damage (8-hydroxy-2'deoxyguanosine, pg/mL) and malondialdehyde (MDA, nmoL/g tissue) levels were determined. Our main finding was the increased oxidative DNA damage to brain after 10 days of exposure with the decreased oxidative DNA damage following 40 days of exposure compared to their control groups. Besides decreased lipid peroxidation end product, MDA, was observed after 40 days of exposure. The measured decreased quantities of damage during the 40 days of exposure could be the means of adapted and increased DNA repair mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Transplanted bone marrow stromal cells protect neurovascular units and ameliorate brain damage in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Ito, Masaki; Kuroda, Satoshi; Sugiyama, Taku; Maruichi, Katsuhiko; Kawabori, Masahito; Nakayama, Naoki; Houkin, Kiyohiro; Iwasaki, Yoshinobu

    2012-10-01

    This study was aimed to assess whether bone marrow stromal cells (BMSC) could ameliorate brain damage when transplanted into the brain of stroke-prone spontaneously hypertensive rats (SHR-SP). The BMSC or vehicle was stereotactically engrafted into the striatum of male SHR-SP at 8 weeks of age. Daily loading with 0.5% NaCl-containing water was started from 9 weeks. MRIs and histological analysis were performed at 11 and 12 weeks, respectively. Wistar-Kyoto rats were employed as the control. As a result, T2-weighted images demonstrated neither cerebral infarct nor intracerebral hemorrhage, but identified abnormal dilatation of the lateral ventricles in SHR-SP. HE staining demonstrated selective neuronal injury in their neocortices. Double fluorescence immunohistochemistry revealed that they had a decreased density of the collagen IV-positive microvessels and a decreased number of the microvessels with normal integrity between basement membrane and astrocyte end-feet. BMSC transplantation significantly ameliorated the ventricular dilatation and the breakdown of neurovascular integrity. These findings strongly suggest that long-lasting hypertension may primarily damage neurovascular integrity and neurons, leading to tissue atrophy and ventricular dilatation prior to the occurrence of cerebral stroke. The BMSC may ameliorate these damaging processes when directly transplanted into the brain, opening the possibility of prophylactic medicine to prevent microvascular and parenchymal-damaging processes in hypertensive patients at higher risk for cerebral stroke. © 2012 Japanese Society of Neuropathology.

  16. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor.

    Science.gov (United States)

    Taliaz, Dekel; Loya, Assaf; Gersner, Roman; Haramati, Sharon; Chen, Alon; Zangen, Abraham

    2011-03-23

    Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

  17. Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

    Science.gov (United States)

    Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

    2016-01-01

    Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

  18. Central condylar displacement with brain abscess from chronic mandibular osteomyelitis.

    Science.gov (United States)

    Lee, Thomas; Green, Ross; Hsu, Jack

    2013-06-01

    In this case report, we describe a unique long-term complication from undiagnosed mandibular osteomyelitis. A 53-year-old female who underwent a dental extraction complicated by chronic postoperative odontogenic infection and cutaneous parotid fistula formation 2 years earlier presented with acute mental status change, gradual unilateral facial nerve palsy (House-Brackmann score V), and nontraumatic dislocation of the condylar head into the middle cranial fossa. The patient's chronic mandibular osteomyelitis led to glenoid fossa erosion, middle cranial fossa penetration, and temporal lobe abscess formation. A combined middle cranial fossa approach through a burr hole placed in the squamous temporal bone near the zygomatic root and intraoral mandibular approach to ipsilateral condylar head was performed to complete partial mandibulectomy, including condylectomy. The patient was treated with 6 weeks of meropenem perioperatively. Four months after the surgery, the patient had complete resolution of skull base osteomyelitis, parotid fistula, and neurologic deficits and full recovery of facial nerve function (House-Brackmann score of I). Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.

  19. Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia.

    Directory of Open Access Journals (Sweden)

    Wanchao Yang

    Full Text Available Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30-39 mmHg, 40-49 mmHg, 50-59 mmHg, and 60-69 mmHg, respectively or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60-80 mmHg for 180 min. The mean artery pressure (MAP, blood gas, and cerebral blood flow (CBF were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4 expression. In rats treated with severe hypoxia (PaO2 50 mmHg, hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg; especially under mild hypoxemia (PaO2 > 60 mmHg, hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05. Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia.

  20. Neuroendocrine Disturbances after Brain Damage: An Important and Often Undiagnosed Disorder

    Directory of Open Access Journals (Sweden)

    Fatih Tanriverdi

    2015-04-01

    Full Text Available Traumatic brain injury (TBI is a common and significant public health problem all over the world. Until recently, TBI has been recognized as an uncommon cause of hypopituitarism. The studies conducted during the last 15 years revealed that TBI is a serious cause of hypopituitarism. Although the underlying pathophysiology has not yet been fully clarified, new data indicate that genetic predisposition, autoimmunity and neuroinflammatory changes may play a role in the development of hypopituitarism. Combative sports, including boxing and kickboxing, both of which are characterized by chronic repetitive head trauma, have been shown as new causes of neuroendocrine abnormalities, mainly hypopituitarism, for the first time during the last 10 years. Most patients with TBI-induced pituitary dysfunction remain undiagnosed and untreated because of the non-specific and subtle clinical manifestations of hypopituitarism. Replacement of the deficient hormones, of which GH is the commonest hormone lost, may not only reverse the clinical manifestations and neurocognitive dysfunction, but may also help posttraumatic disabled patients resistant to classical treatment who have undiagnosed hypopituitarism and GH deficiency in particular. Therefore, early diagnosis, which depends on the awareness of TBI as a cause of neuroendocrine abnormalities among the medical community, is crucially important.

  1. The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain.

    Science.gov (United States)

    Generaal, Ellen; Milaneschi, Yuri; Jansen, Rick; Elzinga, Bernet M; Dekker, Joost; Penninx, Brenda W J H

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) disturbances and life stress, both independently and in interaction, have been hypothesized to induce chronic pain. We examined whether (a) the BDNF pathway (val(66)met genotype, gene expression, and serum levels), (b) early and recent life stress, and (c) their interaction are associated with the presence and severity of chronic multi-site musculoskeletal pain. Cross-sectional data are from 1646 subjects of the Netherlands Study of Depression and Anxiety. The presence and severity of chronic multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG) questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF serum levels were measured. Early life stress before the age of 16 was assessed by calculating a childhood trauma index using the Childhood Trauma Interview. Recent life stress was assessed as the number of recent adverse life events using the List of Threatening Events Questionnaire. Compared to val(66)val, BDNF met carriers more often had chronic pain, whereas no differences were found for BDNF gene expression and serum levels. Higher levels of early and recent stress were both associated with the presence and severity of chronic pain (p impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain. © The Author(s) 2016.

  2. Effect of Shock-Induced Cavitation Bubble Collapse on the damage in the Simulated Perineuronal Net of the Brain.

    Science.gov (United States)

    Wu, Yuan-Ting; Adnan, Ashfaq

    2017-07-13

    The purpose of this study is to conduct modeling and simulation to understand the effect of shock-induced mechanical loading, in the form of cavitation bubble collapse, on damage to the brain's perineuronal nets (PNNs). It is known that high-energy implosion due to cavitation collapse is responsible for corrosion or surface damage in many mechanical devices. In this case, cavitation refers to the bubble created by pressure drop. The presence of a similar damage mechanism in biophysical systems has long being suspected but not well-explored. In this paper, we use reactive molecular dynamics (MD) to simulate the scenario of a shock wave induced cavitation collapse within the perineuronal net (PNN), which is the near-neuron domain of a brain's extracellular matrix (ECM). Our model is focused on the damage in hyaluronan (HA), which is the main structural component of PNN. We have investigated the roles of cavitation bubble location, shockwave intensity and the size of a cavitation bubble on the structural evolution of PNN. Simulation results show that the localized supersonic water hammer created by an asymmetrical bubble collapse may break the hyaluronan. As such, the current study advances current knowledge and understanding of the connection between PNN damage and neurodegenerative disorders.

  3. Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain.

    OpenAIRE

    Oliver, C N; Starke-Reed, P E; Stadtman, E. R.; Liu,G.J.; Carney, J M; Floyd, R A

    1990-01-01

    Free radical-mediated oxidative damage has been implicated in tissue injury resulting from ischemia/reperfusion events. Global cortical ischemia/reperfusion injury to Mongolian gerbil brains was produced by transient occlusion of both common carotid arteries. Protein oxidation, as measured by protein carbonyl content, increased significantly during the reperfusion phase that followed 10 min of ischemia. The activity of glutamine synthetase, an enzyme known to be inactivated by metal-catalyzed...

  4. Effect of a chronic GSM 900 MHz exposure on glia in the rat brain.

    Science.gov (United States)

    Ammari, Mohamed; Brillaud, Elsa; Gamez, Christelle; Lecomte, Anthony; Sakly, Mohsen; Abdelmelek, Hafedh; de Seze, René

    2008-01-01

    Extension of the mobile phone technology raises concern about the health effects of 900 MHz microwaves on the central nervous system (CNS). In this study we measured GFAP expression using immunocytochemistry method, to evaluate glial evolution 10 days after a chronic exposure (5 days a week for 24 weeks) to GSM signal for 45 min/day at a brain-averaged specific absorption rate (SAR)=1.5 W/kg and for 15 min/day at a SAR=6 W/kg in the following rat brain areas: prefrontal cortex (PfCx), caudate putamen (Cpu), lateral globus pallidus of striatum (LGP), dentate gyrus of hippocampus (DG) and cerebellum cortex (CCx). In comparison to sham or cage control animals, rats exposed to chronic GSM signal at 6 W/kg have increased GFAP stained surface areas in the brain (pGSM at 1.5 W/kg did not increase GFAP expression. Our results indicated that chronic exposure to GSM 900 MHz microwaves (SAR=6 W/kg) may induce persistent astroglia activation in the rat brain (sign of a potential gliosis).

  5. Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain

    Directory of Open Access Journals (Sweden)

    Natalia Egorova

    2015-01-01

    Full Text Available Acupuncture, an ancient East Asian therapy, is aimed at rectifying the imbalance within the body caused by disease. Studies evaluating the efficacy of acupuncture with neuroimaging tend to concentrate on brain regions within the pain matrix, associated with acute pain. We, however, focused on the effect of repeated acupuncture treatment specifically on brain regions known to support functions dysregulated in chronic pain disorders. Transition to chronic pain is associated with increased attention to pain, emotional rumination, nociceptive memory and avoidance learning, resulting in brain connectivity changes, specifically affecting the periaqueductal gray (PAG, medial frontal cortex (MFC and bilateral hippocampus (Hpc. We demonstrate that the PAG–MFC and PAG–Hpc connectivity in patients with chronic pain due to knee osteoarthritis indeed correlates with clinical severity scores and further show that verum acupuncture-induced improvement in pain scores (compared to sham is related to the modulation of PAG–MFC and PAG–Hpc connectivity in the predicted direction. This study shows that repeated verum acupuncture might act by restoring the balance in the connectivity of the key pain brain regions, altering pain-related attention and memory.

  6. The Emotional Brain as a Predictor and Amplifier of Chronic Pain

    Science.gov (United States)

    Vachon-Presseau, E.; Centeno, M.V.; Ren, W.; Berger, S.E.; Tétreault, P.; Ghantous, M.; Baria, A.; Farmer, M.; Baliki, M.N.; Schnitzer, T.J.; Apkarian, A.V.

    2016-01-01

    Human neuroimaging studies and complementary animal experiments now identify the gross elements of the brain involved in the chronification of pain. We briefly review these advances in relation to somatic and orofacial persistent pain conditions. First, we emphasize the importance of reverse translational research for understanding chronic pain—that is, the power of deriving hypotheses directly from human brain imaging of clinical conditions that can be invasively and mechanistically studied in animal models. We then review recent findings demonstrating the importance of the emotional brain (i.e., the corticolimbic system) in the modulation of acute pain and in the prediction and amplification of chronic pain, contrasting this evidence with recent findings regarding the role of central sensitization in pain chronification, especially for orofacial pain. We next elaborate on the corticolimbic circuitry and underlying mechanisms that determine the transition to chronic pain. Given this knowledge, we advance a new mechanistic definition of chronic pain and discuss the clinical implications of this new definition as well as novel therapeutic potentials suggested by these advances. PMID:26965423

  7. Blood-brain barrier permeability and nerve cell damage in rat brain 14 and 28 days after exposure to microwaves from GSM mobile phones.

    Science.gov (United States)

    Eberhardt, Jacob L; Persson, Bertil R R; Brun, Arne E; Salford, Leif G; Malmgren, Lars O G

    2008-01-01

    We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier and signs of neuronal damage in rats using a real GSM programmable mobile phone in the 900 MHz band. Ninety-six non-anaesthetized rats were either exposed to microwaves or sham exposed in TEM-cells for 2 h at specific absorption rates of average whole-body Specific Absorption Rates (SAR) of 0.12, 1.2, 12, or 120 mW/kg. The rats were sacrificed after a recovery time of either 14 or 28 d, following exposure and the extravazation of albumin, its uptake into neurons, and occurrence of damaged neurons was assessed. Albumin extravazation and also its uptake into neurons was seen to be enhanced after 14 d (Kruskal Wallis test: p = 0.02 and 0.002, respectively), but not after a 28 d recovery period. The occurrence of dark neurons in the rat brains, on the other hand, was enhanced later, after 28 d (p = 0.02). Furthermore, in the 28-d brain samples, neuronal albumin uptake was significantly correlated to occurrence of damaged neurons (Spearman r = 0.41; p < 0.01).

  8. Reorganization of Visual Callosal Connections Following Alterations of Retinal Input and Brain Damage.

    Science.gov (United States)

    Restani, Laura; Caleo, Matteo

    2016-01-01

    Vision is a very important sensory modality in humans. Visual disorders are numerous and arising from diverse and complex causes. Deficits in visual function are highly disabling from a social point of view and in addition cause a considerable economic burden. For all these reasons there is an intense effort by the scientific community to gather knowledge on visual deficit mechanisms and to find possible new strategies for recovery and treatment. In this review, we focus on an important and sometimes neglected player of the visual function, the corpus callosum (CC). The CC is the major white matter structure in the brain and is involved in information processing between the two hemispheres. In particular, visual callosal connections interconnect homologous areas of visual cortices, binding together the two halves of the visual field. This interhemispheric communication plays a significant role in visual cortical output. Here, we will first review the essential literature on the physiology of the callosal connections in normal vision. The available data support the view that the callosum contributes to both excitation and inhibition to the target hemisphere, with a dynamic adaptation to the strength of the incoming visual input. Next, we will focus on data showing how callosal connections may sense visual alterations and respond to the classical paradigm for the study of visual plasticity, i.e., monocular deprivation (MD). This is a prototypical example of a model for the study of callosal plasticity in pathological conditions (e.g., strabismus and amblyopia) characterized by unbalanced input from the two eyes. We will also discuss the findings of callosal alterations in blind subjects. Noteworthy, we will discuss data showing that inter-hemispheric transfer mediates recovery of visual responsiveness following cortical damage. Finally, we will provide an overview of how callosal projections dysfunction could contribute to pathologies such as neglect and occipital

  9. REORGANIZATION OF VISUAL CALLOSAL CONNECTIONS FOLLOWING ALTERATIONS OF RETINAL INPUT AND BRAIN DAMAGE

    Directory of Open Access Journals (Sweden)

    LAURA RESTANI

    2016-11-01

    Full Text Available Vision is a very important sensory modality in humans. Visual disorders are numerous and arising from diverse and complex causes. Deficits in visual function are highly disabling from a social point of view and in addition cause a considerable economic burden. For all these reasons there is an intense effort by the scientific community to gather knowledge on visual deficit mechanisms and to find possible new strategies for recovery and treatment. In this review we focus on an important and sometimes neglected player of the visual function, the corpus callosum (CC. The CC is the major white matter structure in the brain and is involved in information processing between the two hemispheres. In particular, visual callosal connections interconnect homologous areas of visual cortices, binding together the two halves of the visual field. This interhemispheric communication plays a significant role in visual cortical output. Here, we will first review essential literature on the physiology of the callosal connections in normal vision. The available data support the view that the callosum contributes to both excitation and inhibition to the target hemisphere, with a dynamic adaptation to the strength of the incoming visual input. Next, we will focus on data showing how callosal connections may sense visual alterations and respond to the classical paradigm for the study of visual plasticity, i.e. monocular deprivation. This is a prototypical example of a model for the study of callosal plasticity in pathological conditions (e.g. strabismus and amblyopia characterized by unbalanced input from the two eyes. We will also discuss findings of callosal alterations in blind subjects. Noteworthy, we will discuss data showing that inter-hemispheric transfer mediates recovery of visual responsiveness following cortical damage. Finally, we will provide an overview of how callosal projections dysfunction could contribute to pathologies such as neglect and occipital

  10. Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

    Science.gov (United States)

    Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

    2013-05-01

    Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

  11. Changes in markers of brain serotonin activity in response to chronic exercise in senior men.

    Science.gov (United States)

    Melancon, Michel O; Lorrain, Dominique; Dionne, Isabelle J

    2014-11-01

    Aging is associated with noticeable impairments in brain serotonin transmission, which might contribute to increased vulnerability to developing depression in later life. Animal and human studies have shown that aerobic exercise can stimulate brain serotonin activity and trigger parallel elevations in tryptophan (TRP, the serotonin precursor) availability in blood plasma. However, the influence of chronic exercise on serotonergic activity in older adults is not yet known. Sixteen men aged 64 ± 3 years exercised for 1 h (67%-70% peak oxygen consumption) at baseline and following 16 weeks of aerobic training. The main outcome measures were cardiorespiratory fitness, body composition, branched-chain amino acids (BCAA), TRP, prolactin, lactate, and free fatty acids (FFA). Changes in plasma free-TRP/BCAA and prolactin served as surrogates for TRP availability and serotonin activity, respectively. Chronic exercise decreased body mass (P brain at rest, both pre- and post-training exercise challenges markedly increased TRP availability (P exercise that was lower following training (P exercise elicits consistent transient elevations in plasma TRP availability to the brain in older men; the elevations were independent from physical training, although less pronounced following training. The data support the contention that repeated elevations in brain serotonin activity might be involved in the antidepressant effect of exercise training in older adults.

  12. Induction of neuronal damage in guinea pig brain by intratracheal infusion of 2-chloroethyl ethyl sulfide, a mustard gas analog.

    Science.gov (United States)

    Gadsden-Gray, Jessica; Mukherjee, Shyamali; Ogunkua, Olugbemiga; Das, Salil K

    2012-01-01

    Intratracheal infusion of 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog and a chemical warfare agent is known to cause massive damage to lung. The purpose of this study was to determine whether intratracheal CEES infusion causes neuronal damage. Histological, immunohistochemical, and Western blot studies indicated that CEES treatment caused dose-dependent increases in blood cell aggregation, microglial cell number, microglial activation, and brain inflammation. In addition, an increased expression of α-synuclein and a decreased expression of the dopamine transporter were observed. The results indicate that intratracheal CEES infusion is associated with changes in brain morphology mediated by an increase in α-synuclein expression, leading to neurotoxicity in a guinea pig model. These changes may be mediated by oxidative stress. Furthermore, the present study indicates for the first time that intratracheal infusion of a single dose of CEES can cause neuroinflammation, which may lead to neurological disorders in later part of life. Copyright © 2011 Wiley Periodicals, Inc.

  13. Use of Early Biomarkers in Neonatal Brain Damage and Sepsis: State of the Art and Future Perspectives

    Science.gov (United States)

    Bersani, Iliana; Auriti, Cinzia; Ronchetti, Maria Paola; Prencipe, Giusi; Gazzolo, Diego; Dotta, Andrea

    2015-01-01

    The identification of early noninvasive biochemical markers of disease is a crucial issue of the current scientific research, particularly during the first period of life, since it could provide useful and precocious diagnostic information when clinical and radiological signs are still silent. The ideal biomarker should be practical and sensitive in the precocious identification of at risk patients. An earlier diagnosis may lead to a larger therapeutic window and improve neonatal outcome. Brain damage and sepsis are common causes of severe morbidity with poor outcome and mortality during the perinatal period. A large number of potential biomarkers, including neuroproteins, calcium binding proteins, enzymes, oxidative stress markers, vasoactive agents, and inflammatory mediators, have been so far investigated. The aim of the present review was to provide a brief overview of some of the more commonly investigated biomarkers used in case of neonatal brain damage and sepsis. PMID:25685774

  14. Structural Brain Anomalies and Chronic Pain: A Quantitative Meta-Analysis of Gray Matter Volume

    Science.gov (United States)

    Smallwood, Rachel F.; Laird, Angela R.; Ramage, Amy E.; Parkinson, Amy L.; Lewis, Jeffrey; Clauw, Daniel J.; Williams, David A.; Schmidt-Wilcke, Tobias; Farrell, Michael J.; Eickhoff, Simon B.; Robin, Donald A.

    2016-01-01

    The diversity of chronic pain syndromes and the methods employed to study them make integrating experimental findings challenging. This study performed coordinate-based meta-analyses using voxel-based morphometry imaging results to examine gray matter volume (GMV) differences between chronic pain patients and healthy controls. There were 12 clusters where GMV was decreased in patients compared with controls, including many regions thought to be part of the “pain matrix” of regions involved in pain perception, but also including many other regions that are not commonly regarded as pain-processing areas. The right hippocampus and parahippocampal gyrus were the only regions noted to have increased GMV in patients. Functional characterizations were implemented using the BrainMap database to determine which behavioral domains were significantly represented in these regions. The most common behavioral domains associated with these regions were cognitive, affective, and perceptual domains. Because many of these regions are not classically connected with pain and because there was such significance in functionality outside of perception, it is proposed that many of these regions are related to the constellation of comorbidities of chronic pain, such as fatigue and cognitive and emotional impairments. Further research into the mechanisms of GMV changes could provide a perspective on these findings. Perspective Quantitative meta-analyses revealed structural differences between brains of individuals with chronic pain and healthy controls. These differences may be related to comorbidities of chronic pain. PMID:23685185

  15. Effects of neurofeedback training with an electroencephalogram-based brain-computer interface for hand paralysis in patients with chronic stroke: a preliminary case series study.

    Science.gov (United States)

    Shindo, Keiichiro; Kawashima, Kimiko; Ushiba, Junichi; Ota, Naoki; Ito, Mari; Ota, Tetsuo; Kimura, Akio; Liu, Meigen

    2011-10-01

    To explore the effectiveness of neurorehabilitative training using an electroencephalogram-based brain- computer interface for hand paralysis following stroke. A case series study. Eight outpatients with chronic stroke demonstrating moderate to severe hemiparesis. Based on analysis of volitionally decreased amplitudes of sensory motor rhythm during motor imagery involving extending the affected fingers, real-time visual feedback was provided. After successful motor imagery, a mechanical orthosis partially extended the fingers. Brain-computer interface interventions were carried out once or twice a week for a period of 4-7 months, and clinical and neurophysiological examinations pre- and post-intervention were compared. New voluntary electromyographic activity was measured in the affected finger extensors in 4 cases who had little or no muscle activity before the training, and the other participants exhibited improvement in finger function. Significantly greater suppression of the sensory motor rhythm over both hemispheres was observed during motor imagery. Transcranial magnetic stimulation showed increased cortical excitability in the damaged hemisphere. Success rates of brain-computer interface training tended to increase as the session progressed in 4 cases. Brain-computer interface training appears to have yielded some improvement in motor function and brain plasticity. Further controlled research is needed to clarify the role of the brain-computer interface system.

  16. Alterations in rat brain ( sup 3 H)-TCP binding following chronic phencyclidine administration

    Energy Technology Data Exchange (ETDEWEB)

    Massey, B.W.; Wessinger, W.D. (Univ. of Arkansas, Little Rock (USA))

    1990-01-01

    Rats were chronically infused with phencyclidine (PCP, 13.3 mg PCP{center dot}HCl/kg/day) or saline, s.c., for 10 days using osmotic minipumps (n = 5 for each group). Twenty-four hours after the cessation of dosing, the rats were sacrificed, and brains were removed for analysis of PCP receptor binding. Saturation studies of the binding of ({sup 3}H)-TCP to brain homogenates revealed statistically significant increases in the maximum binding capacity (B{sub max}) and decreases in the affinity for ({sup 3}H)-TCP in the PCP-treated group.

  17. Efficient neuroplasticity induction in chronic stroke patients by an associative brain-computer interface

    DEFF Research Database (Denmark)

    Mrachacz-Kersting, Natalie; Jiang, Ning; Stevenson, Andrew James Thomas

    2016-01-01

    Brain-computer interfaces (BCIs) have the potential to improve functionality in chronic stoke patients when applied over a large number of sessions. Here, we evaluate the effect and the underlying mechanisms of three BCI training sessions in a double-blind-sham-controlled design. The applied BCI......-associative group. Fugl-Meyer motor scores (0.8±0.46 point difference p=0.01), foot (but not finger) tapping frequency, and 10-m walking speed improved significantly for the BCIassociative group, indicating clinically relevant improvements. For the BCI as applied here, the precise coupling between the brain command...

  18. Cingulate neglect in humans: disruption of contralesional reward learning in right brain damage.

    Science.gov (United States)

    Lecce, Francesca; Rotondaro, Francesca; Bonnì, Sonia; Carlesimo, Augusto; Thiebaut de Schotten, Michel; Tomaiuolo, Francesco; Doricchi, Fabrizio

    2015-01-01

    Motivational valence plays a key role in orienting spatial attention. Nonetheless, clinical documentation and understanding of motivationally based deficits of spatial orienting in the human is limited. Here in a series of one group-study and two single-case studies, we have examined right brain damaged patients (RBD) with and without left spatial neglect in a spatial reward-learning task, in which the motivational valence of the left contralesional and the right ipsilesional space was contrasted. In each trial two visual boxes were presented, one to the left and one to the right of central fixation. In one session monetary rewards were released more frequently in the box on the left side (75% of trials) whereas in another session they were released more frequently on the right side. In each trial patients were required to: 1) point to each one of the two boxes; 2) choose one of the boxes for obtaining monetary reward; 3) report explicitly the position of reward and whether this position matched or not the original choice. Despite defective spontaneous allocation of attention toward the contralesional space, RBD patients with left spatial neglect showed preserved contralesional reward learning, i.e., comparable to ipsilesional learning and to reward learning displayed by patients without neglect. A notable exception in the group of neglect patients was L.R., who showed no sign of contralesional reward learning in a series of 120 consecutive trials despite being able of reaching learning criterion in only 20 trials in the ipsilesional space. L.R. suffered a cortical-subcortical brain damage affecting the anterior components of the parietal-frontal attentional network and, compared with all other neglect and non-neglect patients, had additional lesion involvement of the medial anterior cingulate cortex (ACC) and of the adjacent sectors of the corpus callosum. In contrast to his lateralized motivational learning deficit, L.R. had no lateral bias in the early phases of

  19. Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

    Directory of Open Access Journals (Sweden)

    Eugenia Mata-Greenwood

    2017-05-01

    Full Text Available Background : Hypoxia inducible factor 1 alpha (HIF1A is a master regulator of acute hypoxia; however, with chronic hypoxia, HIF1A levels return to the normoxic levels. Importantly, the genes that are involved in the cell survival and viability under chronic hypoxia are not known. Therefore, we tested the hypothesis that chronic hypoxia leads to the upregulation of a core group of genes with associated changes in the promoter DNA methylation that mediates the cell survival under hypoxia.Results : We examined the effect of chronic hypoxia (3 days; 0.5% oxygen on human brain micro endothelial cells (HBMEC viability and apoptosis. Hypoxia caused a significant reduction in cell viability and an increase in apoptosis. Next, we examined chronic hypoxia associated changes in transcriptome and genome-wide promoter methylation. The data obtained was compared with 16 other microarray studies on chronic hypoxia. Nine genes were altered in response to chronic hypoxia in all 17 studies. Interestingly, HIF1A was not altered with chronic hypoxia in any of the studies. Furthermore, we compared our data to three other studies that identified HIF-responsive genes by various approaches. Only two genes were found to be HIF dependent. We silenced each of these 9 genes using CRISPR/Cas9 system. Downregulation of EGLN3 significantly increased the cell death under chronic hypoxia, whereas downregulation of ERO1L, ENO2, adrenomedullin, and spag4 reduced the cell death under hypoxia.Conclusions : We provide a core group of genes that regulates cellular acclimatization under chronic hypoxic stress, and most of them are HIF independent.

  20. Neurocognitive, psychosocial and functional status of individuals with alcohol-related brain damage (ARBD) on admission to specialist residential care

    OpenAIRE

    Horton, Lindsay; Duffy, Tim; Martin, Colin R

    2015-01-01

    Alcohol-related brain damage (ARBD) is a complex neuropsychiatric condition with a multifaceted impact on functioning and the ability to live independently. A comprehensive approach to assessing ARBD is therefore necessary. This study aimed to investigate the neurocognitive, psychosocial and everyday functioning of a group of individuals with ARBD on admission to specialist residential care. A comprehensive assessment framework was used to investigate the baseline functioning of 20 individual...

  1. Minimal Brain Damage/Dysfunction (MBD) en de ontwikkeling van de wetenschappelijke kinderstudie in Nederland, ca. 1950–1990

    OpenAIRE

    Nelleke Bakker

    2014-01-01

    This paper discusses the reception in the Netherlands of Minimal Brain Damage/Dysfunction (MBD) and related labels for normally gifted children with learning disabilities and behavioural problems by child scientists of all sorts from the 1950s up to the late 1980s, when MBD was replaced with Attention Deficit Hyperactivity Disorder (ADHD). Unlike what has been suggested, as compared to ADHD, MBD turns out to have been all but a rare diagnosis for children who were not handicapped more serious...

  2. Brain damage due to episodic alcohol exposure in vivo and in vitro: furosemide neuroprotection implicates edema-based mechanism.

    Science.gov (United States)

    Collins, M A; Zou, J Y; Neafsey, E J

    1998-02-01

    Adult rats intubated with a single dose of ethanol (alcohol; approximately 5 g/kg) for 5 to 10 successive days incur neurodegeneration in the entorhinal cortex, dentate gyrus, and olfactory bulbs accompanied by cerebrocortical edema and electrolyte (Na+, K+) accumulation. The brain damage is not lessened by cotreatment with the NMDA receptor antagonist MK-801; also, as reported elsewhere, MK-801 as well as non-NMDA receptor and Ca2+ channel antagonists are not neuroprotective in a similar, but more compressed, intoxication protocol. However, cotreatment with the electrolyte transport inhibitor/diuretic furosemide reduces alcohol-dependent cerebrocortical damage by 75-85% while preventing brain hydration and electrolyte elevations; olfactory bulb neurodegeneration is not attenuated. In parallel in vitro studies, rat organotypic entorhinal/hippocampal slice cultures exposed to alcohol (50-200 mM) 15 h/day for 6 days, mirroring episodic intoxication in vivo, demonstrate concentration-related release of the cytotoxic indicator, lactate dehydrogenase. Analogous to the in vivo findings, furosemide blocks this alcohol-induced in vitro cytotoxicity. Our results showing neuroprotection by furosemide indicate that brain edema and swelling are essential events in the brain damage induced by episodic alcohol exposure. Furosemide and related agents might be useful as neuroprotective agents in alcohol abuse. We suggest that the neurodegeneration is elicited in part by edema-dependent oxidative stress, but the regional selectivity of the damage may be best explained by physical (mechanical) compression of the limbic cortex against the adjacent tympanic bulla and subsequent neuronal cytoskeletal collapse. A scheme for these apparently nonexcitotoxic metabolic and mechanical pathways initiated by repeated alcohol exposure is proposed.

  3. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury.

    Science.gov (United States)

    Williamson, John; Isaki, Emi

    2015-01-01

    The use of a modified Facial Affect Recognition (FAR) training to identify emotions was investigated with two case studies of adults with moderate to severe chronic (> five years) traumatic brain injury (TBI). The modified FAR training was administered via telepractice to target social communication skills. Therapy consisted of identifying emotions through static facial expressions, personally reflecting on those emotions, and identifying sarcasm and emotions within social stories and role-play. Pre- and post-therapy measures included static facial photos to identify emotion and the Prutting and Kirchner Pragmatic Protocol for social communication. Both participants with chronic TBI showed gains on identifying facial emotions on the static photos.

  4. Anatomical and spatial matching in imitation: Evidence from left and right brain-damaged patients.

    Science.gov (United States)

    Mengotti, Paola; Ripamonti, Enrico; Pesavento, Valentina; Rumiati, Raffaella Ida

    2015-12-01

    Imitation is a sensorimotor process whereby the visual information present in the model's movement has to be coupled with the activation of the motor system in the observer. This also implies that greater the similarity between the seen and the produced movement, the easier it will be to execute the movement, a process also known as ideomotor compatibility. Two components can influence the degree of similarity between two movements: the anatomical and the spatial component. The anatomical component is present when the model and imitator move the same body part (e.g., the right hand) while the spatial component is present when the movement of the model and that of the imitator occur at the same spatial position. Imitation can be achieved by relying on both components, but typically the model's and imitator's movements are matched either anatomically or spatially. The aim of this study was to ascertain the contribution of the left and right hemisphere to the imitation accomplished either with anatomical or spatial matching (or with both). Patients with unilateral left and right brain damage performed an ideomotor task and a gesture imitation task. Lesions in the left and right hemispheres gave rise to different performance deficits. Patients with lesions in the left hemisphere showed impaired imitation when anatomical matching was required, and patients with lesions in the right hemisphere showed impaired imitation when spatial matching was required. Lesion analysis further revealed a differential involvement of left and right hemispheric regions, such as the parietal opercula, in supporting imitation in the ideomotor task. Similarly, gesture imitation seemed to rely on different regions in the left and right hemisphere, such as parietal regions in the left hemisphere and premotor, somatosensory and subcortical regions in the right hemisphere. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Brain Metal Distribution and Neuro-Inflammatory Profiles after Chronic Vanadium Administration and Withdrawal in Mice

    OpenAIRE

    Folarin, Oluwabusayo R.; Snyder, Amanda M.; Peters, Douglas G.; Funmilayo Olopade; Connor, James R.; Olopade, James O

    2017-01-01

    Vanadium is a potentially toxic environmental pollutant and induces oxidative damage in biological systems including the central nervous system (CNS). Its deposition in brain tissue may be involved in the pathogenesis of certain neurological disorders which after prolonged exposure can culminate into more severe pathology. Most studies on vanadium neurotoxicity have been done after acute exposure but in reality some populations are exposed for a lifetime. This work was designed to ascertain n...

  6. Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Östberg, Anna; Virta, Jere; Rinne, Juha O

    2017-01-01

    subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication. DESIGN:: Cholinergic function was assessed with [methyl-C] N-methylpiperidyl-4-acetate-PET (C-MP4A-PET), which reflects the activity...

  7. Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments.

    Science.gov (United States)

    Hope, B T; Nye, H E; Kelz, M B; Self, D W; Iadarola, M J; Nakabeppu, Y; Duman, R S; Nestler, E J

    1994-11-01

    Following chronic cocaine treatment, we have found a long-lasting increase in AP-1 binding in the rat nucleus accumbens and striatum, two important targets of the behavioral effects of cocaine. This increase develops gradually over several days and remains at 50% of maximal levels 7 days after the last cocaine exposure. Supershift experiments, along with one- and two-dimensional Western blots, indicate that this chronic AP-1 complex contains at least four Fos-related antigens (FRAs), some of which display delta FosB-like immunoreactivity, that are induced selectively by chronic, but not acute, cocaine treatment. The same chronic FRAs were also induced by several different types of chronic treatments in a region-specific manner in the brain. Thus, the chronic FRAs and associated chronic AP-1 complex could mediate some of the long-term changes in gene expression unique to the chronic-treated state as opposed to the acute-treated and normal states.

  8. Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease.

    Science.gov (United States)

    Hokamp, J A; Cianciolo, R E; Boggess, M; Lees, G E; Benali, S L; Kovarsky, M; Nabity, M B

    2016-01-01

    Urine protein loss is common in dogs with chronic kidney disease (CKD). To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD. One hunderd and eighty dogs with naturally occurring kidney disease. Retrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined. Fractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P dogs with proteinuric CKD and might predict specific disease types and survival. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  9. Right-sided representational neglect after left brain damage in a case without visuospatial working memory deficits.

    Science.gov (United States)

    van Dijck, Jean-Philippe; Gevers, Wim; Lafosse, Christophe; Fias, Wim

    2013-10-01

    Brain damaged patients suffering from representational neglect (RN) fail to report, orient to, or verbally describe contra-lesional elements of imagined environments or objects. So far this disorder has only been reported after right brain damage, leading to the idea that only the right hemisphere is involved in this deficit. A widely accepted account attributes RN to a lateralized impairment in the visuospatial component of working memory. So far, however, this hypothesis has not been tested in detail. In the present paper, we describe, for the first time, the case of a left brain damaged patient suffering from right-sided RN while imagining both known and new environments and objects. An in-depth evaluation of her visuospatial working memory abilities, with special focus on the presence of a lateralized deficit, did not reveal any abnormality. In sharp contrast, her ability to memorize visual information was severely compromised. The implications of these results are discussed in the light of recent insights in the neglect syndrome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. [Effect of leptin on long-term spatial memory of rats with white matter damage in developing brain].

    Science.gov (United States)

    Feng, Er-Cui; Jiang, Li

    2017-12-01

    To investigate the neuroprotective effect of leptin by observing its effect on spatial memory of rats with white matter damage in developing brain. A total of 80 neonatal rats were randomly divided into 3 groups: sham-operation (n=27), model (n=27) and leptin intervention (n=27). The rats in the model and leptin intervention groups were used to prepare a model of white matter damage in developing brain, and the rats in the leptin intervention group were given leptin (100 μg/kg) diluted with normal saline immediately after modelling for 4 consecutive days. The survival rate of the rats was observed and the change in body weight was monitored. When the rats reached the age of 21 days, the Morris water maze test was used to evaluate spatial memory. There was no significant difference in the survival rate of rats between the three groups (P>0.05). Within 10 days after birth, the leptin intervention group had similar body weight as the sham-operation group and significantly lower body weight than the model group (P0.05). The results of place navigation showed that from the second day of experiment, there was a significant difference in the latency period between the three groups (Pmemory impairment of rats with white matter damage in developing brain. It thus exerts a neuroprotective effect, and is worthy of further research.

  11. Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

    Science.gov (United States)

    Zhou, Tao; Hong, Guosong; Fu, Tian-Ming; Yang, Xiao; Schuhmann, Thomas G.; Viveros, Robert D.; Lieber, Charles M.

    2017-01-01

    Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2–12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future. PMID:28533392

  12. Differential association between chronic cannabis use and brain function deficits.

    Science.gov (United States)

    Soueif, M I

    1976-01-01

    To summarize, 12 objective tests that generated 16 test variables were administered to 850 male regular cannabis users and 839 nonusers. The tests were designed to assess various modalities, including speed of psychomotor performance, distance estimation, time estimation, immediate memory, and visuomotor coordination. Most of the test variables differentiated significantly between consumers and controls. At the same time, a significant second-order interaction emerged in most cases. This interaction meant that, under certain conditions that relate to the two dimensions "literacy-illiteracy" and/or "urbanism-ruralism," the superiority of controls over cannabis users became impressive, whereas under other conditions it almost disappeared. To account for this complex pattern of results, a working hypothesis was presented to the effect that "other conditions being equal, the lower the nondrug level of proficiency on tests of cognitive and psychomotor performance the smaller the size of function deficit associated with drug usage." For an empirical examination of the hypothesis, six predictions were formulated. Three predictions defined specific relationships between level of performance, on one hand, and each of three organismic variables, on the other: literacy, urbanism, and age. The remaining predictions delineated relationships to be expected between size of function deficit and the three organismic variables. All our predictions were confirmed, showing less function impairment to be contingent with cannabis usage among the illiterates, rurals, and older subjects. Level of cortical arousal was suggested as the central process associated with the three organismic variables. Because the version of our working hypothesis was formulated with reference to chronic material, the possibility of a transposition of the paradign to research on the acute effects of the drug was discussed. The suggestion was made that our working hypothesis, in either version, is capable of

  13. Study on CT changes in autistic children; Anatomical correlation of the damaged brain and delay of psychomotor development

    Energy Technology Data Exchange (ETDEWEB)

    Yaguchi, Katsumi (Juntendo Univ., Tokyo (Japan). School of Medicine)

    1993-05-01

    Since 1979 we have performed CT examinations on 132 autistic children. Neurological diagnosis of the lesion was established by Dr. Segawa's group. On the CT of many autistic children, we found a small low density change located in the anterior wall of the temporal horn, or localized dilatation of the inferior horn near the damaged brain. We reviewed 96 of these patients who all had the obvious low density changes, or localized irregular dilatations in the anterior wall of the temporal horn. By measuring the distance of damage from the midline, we divided the 96 cases into two groups. Group 1 consisted of those with damage located laterally more than 30 mm line from the midline. Group 2 consisted of those with damage medially to the 30 mm line from the midline. Those cases with a large lesion both laterally and medially of the 30 mm line were categorized into group 1. In the adult brain the lateral border of the amygdaloid nucleus was never located laterally more than 30 mm from the midline. Laterally over the 30 mm line there were two marked fiber systems running near the anterior wall of the temporal horn: the fiber of the anterior commissure and the uncinate fascicle. Group 1 consisted of 62 patients and group 2 of 34 patients. The majority of the two group patients were pure autism children. This suggested that the main lesion in autism was in the amygdala. (author).

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

    Directory of Open Access Journals (Sweden)

    Davide Lecca

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

  15. Effects of the acute and chronic ethanol intoxication on acetate metabolism and kinetics in the rat brain.

    Science.gov (United States)

    Hsieh, Ya-Ju; Wu, Liang-Chih; Ke, Chien-Chih; Chang, Chi-Wei; Kuo, Jung-Wen; Huang, Wen-Sheng; Chen, Fu-Du; Yang, Bang-Hung; Tai, Hsiao-Ting; Chen, Sharon Chia-Ju; Liu, Ren-Shyan

    2017-12-05

    Ethanol intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term ethanol consumption were found to have a significant increase in [1-11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1-11 C]-acetate kinetics and acute/chronic ethanol intoxication, however, are still unclear. [1-11 C]-acetate positron emission tomography (PET) with dynamic measurement of K1 and k2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic ethanol intoxication. PET imaging demonstrated decreased [1-11 C]-acetate uptake in rat brain with acute ethanol intoxication, but this increased with chronic ethanol intoxication. Tracer uptake rate constant K1 and clearance rate constant k2 were decreased in acutely intoxicated rats. No significant change was noted in K1 and k2 in chronic ethanol intoxication, although six of seven brain regions showed slightly higher k2 than baseline. These results indicate that acute ethanol intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic ethanol intoxication status showed no significant effect. In vivo PET study confirmed the modulatory role of ethanol, administered acutely or chronically, in [1-11 C]-acetate kinetics and metabolism in the rat brain. Acute ethanol intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic ethanol exposure may lead to the adaptation of the rat brain to ethanol in acetate utilisation. [1-11 C]-Acetate PET imaging is a feasible approach to study the effect of ethanol on acetate metabolism in rat brain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-03

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

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

    Science.gov (United States)

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

    2012-04-15

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

  18. Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain

    Science.gov (United States)

    Duncan, Jeremy; Wang, Niping; Zhang, Xiao; Johnson, Shakevia; Harris, Sharonda; Zheng, Baoying; Zhang, Qinli; Rajkowska, Grazyna; Miguel-Hidalgo, Jose Javier; Sittman, Donald; Ou, Xiao-Ming; Stockmeier, Craig A.; Wang, Jun Ming

    2015-01-01

    Major depressive disorder and alcoholism are significant health burdens that can affect executive functioning, cognitive ability, job responsibilities, and personal relationships. Studies in animal models related to depression or alcoholism reveal that the expression of Krüppel-like factor 11 (KLF11, also called TIEG2) is elevated in frontal cortex, which suggests that KLF11 may play a role in stress- or ethanol-induced psychiatric conditions. KLF11 is a transcriptional activator of monoamine oxidase (MAO) A and B, but also serves other functions in cell cycle regulation and apoptotic cell death. In the present study, immunohistochemistry was used to quantify intensity of nuclear KLF11, combined with an unbiased stereological approach to assess nuclei in fronto-limbic, limbic, and other brain regions of rats exposed chronically to social defeat or ethanol. KLF11 immunoreactivity was increased significantly in the medial prefrontal cortex, frontal cortex and hippocampus of both stressed rats and rats fed ethanol. However, expression of KLF11 protein was not significantly affected in the thalamus, hypothalamus or amygdala in either treatment group compared to respective control rats. Triple-label immunofluorescence revealed that KLF11 protein was localized in nuclei of neurons and astrocytes. KLF11 was also co-localized with the immunoreactivity of cleaved caspase 3. In addition, Western blot analysis revealed a significant reduction in anti-apoptotic protein, Bcl-xL, but an increase of caspase-3 expression in the frontal cortex of ethanol-treated rats compared to ethanol-preferring controls. Thus, KLF11 protein is up-regulated following chronic exposure to stress or ethanol in a region-specific manner and may contribute to pro-apoptotic signaling in ethanol-treated rats. Further investigation into the KLF11 signaling cascade as a mechanism for neurotoxicity and cell death in depression and alcoholism may provide novel pharmacological targets to lessen brain damage

  19. Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats.

    Science.gov (United States)

    Shiha, Ahmed Anis; de Cristóbal, Javier; Delgado, Mercedes; Fernández de la Rosa, Rubén; Bascuñana, Pablo; Pozo, Miguel A; García-García, Luis

    2015-02-01

    The role of serotonin (5-hydroxytryptamine; 5-HT) in epileptogenesis still remains controversial. In this regard, it has been reported that serotonergic drugs can alter epileptogenesis in opposite ways. The main objective of this work was to investigate the effect of the selective 5-HT selective reuptake inhibitor (SSRI) fluoxetine administered subacutely (10mg/kg/day×7 days) on the eventual metabolic impairment induced by the lithium-pilocarpine model of epilepsy in rats. In vivo 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F] FDG) positron emission tomography (PET) was performed to assess the brain glucose metabolic activity on days 3 and 30 after the insult. In addition, at the end of the experiment (day 33), several histochemical and neurochemical assessments were performed for checking the neuronal functioning and integrity. Three days after the insult, a marked reduction of [(18)F] FDG uptake (about 30% according to the brain region) was found in all brain areas studied. When evaluated on day 30, although a hypometabolism tendency was observed, no statistically significant reduction was present in any region analyzed. In addition, lithium-pilocarpine administration was associated with medium-term hippocampal and cortical damage, since it induced neurodegeneration, glial activation and augmented caspase-9 expression. Regarding the effect of fluoxetine, subacute treatment with this SSRI did not significantly reduce the mortality rate observed after pilocarpine-induced seizures. However, fluoxetine did prevent not only the short-term metabolic impairment, but also the aforementioned signs of neuronal damage in surviving animals to lithium-pilocarpine protocol. Finally, fluoxetine increased the density of GABAA receptor both at the level of the dentate gyrus and CA1-CA2 regions in pilocarpine-treated animals. Overall, our data suggest a protective role for fluoxetine against pilocarpine-induced brain damage. Moreover, this action may be associated with an increase of

  20. Endothelial nitric oxide synthase in rat brain is downregulated by sub-chronic antidepressant treatment.

    Science.gov (United States)

    Yoshino, Yuta; Ochi, Shinichiro; Yamazaki, Kiyohiro; Nakata, Shunsuke; Iga, Jun-Ichi; Ueno, Shu-Ichi

    2017-06-01

    Nitric oxide (NO) is a neurotransmitter that may be related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces a dose-dependent antidepressant-like effect. NO modulates major neurotransmitters involved in the neurobiology of MDD, such as norepinephrine, serotonin, dopamine, and glutamate. In this study, we investigated the effects of antidepressants as NO modulators in acute and sub-chronic treatments. Rats were injected with the SSRI paroxetine (PAR, 10 mg/kg), the SNRI milnacipran (MIL, 30 mg/kg), or the NaSSA mirtazapine (MIR, 10 mg/kg) for acute (1 h) or sub-chronic (3 weeks) treatment prior to analysis of nine brain regions (frontal cortex, temporal cortex, striatum, thalamus, hippocampus, midbrain, pons, cerebellum, and olfactory bulb). The mRNA expression levels of three NOS subtypes (neuronal: nNOS, inducible: iNOS, and endothelial: eNOS) were analyzed using real-time PCR with Taqman probes. Acute MIR treatment significantly increased nNOS mRNA expression in the hippocampus, midbrain, cerebellum and olfactory bulb, and iNOS mRNA expression in the frontal cortex and midbrain. Acute PAR and MIR treatments significantly increased eNOS mRNA expression in most brain regions. Conversely, sub-chronic treatment with all types of antidepressants resulted in significant decreases of eNOS mRNA expression in most brain regions. Sub-chronic treatment with the three types of antidepressants consistently decreased eNOS mRNA expression levels in the rat brain. These effects may be associated with the involvement of the NO system in the mechanism of action of antidepressants.

  1. Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology.

    Science.gov (United States)

    Ghajari, Mazdak; Hellyer, Peter J; Sharp, David J

    2017-02-01

    Traumatic brain injury can lead to the neurodegenerative disease chronic traumatic encephalopathy. This condition has a clear neuropathological definition but the relationship between the initial head impact and the pattern of progressive brain pathology is poorly understood. We test the hypothesis that mechanical strain and strain rate are greatest in sulci, where neuropathology is prominently seen in chronic traumatic encephalopathy, and whether human neuroimaging observations converge with computational predictions. Three distinct types of injury were simulated. Chronic traumatic encephalopathy can occur after sporting injuries, so we studied a helmet-to-helmet impact in an American football game. In addition, we investigated an occipital head impact due to a fall from ground level and a helmeted head impact in a road traffic accident involving a motorcycle and a car. A high fidelity 3D computational model of brain injury biomechanics was developed and the contours of strain and strain rate at the grey matter-white matter boundary were mapped. Diffusion tensor imaging abnormalities in a cohort of 97 traumatic brain injury patients were also mapped at the grey matter-white matter boundary. Fifty-one healthy subjects served as controls. The computational models predicted large strain most prominent at the depths of sulci. The volume fraction of sulcal regions exceeding brain injury thresholds were significantly larger than that of gyral regions. Strain and strain rates were highest for the road traffic accident and sporting injury. Strain was greater in the sulci for all injury types, but strain rate was greater only in the road traffic and sporting injuries. Diffusion tensor imaging showed converging imaging abnormalities within sulcal regions with a significant decrease in fractional anisotropy in the patient group compared to controls within the sulci. Our results show that brain tissue deformation induced by head impact loading is greatest in sulcal locations

  2. Effect of Coenzyme Q10 on ischemia and neuronal damage in an experimental traumatic brain-injury model in rats

    Directory of Open Access Journals (Sweden)

    Hanci Volkan

    2011-07-01

    Full Text Available Abstract Background Head trauma is one of the most important clinical issues that not only can be fatal and disabling, requiring long-term treatment and care, but also can cause heavy financial burden. Formation or distribution of free oxygen radicals should be decreased to enable fixing of poor neurological outcomes and to prevent neuronal damage secondary to ischemia after trauma. Coenzyme Q10 (CoQ10, a component of the mitochondrial electron transport chain, is a strong antioxidant that plays a role in membrane stabilization. In this study, the role of CoQ10 in the treatment of head trauma is researched by analyzing the histopathological and biochemical effects of CoQ10 administered after experimental traumatic brain injury in rats. A traumatic brain-injury model was created in all rats. Trauma was inflicted on rats by the free fall of an object of 450 g weight from a height of 70 cm on the frontoparietal midline onto a metal disc fixed between the coronal and the lambdoid sutures after a midline incision was carried out. Results In the biochemical tests, tissue malondialdehyde (MDA levels were significantly higher in the traumatic brain-injury group compared to the sham group (p 10 after trauma was shown to be protective because it significantly lowered the increased MDA levels (p 10 group had SOD levels ranging between those of sham group and traumatic brain-injury group, and no statistically significant increase was detected. Histopathological results showed a statistically significant difference between the CoQ10 and the other trauma-subjected groups with reference to vascular congestion, neuronal loss, nuclear pyknosis, nuclear hyperchromasia, cytoplasmic eosinophilia, and axonal edema (p Conclusion Neuronal degenerative findings and the secondary brain damage and ischemia caused by oxidative stress are decreased by CoQ10 use in rats with traumatic brain injury.

  3. Low Viral Load Does Not Exclude Significant Liver Damage in Patients with Chronic HBV Infection in Bangladesh

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    Mamun Al-Mahtab

    2009-11-01

    Full Text Available Background: In general, it is assumed that patients with chronic hepatitis B virus (HBV infection with high viral load exhibit increased liver damages. Accordingly, the treatment guidelines emphasize on reducing viral load in chronic HBV carriers. The ethical and scientific basis of these observations was mainly accumulated from investigations from developed countries of the world. More than 80% chronic HBV carriers live in the developing nations of the world, but little is known about relationship between HBV viral load and extent of liver damages in these countries. In this study, we addressed this issue to provide insights about this. Methods: In this retrospective study we reviewed the records of 210 chronic hepatitis B (CHB patients from our pool of 561 Bangladeshi CHB patients. All of these 210 patients had low HBV DNA (<105 copies/ml by PCR. Of them 16 were HBeAg +ve and rest 194 HBeAg -ve. They have also been tested for other serologic markers of HBV (i.e. HBsAg, anti-HBe, HCV (i.e. anti-HCV and serum alaninetransaminase (ALT level. All patients also underwent per-cutaneous liver biopsy. Results: 37.5% (6/16 HBeAg +ve patients with low HBV DNA had significant hepatic necro-inflammation (HAI-NI ≥7, whereas this figure was 31.44% (61/194 in case of HBeAg -ve patients. On the other hand significant hepatic fibrosis (HAI-F ≥3 was observed in 31.25% (5/16 and 14.4% (28/194 in HBeAg +ve and -ve patients respectively. Conclusion: This study shows that a correlation could not be established between viral load and liver damage in patients with CHB in Bangladesh. A significant percentage of patients with low HBV DNA may have marked hepatic necro-inflammation and fibrosis, more so in case of HBeAg +ve CHB. Further study may be needed to find out the influence of other factors on liver damages in CHB patients in developing nations like Bangladesh, where about 8 million chronic HBV carriers are living. Most of these patients have not been

  4. Evaluation of Krebs cycle enzymes in the brain of rats after chronic administration of antidepressants.

    Science.gov (United States)

    Scaini, Giselli; Santos, Patricia M; Benedet, Joana; Rochi, Natália; Gomes, Lara M; Borges, Lislaine S; Rezin, Gislaine T; Pezente, Daiana P; Quevedo, João; Streck, Emilio L

    2010-05-31

    Several works report brain impairment of metabolism as a mechanism underlying depression. Citrate synthase and succinate dehydrogenase are enzymes localized within cells in the mitochondrial matrix and are important steps of Krebs cycle. In addition, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase and succinate dehydrogenase activities from rat brain after chronic administration of paroxetine, nortriptiline and venlafaxine. Adult male Wistar rats received daily injections of paroxetine (10mg/kg), nortriptiline (15mg/kg), venlafaxine (10mg/kg) or saline in 1.0mL/kg volume for 15 days. Twelve hours after the last administration, the rats were killed by decapitation, the hippocampus, striatum and prefrontal cortex were immediately removed, and activities of citrate synthase and succinate dehydrogenase were measured. We verified that chronic administration of paroxetine increased citrate synthase activity in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected. Chronic administration of nortriptiline and venlafaxine did not affect the enzyme activity in these brain areas. Succinate dehydrogenase activity was increased by chronic administration of paroxetine and nortriptiline in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected either. Chronic administration of venlafaxine increased succinate dehydrogenase activity in prefrontal cortex, but did not affect the enzyme activity in cerebellum, hippocampus, striatum and cerebral cortex. Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, an increase in these enzymes by antidepressants may be an important mechanism of action of these drugs. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  5. Three-year follow-up results of a residential community reintegration program for patients with chronic acquired brain injury.

    NARCIS (Netherlands)

    Geurtsen, G.J.; Heugten, C.M. van; Martina, J.D.; Rietveld, A.C.; Meijer, R.; Geurts, A.C.H.

    2012-01-01

    OBJECTIVE: To evaluate outcomes of a residential community reintegration program 3 years after treatment on independent living, societal participation, emotional well-being, and quality of life in patients with chronic acquired brain injury and psychosocial problems hampering societal participation.

  6. No Value of Routine Brain Computed Tomography 6 Weeks after Evacuation of Chronic Subdural Hematoma

    DEFF Research Database (Denmark)

    Pedersen, Christian Bonde; Sundbye, Filippa; Poulsen, Frantz Rom

    2017-01-01

    Background  The aim of this study was to evaluate the value of planned control postoperative brain computed tomography (CT) scan performed 4 to 6 weeks after the evacuation of chronic subdural hematoma. Materials and Methods  This retrospective study examined 202 patients who during a 2-year period...... was retrieved from patient charts. Results  Overall, 27 out of 202 patients had a recurrence of CSDH and re-evacuation of the hematoma was performed. In all patients recurrence of neurological symptoms preceded the planned postoperative control brain CT 4 to 6 weeks after primary surgery. Conclusion  Routinely...... postoperative control brain CT scan 4 to 6 weeks after the evacuation of a CSDH has no clinical value....

  7. Hippotherapy in adult patients with chronic brain disorders: a pilot study.

    Science.gov (United States)

    Sunwoo, Hyuk; Chang, Won Hyuk; Kwon, Jeong-Yi; Kim, Tae-Won; Lee, Ji-Young; Kim, Yun-Hee

    2012-12-01

    To investigate the effects of hippotherapy for adult patients with brain disorders. Eight chronic brain disorder patients (7 males, mean age 42.4±16.6 years) were recruited. The mean duration from injury was 7.9±7.7 years. The diagnoses were stroke (n=5), traumatic brain disorder (n=2), and cerebral palsy (n=1). Hippotherapy sessions were conducted twice a week for eight consecutive weeks in an indoor riding arena. Each hippotherapy session lasted 30 minutes. All participants were evaluated by the Berg balance scale, Tinetti Performance-Oriented Mobility Assessment, 10 Meter Walking Test, Functional Ambulatory Category, Korean Beck Depression Inventory, and Hamilton Depression Rating Scale. We performed baseline assessments twice just before starting hippotherapy. We also assessed the participants immediately after hippotherapy and at eight weeks after hippotherapy. All participants showed no difference in balance, gait function, and emotion between the two baseline assessments before hippotherapy. During the eight-week hippotherapy program, all participants showed neither adverse effects nor any accidents; all had good compliance. After hippotherapy, there were significant improvements in balance and gait speed in comparison with the baseline assessment (phippotherapy. However, there was no significant difference in emotion after hippotherapy. We could observe hippotherapy to be a safe and effective alternative therapy for adult patients with brain disorders in improving balance and gait function. Further future studies are warranted to delineate the benefits of hippotherapy on chronic stroke patients.

  8. Comparison of Regional Brain Perfusion Levels in Chronically Smoking and Non-Smoking Adults

    Directory of Open Access Journals (Sweden)

    Timothy C. Durazzo

    2015-07-01

    Full Text Available Chronic cigarette smoking is associated with numerous abnormalities in brain neurobiology, but few studies specifically investigated the chronic effects of smoking (compared to the acute effects of smoking, nicotine administration, or nicotine withdrawal on cerebral perfusion (i.e., blood flow. Predominately middle-aged male (47 ± 11 years of age smokers (n = 34 and non-smokers (n = 27 were compared on regional cortical perfusion measured by continuous arterial spin labeling magnetic resonance studies at 4 Tesla. Smokers showed significantly lower perfusion than non-smokers in the bilateral medial and lateral orbitofrontal cortices, bilateral inferior parietal lobules, bilateral superior temporal gyri, left posterior cingulate, right isthmus of cingulate, and right supramarginal gyrus. Greater lifetime duration of smoking (adjusted for age was related to lower perfusion in multiple brain regions. The results indicated smokers showed significant perfusion deficits in anterior cortical regions implicated in the development, progression, and maintenance of all addictive disorders. Smokers concurrently demonstrated reduced blood flow in posterior brain regions that show morphological and metabolic aberrations as well as elevated beta amyloid deposition demonstrated by those with early stage Alzheimer disease. The findings provide additional novel evidence of the adverse effects of cigarette smoking on the human brain.

  9. Long-term consequences of repetitive brain trauma: chronic traumatic encephalopathy.

    Science.gov (United States)

    Stern, Robert A; Riley, David O; Daneshvar, Daniel H; Nowinski, Christopher J; Cantu, Robert C; McKee, Ann C

    2011-10-01

    Chronic traumatic encephalopathy (CTE) has been linked to participation in contact sports such as boxing and American football. CTE results in a progressive decline of memory and cognition, as well as depression, suicidal behavior, poor impulse control, aggressiveness, parkinsonism, and, eventually, dementia. In some individuals, it is associated with motor neuron disease, referred to as chronic traumatic encephalomyelopathy, which appears clinically similar to amyotrophic lateral sclerosis. Results of neuropathologic research has shown that CTE may be more common in former contact sports athletes than previously believed. It is believed that repetitive brain trauma, with or possibly without symptomatic concussion, is responsible for neurodegenerative changes highlighted by accumulations of hyperphosphorylated tau and TDP-43 proteins. Given the millions of youth, high school, collegiate, and professional athletes participating in contact sports that involve repetitive brain trauma, as well as military personnel exposed to repeated brain trauma from blast and other injuries in the military, CTE represents an important public health issue. Focused and intensive study of the risk factors and in vivo diagnosis of CTE will potentially allow for methods to prevent and treat these diseases. Research also will provide policy makers with the scientific knowledge to make appropriate guidelines regarding the prevention and treatment of brain trauma in all levels of athletic involvement as well as the military theater. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  10. Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains.

    Science.gov (United States)

    Adzovic, Linda; Lynn, Ashley E; D'Angelo, Heather M; Crockett, Alexis M; Kaercher, Roxanne M; Royer, Sarah E; Hopp, Sarah C; Wenk, Gary L

    2015-04-02

    The role of insulin in the brain is still not completely understood. In the periphery, insulin can decrease inflammation induced by lipopolysaccharide (LPS); however, whether insulin can reduce inflammation within the brain is unknown. Experiments administrating intranasal insulin to young and aged adults have shown that insulin improves memory. In our animal model of chronic neuroinflammation, we administered insulin and/or LPS directly into the brain via the fourth ventricle for 4 weeks in young rats; we then analyzed their spatial memory and neuroinflammatory response. Additionally, we administered insulin or artificial cerebral spinal fluid (aCSF), in the same manner, to aged rats and then analyzed their spatial memory and neuroinflammatory response. Response to chronic neuroinflammation in young rats was analyzed in the presence or absence of insulin supplementation. Here, we show for the first time that insulin infused (i.c.v.) to young rats significantly attenuated the effects of LPS by decreasing the expression of neuroinflammatory markers in the hippocampus and by improving performance in the Morris water pool task. In young rats, insulin infusion alone significantly improved their performance as compared to all other groups. Unexpectedly, in aged rats, the responsiveness to insulin was completely absent, that is, spatial memory was still impaired suggesting that an age-dependent insulin resistance may contribute to the cognitive impairment observed in neurodegenerative diseases. Our data suggest a novel therapeutic effect of insulin on neuroinflammation in the young but not the aged brain.

  11. Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Osterndorff-Kahanek

    Full Text Available Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY, nucleus accumbens (NAC, prefrontal cortex (PFC, and liver after four weekly cycles of chronic intermittent ethanol (CIE vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000 at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600. Within each region, there was little gene overlap across time (~20%. All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.

  12. Exercise Ameliorates Endocrine Pancreas Damage Induced by Chronic Cola Drinking in Rats.

    Directory of Open Access Journals (Sweden)

    Matilde Otero-Losada

    Full Text Available This study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats.Forty-eight Wistar rats were randomly assigned to 4 groups depending on a beverage consumption ad libitum, water (W or cola beverage (C, and b physical activity, sedentary (S or treadmill running (R. Accordingly, 4 groups were studied: WS (water sedentary, WR (water runner, CS (cola sedentary and CR (cola runner. Body weight, nutritional data, plasma levels of glucose, creatinine, total cholesterol and cholesterol fractions, and triglycerides (enzymocolorimetry, and systolic blood pressure (plethysmography were measured. After 6 months, euthanasia was performed (overdose sodium thiopental. Pancreatic tissue was immediately excised and conventionally processed for morphometrical and immunohistochemical determinations.The effects of running and chronic cola drinking on pancreas morphology showed interaction (p<0.001 rather than simple summation. Cola drinking (CS vs WS reduced median pancreatic islet area (-30%, 1.8 104 μm2 vs 2.58 104 μm2, p<0.0001 and median β-cell mass (-43%, 3.81 mg vs 6.73 mg, p<0.0001, and increased median α/β ratio (+49%, 0.64 vs 0.43, p< 0.001. In water drinking rats (WR vs WS, running reduced median α-cell mass (-48%, 1.48 mg vs 2.82 mg, p<0.001 and α/β ratio (-56%, 0.19 vs 0.43, p<0.0001. Differently, in cola drinking rats (CR vs CS, running partially restored median islet area (+15%, 2.06 104 μm2 vs 1.79 104 μm2, p<0.05, increased median β-cell mass (+47%, 5.59 mg vs 3.81 mg, p <0.0001 and reduced median α/β ratio (-6%, 0.60 vs 0.64, p<0.05.This study is likely the first reporting experimental evidence of the beneficial effect of exercise on pancreatic morphology in cola-drinking rats. Presently, the increase of nearly 50% in β cells mass by running in cola drinking rats is by far the most relevant finding. Moderate running, advisably indicated in cola consumers and

  13. [Asymptomatic renal damages in persons with chronic professional exposure to elementary mercury low concentrations].

    Science.gov (United States)

    Durić, Stevan; Jovanović, Dragan; Hrvacević, Rajko; Kovacević, Zoran; Konjević, Marija

    2008-09-01

    Any forms of mercury have toxic action on the majority of organs, especially kidneys. The major source of professional exposure to mercury are departments for the production of chlorine which use mercury as catode. The aim of the study was to prove that chronic exposure to elementary mercury low concentrations could cause asymptomatic damages of the kidneys. A total of 40 workers from the factory ,,HIP Petrohemija" Pancevo, of the mean age 45+/-8 years, who were exposed to the effects of mercury for more than 20 years within the production procedure, and 20 workers from the factory "Panonijaplast" Pancevo, of the mean age 44+/-7 years, who were not exposed to mercury nor to other nephrotoxic agents, were submitted to laboratory analysis, renal function testing, and determination of mercury concentration in urine. Mercury concentration was also measured in the air of working premises of the factory. The performed measurements confirmed that the concentrations of mercury at any tested working place in the Department of Electrolysis were not more than the maximally permitted concentration for an 8-hour exposition. In the exposed group (40 examinees) 75% of the examinees had mercury in urine in the concentration < 0.1 micromol/l, while in 25% of them it was 0.1-0.75 micromol/l. In the control group (20 examinees) all of the examinees showed to have < 0.1 mol/l mercury in urine. There was determined a positive corelation between the concentration of mercury in urine and the value of beta2-microglobulin (p < 0.05), as well as between the corrcentration of mercury in urine and gammaGT activity (p < 0.05), and between the concentration of mercury in urine and the value of retinol-binding protein (p < 0.01). In 25% of the examinees excretion of mercury was significantly higher than in the control group. The frequency of asymptomatic renal tubular lesions and dysfunction of moderate extent were found to be higher in the exposed group than in the control one.

  14. Asymptomatic renal damages in persons with chronic professional exposure to elementary mercury low concentrations

    Directory of Open Access Journals (Sweden)

    Đurić Stevan

    2008-01-01

    Full Text Available Background/Aim. Any forms of mercury have toxic action on the majority of organs, especially kidneys. The major source of professional exposure to mercury are departments for the production of chlorine which use mercury as catode. The aim of the study was to prove that chronic exposure to elementary mercury low concentrations could cause asymptomatic damages of the kidneys. Methods. A total of 40 workers from the factory "HIP Petrohemija" Pančevo, of the mean age 45±8 years, who were exposed to the effects of mercury for more than 20 years within the production procedure, and 20 workers from the factory "Panonijaplast" Pančevo, of the mean age 44±7 years, who were not exposed to mercury nor to other nephrotoxic agents, were submitted to laboratory analysis, renal function testing, and determination of mercury concentration in urine. Mercury concentration was also measured in the air of working premises of the factory. Results. The performed measurements confirmed that the concentrations of mercury at any tested working place in the Department of Electrolysis were not more than the maximally permitted concentration for an 8-hour exposition. In the exposed group (40 examinees 75% of the examinees had mercury in urine in the concentration < 0.1 μmol/l, while in 25% of them it was 0.1-0.75 μmol/l. In the control group (20 examinees all of the examinees showed to have < 0.1 mol/l mercury in urine. There was determined a positive corelation between the concentration of mercury in urine and the value of β2-microglobulin (p < 0.05, as well as between the corrcentration of mercury in urine and γGT activity (p < 0.05, and between the concentration of mercury in urine and the value of retinol-binding protein (p < 0.01. Conclusion. In 25% of the examinees excretion of mercury was significantly higher than in the control group. The frequency of asymptomatic renal tubular lesions and dysfunction of moderate extent were found to be higher in the

  15. DNA-damage response associated with occupational exposure, age and chronic inflammation in workers in the automotive industry.

    Science.gov (United States)

    Savina, Natalya V; Smal, Marharyta P; Kuzhir, Tatyana D; Ershova-Pavlova, Alla A; Goncharova, Roza I

    2012-10-09

    The evaluation of genome integrity in populations occupationally exposed to combine industrial factors is of medical importance. In the present study, the DNA-damage response was estimated by means of the alkaline comet assay in a sizeable cohort of volunteers recruited among workers in the automotive industry. For this purpose, freshly collected lymphocytes were treated with hydrogen peroxide (100μM, 1min, 4°C) in vitro, and the levels of basal and H(2)O(2)-induced DNA damage, and the kinetics and efficiency of DNA repair were measured during a 180-min interval after exposure. The parameters studied in the total cohort of workers were in a range of values prescribed for healthy adult residents of Belarus. Based on the 95th percentiles, individuals possessing enhanced cellular sensitivity to DNA damage were present in different groups, but the frequency was significantly higher among elderly persons and among individuals with chronic inflammatory diseases. The results indicate that the inter-individual variations in DNA-damage response should be taken into account to estimate adequately the environmental genotoxic effects and to identify individuals with an enhanced DNA-damage response due to the influence of some external factors or intrinsic properties of the organism. Underling mechanisms need to be further explored. © 2012 Elsevier B.V. All rights reserved.

  16. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

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    Kanoto, Masafumi, E-mail: mkanoto@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Hosoya, Takaaki, E-mail: thosoya@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Toyoguchi, Yuuki, E-mail: c-elegans_0201g@mail.goo.ne.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Oda, Atsuko, E-mail: a.oda@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan)

    2013-01-15

    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis.

  17. Caught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Anthony James Ocon

    2013-04-01

    Full Text Available Chronic Fatigue Syndrome (CFS is defined as greater than 6 months of persistent fatigue that is experienced physically and cognitively. The cognitive symptoms are generally thought to be a mild cognitive impairment, but individuals with CFS subjectively describe them as brain fog. The impairment is not fully understood and often is described as slow thinking, difficulty focusing, confusion, lack of concentration, forgetfulness, or a haziness in thought processes. Causes of brain fog and mild cognitive impairment have been investigated. Possible physiological correlates may be due to the effects of chronic orthostatic intolerance in the form of the Postural Tachycardia Syndrome and decreases in cerebral blood flow. In addition, fMRI studies suggest that individuals with CFS may require increased cortical and subcortical brain activation to complete difficult mental tasks. Furthermore, neurocognitive testing in CFS has demonstrated deficits in speed and efficiency of information processing, attention, concentration, and working memory. The cognitive impairments are then perceived as an exaggerated mental fatigue. As a whole, this is experienced by those with CFS as brain fog and may be viewed as the interaction of physiological, cognitive, and perceptual factors. Thus, the cognitive symptoms of CFS may be due to altered cerebral blood flow activation and regulation that are exacerbated by a stressor, such as orthostasis or a difficult mental task, resulting in the decreased ability to readily process information, which is then perceived as fatiguing and experienced as brain fog. Future research looks to further explore these interactions, how they produce cognitive impairments, and explain the perception of brain fog from a mechanistic standpoint.

  18. Evaluation of Early Kidney Damage Caused by Brain Death Using Real-Time Ultrasound Elastography in a Bama Pig Model.

    Science.gov (United States)

    Tang, Ying; Zhao, Jingwen; Liu, Dongyang; Niu, Ningning; Yu, Huimin

    2017-10-01

    The aim of this study was to investigate the value of real-time tissue elastography (RTE) in the evaluation of early graft damage resulting from brain death. We performed RTE before and 0, 3, 6 and 9 h after brain death in a Bama pig model. Eleven RTE parameters were compared among time groups, and their correlations with electron microscopic findings were analyzed. Receiver operating characteristic curve analysis was used to find the RTE parameter cutoff values. The mean relative strain value within the region of interest (MEAN), standard deviation of the relative strain value within the region of interest (SD), percentage area of low strain within the region of interest (%AREA), complexity of low-strain area within the region of interest (COMP), kurtosis (KURT), skewness (SKEW), contrast (CONT) and entropy (ENT) and inverse difference moment (IDM) differed statistically significantly between groups (p < 0.05). Electron microscopy of kidney tissue revealed that irreversible damage gradually occurred with longer brain death duration and was marked at 9 h (p < 0.05). These findings correlated best with MEAN (r = 0.632, p < 0.05). Receiver operating characteristic curve analysis of RTE parameters identified a cutoff value of 63.43 for MEAN for optimal diagnostic performance. RTE allows non-invasive, preliminary evaluation of early renal graft damage resulting from brain death. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  19. Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function?

    Science.gov (United States)

    Tyler, Lorraine K; Wright, Paul; Randall, Billi; Marslen-Wilson, William D; Stamatakis, Emmanuel A

    2010-11-01

    The extent to which the human brain shows evidence of functional plasticity across the lifespan has been addressed in the context of pathological brain changes and, more recently, of the changes that take place during healthy ageing. Here we examine the potential for plasticity by asking whether a strongly left-lateralized system can successfully reorganize to the right-hemisphere following left-hemisphere brain damage. To do this, we focus on syntax, a key linguistic function considered to be strongly left-lateralized, combining measures of tissue integrity, neural activation and behavioural performance. In a functional neuroimaging study participants heard spoken sentences that differentially loaded on syntactic and semantic information. While healthy controls activated a left-hemisphere network of correlated activity including Brodmann areas 45/47 and posterior middle temporal gyrus during syntactic processing, patients activated Brodmann areas 45/47 bilaterally and right middle temporal gyrus. However, voxel-based morphometry analyses showed that only tissue integrity in left Brodmann areas 45/47 was correlated with activity and performance; poor tissue integrity in left Brodmann area 45 was associated with reduced functional activity and increased syntactic deficits. Activity in the right-hemisphere was not correlated with damage in the left-hemisphere or with performance. Reduced neural integrity in the left-hemisphere through brain damage or healthy ageing results in increased right-hemisphere activation in homologous regions to those left-hemisphere regions typically involved in the young. However, these regions do not support the same linguistic functions as those in the left-hemisphere and only indirectly contribute to preserved syntactic capacity. This establishes the unique role of the left hemisphere in syntax, a core component in human language.

  20. Chronic Lead Exposure and Mixed Factors of Gender×Age×Brain Regions Interactions on Dendrite Growth, Spine Maturity and NDR Kinase

    Science.gov (United States)

    Xue, Weizhen; Yang, Qian-Qian; Wang, Shuang; Xu, Yi; Wang, Hui-Li

    2015-01-01

    NDR1/2 kinase is essential in dendrite morphology and spine formation, which is regulated by cellular Ca2+. Lead (Pb) is a potent blocker of L-type calcium channel and our recent work showed Pb exposure impairs dendritic spine outgrowth in hippocampal neurons in rats. But the sensitivity of Pb-induced spine maturity with mixed factors (gender×age×brain regions) remains unknown. This study aimed to systematically investigate the effect of Pb exposure on spine maturity in rat brain with three factors (gender×age×brain regions), as well as the NDR1/2 kinase expression. Sprague–Dawley rats were exposed to Pb from parturition to postnatal day 30, 60, 90, respectively. Golgi-Cox staining was used to examine spine maturity. Western blot assay was applied to measure protein expression and real-time fluorescence quantitative PCR assay was used to examine mRNA levels. The results showed chronic Pb exposure significantly decreased dendritic length and impaired spine maturity in both rat hippocampus and medial prefrontal cortex. The impairment of dendritic length induced by Pb exposure tended to adolescence > adulthood, hippocampus > medial prefrontal cortex and female > male. Pb exposure induced significant damage in spine maturity during adolescence and early adult while little damage during adult in male rat brain and female medial prefrontal cortex. Besides, there was sustained impairment from adolescence to adulthood in female hippocampus. Interestingly, impairment of spine maturity followed by Pb exposure was correlated with NDR1/2 kinase. The reduction of NDR1/2 kinase protein expression after Pb exposure was similar to the result of spine maturity. In addition, NDR2 and their substrate Rabin3 mRNA levels were significantly decreased by Pb exposure in developmental rat brain. Taken together, Pb exposure impaired dendrite growth and maturity which was subject to gender×age×brain regions effects and related to NDR1/2 signal expression. PMID:26368815

  1. A novel, implicit treatment for language comprehension processes in right hemisphere brain damage: Phase I data.

    Science.gov (United States)

    Tompkins, Connie A; Blake, Margaret T; Wambaugh, Julie; Meigh, Kimberly

    2011-03-22

    BACKGROUND: This manuscript reports the initial phase of testing for a novel, "Contextual constraint" treatment, designed to stimulate inefficient language comprehension processes in adults with right hemisphere brain damage (RHD). Two versions of treatment were developed to target two normal comprehension processes that have broad relevance for discourse comprehension and that are often disrupted by RHD: coarse semantic coding and suppression. The development of the treatment was informed by two well-documented strengths of the RHD population. The first is consistently better performance on assessments that are implicit, or nearly so, than on explicit, metalinguistic measures of language and cognitive processing. The second is improved performance when given linguistic context that moderately-to-strongly biases an intended meaning. Treatment consisted of providing brief context sentences to prestimulate, or constrain, intended interpretations. Participants made no explicit associations or judgments about the constraint sentences; rather, these contexts served only as implicit primes. AIMS: This Phase I treatment study aimed to determine the effects of a novel, implicit, Contextual Constraint treatment in adults with RHD whose coarse coding or suppression processes were inefficient. Treatment was hypothesized to speed coarse coding or suppression function in these individuals. METHODS #ENTITYSTARTX00026; PROCEDURES: Three adults with RHD participated in this study, one (P1) with a coarse coding deficit and two (P2, P3) with suppression deficits. Probe tasks were adapted from prior studies of coarse coding and suppression in RHD. The dependent measure was the percentage of responses that met predetermined response time criteria. When pre-treatment baseline performance was stable, treatment was initiated. There were two levels of contextual constraint, Strong and Moderate, and treatment for each item began with the provision of the Strong constraint context. OUTCOMES

  2. Extracellular Mitochondria and Mitochondrial Components Act as Damage-Associated Molecular Pattern Molecules in the Mouse Brain.

    Science.gov (United States)

    Wilkins, Heather M; Koppel, Scott J; Weidling, Ian W; Roy, Nairita; Ryan, Lauren N; Stanford, John A; Swerdlow, Russell H

    2016-12-01

    Mitochondria and mitochondrial debris are found in the brain's extracellular space, and extracellular mitochondrial components can act as damage associated molecular pattern (DAMP) molecules. To characterize the effects of potential mitochondrial DAMP molecules on neuroinflammation, we injected either isolated mitochondria or mitochondrial DNA (mtDNA) into hippocampi of C57BL/6 mice and seven days later measured markers of inflammation. Brains injected with whole mitochondria showed increased Tnfα and decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation. Some of these effects were also observed in brains injected with mtDNA (decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation), and mtDNA injection also caused several unique changes including increased CSF1R protein and AKT phosphorylation. To further establish the potential relevance of this response to Alzheimer's disease (AD), a brain disorder characterized by neurodegeneration, mitochondrial dysfunction, and neuroinflammation we also measured App mRNA, APP protein, and Aβ 1-42 levels. We found mitochondria (but not mtDNA) injections increased these parameters. Our data show that in the mouse brain extracellular mitochondria and its components can induce neuroinflammation, extracellular mtDNA or mtDNA-associated proteins can contribute to this effect, and mitochondria derived-DAMP molecules can influence AD-associated biomarkers.

  3. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    Energy Technology Data Exchange (ETDEWEB)

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  4. PGC-1α Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Shiqin Xiong

    2015-09-01

    Full Text Available Cellular senescence and organismal aging predispose age-related chronic diseases, such as neurodegenerative, metabolic, and cardiovascular disorders. These diseases emerge coincidently from elevated oxidative/electrophilic stress, inflammation, mitochondrial dysfunction, DNA damage, and telomere dysfunction and shortening. Mechanistic linkages are incompletely understood. Here, we show that ablation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α accelerates vascular aging and atherosclerosis, coinciding with telomere dysfunction and shortening and DNA damage. PGC-1α deletion reduces expression and activity of telomerase reverse transcriptase (TERT and increases p53 levels. Ectopic expression of PGC-1α coactivates TERT transcription and reverses telomere malfunction and DNA damage. Furthermore, alpha lipoic acid (ALA, a non-dispensable mitochondrial cofactor, upregulates PGC-1α-dependent TERT and the cytoprotective Nrf-2-mediated antioxidant/electrophile-responsive element (ARE/ERE signaling cascades, and counteracts high-fat-diet-induced, age-dependent arteriopathy. These results illustrate the pivotal importance of PGC-1α in ameliorating senescence, aging, and associated chronic diseases, and may inform novel therapeutic approaches involving electrophilic specificity.

  5. Processing Homonymy and Polysemy: Effects of Sentential Context and Time-Course Following Unilateral Brain Damage

    Science.gov (United States)

    Klepousniotou, Ekaterini; Baum, Shari R.

    2005-01-01

    The present study investigated the abilities of left-hemisphere-damaged (LHD) non-fluent aphasic, right-hemisphere-damaged (RHD), and normal control individuals to access, in sentential biasing contexts, the multiple meanings of three types of ambiguous words, namely homonyms (e.g., ''punch''), metonymies (e.g., ''rabbit''), and metaphors (e.g.,…

  6. Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.

    Science.gov (United States)

    Son, Seung-Wan; Lee, Jin-Seok; Kim, Hyeong-Geug; Kim, Dong-Woon; Ahn, Yo-Chan; Son, Chang-Gue

    2016-01-01

    Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations

  7. Chronic cocaine induces HIF-VEGF pathway activation along with angiogenesis in the brain.

    Directory of Open Access Journals (Sweden)

    Wei Yin

    Full Text Available Cocaine induces vasoconstriction in cerebral vessels, which with repeated use can result in transient ischemic attacks and cerebral strokes. However, the neuroadaptations that follow cocaine's vasoconstricting effects are not well understood. Here, we investigated the effects of chronic cocaine exposure (2 and 4 weeks on markers of vascular function and morphology in the rat brain. For this purpose we measured nitric oxide (NO concentration in plasma, brain neuronal nitric oxide synthase (nNOS or NOS1, HIF-1α, and VEGF expression in different brain regions, i.e., middle prefrontal cortex, somatosensory cortex, nucleus accumbens, and dorsal striatum, using ELISA or Western blot. Additionally, microvascular density in these brain regions was measured using immunofluorescence microscopy. We showed that chronic cocaine significantly affected NOS1, HIF-1α and VEGF expression, in a region- and cocaine treatment-time- dependent manner. Cerebral microvascular density increased significantly in parallel to these neurochemical changes. Furthermore, significant correlations were detected between VEGF expression and microvascular density in cortical regions (middle prefrontal cortex and somatosensory cortex, but not in striatal regions (nucleus accumbens and dorsal striatum. These results suggest that following chronic cocaine use, as cerebral ischemia developed, NOS1, the regulatory protein to counteract blood vessel constriction, was upregulated; meanwhile, the HIF-VEGF pathway was activated to increase microvascular density (i.e., angiogenesis and thus restore local blood flow and oxygen supply. These physiological responses were triggered presumably as an adaptation to minimize ischemic injury caused by cocaine. Therefore, effectively promoting such physiological responses may provide novel and effective therapeutic solutions to treat cocaine-induced cerebral ischemia and stroke.

  8. Chronic cocaine induces HIF-VEGF pathway activation along with angiogenesis in the brain.

    Science.gov (United States)

    Yin, Wei; Clare, Kevin; Zhang, Qiujia; Volkow, Nora D; Du, Congwu

    2017-01-01

    Cocaine induces vasoconstriction in cerebral vessels, which with repeated use can result in transient ischemic attacks and cerebral strokes. However, the neuroadaptations that follow cocaine's vasoconstricting effects are not well understood. Here, we investigated the effects of chronic cocaine exposure (2 and 4 weeks) on markers of vascular function and morphology in the rat brain. For this purpose we measured nitric oxide (NO) concentration in plasma, brain neuronal nitric oxide synthase (nNOS or NOS1), HIF-1α, and VEGF expression in different brain regions, i.e., middle prefrontal cortex, somatosensory cortex, nucleus accumbens, and dorsal striatum, using ELISA or Western blot. Additionally, microvascular density in these brain regions was measured using immunofluorescence microscopy. We showed that chronic cocaine significantly affected NOS1, HIF-1α and VEGF expression, in a region- and cocaine treatment-time- dependent manner. Cerebral microvascular density increased significantly in parallel to these neurochemical changes. Furthermore, significant correlations were detected between VEGF expression and microvascular density in cortical regions (middle prefrontal cortex and somatosensory cortex), but not in striatal regions (nucleus accumbens and dorsal striatum). These results suggest that following chronic cocaine use, as cerebral ischemia developed, NOS1, the regulatory protein to counteract blood vessel constriction, was upregulated; meanwhile, the HIF-VEGF pathway was activated to increase microvascular density (i.e., angiogenesis) and thus restore local blood flow and oxygen supply. These physiological responses were triggered presumably as an adaptation to minimize ischemic injury caused by cocaine. Therefore, effectively promoting such physiological responses may provide novel and effective therapeutic solutions to treat cocaine-induced cerebral ischemia and stroke.

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

    Science.gov (United States)

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

    2007-12-01

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

  10. False memories to emotional stimuli are not equally affected in right- and left-brain-damaged stroke patients.

    Science.gov (United States)

    Buratto, Luciano Grüdtner; Zimmermann, Nicolle; Ferré, Perrine; Joanette, Yves; Fonseca, Rochele Paz; Stein, Lilian Milnitsky

    2014-10-01

    Previous research has attributed to the right hemisphere (RH) a key role in eliciting false memories to visual emotional stimuli. These results have been explained in terms of two right-hemisphere properties: (i) that emotional stimuli are preferentially processed in the RH and (ii) that visual stimuli are represented more coarsely in the RH. According to this account, false emotional memories are preferentially produced in the RH because emotional stimuli are both more strongly and more diffusely activated during encoding, leaving a memory trace that can be erroneously reactivated by similar but unstudied emotional items at test. If this right-hemisphere hypothesis is correct, then RH damage should result in a reduction in false memories to emotional stimuli relative to left-hemisphere lesions. To investigate this possibility, groups of right-brain-damaged (RBD, N=15), left-brain-damaged (LBD, N=15) and healthy (HC, N=30) participants took part in a recognition memory experiment with emotional (negative and positive) and non-emotional pictures. False memories were operationalized as incorrect responses to unstudied pictures that were similar to studied ones. Both RBD and LBD participants showed similar reductions in false memories for negative pictures relative to controls. For positive pictures, however, false memories were reduced only in RBD patients. The results provide only partial support for the right-hemisphere hypothesis and suggest that inter-hemispheric cooperation models may be necessary to fully account for false emotional memories. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. [Arm Motor Function Recovery during Rehabilitation with the Use of Hand Exoskeleton Controlled by Brain-Computer Interface: a Patient with Severe Brain Damage].

    Science.gov (United States)

    Biryukova, E V; Pavlova, O G; Kurganskaya, M E; Bobrov, P D; Turbina, L G; Frolov, A A; Davydov, V I; Sil'tchenko, A V; Mokienko, O A

    2016-01-01

    We studied the dynamics of motor function recovery in a patient with severe brain damage in the course of neurorehabilitation using hand exoskeleton controlled by brain-computer interface. For estimating the motor function of paretic arm, we used the biomechanical analysis of movements registered during the course of rehabilitation. After 15 weekly sessions of hand exoskeleton control, the following results were obtained: a) the velocity profile of goal-directed movements of paretic hand became bell-shaped, b) the patient began to extend and abduct the hand which was flexed and adducted in the beginning of rehabilitation, and c) the patient began to supinate the forearm which was pronated in the beginning of rehabilitation. The first result is an evidence of the general improvement of the quality of motor control, while the second and third results prove that the spasticity of paretic arm has decreased.

  12. [Depersonalization syndrome after acquired brain damage. Overview based on 3 case reports and the literature and discussion of etiological models].

    Science.gov (United States)

    Paulig, M; Böttger, S; Sommer, M; Prosiegel, M

    1998-12-01

    Depersonalization after brain damage is still only rarely reported and poorly understood. We describe three patients between the ages of 21 and 25 who experienced depersonalization and derealization for periods of 6 weeks to 4 months, two after traumatic brain injury, the third after surgical and radiation treatment of a pineocytoma. Each one believed to be living in a nightmare and thought about committing suicide in order to wake up. One patient developed symptoms as described in Cotard delusion. Aspects of neuroanatomy, psychodynamics, and anthropology are discussed with reference to the literature. Frontal and temporal lesions seem only to play a facilitating role but not to be a necessary condition. There is evidence for additional influence of psychological and premorbid personality factors. Summarizing the current state of information we consider depersonalization with the experience of being in a dream or being dead as a heuristic reaction to brain damage. Similar models have already been discussed in neuropsychological disorders as for instance reduplicative paramnesias, neglect, and anosognosia.

  13. Low-level light emitting diode (LED) therapy suppresses inflammasome-mediated brain damage in experimental ischemic stroke.

    Science.gov (United States)

    Lee, Hae In; Lee, Sae-Won; Kim, Nam Gyun; Park, Kyoung-Jun; Choi, Byung Tae; Shin, Yong-Il; Shin, Hwa Kyoung

    2017-11-01

    Use of photostimulation including low-level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post-ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score. LED therapy profoundly reduced neuroinflammatory responses including neutrophil infiltration and microglia activation in the ischemic cortex. LED therapy also decreased cell death and attenuated the NLRP3 inflammasome, in accordance with down-regulation of pro-inflammatory cytokines IL-1β and IL-18 in the ischemic brain. Moreover, the mice with post-ischemic LED therapy showed suppressed TLR-2 levels, MAPK signaling and NF-kB activation. These findings suggest that by suppressing the inflammasome, LED therapy can attenuate neuroinflammatory responses and tissue damage following ischemic stroke. Therapeutic interventions targeting the inflammasome via photostimulation with LED may be a novel approach to ameliorate brain injury following ischemic stroke. Effect of post-ischemic low-level light emitting diode therapy (LED-T) on infarct reduction was mediated by inflammasome suppression. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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    S. Mojtaba Mousavi

    2015-01-01

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

  15. A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

    Science.gov (United States)

    Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

    2017-09-01

    Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

  16. Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals.

    Science.gov (United States)

    Rowland, Jared A; Stapleton-Kotloski, Jennifer R; Alberto, Greg E; Davenport, April T; Kotloski, Robert J; Friedman, David P; Godwin, Dwayne W; Daunais, James B

    2017-08-01

    Chronic alcohol abuse is associated with neurophysiological changes in brain activity; however, these changes are not well localized in humans. Non-human primate models of alcohol abuse enable control over many potential confounding variables associated with human studies. The present study utilized high-resolution magnetoencephalography (MEG) to quantify the effects of chronic EtOH self-administration on resting state (RS) brain function in vervet monkeys. Adolescent male vervet monkeys were trained to self-administer ethanol (n=7) or an isocaloric malto-dextrin solution (n=3). Following training, animals received 12 months of free access to ethanol. Animals then underwent RS magnetoencephalography (MEG) and subsequent power spectral analysis of brain activity at 32 bilateral regions of interest associated with the chronic effects of alcohol use. demonstrate localized changes in brain activity in chronic heavy drinkers, including reduced power in the anterior cingulate cortex, hippocampus, and amygdala as well as increased power in the right medial orbital and parietal areas. The current study is the first demonstration of whole-head MEG acquisition in vervet monkeys. Changes in brain activity were consistent with human electroencephalographic studies; however, MEG was able to extend these findings by localizing the observed changes in power to specific brain regions. These regions are consistent with those previously found to exhibit volume loss following chronic heavy alcohol use. The ability to use MEG to evaluate changes in brain activity following chronic ethanol exposure provides a potentially powerful tool to better understand both the acute and chronic effects of alcohol on brain function. Published by Elsevier B.V.

  17. Brain Magnetic Resonance Imaging Does Not Contribute to the Diagnosis of Chronic Neuroborreliosis

    Energy Technology Data Exchange (ETDEWEB)

    Aalto, A.; Sjoewall, J.; Davidsson, L.; Forsberg, P.; Smedby, Oe. [Div. of Radiology, Dept. of Medicine and Care, and Div. of Infectious Diseases, Dept. of Molecular and Clinical Medicine, Linkoeping Univ., Linkoeping (Sweden)

    2007-09-15

    Background: Borrelia infections, especially chronic neuroborreliosis (NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging (MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well-characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- (with and without gadolinium), T2-, and diffusion-weighted imaging plus fluid-attenuated inversion recovery (FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls (no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( = 0.83, P<0.01) and in controls ( = 0.61, P<0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2-weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.

  18. Damage to tumour and brain by interstitial photodynamic therapy in the 9L rat tumour model comparing intravenous and intratumoral administration of the photosensitiser

    NARCIS (Netherlands)

    Hebeda, K. M.; Kamphorst, W.; Sterenborg, H. J.; Wolbers, J. G.

    1998-01-01

    In the 9L rat brain tumour model the damage to tumour and normal brain by photodynamic therapy after intratumoural photosensitizer administration (intratumoural PDT) was studied. Twenty four rats received an intratumoural injection of 4 or 40 mm3 haematoporphyrin derivative (HpD, 5 mg ml-1),

  19. The effects of chronic alcohol self-administration in nonhuman primate brain networks.

    Science.gov (United States)

    Telesford, Qawi K; Laurienti, Paul J; Davenport, April T; Friedman, David P; Kraft, Robert A; Daunais, James B

    2015-04-01

    Long-term alcohol abuse is associated with change in behavior, brain structure, and brain function. However, the nature of these changes is not well understood. In this study, we used network science to analyze a nonhuman primate model of ethanol self-administration to evaluate functional differences between animals with chronic alcohol use and animals with no exposure to alcohol. Of particular interest was how chronic alcohol exposure may affect the resting state network. Baseline resting state functional magnetic resonance imaging was acquired in a cohort of vervet monkeys. Animals underwent an induction period where they were exposed to an isocaloric maltose dextrin solution (control) or ethanol in escalating doses over three 30-day epochs. Following induction, animals were given ad libitum access to water and a maltose dextrin solution (control) or water and ethanol for 22 h/d over 12 months. Cross-sectional analyses examined region of interests in hubs and community structure across animals to determine differences between drinking and nondrinking animals after the 12-month free access period. Animals were classified as lighter (Animals that consume alcohol show topological differences in brain network organization, particularly in animals that drink heavily. Differences in the resting state network were linked to areas that are associated with spatial association, working memory, and visuomotor processing. Copyright © 2015 by the Research Society on Alcoholism.

  20. Numerical Characterization of Intraoperative and Chronic Electrodes in Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Alessandra ePaffi

    2015-02-01

    Full Text Available Intraoperative electrode is used in the Deep Brain stimulation (DBS technique to pinpoint the brain target and to choose the best parameters for the stimulating signal. However, when the intraoperative electrode is replaced with the chronic one, the observed effects do not always coincide with predictions.To investigate the causes of such discrepancies, in this work, a 3D model of the basal ganglia has been considered and realistic models of both intraoperative and chronic electrodes have been developed and numerically solved.Results of simulations on the electric potential and the activating function along neuronal fibers show that the different geometries and sizes of the two electrodes do not change shapes and polarities of these functions, but only the amplitudes. A similar effect is caused by the presence of different tissue layers (edema or glial tissue in the peri-electrode space. On the contrary, a not accurate positioning of the chronic electrode with respect to the intraoperative one (electric centers not coincident may induce a complete different electric stimulation on some groups of fibers.

  1. EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA

    Directory of Open Access Journals (Sweden)

    Hector Lafuente

    2016-07-01

    Full Text Available Background: Hypothermia is standard treatment for neonatal encephalopathy, but near 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms to hypothermia and would improve neuroprotection. Cannabidiol could be a good candidate.Objective: To test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets.Methods: Hypoxic-ischemic animals were randomized to receive 30 min after the insult: 1 normothermia- and vehicle-treated group; 2 normothermia- and cannabidiol-treated group; 3 hypothermia- and vehicle-treated group; and 4 hypothermia- and cannabidiol-treated group. Six hours after treatment, brains were processed to qualify the number of neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate and excitotoxicity (glutamate/Nacetyl-aspartate. Western blot studies were performed to quantify protein nitrosylation (oxidative stress and expression of caspase-3 (apoptosis and TNFα (inflammation.Results: Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on histological damage, was greater than either hypothermia or cannabidiol alone.Conclusion: Cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage.

  2. Commonalities and Discrepancies in the Relationships between Behavioural Outcome and the Results of Neuroimaging in Brain-Damaged Patients

    Directory of Open Access Journals (Sweden)

    Hans J. Markowitsch

    1996-01-01

    Full Text Available Variables which are of influence in establishing clear predictions of neuropsychological alterations from neuroradiological data (and vice versa are documented and discussed. It is concluded that personality factors and the kind and locus of brain lesions are the most crucial determinants. The locus of the brain damage may have cumulative effects either when it is situated in a strategic place (usually within the white matter, affecting interneuronal communication or when various types of lesions appear superimposed (combination of focal and diffuse lesions. Consequently, the consideration of the patient's personality background and of as many neuropsychological facts as possible may considerably increase the validity of outcome predictions. When static or dynamic neuroimaging fails to show abnormalities in spite of obvious psychological alterations, an intensive neuropsychological documentation may even replace neuroradiology.

  3. MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, Stephan A.; O' Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V. [Hammersmith Hospital Campus, Imaging Sciences Department, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London (United Kingdom); Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P. [MRC Clinical Sciences Centre, Clinical Research Facility, London (United Kingdom); Hammersmith Hospital, Lipid Clinic, London (United Kingdom)

    2007-11-15

    Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 {+-} 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 {+-} 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 {+-} 4.2 vs. 4.5 {+-} 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

  4. New Doppler index for prediction of perinatal brain damage in growth‐restricted and hypoxic fetuses

    National Research Council Canada - National Science Library

    Jugović, D; Tumbri, J; Medić, M; Jukić, M. Kušan; Kurjak, A; Arbeille, P; Salihagić‐Kadić, A

    2007-01-01

    .... percentage below the cut-off value of 1, over the period of observation) were calculated. After delivery, neonatal outcome was evaluated according to obstetric parameters and ultrasound examinations of the brain...

  5. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

    Science.gov (United States)

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC’s efficacy and mechanism of action. Results: ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. Conclusions: ARC treatment confers

  6. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion.

    Science.gov (United States)

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC's efficacy and mechanism of action. ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. ARC treatment confers neuroprotection of brain tissue

  7. A Search for Mitochondrial Damage in Alzheimer's Disease Using Isolated Rat Brain Mitochondria.

    Science.gov (United States)

    Faizi, Mehrdad; Seydi, Enayatollah; Abarghuyi, Sadegh; Salimi, Ahmad; Nasoohi, Sanaz; Pourahmad, Jalal

    2016-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects regions of the brain that control cognition, memory, language, speech and awareness to one's physical surroundings. The pathological initiation and progression of AD is highly complex and its prevalence is on the rise. In his study, Alzheimer's disease was induced with single injection of amyloid-β (Aβ) peptides (30ng, by stereotaxy) in each hemisphere of the Wistar rat brain. Then memory dysfunction, oxidative stress and apoptosis induced by Aβ peptide were investigated on isolated brain mitochondria obtained from infected rat. Our results showed memory impairment in rats after receiving an Aβ peptide. We also found significant rise (Pmitochondrial membrane depolarization, mitochondria swelling, cytochrome c release and significant decrease in ATP/ADP ratio on mitochondria isolated from brain of these memory impaired rats compared with those of untreated control rat group. Activation of caspase-3 the final mediator of apoptosis in the brain homogenate of the memory impaired rats was another justification for occurrence of neuron loss in the experimental model of AD. Our results suggest that oxidative stress and mitochondria mediated apoptosis in brain neurons play very important role in initiation of AD.

  8. Change in brain activity through virtual reality-based brain-machine communication in a chronic tetraplegic subject with muscular dystrophy

    OpenAIRE

    Liu Meigen; Kimura Akio; Ushiba Junichi; Hashimoto Yasunari; Tomita Yutaka

    2010-01-01

    Abstract Background For severely paralyzed people, a brain-computer interface (BCI) provides a way of re-establishing communication. Although subjects with muscular dystrophy (MD) appear to be potential BCI users, the actual long-term effects of BCI use on brain activities in MD subjects have yet to be clarified. To investigate these effects, we followed BCI use by a chronic tetraplegic subject with MD over 5 months. The topographic changes in an electroencephalogram (EEG) after long-term use...

  9. Transcriptomic responses in mouse brain exposed to chronic excess of the neurotransmitter glutamate

    Directory of Open Access Journals (Sweden)

    Pal Ranu

    2010-06-01

    Full Text Available Abstract Background Increases during aging in extracellular levels of glutamate (Glu, the major excitatory neurotransmitter in the brain, may be linked to chronic neurodegenerative diseases. Little is known about the molecular responses of neurons to chronic, moderate increases in Glu levels. Genome-wide gene expression in brain hippocampus was examined in a unique transgenic (Tg mouse model that exhibits moderate Glu hyperactivity throughout the lifespan, the neuronal Glutamate dehydrogenase (Glud1 mouse, and littermate 9 month-old wild type mice. Results Integrated bioinformatic analyses on transcriptomic data were used to identify bio-functions, pathways and gene networks underlying neuronal responses to increased Glu synaptic release. Bio-functions and pathways up-regulated in Tg mice were those associated with oxidative stress, cell injury, inflammation, nervous system development, neuronal growth, and synaptic transmission. Increased gene expression in these functions and pathways indicated apparent compensatory responses offering protection against stress, promoting growth of neuronal processes (neurites and re-establishment of synapses. The transcription of a key gene in the neurite growth network, the kinase Ptk2b, was significantly up-regulated in Tg mice as was the activated (phosphorylated form of the protein. In addition to genes related to neurite growth and synaptic development, those associated with neuronal vesicle trafficking in the Huntington's disease signalling pathway, were also up-regulated. Conclusions This is the first study attempting to define neuronal gene expression patterns in response to chronic, endogenous Glu hyperactivity at brain synapses. The patterns observed were characterized by a combination of responses to stress and stimulation of nerve growth, intracellular transport and recovery.

  10. Imaging chronic traumatic brain injury as a risk factor for neurodegeneration.

    Science.gov (United States)

    Little, Deborah M; Geary, Elizabeth K; Moynihan, Michael; Alexander, Aristides; Pennington, Michelle; Glang, Patrick; Schulze, Evan T; Dretsch, Michael; Pacifico, Anthony; Davis, Matthew L; Stevens, Alan B; Huang, Jason H

    2014-06-01

    Population-based studies have supported the hypothesis that a positive history of traumatic brain injury (TBI) is associated with an increased incidence of neurological disease and psychiatric comorbidities, including chronic traumatic encephalopathy, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. These epidemiologic studies, however, do not offer a clear definition of that risk, and leave unanswered the bounding criteria for greater lifetime risk of neurodegeneration. Key factors that likely mediate the degree of risk of neurodegeneration include genetic factors, significant premorbid and comorbid medical history (e.g. depression, multiple head injuries and repetitive subconcussive impact to the brain, occupational risk, age at injury, and severity of brain injury). However, given the often-described concerns in self-report accuracy as it relates to history of multiple TBIs, low frequency of patient presentation to a physician in the case of mild brain injuries, and challenges with creating clear distinctions between injury severities, disentangling the true risk for neurodegeneration based solely on population-based studies will likely remain elusive. Given this reality, multiple modalities and approaches must be combined to characterize who are at risk so that appropriate interventions to alter progression of neurodegeneration can be evaluated. This article presents data from a study that highlights uses of neuroimaging and areas of needed research in the link between TBI and neurodegenerative disease. Copyright © 2014. Published by Elsevier Inc.

  11. Increased levels of 3-hydroxykynurenine in different brain regions of rats with chronic renal insufficiency.

    Science.gov (United States)

    Topczewska-Bruns, Joanna; Pawlak, Dariusz; Chabielska, Ewa; Tankiewicz, Anna; Buczko, Wlodzimierz

    2002-08-15

    Tryptophan (TRP) metabolism via the kynurenine pathway leads to formations of neuroactive substances like kynurenine (KYN) and 3-hydroxykynurenine (3-HK), which may be involved in the pathogenesis of several human brain diseases. 3-Hydroxykynurenine especially is known to have strong neurotoxic properties. The generation of reactive oxygen species (ROS) leads to neuronal cell death with apoptotic features. Because the chronic renal insufficiency (CRI) results in disturbances in the functioning of the central nervous system (CNS), it is conceivable that the metabolism of some kynurenines may be altered and could play an important role in uremic encephalopathy. The levels of TRP, KYN and 3-HK were measured in the plasma and in different brain regions of uremic rats. The total plasma concentration of TRP as well as in all the studied brain samples was significantly diminished during uremia. Surprisingly, the level of KYN and 3-HK were elevated both in the plasma and different brain regions of CRI animals. KYN concentrations were approximately two times higher in the cerebellum, midbrain and cortex compared to the control group. The changes of 3-HK levels were more pronounced in the striatum and medulla than in other structures. This data suggests that CRI results in deep disturbances on the kynurenine pathway in CNS, which could be responsible for neurological abnormalities seen in uremia.

  12. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    John Williamson

    2015-07-01

    Full Text Available The use of a modified Facial Affect Recognition (FAR training to identify emotions was investigated with two case studies of adults with moderate to severe chronic (> five years traumatic brain injury (TBI.  The modified FAR training was administered via telepractice to target social communication skills.  Therapy consisted of identifying emotions through static facial expressions, personally reflecting on those emotions, and identifying sarcasm and emotions within social stories and role-play.  Pre- and post-therapy measures included static facial photos to identify emotion and the Prutting and Kirchner Pragmatic Protocol for social communication.  Both participants with chronic TBI showed gains on identifying facial emotions on the static photos.               

  13. (/sup 3/H)muscimol binding sites increased in autopsied brains of chronic schizophrenics

    Energy Technology Data Exchange (ETDEWEB)

    Hanada, S.; Mita, T.; Nishino, N.; Tanaka, C.

    1987-01-19

    (/sup 3/H)muscimol binding and glutamic acid decarboxylase (GAD) activity in the prefrontal cortex and caudate nucleus of autopsied brains from 19 chronic schizophrenics and 17 control subjects were investigated. In the schizophrenics, saturation analysis with varying concentrations of (/sup 3/H)muscimol revealed an increase in the number GABA/sub A/ receptors, but there was no significant difference in the affinity. In addition, the enhancement of (/sup 3/H)muscimol binding by diazepam was significantly greater in schizophrenics than in controls. GAD activity did not differ between controls and schizophrenics. The possibility that GABAergic mechanisms might play a role in case of chronic schizophrenia should be given further attention.

  14. Findings of chronic sinusitis on brain computed tomography are not associated with acute headaches.

    Science.gov (United States)

    Kroll, Katherine E; Camacho, Marc A; Gautam, Shiva; Levenson, Robin B; Edlow, Jonathan A

    2014-06-01

    Headache is a common complaint in emergency department (ED) patients. Nearly 15% of ED headache patients will have brain computed tomography (CT) done. One frequent finding on these scans is "chronic sinusitis." Assuming that "chronic sinusitis" is the cause of the patient's headache is a potential source of mis-diagnosis. We hypothesized that CT findings of chronic sinusitis occur with equal frequency in patients with atraumatic headache as in control patients with minor head injury. This is a retrospective, single-center medical record review of consecutive discharged patients who received noncontrast head CT scans in an urban ED for either minor closed head injury or atraumatic headache. Each patient's head CT radiologic report was reviewed for findings of sinusitis and classified as chronic sinusitis, indeterminate for sinusitis, air-fluid levels, or no findings of sinusitis. We enrolled 500 patients (234 in the atraumatic headache group, 266 in the minor head injury group). The two groups were similar except that more women were enrolled in the atraumatic headache group. CT findings of chronic sinusitis in the atraumatic headache group (22.2%) and the minor head injury group (17.7%; difference 4.5%; 95% confidence interval of -2.5-11.6%). Prevalence of CT findings of sinusitis in ED patients with atraumatic headaches and mild head injury are similar. This strongly suggests that CT findings of chronic sinusitis in patients with atraumatic headache may be incidental, and are rarely the cause of a patient's acute headache. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Anatomical location of effective deep brain stimulation electrodes in chronic cluster headache.

    Science.gov (United States)

    Fontaine, Denys; Lanteri-Minet, Michel; Ouchchane, Lemlih; Lazorthes, Yves; Mertens, Patrick; Blond, Serge; Geraud, G; Fabre, Nelly; Navez, Malou; Lucas, Christian; Dubois, Francois; Sol, Jean Christophe; Paquis, Philippe; Lemaire, Jean Jacques

    2010-04-01

    Deep brain stimulation of the posterior hypothalamus is a therapeutic approach to the treatment of refractory chronic cluster headache, but the precise anatomical location of the electrode contacts has not been clearly assessed. Our aim was to study the location of the contacts used for chronic stimulation, projecting each contact centre on anatomic atlases. Electrodes were implanted in a series of 10 patients (prospective controlled trial) in the so-called 'posteroinferior hypothalamus' according to previously described coordinates, i.e. 2 mm lateral, 3 mm posterior and 5 mm below the mid-commissural point. The coordinates of the centre of each stimulating contact were measured on postoperative computed tomography or magnetic resonance imaging scans, taking into account the artefact of the electrode. Each contact centre (n=10; left and right hemispheres pooled) was displayed on the Schaltenbrand atlas and a stereotactic three dimensional magnetic resonance imaging atlas (4.7 tesla) of the diencephalon-mesencephalic junction for accurate anatomical location. Of the 10 patients with 1-year follow-up, 5 responded to deep brain stimulation (weekly frequency of attacks decrease >50%). In responders, the mean (standard deviation) coordinates of the contacts were 2.98 (1.16) mm lateral, 3.53 (1.97) mm posterior and 3.31 (1.97) mm below the mid-commissural point. All the effective contacts were located posterior to the hypothalamus. In responders, structures located deep brain stimulation treatment in cluster headache may be due to factors unrelated to electrode misplacement. They also suggest that the therapeutic effect is probably not related to direct hypothalamic stimulation. Deep brain stimulation might modulate either a local cluster headache generator, located in the hypothalamus or in the mesencephalic grey substance, or non-specific anti-nocioceptive systems.

  16. Ficus sycomorus extract reversed behavioral impairment and brain oxidative stress induced by unpredictable chronic mild stress in rats.

    Science.gov (United States)

    Foyet, Harquin Simplice; Tchinda Deffo, Serge; Koagne Yewo, Pascaline; Antioch, Iulia; Zingue, Stéphane; Asongalem, Emmanuel Acha; Kamtchouing, Pierre; Ciobica, Alin

    2017-11-28

    Stress, regardless of its nature is nowadays recognized as one of the major risk factors for neuropsychiatric diseases, such as mood and anxiety disorders. The brain compared with other organs is more vulnerable to oxidative damage mainly due to its high rate of oxygen consumption, abundant lipid content, and relative insufficiency of antioxidant enzymes. Thus, the identification of neural mechanisms underlying resistance and vulnerability to stress is of crucial importance in understanding the pathophysiology of neuropsychiatric disorders and in developing new treatments, since the existing ones are for several reasons subject to increasing limitations. This study was aimed to assess the effects of hydromethanolic extract of Ficus sycomorus stem bark on depression, anxiety and memory impairment induced by unpredictable chronic mild stress (UCMS) in rats. These effects were studied using anxiety-related behavior, depression-related behavior, anhedonia-like behavior and the Y maze task. Sucrose test was performed twice (before and after UCMS) to assess anhedonia in rats. Liquid chromatography-mass spectrometry analysis of the extract were performed. The antioxidant activities of the extract were assessed using total glutathione (GSH) content and malondialdehyde (MDA) level (lipid peroxidation) in the rat temporal lobe homogenates. The extract of F. sycomorus in a dose of 100 mg/kg significantly increased the sucrose consumption and the swimming time which had been reduced by the unpredictable chronic mild stress (p extract also significantly reduced (p extract (100 and 200 mg/kg) significantly reduced (p extracts also significantly increased alternation in the Y-maze (p extract significantly increased the total GSH content and reduced MDA level in rat temporal lobe. For the LC-MS analysis, the major compound in the extract was a flavonoid with formula C22H28O14. F. sycomorus reversed the harmful effects of UCMS on mood and behaviors in rats and it

  17. Orotracheal intubation and dysphagia: comparison of patients with and without brain damage

    Directory of Open Access Journals (Sweden)

    Aline Rodrigues Padovani

    2008-09-01

    Full Text Available Objectives: To compare the swallowing and feeding abilities in extubated patients with and without brain injury. Methods: A retrospective study including 44 patients aged 20 to 50 years submitted to prolonged orotracheal intubation (> 48 hours. Two groups were analyzed: Group 1 composed of nontraumatic brain injury patients, and Group 2 composed of patients with traumatic brain injury. Two scales for characterization of functional swallowing and feeding abilities were used to compare both groups; the levels of alertness, awareness and patient collaboration were also assessed. Rresults: The groups were equal in age, number and time of orotracheal intubation and extubation on the date of the assessment. Regarding the speech and language diagnosis, Group 1 presented higher percentage of functional swallowing and mild dysphagia, while Group 2 showed higher rates of moderate to severe dysphagia and severe dysphagia. The Functional Oral Intake Scale average was higher in Group 1. In addition, the injured brain group was sleepier, less collaborative and had less contact in the first evaluation. Cconclusions: In this study, patients who underwent prolonged orotracheal intubation had dysphagia in different degrees, but the patients with brain injury presented more frequent and severe disorder. Thus, this study suggested that orotracheal intubation cannot be considered as the single factor causing dysphagia, especially in neurological patients. Moreover, some cognitive factors may influence the possibility of providing oral feeding.

  18. No adaptation to UV-induced immunosuppression and DNA damage following exposure of mice to chronic UV-exposure.

    Science.gov (United States)

    Steerenberg, Peter A; Daamen, Frieda; Weesendorp, Eefke; Van Loveren, Henk

    2006-07-03

    It is well known that ultraviolet (UV) radiation induces erythema, immunosuppression and carcinogenesis. We hypothesized that chronic exposure to solar UV radiation induces adaptation that eventually prevents the suppression of acquired immunity. We studied adaptation for UV-induced immunosuppression after chronic exposure of mice to a suberythemal dose of solar simulated radiation (SSR) with Cleo Natural lamps, and subsequent exposure to an immunosuppressive dose of solar or UVB radiation (TL12). After UV dosing, the mice were sensitized and challenged with either diphenylcyclopropenone (DPCP) or picryl chloride (PCl). To assess the adaptation induced by solar simulated radiation, we measured the proliferative response and cytokine production of skin-draining lymph node cells after immunization to DPCP, the contact hypersensitivity (CHS) response to PCl, and thymine-thymine (T-T) cyclobutane dimers in the skin of mice. After induction of immunosuppression by SSR or by TL12 lamps, the proliferative response of draining lymph node cells after challenge with DPCP, or the CHS after challenge with PCl, showed significant suppression of the immune response. Chronic irradiation from SSR preceding the immunosuppressive dose of UV failed to restore the suppressed immune response. Reduced lipopolysaccharide-triggered cytokine production (of IL-12p40, IFN-gamma, IL-6 and TNF-alpha) by draining lymph node cells of mice sensitized and challenged with DPCP indicated that no adaptation is induced. In addition, the mice were not protected from T-T dimer DNA damage after chronic solar irradiation. Our studies reveal no evidence that chronic exposure to low doses of SSR induces adaptation to UV-induced suppression of acquired immunity.

  19. Laser Acupuncture at GV20 Improves Brain Damage and Oxidative Stress in Animal Model of Focal Ischemic Stroke.

    Science.gov (United States)

    Jittiwat, Jinatta

    2017-10-01

    The burden of stroke is high and is continually increasing due to a dramatic growth in the world's elderly population. Novel therapeutic strategies are therefore required. The present study sought to determine the effect of laser acupuncture at GV20 on brain damage, oxidative-status markers in the cerebral cortex, and superoxide dismutase in the mitochondria of an animal model of focal ischemic stroke. Wistar rats, weighing 300-350 g, were divided into the following four groups: (1) control; (2) permanent occlusion of the right middle cerebral artery (Rt.MCAO) alone; (3) Rt.MCAO plus sham laser acupuncture; and (4) Rt.MCAO plus laser-acupuncture groups. Sham laser acupuncture or laser acupuncture was performed once daily at the GV20 (Baihui) acupoint for 14 days following Rt.MCAO. Half of the rats in each group were examined by 2,3,5-triphenyltetrazolium chloride staining to determine the brain infarct volume, while the other half were examined by biochemical assays to determine the malondialdehyde level, and the glutathione peroxidase, catalase, and superoxide-dismutase activities in the brain-cortex mitochondria. The results showed that laser acupuncture at GV20 significantly decreased the brain infarct volume and malondialdehyde level, and increased the catalase, glutathione peroxidase, and superoxide-dismutase activities in cerebral ischemic rats. In conclusion, laser acupuncture at GV20 decreases the brain infarct volume in cerebral ischemic rats, at least in part due to decreased oxidative stress. Further study is warranted to investigate other possible underlying mechanisms. Copyright © 2017. Published by Elsevier B.V.

  20. Brain damage and behavioural disorders in fish induced by plastic nanoparticles delivered through the food chain.

    Science.gov (United States)

    Mattsson, Karin; Johnson, Elyse V; Malmendal, Anders; Linse, Sara; Hansson, Lars-Anders; Cedervall, Tommy

    2017-09-13

    The tremendous increases in production of plastic materials has led to an accumulation of plastic pollution worldwide. Many studies have addressed the physical effects of large-sized plastics on organisms, whereas few have focused on plastic nanoparticles, despite their distinct chemical, physical and mechanical properties. Hence our understanding of their effects on ecosystem function, behaviour and metabolism of organisms remains elusive. Here we demonstrate that plastic nanoparticles reduce survival of aquatic zooplankton and penetrate the blood-to-brain barrier in fish and cause behavioural disorders. Hence, for the first time, we uncover direct interactions between plastic nanoparticles and brain tissue, which is the likely mechanism behind the observed behavioural disorders in the top consumer. In a broader perspective, our findings demonstrate that plastic nanoparticles are transferred up through a food chain, enter the brain of the top consumer and affect its behaviour, thereby severely disrupting the function of natural ecosystems.

  1. MRI: A method to detect minor brain damage following coronary bypass surgery

    Energy Technology Data Exchange (ETDEWEB)

    Vik, A.; Brubakk, A.O. (Trondheim Univ. (Norway). Dept. of Biomedical Engineering); Rinck, P.A. (Trondheim Univ. (Norway). MR Center); Sande, E.; Levang, O.W. (Trondheim Univ. Hospital (Norway). Dept. of Surgery); Sellevold, O. (Trondheim Univ. Hospital (Norway). Dept. of Anaesthesiology)

    1991-10-01

    In order to assess the occurrence of minor focal brain lesions after coronary bypass surgery, magnetic resonance imaging (MRI) was used. Nine male patients (age 42-63) with angina pectoris were investigated at 0.5 Tesla. The investigation was performed one to seven weeks prior to the operation and one month after the operation. Before surgery, the images demonstrated more than five high intensity spots in the white matter of the brain in all but two patients. No additional spots were found after operation. This pilot study indicates that it might be difficult to use MRI to detect minor parenchymal lesions after cardiopulmonary bypass surgery. (orig.).

  2. GCR Transport in the Brain: Assessment of Self-Shielding, Columnar Damage, and Nuclear Reactions on Cell Inactivation Rates

    Science.gov (United States)

    Shavers, M. R.; Atwell, W.; Cucinotta, F. A.; Badhwar, G. D. (Technical Monitor)

    1999-01-01

    Radiation shield design is driven by the need to limit radiation risks while optimizing risk reduction with launch mass/expense penalties. Both limitation and optimization objectives require the development of accurate and complete means for evaluating the effectiveness of various shield materials and body-self shielding. For galactic cosmic rays (GCR), biophysical response models indicate that track structure effects lead to substantially different assessments of shielding effectiveness relative to assessments based on LET-dependent quality factors. Methods for assessing risk to the central nervous system (CNS) from heavy ions are poorly understood at this time. High-energy and charge (HZE) ion can produce tissue events resulting in damage to clusters of cells in a columnar fashion, especially for stopping heavy ions. Grahn (1973) and Todd (1986) have discussed a microlesion concept or model of stochastic tissue events in analyzing damage from HZE's. Some tissues, including the CNS, maybe sensitive to microlesion's or stochastic tissue events in a manner not illuminated by either conventional dosimetry or fluence-based risk factors. HZE ions may also produce important lateral damage to adjacent cells. Fluences of high-energy proton and alpha particles in the GCR are many times higher than HZE ions. Behind spacecraft and body self-shielding the ratio of protons, alpha particles, and neutrons to HZE ions increases several-fold from free-space values. Models of GCR damage behind shielding have placed large concern on the role of target fragments produced from tissue atoms. The self-shielding of the brain reduces the number of heavy ions reaching the interior regions by a large amount and the remaining light particle environment (protons, neutrons, deuterons. and alpha particles) may be the greatest concern. Tracks of high-energy proton produce nuclear reactions in tissue, which can deposit doses of more than 1 Gv within 5 - 10 cell layers. Information on rates of

  3. α-Tocopherol mitigates ethanol induced malformations and cell damage in the eye and brain of the chick embryo

    Directory of Open Access Journals (Sweden)

    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.

  4. DNA-based MRI probes for specific detection of chronic exposure to amphetamine in living brains.

    Science.gov (United States)

    Liu, Christina H; Ren, Jia Q; Yang, Jinsheng; Liu, Charng-ming; Mandeville, Joseph B; Rosen, Bruce R; Bhide, Pradeep G; Yanagawa, Yuchio; Liu, Philip K

    2009-08-26

    We designed phosphorothioate-modified DNA probes linked to superparamagnetic iron oxide nanoparticles (SPION) for in vivo magnetic resonance imaging (MRI) of fosB and Delta fosB mRNA after amphetamine (AMPH) exposure in mice. Specificity of both the fosB and Delta fosB probes was verified by in vitro reverse transcriptase-PCR amplification to a single fragment of total cDNA obtained from acutely AMPH-exposed mouse brains. We confirmed time-dependent uptake and retention profiles of both probes in neurons of GAD67-green fluorescent protein knock-in mice. MRI signal of SPION-labeled fosB probe delivered via intracerebroventricular route was elevated in both acutely and chronically AMPH-exposed mice; the signal was suppressed by dopaminergic receptor antagonist pretreatment. SPION-labeled Delta fosB probe signal elevation occurred only in chronically AMPH-exposed mice. The in vivo target specificity of these probes permits reliable MRI visualization of AMPH-induced differential elevations of fosB and Delta fosB mRNA in living brains.

  5. Neurodegeneration after mild and repetitive traumatic brain injury: Chronic traumatic encepalopathy

    Directory of Open Access Journals (Sweden)

    Stanescu Ioana

    2015-09-01

    Full Text Available Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE. Although research on the long-term effects of TBI is advancing quickly, the incidence and prevalence of post-traumatic neurodegeneration and CTE are unknown. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently under research. CTE can be diagnosed only by post mortem neuropathological examination of the brain. Great efforts are being made to better understand the clinical signs and symptoms of CTE, obtained in most cases retrospectively from families of affected persons.Patients with CTE are described as having behavioral, mood, cognitive and motor impairments, occurring after a long latency from the traumatic events. Recent pathogenetic studies have provided new insights to CTE mechanisms, offering important clues in understanding neurodegenerative process and relations between physical factors and pathologic protein deposition. Further research is needed to better identify the genetic and environmental risk factors for CTE, as well as rehabilitation and treatment strategies.

  6. Visualization of damaged brain tissue after ischemic stroke with cobalt-55 positron emission tomography

    NARCIS (Netherlands)

    Jansen, H M; Pruim, J; vd Vliet, A M; Paans, A M; Hew, J M; Franssen, E J; de Jong, B M; Kosterink, J G; Haaxma, R; Korf, J

    UNLABELLED: In animal experiments, the radionuclide 55Co2+ has been shown to accumulate in degenerating cerebral tissue similar to Ca2+. METHODS: The potential role of 55Co2+ for in vivo brain PET imaging was investigated in four patients after ischemic stroke. RESULTS: PET showed uptake of 55Co2+

  7. Psychosocial Adjustment and Life Satisfaction until 5 Years after Severe Brain Damage

    Science.gov (United States)

    Sorbo, Ann K.; Blomqvist, Maritha; Emanuelsson, Ingrid M.; Rydenhag, Bertil

    2009-01-01

    The objectives of this study were to describe psychosocial adjustment and outcome over time for severely brain-injured patients and to find suitable outcome measures for clinical practice during the rehabilitation process and for individual rehabilitation planning after discharge from hospital. The methods include a descriptive, prospective,…

  8. Dynamical signatures of structural connectivity damage to a model of the brain posed at criticality

    NARCIS (Netherlands)

    Haimovici, Ariel; Balenzuela, Pablo; Tagliazucchi, E.

    2016-01-01

    Synchronization of brain activity fluctuations is believed to represent communication between spatially distant neural processes. These inter-areal functional interactions develop in the background of a complex network of axonal connections linking cortical and sub-cortical neurons, termed the human

  9. Acute stress potentiates brain response to milkshake as a function of body weight and chronic stress.

    Science.gov (United States)

    Rudenga, K J; Sinha, R; Small, D M

    2013-02-01

    Stress is associated with an increased intake of palatable foods and with weight gain, particularly in overweight women. Stress, food and body mass index (BMI) have been separately shown to affect amygdala activity. However, it is not known whether stress influences amygdala responses to palatable foods, and whether this response is associated with chronic stress or BMI. A total of 14 overweight and obese women participated in a functional magnetic resonance imaging (fMRI) scan as they consumed a palatable milkshake during script-driven, autobiographical, guided imagery of stressful and neutral-relaxing scenarios. We report that a network including insula, somatomotor mouth area, ventral striatum and thalamus responds to milkshake receipt, but none of these areas are affected by stress. In contrast, whereas the left amygdala responds to milkshake irrespective of condition, the right amygdala responds to milkshake only under stressful conditions. Moreover, this right amygdala response is positively associated with basal cortisol levels, an objective measure of chronic stress. We also found a positive relationship between BMI and stress-related increased response to milkshake in the orbitofrontal cortex(OFC). These results demonstrate that acute stress potentiates response to food in the right amygdala and OFC as a function of chronic stress and body weight, respectively. This suggests that the influence of acute stress in potentiating amygdala and OFC responses to food is dependent upon individual factors like BMI and chronic stress. We conclude that BMI and chronic stress play a significant role in brain response to food and in stress-related eating.

  10. Non-invasive electrical brain stimulation: from acute to late-stage treatment of central nervous system damage

    Directory of Open Access Journals (Sweden)

    Petra Henrich-Noack

    2017-01-01

    Full Text Available Non-invasive brain current stimulation (NIBS is a promising and versatile tool for inducing neuroplasticity, protection and functional rehabilitation of damaged neuronal systems. It is technically simple, requires no surgery, and has significant beneficial effects. However, there are various technical approaches for NIBS which influence neuronal networks in significantly different ways. Transcranial direct current stimulation (tDCS, alternating current stimulation (ACS and repetitive transcranial magnetic stimulation (rTMS all have been applied to modulate brain activity in animal experiments under normal and pathological conditions. Also clinical trials have shown that tDCS, rTMS and ACS induce significant behavioural effects and can – depending on the parameters chosen – enhance or decrease brain excitability and influence performance and learning as well as rehabilitation and protective mechanisms. The diverse phaenomena and partially opposing effects of NIBS are not yet fully understood and mechanisms of action need to be explored further in order to select appropriate parameters for a given task, such as current type and strength, timing, distribution of current densities and electrode position. In this review, we will discuss the various parameters which need to be considered when designing a NIBS protocol and will put them into context with the envisaged applications in experimental neurobiology and medicine such as vision restoration, motor rehabilitation and cognitive enhancement.

  11. Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia.

    Science.gov (United States)

    Chen, Yingzhu; Yi, Qiong; Liu, Gang; Shen, Xue; Xuan, Lihui; Tian, Ye

    2013-02-07

    Myelin sheath, either in white matter or in other regions of brain, is vulnerable to ischemia. The specific events involved in the progression of ischemia in white matter have not yet been elucidated. The aim of this study was to determine histopathological alterations in cerebral white matter and levels of myelin basic protein (MBP) in ischemia-injured brain tissue during the acute and subacute phases of central nervous injury following whole-brain ischemia. The whole cerebral ischemia model (four-vessel occlusion (4-VO)) was established in adult Sprague-Dawley rats and MBP gene expression and protein levels in the brain tissue were measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at 2 days, 4 days, 7 days, 14 days, and 28 days following ischemia. Demyelination was determined by Luxol fast blue myelin staining, routine histopathological staining, and electron microscopy in injured brain tissue. Results showed that edema, vascular dilation, focal necrosis, demyelination, adjacent reactive gliosis and inflammation occurred 7 days after ischemia in HE staining and recovered to control levels at 28 days. The absence of Luxol fast blue staining and vacuolation was clearly visible at 7 days, 14 days, and 28 days. Semiquantitative analysis showed that the transparency of myelin had decreased significantly by 7 days, 14 days, and 28 days. Demyelination and ultrastructual changes were detected 7 days after ischemia. The relative levels of MBP mRNA decreased 2 days after ischemia and this trend continued throughout the remaining four points in time. The MBP levels measured using ELISA also decreased significantly at 2 days and 4 days, but they recovered by 7 days and returned to control levels by 14 days. These results suggest that the impact of ischemia on cerebral white matter is time-sensitive and that different effects may follow different courses over time. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Previous physical exercise alters the hepatic profile of oxidative-inflammatory status and limits the secondary brain damage induced by severe traumatic brain injury in rats.

    Science.gov (United States)

    de Castro, Mauro Robson Torres; Ferreira, Ana Paula de Oliveira; Busanello, Guilherme Lago; da Silva, Luís Roberto Hart; da Silveira Junior, Mauro Eduardo Porto; Fiorin, Fernando da Silva; Arrifano, Gabriela; Crespo-López, Maria Elena; Barcelos, Rômulo Pillon; Cuevas, María J; Bresciani, Guilherme; González-Gallego, Javier; Fighera, Michele Rechia; Royes, Luiz Fernando Freire

    2017-09-01

    An early inflammatory response and oxidative stress are implicated in the signal transduction that alters both hepatic redox status and mitochondrial function after traumatic brain injury (TBI). Peripheral oxidative/inflammatory responses contribute to neuronal dysfunction after TBI Exercise training alters the profile of oxidative-inflammatory status in liver and protects against acute hyperglycaemia and a cerebral inflammatory response after TBI. Approaches such as exercise training, which attenuates neuronal damage after TBI, may have therapeutic potential through modulation of responses by metabolic organs. The vulnerability of the body to oxidative/inflammatory in TBI is significantly enhanced in sedentary compared to physically active counterparts. Although systemic responses have been described after traumatic brain injury (TBI), little is known regarding potential interactions between brain and peripheral organs after neuronal injury. Accordingly, we aimed to investigate whether a peripheral oxidative/inflammatory response contributes to neuronal dysfunction after TBI, as well as the prophylactic role of exercise training. Animals were submitted to fluid percussion injury after 6 weeks of swimming training. Previous exercise training increased mRNA expression of X receptor alpha and ATP-binding cassette transporter, and decreased inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α and interleukin (IL)-6 expression per se in liver. Interestingly, exercise training protected against hepatic inflammation (COX-2, iNOS, TNF-α and IL-6), oxidative stress (decreases in non-protein sulfhydryl and glutathione, as well as increases in 2',7'-dichlorofluorescein diacetate oxidation and protein carbonyl), which altered hepatic redox status (increases in myeloperoxidase and superoxide dismutase activity, as well as inhibition of catalase activity) mitochondrial function (decreases in methyl-tetrazolium and Δψ, as well as

  13. Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease.

    Science.gov (United States)

    Hakim, Frances T; Memon, Sarfraz; Jin, Ping; Imanguli, Matin M; Wang, Huan; Rehman, Najibah; Yan, Xiao-Yi; Rose, Jeremy; Mays, Jacqueline W; Dhamala, Susan; Kapoor, Veena; Telford, William; Dickinson, John; Davis, Sean; Halverson, David; Naik, Haley B; Baird, Kristin; Fowler, Daniel; Stroncek, David; Cowen, Edward W; Pavletic, Steven Z; Gress, Ronald E

    2016-11-01

    Although chronic graft-versus-host disease (CGVHD) is the primary nonrelapse complication of allogeneic transplantation, understanding of its pathogenesis is limited. To identify the main operant pathways across the spectrum of CGVHD, we analyzed gene expression in circulating monocytes, chosen as in situ systemic reporter cells. Microarrays identified two interrelated pathways: 1) IFN-inducible genes, and 2) innate receptors for cellular damage. Corroborating these with multiplex RNA quantitation, we found that multiple IFN-inducible genes (affecting lymphocyte trafficking, differentiation, and Ag presentation) were concurrently upregulated in CGVHD monocytes compared with normal subjects and non-CGVHD control patients. IFN-inducible chemokines were elevated in both lichenoid and sclerotic CGHVD plasma and were linked to CXCR3(+) lymphocyte trafficking. Furthermore, the levels of the IFN-inducible genes CXCL10 and TNFSF13B (BAFF) were correlated at both the gene and the plasma levels, implicating IFN induction as a factor in elevated BAFF levels in CGVHD. In the second pathway, damage-/pathogen-associated molecular pattern receptor genes capable of inducing type I IFN were upregulated. Type I IFN-inducible MxA was expressed in proportion to CGVHD activity in skin, mucosa, and glands, and expression of TLR7 and DDX58 receptor genes correlated with upregulation of type I IFN-inducible genes in monocytes. Finally, in serial analyses after transplant, IFN-inducible and damage-response genes were upregulated in monocytes at CGVHD onset and declined upon therapy and resolution in both lichenoid and sclerotic CGVHD patients. This interlocking analysis of IFN-inducible genes, plasma analytes, and tissue immunohistochemistry strongly supports a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD.

  14. Chronic exposure to volcanic air pollution and DNA damage in Furnas Volcano (São Miguel Island, Azores, Portugal) inhabitants

    Science.gov (United States)

    Linhares, Diana; Garcia, Patricia; Silva, Catarina; Ferreira, Teresa; Barroso, Joana; Camarinho, Ricardo; Rodrigues, Armindo

    2015-04-01

    Many studies in volcanic air pollution only have in consideration the acute toxic effects of gas or ash releases however the impact of chronic exposure to ground gas emissions in human health is yet poorly known. In the Azores archipelago (Portugal), São Miguel island has one of the most active and dangerous volcanoes: Furnas Volcano. Highly active fumarolic fields, hot springs and soil diffuse degassing phenomena are the main secondary volcanic phenomena that can be seen at the volcano surroundings. One of the main gases released in these diffuse degassing areas is radon (222Rn), which decay results in solid particles that readily settle within the airways. These decay particles emit alpha radiation that is capable of causing severe DNA damage that cumulatively can eventually cause cancer. Previous studies have established that chronic exposure to chromosome-damaging agents can lead to the formation of nuclear anomalies, such as micronuclei that is used for monitoring DNA damage in human populations. The present study was designed to evaluate whether chronic exposure to volcanic air pollution, associated to 222Rn, might result in DNA damage in human oral epithelial cells. A cross sectional study was performed in a study group of 142 individuals inhabiting an area where volcanic activity is marked by active fumarolic fields and soil degassing (hydrothermal area), and a reference group of 368 individuals inhabiting an area without these secondary manifestations of volcanism (non-hydrothermal area). For each individual, 1000 buccal epithelial cells were analyzed for the frequency of micronucleated cells (MNc) and the frequency of cells with other nuclear anomalies (ONA: pyknosis, karyolysis and karyorrhexis), by using the micronucleus assay. Information on lifestyle factors and an informed consent were obtained from each participant. Assessment of indoor radon was performed with the use of radon detectors. Data were analyzed with logistic regression models, adjusted

  15. Functional Brain Correlates of Upper Limb Spasticity and Its Mitigation following Rehabilitation in Chronic Stroke Survivors

    Directory of Open Access Journals (Sweden)

    Svetlana Pundik

    2014-01-01

    Full Text Available Background. Arm spasticity is a challenge in the care of chronic stroke survivors with motor deficits. In order to advance spasticity treatments, a better understanding of the mechanism of spasticity-related neuroplasticity is needed. Objective. To investigate brain function correlates of spasticity in chronic stroke and to identify specific regional functional brain changes related to rehabilitation-induced mitigation of spasticity. Methods. 23 stroke survivors (>6 months were treated with an arm motor learning and spasticity therapy (5 d/wk for 12 weeks. Outcome measures included Modified Ashworth scale, sensory tests, and functional magnetic resonance imaging (fMRI for wrist and hand movement. Results. First, at baseline, greater spasticity correlated with poorer motor function (P=0.001 and greater sensory deficits (P=0.003. Second, rehabilitation produced improvement in upper limb spasticity and motor function (P<0.0001. Third, at baseline, greater spasticity correlated with higher fMRI activation in the ipsilesional thalamus (rho=0.49, P=0.03. Fourth, following rehabilitation, greater mitigation of spasticity correlated with enhanced fMRI activation in the contralesional primary motor (r=-0.755, P=0.003, premotor (r=−0.565, P=0.04, primary sensory (r=−0.614, P=0.03, and associative sensory (r=−0.597, P=0.03 regions while controlling for changes in motor function. Conclusions. Contralesional motor regions may contribute to restoring control of muscle tone in chronic stroke.

  16. Blood-Brain Barrier Dysfunction as a Hallmark Pathology in Chronic Traumatic Encephalopathy.

    Science.gov (United States)

    Doherty, Colin P; O'Keefe, Eoin; Wallace, Eugene; Loftus, Teresa; Keaney, James; Kealy, John; Humphries, Marian M; Molloy, Michael G; Meaney, James F; Farrell, Michael; Campbell, Matthew

    2016-07-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition associated with repetitive mild traumatic brain injury. In recent years, attention has focused on emerging evidence linking the development of CTE to concussive injuries in athletes and military personnel; however, the underlying molecular pathobiology of CTE remains unclear. Here, we provide evidence that the blood-brain barrier (BBB) is disrupted in regions of dense perivascular p-Tau accumulation in a case of CTE. Immunoreactivity patterns of the BBB-associated tight junction components claudin-5 and zonula occludens-1 were markedly discontinuous or absent in regions of perivascular p-Tau deposition; there was also immunohistochemical evidence of a BBB in these foci. Because the patient was diagnosed premortem clinically as having progressive supranuclear palsy (PSP), we also compromised that the CTE alterations appear to be distinct from those in the brain of a patient with PSP. This report represents the first description of BBB dysfunction in a pathologically proven CTE case and suggests a vascular component in the postconcussion cascade of events that may ultimately lead to development of a progressive degenerative disorder. BBB dysfunction may represent a correlate of neural dysfunction in live subjects suspected of being at risk for development of CTE. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

  17. A systematic review and meta-analysis of sleep architecture and chronic traumatic brain injury.

    Science.gov (United States)

    Mantua, Janna; Grillakis, Antigone; Mahfouz, Sanaa H; Taylor, Maura R; Brager, Allison J; Yarnell, Angela M; Balkin, Thomas J; Capaldi, Vincent F; Simonelli, Guido

    2018-02-02

    Sleep quality appears to be altered by traumatic brain injury (TBI). However, whether persistent post-injury changes in sleep architecture are present is unknown and relatively unexplored. We conducted a systematic review and meta-analysis to assess the extent to which chronic TBI (>6 months since injury) is characterized by changes to sleep architecture. We also explored the relationship between sleep architecture and TBI severity. In the fourteen included studies, sleep was assessed with at least one night of polysomnography in both chronic TBI participants and controls. Statistical analyses, performed using Comprehensive Meta-Analysis software, revealed that chronic TBI is characterized by relatively increased slow wave sleep (SWS). A meta-regression showed moderate-severe TBI is associated with elevated SWS, reduced stage 2, and reduced sleep efficiency. In contrast, mild TBI was not associated with any significant alteration of sleep architecture. The present findings are consistent with the hypothesis that increased SWS after moderate-severe TBI reflects post-injury cortical reorganization and restructuring. Suggestions for future research are discussed, including adoption of common data elements in future studies to facilitate cross-study comparability, reliability, and replicability, thereby increasing the likelihood that meaningful sleep (and other) biomarkers of TBI will be identified. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Clinical Utility of '9{sup 9m}Tc-HMPAO Brain SPECT Findings in Chronic Head Injury

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jin ll; Chung, Tae Sub; Suh, Jung Ho; Kim, Dong Ik; Lee, Jong Doo; Park, Chang Yoon; Kim, Young Soo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1992-03-15

    Minima deterioration of cerebral perfusion or microanatomical changes were undetectable on conventional Brain CT or MRI. So evaluation of focal functional changes of the brain parenchyme is essential in chronic head injury patients, who did not show focal anatomical changes on these radiological studies. However, the patients who had longstanding neurologic sequelae following head injury, there had been no available imaging modalities for evaluating these patients precisely. Therefore we tried to detect the focal functional changes on the brain parenchyme using {sup 99m}Tc-HMPAO Brain SPECT on the patients of chronic head injuries. Twenty three patients who had suffered from headache, memory dysfunction, personality change and insomnia lasting more than six months following head injury were included in our cases, which showed no anatomical abnormalities on Brain CT or MRI. At first they underwent psychological test whether the symptoms were organic or not. Also we were able to evaluate the cerebral perfusion changes with {sup 99m}Tc-HMPAO Brain SPECT in 22 patients among the 23, which five patients were focal and 17 patients were nonfocally diffuse perfusion changes. Thus we can predict the perfusion changes such as local vascular deterioration or functional defects using {sup 99m}Tc-HMPAO Brain SPECT in the patients who had suffered from post-traumatic sequelae, which changes were undetectable on Brain CT or MRI.

  19. Mitochondrial Damage: A Diagnostic and Metabolic Approach in Traumatic Brain Injury and Post-Traumatic Disorder

    Science.gov (United States)

    2013-01-29

    In comparison to the baseline, all animals gained significant weight at the time of sacrifice. As shown in table 1 and 2. In comparison to controls...or stress - Serum cortisol was not altered in any of the group examined. However, CPK (creatine phosphokinase) as a marker of cell injury was...and brain injury after TBI or TBI with preexisting stress (PTSD+TBI), b)study pyruvate as a countermeasure to mitigate mitochondrial functions in

  20. Automated Quantification of Stroke Damage on Brain Computed Tomography Scans: e-ASPECTS

    Directory of Open Access Journals (Sweden)

    James Hampton-Till

    2015-08-01

    Full Text Available Emergency radiological diagnosis of acute ischaemic stroke requires the accurate detection and appropriate interpretation of relevant imaging findings. Non-contrast computed tomography (CT provides fast and low-cost assessment of the early signs of ischaemia and is the most widely used diagnostic modality for acute stroke. The Alberta Stroke Program Early CT Score (ASPECTS is a quantitative and clinically validated method to measure the extent of ischaemic signs on brain CT scans. The CE-marked electronic-ASPECTS (e-ASPECTS software automates the ASPECTS score. Anglia Ruskin Clinical Trials Unit (ARCTU independently carried out a clinical investigation of the e-ASPECTS software, an automated scoring system which can be integrated into the diagnostic pathway of an acute ischaemic stroke patient, thereby assisting the physician with expert interpretation of the brain CT scan. Here we describe a literature review of the clinical importance of reliable assessment of early ischaemic signs on plain CT scans, and of technologies automating these processed scoring systems in ischaemic stroke on CT scans focusing on the e-ASPECTS software. To be suitable for critical appraisal in this evaluation, the published studies needed a sample size of a minimum of 10 cases. All randomised studies were screened and data deemed relevant to demonstration of performance of ASPECTS were appraised. The literature review focused on three domains: i interpretation of brain CT scans of stroke patients, ii the application of the ASPECTS score in ischaemic stroke, and iii automation of brain CT analysis. Finally, the appraised references are discussed in the context of the clinical impact of e-ASPECTS and the expected performance, which will be independently evaluated by a non-inferiority study conducted by the ARCTU.

  1. Brain damage in former association football players. An evaluation by cerebral computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Sortland, O.; Tysvaer, A.T.

    1989-03-01

    Thirty-three former football players from the National Football Team of Norway were examined by cerebral computer tomography (CT). The CT studies, evaluated for brain atrophy, visually and by linear measurements compared two different normal materials. One third of the players were found to have central cerebral atrophy. It is concluded that the atrophy probably was caused by repeated small head injuries during the football play, mainly in connection with heading the ball.

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

    DEFF Research Database (Denmark)

    Undén, Johan; Strandberg, Karin; Malm, Jan

    2009-01-01

    diagnostic tools for stroke subtypes. METHODS: Ninety-seven stroke patients were prospectively investigated in a multicenter design with blood levels of brain biomarkers S100B, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) as well as a coagulation biomarker, activated protein C......: This exploratory study indicated that blood levels of biomarkers GFAP and APC-PCI, prior to neuroimaging, may rule out ICH in a mixed stroke population....

  3. Brain contusion as the main risk factor of memory or emotional complaints in chronic complicated mild traumatic brain injury.

    Science.gov (United States)

    Su, Bei-Yi; Guo, Nai-Wen; Chen, Nan-Chun; Lin, Sheng-Sian; Chuang, Ming-Tsung; Liao, Yu-Chi; Kuo, Chia-Min; Lin, Cheng-Wei; Chou, Willy; Kuo, Jinn-Rung; Yen, Shih-Yin

    2017-01-01

    To investigate the risk factors for memory or emotional complaints in patients with complicated mild traumatic brain injury (mTBI). Retrospective analysis of medical records was conducted by physicians in a teaching hospital in Southern Taiwan, and complicated mTBI had been identified by means of computed tomography. Psychological complaints, including problems with memory and emotions, were collected by structured telephone interviews, 10-15 minutes long, and were held with subjects who agreed to participate in our study. Among 327 patients who were injured for more than two years, 190 agreed to join this study (mean age: 41.6 years; male: 60.5%; stably employed: 50.0%). We used demographic data and neurological factors to predict memory or emotional complaints without muscle power or response speed (MEMR) complaints. Only the presence or absence of cerebral contusions predicted memory or emotional complaints without MEMR complaints in different employed status, and the odds ratio was 4.82-13.50 times higher for those with cerebral contusions than for those without. Cerebral contusions were the primary risk factor for MEMR complaints in chronic complicated mTBI. Early preventive psychological intervention might be necessary for patients with complicated mTBI and cerebral contusions.

  4. Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

    Directory of Open Access Journals (Sweden)

    Yong-Hong Yi

    2008-06-01

    Full Text Available Yong-Hong Yi1, Wen-Chao Guo1, Wei-Wen Sun1, Tao Su1, Han Lin1, Sheng-Qiang Chen1, Wen-Yi Deng1, Wei Zhou2, Wei-Ping Liao11Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital, 2Department of Neonatology, Affiliated Guangzhou Children’s Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, P.R. ChinaAbstract: Lamotrigine (LTG, an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen. LTG was administered intraperitoneally with the doses of 5, 10, 20, and 40 mg/kg 3 h after operation and the dose of 20 mg/kg 1 h before and 3 h, 6 h after operation. Blood and brain were sampled 24 h after operation. Nissl staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL, and neuron-specific enolase (NSE immunohistochemical staining were used for morphological studies. Water content in left cortex and NSE concentration in serum were determined. LTG significantly reduced water content in the cerebral cortex, as well as the number of TUNEL staining neurons in the dentate gyrus and cortex in hypoxic-ischemia (HI model. Furthermore, LTG significantly decreased the NSE level in serum and increased the number of NSE staining neurons in the cortex. These effects, except that on water content, were dose-dependent and were more remarkable in the pre-treated group than in the post-treated groups. These results demonstrate that LTG may have a neuroprotective effect on acute HIBD in neonates. The effect is more prominent when administrated with higher doses and before HI.Keywords: hypoxic-ischemic brain

  5. Lesion characteristics driving right-hemispheric language reorganization in congenital left-hemispheric brain damage.

    Science.gov (United States)

    Lidzba, Karen; de Haan, Bianca; Wilke, Marko; Krägeloh-Mann, Ingeborg; Staudt, Martin

    2017-10-01

    Pre- or perinatally acquired ("congenital") left-hemispheric brain lesions can be compensated for by reorganizing language into homotopic brain regions in the right hemisphere. Language comprehension may be hemispherically dissociated from language production. We investigated the lesion characteristics driving inter-hemispheric reorganization of language comprehension and language production in 19 patients (7-32years; eight females) with congenital left-hemispheric brain lesions (periventricular lesions [n=11] and middle cerebral artery infarctions [n=8]) by fMRI. 16/17 patients demonstrated reorganized language production, while 7/19 patients had reorganized language comprehension. Lesions to the insular cortex and the temporo-parietal junction (predominantly supramarginal gyrus) were significantly more common in patients in whom both, language production and comprehension were reorganized. These areas belong to the dorsal stream of the language network, participating in the auditory-motor integration of language. Our data suggest that the integrity of this stream might be crucial for a normal left-lateralized language development. Copyright © 2017. Published by Elsevier Inc.

  6. Ecological Assessment Battery for Numbers (EABN) for brain-damaged patients: standardization and validity study.

    Science.gov (United States)

    Villain, M; Tarabon-Prevost, C; Bayen, E; Robert, H; Bernard, B; Hurteaux, E; Pradat-Diehl, P

    2015-10-01

    Number-processing may be altered following brain injury and might affect the everyday life of patients. We developed the first ecological tool to assess number-processing disorders in brain-injured patients, the Ecological Assessment Battery for Numbers (EABN; in French, the BENQ). The aim of the present study was to standardize and validate this new tool. Standardization included 126 healthy controls equally distributed by age, sex and sociocultural level. First, 17 patients were evaluated by the EABN; then scores for a subgroup of 10 were compared with those from a French analytical calculation test, the Évaluation Clinique des Aptitudes Numériques (ECAN). The concordance between the EABN and the ECAN was analyzed to determine construct validity. Discrimination indexes were calculated to assess the sensitivity of the subtests. Standardization highlighted a major effect of sociocultural level. In total, 9 of 17 patients had a pathological EABN score, with difficulties in telling time, making appointments and reading numerical data. The results of both the EABN and ECAN tests were concordant (Kendall's w=0.97). Finally, the discriminatory power was good, particularly for going to the movies, cheque-writing and following a recipe: scores were>0.4. The EABN is a new tool to assess number-processing disorders in adults. This tool has been standardized and has good psychometric properties for patients with brain injury. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. USING OF MSC WITH DIFFERENT ONTOGENETIC MATURITY FOR CORRECTION OF CHRONIC FIBROSING LIVER DAMAGE

    Directory of Open Access Journals (Sweden)

    M. Y. Shagidulin

    2013-01-01

    Full Text Available Aim. To compare the effectiveness of MSC with different degree of ontogenetic maturity (MSC bone marrow – MSC BM and MSC umbilical cord – MSC UC on regenerative processes in injured liver. Methods. In 4 groups of experiments on Wistar rats (n = 80 with a model of fibrotic toxic liver damage (FLD it was studied the effect of MSCs with different degree of ontogenetic maturity on recovery processes at the regeneration of damaged liver: 1 gr. – Control, 2 gr. and 3 gr. introduction of MSC BM, included in Sphero®GEL-long in doses of 2.5 ×106 and 5.0 x 106 cells, respectively, and 4 gr. – introduction of MSC UC in the form of cell-spheroids (8–10 × 105 cells. The cells were injected into the damaged liver in 7 days after the end of FDL-modeling. The effect of cell therapy was studied during 180 days. The effectiveness of corrective therapy was evaluated by the results of functional and morphological investigations of livers (histological control of parenchymal and nonparenchy- mal liver tissue. Results. MSC BM in both doses and MSC UC contributed to a more rapid normalization of liver enzyme indices compared with the control (1 gr., but the differences in the rate of recovery of disturbed enzymatic liver functions between groups 2, 3 and 4 – were absent. In 90 days after the cell application it was determined a more pronounced recovery activity of cells in groups 3 and 4; in 180 days the more pronounced activation of recovery processes was observed in group 3; but in group 4 the sclerotic processes were more pro- nounced in this period. Conclusion. For the induction of recovery processes in damage liver it is advisable not to use the MSC UC, but to use MSC BM in the Sphero®GEL, because MSC BM exert not only local but also systemic immune-regulatory effect, increasing the pool of T-reg. cells, which are additional carriers of regenera- tion information in organism. 

  8. Considerations for developing chronic care system for traumatic brain injury based on comparisons of cancer survivorship and diabetes management care.

    Science.gov (United States)

    Heiden, Siobhan M; Caldwell, Barrett S

    2018-01-01

    Experts in traumatic brain injury (TBI) rehabilitation recently proposed the framing of TBI as a chronic disease rather than a discrete event. Within the framework of the Chronic Care Model (CCM), a systematic comparison of three diseases - cancer survivorship, diabetes management and TBI chronic care - was conducted regarding chronic needs and the management of those needs. In addition, comparisons of these conditions require comparative evaluations of disease management characteristics and the survivor concept. The analysis found diabetes is more established within the CCM, where care is integrated across specialists and primary care providers. No single comparison provides a full analogue for understanding the chronic care health delivery system for TBI, indicating the need for a separate model to address needs and resources for TBI survivors. The findings from this research can provide practitioners with a context to develop a robust continued care health system for TBI. Practitioner Summary: We examine development of a chronic care system for traumatic brain injury. We conducted a systematic comparison of Chronic Care Model elements of decision and information support. Development of capabilities using a benchmark of diabetes care, with additional insights from cancer care, provides insights for implementing TBI chronic care systems.

  9. [Effects of bone marrow mesenchymal stem cells on learning and memory functional recovery in neonatal rats with hypoxic-ischemic brain damage].

    Science.gov (United States)

    Liu, Yang; Zhang, Xuan; Dai, Ying; Shu, Chang; Qu, Ping; Liu, You-xue; Yang, Li; Li, Ting-yu

    2008-09-01

    Neonatal hypoxic-ischemic brain damage (HIBD) causes acute death and chronic nervous system sequelae in newborn infants and children. Whereas there have been no specific treatment towards it up to now. Studies have shown that bone marrow mesenchymal stem cells (MSCs) have the therapeutic potential in many nervous system diseases and the authors previously found that retinoid acid (RA), which plays an important role in brain development, could enhance the neural differentiation of rat MSCs (rMSCs) in vitro. This study aimed to examine effects of rMSCs and RA-preinduced rMSC on learning and memory functional recovery after HIBD in neonatal rats in order to explore a new treatment strategy for clinical application, and explore the mechanism of action of rMSCs. Rat MSCs were isolated and purified from the whole bone marrow of juvenile Wistar rats by removing the non-adherent cells in primary and passage cultures. Neonatal hypoxic-ischemic brain damage rat models were built according to the methods described by Rice: the right carotid artery of 7-day-postnatal Wistar rats was ligated under anesthesia, and then the rats were exposed to 8% - 9% O2 in a container. At 5 days after hypoxia-ischemia, the HIBD neonatal rats were randomly divided into 3 groups and respectively transplanted with saline, BrdU marked rMSCs (1 - 2 x 10(5)) or RA-preinduced rMSCs (1 - 2 x 10(5)) into their lateral cerebral ventricle. Immunohistochemistry for nestin, neuron-specific enolase (NSE), neurofilament protein-heavy chain (NF-H) and glial fibrillary acidic protein (GFAP) were used to identify cells derived from rMSCs at 14 days and 42 days after transplantation. Shuttle box test was performed to evaluate the condition of learning and memory functional recovery when animals were 7 weeks old. Neurotrophin and receptors cDNA microarray were also employed at 14 days after transplantation to investigate the underlying action mechanisms of rMSCs treatment. Real-time PCR was used to confirm some of

  10. Sub-chronic copper pretreatment reduces oxidative damage in an experimental Huntington's disease model.

    Science.gov (United States)

    Martínez-Lazcano, Juan Carlos; Montes, Sergio; Sánchez-Mendoza, María Alicia; Rodríguez-Páez, Lorena; Pérez-Neri, Iván; Boll, Marie Catherine; Campos-Arroyo, Hortensia Denise; Ríos, Camilo; Pérez-Severiano, Francisca

    2014-12-01

    Quinolinic acid (QUIN) striatal injection in rat reproduces the main neurochemical features of Huntington's disease (HD), including oxidative damage. In this study, we evaluated the effect of a copper (Cu) supplement in drinking water (90 ppm Cu, 28 days) on the QUIN-induced HD model in the rat. Copper exposure caused no signs of liver toxicity; however, it produced significant Cu accumulation in striatum. It is noteworthy that QUIN also caused increased striatal Cu content; when the supplement was administered to animals with QUIN-injury, an even higher metal striatal accumulation was observed. Cu pre-treatment preserved striatal gamma-aminobutyric acid (GABA) content, which was reduced by QUIN intrastriatal injection. Similarly, apomorphine-induced circling behavior was reduced in Cu-pretreated QUIN-damaged rats. Metal supplement in drinking water prevented both lipid peroxidation and reactive oxygen species (ROS) formation caused by QUIN in striatum. In Cu-treated groups, superoxide dismutase-1 (SOD1) activity showed a significant increase, while SOD2 activity was slightly enhanced. Although the pathophysiological role for higher Cu levels in patients with HD and in experimental models of the disease is not fully understood, results in the present study suggest that Cu oral intake stimulates anti-oxidant defenses, an effect that may be a potential factor for reducing the progression of HD.

  11. Chronic stress and moderate physical exercise prompt widespread common activation and limited differential activation in specific brain regions.

    Science.gov (United States)

    Kim, Tae-Kyung; Han, Pyung-Lim

    2016-10-01

    Chronic stress in rodents produces depressive behaviors, whereas moderate physical exercise counteracts stress-induced depressive behaviors. Chronic stress and physical exercise appear to produce such opposing effects by changing the neural activity of specific brain regions. However, the detailed mechanisms through which the two different types of stimuli regulate brain function in opposite directions are not clearly understood. In the present study, we attempted to explore the neuroanatomical substrates mediating stress-induced behavioral changes and anti-depressant effects of exercise by examining stimulus-dependent c-Fos induction in the brains of mice that were exposed to repeated stress or exercise in a scheduled manner. Systematic and integrated analyses of c-Fos expression profiles indicated that various brain areas, including the prelimbic cortex, lateral septal area, and paraventricular nuclei of hypothalamus were commonly and strongly activated by both stress and exercise, while the lateral habenula and hippocampus were identified as being preferentially activated by stress and exercise, respectively. Exercise-dependent c-Fos expression in all regions examined in the brain occurred in both glutamatergic and GABAergic neurons. These results suggest that chronic stress and moderate exercise produce counteractive effects on mood behaviors, along with prompting widespread common activation and limited differential activation in specific brain regions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. THE DAMAGING EFFECTS OF ALCOHOL: CHRONIC AND PATTERN ALCOHOL USE EXPLAIN WHY SEXUAL ASSAULT FIGURES HAVE NOT SIGNIFICANTLY DROPPED IN THE UNITED STATES MILITARY

    Science.gov (United States)

    2015-10-01

    demographics, prevalence rates of prior military sexual abuse or perpetration, military culture as a promoter, emphasis on violence and hyper... masculinity .22 While it is clear these factors do bare some relevance, it is not the full picture. A Systemic Lens is Required Research on the topic...affect areas of the brain that lead to violence . Alcohol related brain damage during adolescence further sets the stage for antisocial behavior and

  13. The accumulation of brain water-free sodium is associated with ischemic damage independent of the blood pressure in female rats.

    Science.gov (United States)

    Sumiyoshi, Manabu; Kitazato, Keiko T; Yagi, Kenji; Miyamoto, Takeshi; Kurashiki, Yoshitaka; Matsushita, Nobuhisa; Kinouchi, Tomoya; Kuwayama, Kazuyuki; Satomi, Junichiro; Nagahiro, Shinji

    2015-08-07

    Estrogen deficiency worsens ischemic stroke outcomes. In ovariectomized (OVX(+)) rats fed a high-salt diet (HSD), an increase in the body Na(+)/water ratio, which characterizes water-free Na(+) accumulation, was associated with detrimental vascular effects independent of the blood pressure (BP). We hypothesized that an increase in brain water-free Na(+) accumulation is associated with ischemic brain damage in OVX(+)/HSD rats. To test our hypothesis we divided female Wistar rats into 4 groups, OVX(+) and OVX(-) rats fed HSD or a normal diet (ND), and subjected them to transient cerebral ischemia. The brain Na(+)/water ratio was increased even in OVX(+)/ND rats and augmented in OVX(+)/HSD rats. The increase in the brain Na(+)/water ratio was positively correlated with expansion of the cortical infarct volum