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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. Late damage to brain microvasculature after chronic irradiation

    International Nuclear Information System (INIS)

    The effects on mouse brain microvasculature were examined 12 months after exposure to chronic γ- 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)

  3. Structural Brain Changes in Chronic Pain Reflect Probably Neither Damage Nor Atrophy

    OpenAIRE

    Rodriguez-Raecke, Rea; Niemeier, Andreas; Ihle, Kristin; Ruether, Wolfgang; May, Arne

    2013-01-01

    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, 1...

  4. 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.

  5. 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.

  6. 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...

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

    Science.gov (United States)

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

    2016-06-01

    Both pathological and neuroimaging studies demonstrate that chronic alcohol abuse causes brain atrophy with widespread white matter loss limited gray matter loss. Recent neuroimaging studies suggest that tobacco smoking also causes brain atrophy in both alcoholics and neurologically normal individuals; however, this has not been confirmed pathologically. In this study, the effects of smoking and the potential additive effects of concomitant alcohol and tobacco consumption were investigated in autopsied human brains. A total of 44 cases and controls were divided into four groups: 16 non-smoking controls, nine smoking controls, eight non-smoking alcoholics, and 11 smoking alcoholics. The volumes of 26 gray and white matter regions were measured using an established point-counting technique. The results showed trends for widespread white matter loss in alcoholics (p contrast, smoking alone had no effect on brain atrophy and the combination of smoking and alcohol showed no additional effect. Neuronal density was analyzed as a more sensitive assay of gray matter integrity. Similar to the volumetric analysis, there was a reduction in neurons (29%) in the prefrontal cortex of alcoholics, albeit this was only a trend when adjusted for potential confounders (p generalized white matter atrophy. These disparate effects suggest that two different pathogenic mechanisms may be operating in the alcoholic brain. Future studies using ultrastructural or molecular techniques will be required to determine if smoking has more subtle effects on the brain and how chronic alcohol consumption leads to widespread white matter loss. PMID:27286935

  8. Protective Effects of Crocus Sativus L. Extract and Crocin against Chronic-Stress Induced Oxidative Damage of Brain, Liver and Kidneys in Rats

    OpenAIRE

    Bandegi, Ahmad Reza; Rashidy-Pour, Ali; Vafaei, Abbas Ali; Ghadrdoost, Behshid

    2014-01-01

    Purpose: Chronic stress has been reported to induce oxidative damage of the brain. A few studies have shown that Crocus Sativus L., commonly known as saffron and its active constituent crocin may have a protective effect against oxidative stress. The present work was designed to study the protective effects of saffron extract and crocin on chronic – stress induced oxidative stress damage of the brain, liver and kidneys.

  9. Contextualizing aquired brain damage

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    Contextualizing aquired brain damage Traditional approaches study ’communicational problems’ often in a discourse of disabledness or deficitness. With an ontology of communcation as something unique and a presupposed uniqueness of each one of us, how could an integrational approach (Integrational...... 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....

  10. 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…

  11. Experience-dependent neural plasticity in the adult damaged brain

    OpenAIRE

    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 extremity (hand and arm) impairments. A prolonged and widespread process of repair and reorganization of surviving neural circuits is instigated by in...

  12. Chronic actinic damage of facial skin.

    Science.gov (United States)

    Bilaç, Cemal; Şahin, Mustafa Turhan; Öztürkcan, Serap

    2014-01-01

    Chronic actinic damage of the skin manifests itself as extrinsic skin aging (photoaging) and photocarcinogenesis. During the last decade, substantial progress has been made in understanding cellular and molecular mechanisms of photoaging. DNA photodamage and ultraviolet-generated reactive oxygen species are the initial events that lead to most of the typical histologic and clinical manifestations of chronic photodamage of the skin. Chronic actinic damage affects all layers of the skin. Keratinocytes, melanocytes, fibroblasts, and endothelial cells are altered by ultraviolet radiation and can result in numerous changes in human skin, particularly the skin of fair-skinned individuals. These changes include actinic keratosis, thickening and wrinkling, elastosis, telengiectasia, solar comedones, diffuse or mottled hyperpigmentation, and skin cancers. There are many options in the treatment of changes caused by chronic actinic damage. The most effective measure of prevention of the photoaging and photocarcinogenesis is sun protection. PMID:25441468

  13. [Imaging of brain changes in chronic pain].

    Science.gov (United States)

    Vartiainen, Nuutti; Forss, Nina

    2014-01-01

    Modern methods of brain imaging have enabled objective measurements of functional and structural brain changes associated with chronic pain conditions. According to recent investigations, chronic pain is not only associated with abnormally strong or prolonged activity of regions processing acute pain, but also with activation of brain networks that are characteristic for each pain state, changes in cortical remodeling, as well as local reduction of grey matter in several regions of the brain. Brain changes associated with chronic pain facilitate the understanding of mechanisms of various chronic pain conditions. PMID:25211820

  14. Alcohol-related brain damage in humans.

    Directory of Open Access Journals (Sweden)

    Amaia M Erdozain

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

  15. Computerized axial tomography in the detection of brain damage

    International Nuclear Information System (INIS)

    The cranial computerized axial tomography (CAT) findings in groups of patients with epilepsy, migraine, hypertension, and other general medical disorders have been reviewed to assess the frequency and patterns of focal and diffuse brain damage. In addition to demonstrating focal lesions in a proportion of patients with seizures and in patients presenting with a stroke, the CAT scan showed a premature degree of cerebral atrophy in an appreciable proportion of patients with long-standing epilepsy, hypertension and diabetes, and in some patients with migraine, valvular and ischaemic heart disease, chronic obstructive airways disease, and chronic renal failure. The value of CAT as a means of screening for brain damage in groups of individuals at risk is discussed

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

    OpenAIRE

    Wang, Chunmei; Zheng, Dong; Xu, Jie; Lam, Waiping; Yew, D. T.

    2013-01-01

    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 fi...

  17. Clincal Aspects of Biological Brain Damage Markers

    OpenAIRE

    Undén, Johan

    2006-01-01

    Biomarkers for organ damage and/or dysfuntion are used in almost all areas of medicine. The brain has eluded this technological development for some time. Recently, the S100B protein has been shown to be a promising marker of brain damage. However, before S100S can reach clinical reality, several problems must be solved. The specificity of S100B requires special investigative attention. Although the sensitivity has seldom been criticised in the literature and assumed to be very high for S100B...

  18. Brain Damage in School Age Children.

    Science.gov (United States)

    Haywood, H. Carl, Ed.

    The product of a professional workshop, 10 papers discuss brain damage. An introduction to clinical neuropsychology is presented by H. Carl Haywood. A section on neurological foundations includes papers on the organization of the central nervous system by Jack T. Tapp and Lance L. Simpson, on epilepsy by Angela T. Folsom, and on organic language…

  19. Perioperative brain damage after cardiovascular surgery

    International Nuclear Information System (INIS)

    We examined 39 cases (1.6%) of post-operative brain damages out of 2,445 sequential cases of cardiovascular surgery in NCVC during past three years. In this study, we investigated clinical course and CT findings of each patient in details and analyzed the causes of the post operative brain damages. Of 39 cases, 23 (59%) were complicated with cerebral ischemia, 8 (21%) with subdural hematoma (SDH), 2 (5%) with intracranial hemorrhage (ICH) and 1 (2%) with subarachnoid hemorrhage (SAH), respectively. 5 cases (13%) had unclassified brain damages. In 23 cases of cerebral ischemia there were 5 cases of hypotension-induced ischemia, 4 cases of hypoxic encephalopathy, 3 cases of ischemia induced by intra-operative maneuvers, 3 cases of embolism after operation and a single case of 'microembolism'. Seven cases could not be classified into any of these categories. Duration of ECC was 169.9±48.5 min on the average in patients with such brain damages as SDH, ICH, SAH and cardiogenic embolism, which were thought not to be related with ECC. On the other hand, that of the patients hypotensive ischemia or 'microembolism' gave an average value of 254.5±96.8 min. And these patients were thought to have occurred during ECC. There was a statistically significant difference between these two mean values. (J.P.N.)

  20. Intensive language training enhances brain plasticity in chronic aphasia

    OpenAIRE

    Meinzer Marcus; Elbert Thomas; Wienbruch Christian; Djundja Daniela; Barthel Gabriela; Rockstroh Brigitte

    2004-01-01

    Abstract Background Focal clusters of slow wave activity in the delta frequency range (1–4 Hz), as measured by magnetencephalography (MEG), are usually located in the vicinity of structural damage in the brain. Such oscillations are usually considered pathological and indicative of areas incapable of normal functioning owing to deafferentation from relevant input sources. In the present study we investigated the change in Delta Dipole Density in 28 patients with chronic aphasia (>12 months po...

  1. Medical Perspectives on Brain Damage and Development. Revised.

    Science.gov (United States)

    McCrae, Marcia Q.

    The author describes damage and normal development of the brain, as well as assessment and intervention with brain-damaged children. After a brief introduction on the complex and delicate process of brain development and a review of incidence, aspects of etiology such as genetic and postnatal causes are discussed. Brain development is examined…

  2. Imaging Brain Mechanisms in Chronic Visceral Pain

    OpenAIRE

    Mayer, Emeran A.; Gupta, Arpana; Kilpatrick, Lisa A.; Hong, Jui-Yang

    2015-01-01

    Chronic visceral pain syndromes are important clinical problems with largely unmet medical needs. Based on the common overlap with other chronic disorders of visceral or somatic pain, mood and affect, and their responsiveness to centrally targeted treatments, an important role of central nervous system in their pathophysiology is likely. A growing number of brain imaging studies in irritable bowel syndrome, functional dyspepsia and bladder pain syndrome/interstitial cystitis has identified ab...

  3. Feedback and neuroplasticity rehabilitation for brain damage

    Institute of Scientific and Technical Information of China (English)

    Eli Carmeli

    2014-01-01

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

  4. Animal imaging studies of potential brain damage

    Science.gov (United States)

    Gatley, S. J.; Vazquez, M. E.; Rice, O.

    To date, animal studies have not been able to predict the likelihood of problems in human neurological health due to HZE particle exposure during space missions outside the Earth's magnetosphere. In ongoing studies in mice, we have demonstrated that cocaine stimulated locomotor activity is reduced by a moderate dose (120 cGy) of 1 GeV 56Fe particles. We postulate that imaging experiments in animals may provide more sensitive and earlier indicators of damage due to HZE particles than behavioral tests. Since the small size of the mouse brain is not well suited to the spatial resolution offered by microPET, we are now repeating some of our studies in a rat model. We anticipate that this will enable us to identify imaging correlates of behavioral endpoints. A specific hypothesis of our studies is that changes in the metabolic rate for glucose in striatum of animals will be correlated with alterations in locomotor activity. We will also evaluate whether the neuroprotective drug L-deprenyl reduces the effect of radiation on locomotor activity. In addition, we will conduct microPET studies of brain monoamine oxidase A and monoamine oxidase B in rats before and at various times after irradiation with HZE particles. The hypothesis is that monoamine oxidase A, which is located in nerve terminals, will be unchanged or decreased after irradiation, while monoamine oxidase B, which is located in glial cells, will be increased after irradiation. Neurochemical effects that could be measured using PET could in principle be applied in astronauts, in terms of detecting and monitoring subtle neurological damage that might have occurred during long space missions. More speculative uses of PET are in screening candidates for prolonged space missions (for example, for adequate reserve in critical brain circuits) and in optimizing medications to treat impairments after missions.

  5. Imaging brain mechanisms in chronic visceral pain.

    Science.gov (United States)

    Mayer, Emeran A; Gupta, Arpana; Kilpatrick, Lisa A; Hong, Jui-Yang

    2015-04-01

    Chronic visceral pain syndromes are important clinical problems with largely unmet medical needs. Based on the common overlap with other chronic disorders of visceral or somatic pain, mood and affect, and their responsiveness to centrally targeted treatments, an important role of central nervous system in their pathophysiology is likely. A growing number of brain imaging studies in irritable bowel syndrome, functional dyspepsia, and bladder pain syndrome/interstitial cystitis has identified abnormalities in evoked brain responses, resting state activity, and connectivity, as well as in gray and white matter properties. Structural and functional alterations in brain regions of the salience, emotional arousal, and sensorimotor networks, as well as in prefrontal regions, are the most consistently reported findings. Some of these changes show moderate correlations with behavioral and clinical measures. Most recently, data-driven machine-learning approaches to larger data sets have been able to classify visceral pain syndromes from healthy control subjects. Future studies need to identify the mechanisms underlying the altered brain signatures of chronic visceral pain and identify targets for therapeutic interventions. PMID:25789437

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

    Science.gov (United States)

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

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). PMID:24033426

  7. Damage of hippocampal neurons in rats with chronic alcoholism

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deifcits. 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. Endog-enous hydrogen sulifde content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were signiifcantly increased, while F-actin expression was decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a fuzzy nuclear mem-brane, mitochondrial edema, and ruptured mitochondrial crista. These findings suggest that chronic alcoholism can cause learning and memory decline in rats, which may be associated with the hydrogen sulfide/cystathionine-beta-synthase system, mitochondrial damage and reduced expression of F-actin.

  8. Neuronal connectivity, regional differentiation, and brain damage in humans.

    OpenAIRE

    Zaidel, Dahlia W.

    1999-01-01

    When circumscribed brain regions are damaged in humans, highly specific iimpairments in language, memory, problem solving, and cognition are observed. Neurosurgery such as "split brain" or hemispherectomy, for example has shown that encompassing regions, the left and right cerebral hemispheres each control human behavior in unique ways. Observations stretching over 100 years of patients with unilateral focal brain damage have revealed, withouth the theoretical benefits of "cognitive neurosci...

  9. The involvement of secondary neuronal damage in the development of neuropsychiatric disorders following brain insults

    Directory of Open Access Journals (Sweden)

    YunChen

    2014-03-01

    Full Text Available Neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people. Previous publications have demonstrated that neuropsychiatric disorders can cause histomorphological damage in particular regions of the brain. By using a clinical symptom-comparing approach, 55 neuropsychiatric signs or symptoms related usually to 14 types of acute and chronic brain insults were identified and categorized in the present study. Forty percent of the 55 neuropsychiatric signs and symptoms have been found to be commonly shared by the 14 brain insults. A meta-analysis supports existence of the same neuropsychiatric signs or symptoms in all brain insults. The results suggest that neuronal damage might be occurring in the same or similar regions or structures of the brain. Neuronal cell death, neural loss and axonal degeneration in some parts of the brain (the limbic system, basal ganglia system, brainstem, cerebellum, and cerebral cortex might be the histomorphological basis that is responsible for the neuropsychiatric symptom clusters. These morphological alterations may be the result of secondary neuronal damage (a cascade of progressive neural injury and neuronal cell death that is triggered by the initial insult. Secondary neuronal damage causes neuronal cell death and neural injury in not only the initial injured site but also remote brain regions. It may be a major contributor to subsequent neuropsychiatric disorders following brain insults.

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

    Directory of Open Access Journals (Sweden)

    Chunmei eWang

    2013-07-01

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

  11. Neglect severity after left and right brain damage

    OpenAIRE

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

    2012-01-01

    While unilateral spatial neglect after left brain damage is undoubtly 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 af...

  12. Behavioral Evaluation of Consciousness in Severe Brain Damage

    OpenAIRE

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

    2005-01-01

    This paper reviews the current state of bedside behavioral assessment in brain-damaged patients with impaired consciousness (coma, vegetative state, minimally conscious state). As misdiagnosis in this field is unfortunately very frequent, we first discuss a number of fundamental principles of clinical evaluation that should guide the assessment of consciousness in brain-damaged patients in order to avoid confusion between vegetative state and minimally conscious state. The role of standardize...

  13. The impact of chronic stress on the rat brain lipidome

    OpenAIRE

    Oliveira, Tiago Gil; Chan, Robin B.; Bravo, Francisca Vaz; Miranda, André; Silva, Rita Ribeiro; Zhou, Bowen; Marques, Fernanda; Pinto, Vítor; Cerqueira, João José; Di Paolo, Gilbert; Sousa, Nuno

    2015-01-01

    Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer’s disease (AD) and depression. Lipids are a major constituent of the brain, and specifically signaling lipids have been shown to regulate brain fu...

  14. 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…

  15. Brain damage in utero after Chernobyl accident

    International Nuclear Information System (INIS)

    Full text: The report presents research study results of neuropsychiatric consequences of the children exposed in utero, who were born just after the Chernobyl accident (between April 26, 1986 and February 26, 1987). The children were under investigation for three stages: in 1990-1992; 1994-1996; 2002-2004. We use the data on health state, IQ level tests and individual dose reconstruction data. First correlation between prenatal acute exposure after atomic bombing and intellectual level decrease was demonstrated by Japanese scientists. It is known that while the Chernobyl whole body irradiation doses are much lower than the Japanese doses, thyroid doses after the Chernobyl accident are significantly higher. During the first stage the five-year-old prenatally exposed children were under examination. The results showed much more somatic diseases and neurofunctional mental disorders. It was also established in this cohort that starting with the 0.3 Sv threshold dose thyroid-stimulating hormone (TSH) level grown along with fetal thyroid dose increase. Thereupon the radiation-induced malfunction of the thyroid-pituitary system was suggested as an important biological mechanism in the genesis of mental disorders in prenatally irradiated children. The epidemiological WHO project 'Brain Damage in Utero' (IPHECA) was implemented in the second stage. The examination of prenatally exposed children from the contaminated territories (555 kBq/m2 and more) resulted in an increased frequency of moderate mental retardation, emotional and behavioral disorders. Increasing of borderline nervous and psychological disorders of parents from the main group was higher than from the control. However it was rather hard to treat these results because individual dosimetric data were not available. Only in the third stage reconstruction of individual doses of children born to mothers evacuated from the Chernobyl exclusion zone was carried out at taking internal and external exposure. It was

  16. Irreversible brain damage caused by methamphetamine

    Directory of Open Access Journals (Sweden)

    Sebastian Moeller

    2016-03-01

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

  17. 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.

  18. 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.

  19. Damage and repair of irradiated mammalian brain

    International Nuclear Information System (INIS)

    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

  20. Rehabilitation of damage to the visual brain

    OpenAIRE

    Ajina, S; Kennard, C

    2012-01-01

    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 three and certainly six months. Rehabilitative approaches generally target three main areas, encompassing a ...

  1. Methadone-Induced Toxic Brain Damage

    OpenAIRE

    Jérôme Corré; Jérôme Pillot; Gilles Hilbert

    2013-01-01

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

  2. Brain damage in former association football players

    International Nuclear Information System (INIS)

    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. (orig.)

  3. 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 ...

  4. Measuring consciousness in severely damaged brains.

    Science.gov (United States)

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

    2014-01-01

    Significant advances have been made in the behavioral assessment and clinical management of disorders of consciousness (DOC). In addition, functional neuroimaging paradigms are now available to help assess consciousness levels in this challenging patient population. The success of these neuroimaging approaches as diagnostic markers is, however, intrinsically linked to understanding the relationships between consciousness and the brain. In this context, a combined theoretical approach to neuroimaging studies is needed. The promise of such theoretically based markers is illustrated by recent findings that used a perturbational approach to assess the levels of consciousness. Further research on the contents of consciousness in DOC is also needed. PMID:25002279

  5. Bilirubin and its oxidation products damage brain white matter.

    Science.gov (United States)

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-11-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  6. Measuring and inducing brain plasticity in chronic aphasia

    OpenAIRE

    Fridriksson, Julius

    2011-01-01

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

  7. Neurocomputational models of the remote effects of focal brain damage.

    Science.gov (United States)

    Reggia, James A

    2004-11-01

    Sudden localized brain damage, such as occurs in stroke, produces neurological deficits directly attributable to the damaged site. In addition, other clinical deficits occur due to secondary "remote" effects that functionally impair the remaining intact brain regions (e.g., due to their sudden disconnection from the damaged area), a phenomenon known as diaschisis. The underlying mechanisms of these remote effects, particularly those involving interactions between the left and right cerebral hemispheres, have proven somewhat difficult to understand in the context of current theories of hemispheric specialization. This article describes some recent neurocomputational models done in the author's research group that try to explain diaschisis qualitatively. These studies show that both specialization and diaschisis can be accounted for with a single model of hemispheric interactions. Further, the results suggest that left-right subcortical influences may be much more important in influencing hemispheric specialization than is generally recognized. PMID:15564108

  8. Behavioural alteration in chronic pain: are brain glia involved?

    Science.gov (United States)

    Panigada, T; Gosselin, R-D

    2011-10-01

    Behavioural symptoms such as abnormal emotionality (including anxious and depressive episodes) and cognition (for instance weakened decision-making) are highly frequent in both chronic pain patients and their animal models. The theory developed in the present article posits that alterations in glial cells (astrocytes and microglia) in cortical and limbic brain regions might be the origin of such emotional and cognitive chronic pain-associated impairments. Indeed, in mood disorders (unipolar depression, anxiety disorders, autism or schizophrenia) glial changes in brain regions involved in mood control (prefrontal and cingulate cortices, amygdala and the hippocampus) have been recurrently described. Besides, glial cells have been undoubtedly identified as key actors in the sensory component of chronic pain, owing to the profound phenotypical changes they undergo throughout the sensory pathway. Hence, the possibility arises that brain astrocytes and microglia react in upper brain structures as well, mediating the related mood and cognitive dysfunctions in chronic pain. So far, only very few studies have provided results in this prospect, mainly indirectly in pain-independent researches. Nevertheless, the first scant available data seem to merge in a unified description of a brain glial reaction occurring after chronic peripheral lesion. The present article uses this scarce literature to formulate the provocative theory of a glia-driven mood and cognitive dysfunction in chronic pain, expounding upon its validity and putative therapeutical impact as well as its current limitations and expected future developments. PMID:21741179

  9. Hyperschematia after right brain damage: a meaningful entity?

    Directory of Open Access Journals (Sweden)

    Gilles Rode

    2014-01-01

    Full Text Available In recent years we reported three right-brain-damaged patients, who exhibited a left-sided disprortionate expansion of drawings, both by copying and from memory, contralateral to the side of the hemispheric lesion (Neurology, 67: 1801, 2006, Neurocase 14: 369, 2008. We proposed the term “hyperschematia” for such an expansion, with reference to an interpretation in terms of a lateral leftward distortion of the representation of extra-personal space, with a leftward anisometric expansion (relaxation of the spatial medium. The symptom-complex shown by right-brain-damaged patients with “hyperschematia” includes: 1 a disproportionate leftward expansion of drawings (with possible addition of details, by copy and from memory (also in clay modeling, in one patient; 2 an overestimation of left lateral extent, when a leftward movement is required, associated with a perceptual underestimation; 4 unawareness of the disorder; 5 no unilateral spatial neglect. In most right-brain-damaged patients, left “hyperschematia” involves extra-personal space. In one patient the deficit was confined to a body part (left half-face: personal “hyperschematia”. The neural underpinnings of the disorder include damage to the fronto-temporo-parietal cortices, and subcortical structures in the right cerebral hemisphere, in the vascular territory of the middle cerebral artery. Here, four novel additional patients are reported. Finally, “hypeschematia” is reconsidered, in its clinical components, the underlying pathological mechanisms, as well as its neural underpinnings.

  10. Hyperschematia after right brain damage: a meaningful entity?

    Science.gov (United States)

    Rode, Gilles; Ronchi, Roberta; Revol, Patrice; Rossetti, Yves; Jacquin-Courtois, Sophie; Rossi, Irene; Vallar, Giuseppe

    2014-01-01

    In recent years we reported three right-brain-damaged patients, who exhibited a left-sided disprortionate expansion of drawings, both by copying and from memory, contralateral to the side of the hemispheric lesion (Neurology, 67: 1801, 2006, Neurocase 14: 369, 2008). We proposed the term "hyperschematia" for such an expansion, with reference to an interpretation in terms of a lateral leftward distortion of the representation of extra-personal space, with a leftward anisometric expansion (relaxation) of the spatial medium. The symptom-complex shown by right-brain-damaged patients with "hyperschematia" includes: (1) a disproportionate leftward expansion of drawings (with possible addition of details), by copy and from memory (also in clay modeling, in one patient); (2) an overestimation of left lateral extent, when a leftward movement is required, associated in some patients with a perceptual underestimation; (3) unawareness of the disorder; (4) no unilateral spatial neglect. In most right-brain-damaged patients, left "hyperschematia" involves extra-personal space. In one patient the deficit was confined to a body part (left half-face: personal "hyperschematia"). The neural underpinnings of the disorder include damage to the fronto-temporo-parietal cortices, and subcortical structures in the right cerebral hemisphere, in the vascular territory of the middle cerebral artery. Here, four novel additional patients are reported. Finally, "hypeschematia" is reconsidered, in its clinical components, the underlying pathological mechanisms, as well as its neural underpinnings. PMID:24478674

  11. 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.

  12. Patterns of damage in the mature neonatal brain

    International Nuclear Information System (INIS)

    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.)

  13. Influence of Age on Brain Edema Formation, Secondary Brain Damage and Inflammatory Response after Brain Trauma in Mice

    Science.gov (United States)

    Timaru-Kast, Ralph; Luh, Clara; Gotthardt, Philipp; Huang, Changsheng; Schäfer, Michael K.; Engelhard, Kristin; Thal, Serge C.

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ralph Timaru-Kast

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

  15. Intensive language training enhances brain plasticity in chronic aphasia

    Directory of Open Access Journals (Sweden)

    Meinzer Marcus

    2004-08-01

    Full Text Available Abstract Background Focal clusters of slow wave activity in the delta frequency range (1–4 Hz, as measured by magnetencephalography (MEG, are usually located in the vicinity of structural damage in the brain. Such oscillations are usually considered pathological and indicative of areas incapable of normal functioning owing to deafferentation from relevant input sources. In the present study we investigated the change in Delta Dipole Density in 28 patients with chronic aphasia (>12 months post onset following cerebrovascular stroke of the left hemisphere before and after intensive speech and language therapy (3 hours/day over 2 weeks. Results Neuropsychologically assessed language functions improved significantly after training. Perilesional delta activity decreased after therapy in 16 of the 28 patients, while an increase was evident in 12 patients. The magnitude of change of delta activity in these areas correlated with the amount of change in language functions as measured by standardized language tests. Conclusions These results emphasize the significance of perilesional areas in the rehabilitation of aphasia even years after the stroke, and might reflect reorganisation of the language network that provides the basis for improved language functions after intensive training.

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

    Science.gov (United States)

    Schupp, Nicole; Stopper, Helga; Heidland, August

    2016-01-01

    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. PMID:27313827

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

    OpenAIRE

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

    2013-01-01

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

  18. Hyperschematia after right brain damage: a meaningful entity?

    OpenAIRE

    Rode, Gilles; Ronchi, Roberta; Revol, Patrice; Rossetti, Yves; Jacquin-Courtois, Sophie; Rossi, Irene; Vallar, Giuseppe

    2014-01-01

    In recent years we reported three right-brain-damaged patients, who exhibited a left-sided disprortionate expansion of drawings, both by copying and from memory, contralateral to the side of the hemispheric lesion (Neurology, 67: 1801, 2006, Neurocase 14: 369, 2008). We proposed the term “hyperschematia” for such an expansion, with reference to an interpretation in terms of a lateral leftward distortion of the representation of extra-personal space, with a leftward anisometric expansion (rela...

  19. 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. PMID:26772317

  20. Chronic pain: The role of learning and brain plasticity

    OpenAIRE

    Mansour, A.R.; Farmer, M.A.; Baliki, M. N.; Apkarian, A. Vania

    2014-01-01

    Based on theoretical considerations and recent observations, we argue that continued suffering of chronic pain is critically dependent on the state of motivational and emotional mesolimbic-prefrontal circuitry of the brain. The plastic changes that occur within this circuitry in relation to nociceptive inputs dictate the transition to chronic pain, rendering the pain less somatic and more affective in nature. This theoretical construct is a strong departure from the traditional scientific vie...

  1. Chronic cerebrovascular dysfunction after traumatic brain injury.

    Science.gov (United States)

    Jullienne, Amandine; Obenaus, Andre; Ichkova, Aleksandra; Savona-Baron, Catherine; Pearce, William J; Badaut, Jerome

    2016-07-01

    Traumatic brain injuries (TBI) often involve vascular dysfunction that leads to long-term alterations in physiological and cognitive functions of the brain. Indeed, all the cells that form blood vessels and that are involved in maintaining their proper function can be altered by TBI. This Review focuses on the different types of cerebrovascular dysfunction that occur after TBI, including cerebral blood flow alterations, autoregulation impairments, subarachnoid hemorrhage, vasospasms, blood-brain barrier disruption, and edema formation. We also discuss the mechanisms that mediate these dysfunctions, focusing on the cellular components of cerebral blood vessels (endothelial cells, smooth muscle cells, astrocytes, pericytes, perivascular nerves) and their known and potential roles in the secondary injury cascade. © 2016 Wiley Periodicals, Inc. PMID:27117494

  2. Neuroprotection by gonadal steroid hormones in acute brain damage requires cooperation with astroglia and microglia.

    Science.gov (United States)

    Johann, Sonja; Beyer, Cordian

    2013-09-01

    The neuroactive steroids 17β-estradiol and progesterone control a broad spectrum of neural functions. Besides their roles in the regulation of classical neuroendocrine loops, they strongly influence motor and cognitive systems, behavior, and modulate brain performance at almost every level. Such a statement is underpinned by the widespread and lifelong expression pattern of all types of classical and non-classical estrogen and progesterone receptors in the CNS. The life-sustaining power of neurosteroids for tattered or seriously damaged neurons aroused interest in the scientific community in the past years to study their ability for therapeutic use under neuropathological challenges. Documented by excellent studies either performed in vitro or in adequate animal models mimicking acute toxic or chronic neurodegenerative brain disorders, both hormones revealed a high potency to protect neurons from damage and saved neural systems from collapse. Unfortunately, neurons, astroglia, microglia, and oligodendrocytes are comparably target cells for both steroid hormones. This hampers the precise assignment and understanding of neuroprotective cellular mechanisms activated by both steroids. In this article, we strive for a better comprehension of the mutual reaction between these steroid hormones and the two major glial cell types involved in the maintenance of brain homeostasis, astroglia and microglia, during acute traumatic brain injuries such as stroke and hypoxia. In particular, we attempt to summarize steroid-activated cellular signaling pathways and molecular responses in these cells and their contribution to dampening neuroinflammation and neural destruction. This article is part of a Special Issue entitled 'CSR 2013'. PMID:23196064

  3. Partially flexible MEMS neural probe composed of polyimide and sucrose gel for reducing brain damage during and after implantation

    International Nuclear Information System (INIS)

    This paper presents a flexible microelectromechanical systems (MEMS) neural probe that minimizes neuron damage and immune response, suitable for chronic recording applications. MEMS neural probes with various features such as high electrode densities have been actively investigated for neuron stimulation and recording to study brain functions. However, successful recording of neural signals in chronic application using rigid silicon probes still remains challenging because of cell death and macrophages accumulated around the electrodes over time from continuous brain movement. Thus, in this paper, we propose a new flexible MEMS neural probe that consists of two segments: a polyimide-based, flexible segment for connection and a rigid segment composed of thin silicon for insertion. While the flexible connection segment is designed to reduce the long-term chronic neuron damage, the thin insertion segment is designed to minimize the brain damage during the insertion process. The proposed flexible neural probe was successfully fabricated using the MEMS process on a silicon on insulator wafer. For a successful insertion, a biodegradable sucrose gel is coated on the flexible segment to temporarily increase the probe stiffness to prevent buckling. After the insertion, the sucrose gel dissolves inside the brain exposing the polyimide probe. By performing an insertion test, we confirm that the flexible probe has enough stiffness. In addition, by monitoring immune responses and brain histology, we successfully demonstrate that the proposed flexible neural probe incurs fivefold less neural damage than that incurred by a conventional silicon neural probe. Therefore, the presented flexible neural probe is a promising candidate for recording stable neural signals for long-time chronic applications. (paper)

  4. Partially flexible MEMS neural probe composed of polyimide and sucrose gel for reducing brain damage during and after implantation

    Science.gov (United States)

    Jeon, Myounggun; Cho, Jeiwon; Kim, Yun Kyung; Jung, Dahee; Yoon, Eui-Sung; Shin, Sehyun; Cho, Il-Joo

    2014-02-01

    This paper presents a flexible microelectromechanical systems (MEMS) neural probe that minimizes neuron damage and immune response, suitable for chronic recording applications. MEMS neural probes with various features such as high electrode densities have been actively investigated for neuron stimulation and recording to study brain functions. However, successful recording of neural signals in chronic application using rigid silicon probes still remains challenging because of cell death and macrophages accumulated around the electrodes over time from continuous brain movement. Thus, in this paper, we propose a new flexible MEMS neural probe that consists of two segments: a polyimide-based, flexible segment for connection and a rigid segment composed of thin silicon for insertion. While the flexible connection segment is designed to reduce the long-term chronic neuron damage, the thin insertion segment is designed to minimize the brain damage during the insertion process. The proposed flexible neural probe was successfully fabricated using the MEMS process on a silicon on insulator wafer. For a successful insertion, a biodegradable sucrose gel is coated on the flexible segment to temporarily increase the probe stiffness to prevent buckling. After the insertion, the sucrose gel dissolves inside the brain exposing the polyimide probe. By performing an insertion test, we confirm that the flexible probe has enough stiffness. In addition, by monitoring immune responses and brain histology, we successfully demonstrate that the proposed flexible neural probe incurs fivefold less neural damage than that incurred by a conventional silicon neural probe. Therefore, the presented flexible neural probe is a promising candidate for recording stable neural signals for long-time chronic applications.

  5. Positive emotions and brain reward circuits in chronic pain.

    Science.gov (United States)

    Navratilova, Edita; Morimura, Kozo; Xie, Jennifer Y; Atcherley, Christopher W; Ossipov, Michael H; Porreca, Frank

    2016-06-01

    Chronic pain is an important public health problem that negatively impacts the quality of life of affected individuals and exacts enormous socioeconomic costs. Chronic pain is often accompanied by comorbid emotional disorders including anxiety, depression, and possibly anhedonia. The neural circuits underlying the intersection of pain and pleasure are not well understood. We summarize recent human and animal investigations and demonstrate that aversive aspects of pain are encoded in brain regions overlapping with areas processing reward and motivation. We highlight findings revealing anatomical and functional alterations of reward/motivation circuits in chronic pain. Finally, we review supporting evidence for the concept that pain relief is rewarding and activates brain reward/motivation circuits. Adaptations in brain reward circuits may be fundamental to the pathology of chronic pain. Knowledge of brain reward processing in the context of pain could lead to the development of new therapeutics for the treatment of emotional aspects of pain and comorbid conditions. J. Comp. Neurol. 524:1646-1652, 2016. © 2016 Wiley Periodicals, Inc. PMID:26788716

  6. Imaging study of brain damage from methanol intoxication of wine

    International Nuclear Information System (INIS)

    Objective: To investigate the imaging of CT and MRI in brain damage caused by methanol intoxication from false wine, and to study the relations between imaging manifestation and different degrees of the methanol intoxication. Method: Thirty nine cases with methanol intoxication from false wine were retrospectively reported, The latent period of these patients was 0-4 days, and the average latent period of these patients was 0.5 days, All cases were performed by serology examination, brain CT scan, and four cases performed by MRI scan after average 2.5 days (range, 1-6 days) the onset of methanol intoxication. Results: Six cases showed hyperintense signals in bilateral putamen, two cases also showed hyperintense signals in biolateral subcortex white substance regions. Four cases showed hyperintense signals in unilateral internal capsule. One case showed hyperintense changess in subcortex white substance regions. Our study showed the positive correlation between CT features and the amount of methanol and stage of clinic manifestation(χ2=4.232, P2=0.001, P>0.05). Conclusions: MRI was better than CT in finding early brain damage caused by methanol intoxication from false wine. The characteristic finding changes of the patients was showed mainly in in bilateral putamen, Prognosis for the patients combined with subcortex white substance lesion wasn't hopeful. (authors)

  7. Brain viscoelasticity alteration in chronic-progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Kaspar-Josche Streitberger

    Full Text Available INTRODUCTION: Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS. METHODS: We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS. RESULTS: In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001. CONCLUSIONS: Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

  8. Effects ofAstragalus Membranaceus on Ischemia Brain Damage

    Institute of Scientific and Technical Information of China (English)

    Yumin Luo; Zhen Qin

    2000-01-01

    We observed the protective effects of Astragalus Membranaceus on cerebral ischemia. Method: 1. We used intravascular thread rat models with 72hs reperfusion of lh tMCAO for our studies. Astragalus Membranaceus was administrated intraperitoneally in different interval. The rats were sacrificed 72 hours after l h tMCAO. 2. Cerebral infarction volume was determined by TTC staining and image analysis. 3. DTNB method and TBA method were applied to measure the activity of GSH-px and the concentration of MDA respectively. 4. The blood brain barrier damage was evaluated by the area of Evans Blue extravasation. Results:l.The whole brain volume of protective group is larger than its control, but the average infarction volume is significantly less than that of control, and the percentage of average infarction volume to the whole brain is obviously decreased. 2. We found mildly enhanced GSH-px activity and markedly decreased MDA concentration in the protective group compared with its control. But there are no significant changes of GSH-px activity and MDA concentration in the therapy group compared with its control. 3. The area of Evans Blue staining in the protective group is significantly less than that of its control. Conclusion:l.Astragalus Membranaceus can decrease the infarction volume. 2.Astragalus Membranaceus may reduce MDA concentration after cerebral ischemia. 3.Astragalus Membranaceus can protect blood brain barrier.

  9. Brain damage after treatment for acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    In 34 patients treated for acute lymphoblastic leukemia (ALL), central nervous system (CNS) damage was assessed by clinical evaluation and brain magnetic resonance imaging (MRI). Twenty-seven of them had been off therapy from 5 to 109 months (median 64 months) while 7 had not completed the maintenance phase of their treatment. All the patients were disease-free when evaluated. None of the 3 patients who showed clinical CNS damage during the follow-up was symptomatic when submitted to MRI, while periventricular hyperintensity in T2-weighted images, suggestive of leukoencephalopathy, was present in 8 of the 34 patients. These subclinical abnormalities appear to be more frequent, transient in nature and treatment-related in patients evaluated shortly after the induction phase. Similar MRI findings seem, on the contrary, to be consequences of the disease on the CNS when appearing in long-term survivors. (orig.)

  10. Ancillary procedure for early diagnosis of brain damage in children

    International Nuclear Information System (INIS)

    CT scan of the head was performed on 14 patients with cerebral palsy, 16 with central coordination disorders, and 16 controls, and findings showing cerebral atrophy and enlargement of the cerebral ventricle were obtained in cases both of cerebral palsy and of central coordination disorders. To objectify these findings, 10 items were selected and evaluated according to 4 grades (0 - 3) and were compared. As a result, it was concluded that CT scan is an excellent ancillary procedure for early diagnosis of brain damages. (Tsunoda, M.)

  11. Deep brain stimulation for chronic pain.

    Science.gov (United States)

    Boccard, Sandra G J; Pereira, Erlick A C; Aziz, Tipu Z

    2015-10-01

    Deep brain stimulation (DBS) is a neurosurgical intervention popularised in movement disorders such as Parkinson's disease, and also reported to improve symptoms of epilepsy, Tourette's syndrome, obsessive compulsive disorders and cluster headache. Since the 1950s, DBS has been used as a treatment to relieve intractable pain of several aetiologies including post stroke pain, phantom limb pain, facial pain and brachial plexus avulsion. Several patient series have shown benefits in stimulating various brain areas, including the sensory thalamus (ventral posterior lateral and medial), the periaqueductal and periventricular grey, or, more recently, the anterior cingulate cortex. However, this technique remains "off label" in the USA as it does not have Federal Drug Administration approval. Consequently, only a small number of surgeons report DBS for pain using current technology and techniques and few regions approve it. Randomised, blinded and controlled clinical trials that may use novel trial methodologies are desirable to evaluate the efficacy of DBS in patients who are refractory to other therapies. New imaging techniques, including tractography, may help optimise electrode placement and clinical outcome. PMID:26122383

  12. A prospective study to evaluate a new residential community reintegration programme for severe chronic brain injury: the Brain Integration Programme.

    NARCIS (Netherlands)

    Geurtsen, G.J.; Martina, J.D.; Heugten, C.M. van; Geurts, A.C.H.

    2008-01-01

    PURPOSE: To assess the effectiveness of a residential community reintegration programme for participants with chronic sequelae of severe acquired brain injury that hamper community functioning. DESIGN: Prospective cohort study. SUBJECTS: Twenty-four participants with acquired brain injury (traumatic

  13. 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.

  14. 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. PMID:26392628

  15. 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

    Purpose: 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. Materials and Methods: 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. Results: 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. Conclusions: 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. PMID:27458377

  16. Brain damage in a large cohort of solvent abusers.

    Science.gov (United States)

    Al-Hajri, Zahra; Del Bigio, Marc R

    2010-04-01

    The neuropathology of solvent inhalation consists of patchy myelin loss with white matter macrophages that contain granular inclusions. It has been described only in a small number of cases. We sought to characterize the abnormalities in greater detail. In a retrospective study from 1995 to 2009, we encountered 88 autopsy cases with documented history of solvent abuse by inhalation and 1 with industrial exposure. Among these are 6 fetuses and infants with maternal exposure, 23 children (12-17 years), and 60 adults (18-66 years). Available brain samples from 75 cases were stained with solochrome cyanein (to demonstrate myelin) and periodic acid-Schiff (PAS) (to highlight the inclusions). Forty brains of ethanol and/or illicit drug exposed individuals and ten cases of multiple sclerosis were examined as controls. We found that 16 cases (age 23-49, median 37 years) had well-established leukoencephalopathy with multifocal myelin loss and abundant macrophages that stain with PAS and which contain birefringent inclusions. Six cases (age 15-55, median 27 years) had early leukoencephalopathy with scattered macrophages but no obvious myelin changes. Clusters of PAS-staining but non-birefringent macrophages were seen in 2/10 cases of (active) multiple sclerosis and in none of the ethanol/drug exposed brains. Ultrastructurally, inclusions from solvent cases differed from multiple sclerosis cases. Although exposure to solvents is impossible to quantify, there appears to be a duration-dependent effect. Brain damage related to solvent abuse can begin within only a few years of the onset. In the context of substance abuse, the changes are relatively specific for solvent inhalation and do not appear to result from demyelination alone. Interaction with ethanol cannot be excluded as a compounding risk factor. PMID:20300918

  17. Brain perfusion abnormality in patients with chronic pain

    International Nuclear Information System (INIS)

    We performed single photon emission computed tomography (SPECT) of the brain in 15 patients with chronic pain (males, 7; females, 8; average age 49.1±17.9 years) and identified the locus of cerebral blood flow reduction by a new analytical method (easy Z-score Imaging System: eZIS) to clarify the functional neuroanatomical basis of chronic pain. Of the 15 patients, 6 had backache, 2 neck pain, 2 gonalgia, and 5 pain at other sites, with an average Visual analog scale of pain (VAS) value of 6.1±1.9. In comparison with a information on a data base on physically unimpaired persons, the dorsolateral prefrontal area (both sides, right dominant), medial prefrontal area (both sides), dorsal aspect of the anterior cingulate gyrus nociceptive cortex (both sides) and the lateral part of the orbitofrontal cortex (right side) were found to have blood flow reduction in the group of patients with chronic pain. As for chronic pain and its correlation with clinical features such as a depressive state, anticipation anxiety, post-traumatic stress disorder (PTSD), and conversion hysteria, the mechanism in the brain that was suggested by this study should be followed-up by functional neuroimaging studies. (author)

  18. MRI findings of brain damage due to neonatal hypoglycemia

    International Nuclear Information System (INIS)

    Objective: To report the MRI findings of brain damage observed in neonatal patients who suffered from isolated hypoglycemia and to explore the value of diffusion-weighted imaging(DWI) in early detection of neonatal hypoglycemic brain injury. Methods: Twelve neonates with isolated hypoglycemia (10 of the 12 were diagnosed to suffer from hypoglycemic encephalopathy) were enrolled in this study. They were first scanned at age from 3 days to 10 days with T1WI, T2WI and DWI(b is 0 s/mm2, 1000 s/mm2), and 4 of them were then scanned from 7 days to 10 days following the initial scan. All acquired MR images were retrospectively analysed. Results: First series of DWI images showed distinct hyperintense signal in 11 cases in several areas including bilateral occipital cortex (2 cases), right occipital cortex (1 case), left occipital cortex and subcortical white matter(1 case), bilateral occipital cortex and subcortical white matter (2 cases), bilateral parieto-occipital cortex (2 cases), bilateral parieto-occipital cortex and subcortical white matter(2 cases), the splenium of corpus callosum (4 cases), bilateral corona radiata( 2 cases), left caudate nucleus and globus pallidus (1 case), bilateral thalamus (1 case), bilaterally posterior limb of internal capsule (1 case). In the initial T1WI and T2WI images, there were subtle hypointensity in the damaged cortical areas (3 cases), hyperintensity in the bilaterally affected occipital cortex( 1 case) on T1 weighted images, and hyperintensity in the affected cortex and subcortical white matter with poor differentiation on T2 weighted images. The followed-up MRI of 4 cases showed regional encephalomalacia in the affected occipital lobes(4 cases), slightly hyperintensity on T2 weighted images in the damaged occipital cortex (2 cases), extensive demyelination (1 case), disappearance of hyperintensity of the splenium of corpus callosum (1 case), and persistent hyperintensity in the splenium of corpus callosum (1 case) on T2 weighted

  19. Mapping neuroplastic potential in brain-damaged patients.

    Science.gov (United States)

    Herbet, Guillaume; Maheu, Maxime; Costi, Emanuele; Lafargue, Gilles; Duffau, Hugues

    2016-03-01

    It is increasingly acknowledged that the brain is highly plastic. However, the anatomic factors governing the potential for neuroplasticity have hardly been investigated. To bridge this knowledge gap, we generated a probabilistic atlas of functional plasticity derived from both anatomic magnetic resonance imaging results and intraoperative mapping data on 231 patients having undergone surgery for diffuse, low-grade glioma. The atlas includes detailed level of confidence information and is supplemented with a series of comprehensive, connectivity-based cluster analyses. Our results show that cortical plasticity is generally high in the cortex (except in primary unimodal areas and in a small set of neural hubs) and rather low in connective tracts (especially associative and projection tracts). The atlas sheds new light on the topological organization of critical neural systems and may also be useful in predicting the likelihood of recovery (as a function of lesion topology) in various neuropathological conditions-a crucial factor in improving the care of brain-damaged patients. PMID:26912646

  20. 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.

  1. 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. PMID:21543839

  2. Aluminium-induced oxidative DNA damage recognition and cell-cycle disruption in different regions of rat brain

    International Nuclear Information System (INIS)

    The present study was undertaken to reveal the effects of chronic aluminium exposure (10 mg/kg/b.wt, intragastrically for 12 weeks) on the oxidative DNA damage and its implication on the expression of p53 and other cell-cycle regulatory proteins in male Wister rats. Chronic aluminium exposure resulted in increased formation of 8-hydoxydeoxyguanosine in the mitochondrial DNA isolated from different regions of rat brain. The agarose gel electrophoresis revealed the DNA fragmentation pattern in aluminium-treated rat brain regions. Increased expression of p53 demonstrated that aluminium induces DNA damage. Western blot and mRNA expression analysis demonstrated increased expression of cyclin D1, suggesting disruption of cell cycle. The immunohistochemical studies showed nuclear localization of p53; however, the localization of cyclin D1 was both cytoplasmic and nuclear in aluminium-treated rat brain regions. Thus, the findings of the present study reveal that aluminium-induced oxidative damage to DNA may be involved in the neurodegeneration via increase in p53 expression and activation of cell cycle.

  3. Chronic Methamphetamine Effects on Brain Structure and Function in Rats

    Science.gov (United States)

    Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  4. Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

    Directory of Open Access Journals (Sweden)

    Panayotis K Thanos

    Full Text Available Methamphetamine (MA addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET studies have shown decreased brain glucose metabolism (BGluM in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls, or low dose (LD MA (4 mg/kg, or high dose (HD MA (8 mg/kg. Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG, and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

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

    Science.gov (United States)

    Inglis, James; Lawson, J. S.

    1981-05-01

    A sexual dimorphism in the functional asymmetry of the damaged human brain is reflected in a test-specific laterality effect in male but not in female patients. This sex difference explains some contradictions concerning the effects of unilateral brain damage on intelligence in studies in which the influence of sex was overlooked.

  6. Functional brain study of chronic traumatic head injury

    International Nuclear Information System (INIS)

    Explosive aggressive behaviour is a significant clinical and medico-legal problem in patients suffering from head injury. However, experts in neuropsychiatry have proposed a specific category for this disorder: the organic aggressive syndrome:. The basic reason for proposing this diagnosis is that it describes the specificity of the violent conduct secondary to 'brain damage' with greater precision. Early diagnosis and treatment of the injury is critical. The impact of hnetium-99m-hexamethylpropuleneamine oxime (HMPAO) was examined for measuring brain damage in correlation to neuropsychological performance in patients with traumatic brain injury (TBI). We thus report the case of a twelve-year-old child with a history of CET, who presents with serious episodes of heteroaggressiveness and suggest the usefulness of single photon emission computerized tomography (SPECT) to establish the validity of this psychiatric diagnosis. The appearance of modern functional neuro-image techniques (SPECT) may help to increase the validity of clinical diagnoses in the field of psychiatry in general and of forensic psychiatry in particularly, as the related findings may be used as demarcation criteria to establish syndromic diagnoses (Au)

  7. Chronic histological effects of ultrasonic hyperthermia on normal feline brain tissue.

    Science.gov (United States)

    Lyons, B E; Obana, W G; Borcich, J K; Kleinman, R; Singh, D; Britt, R H

    1986-05-01

    The histopathological changes associated with ultrasonic heating of normal cat brain have been correlated with thermal distributions. Ultrasound energy was applied for 50 min at different intensities to generate tissue temperatures from 42 to 48 degrees C. Animals were sacrificed at various intervals from 1 to 56 days. The organization and resolution of thermal damage was characterized by three stages of histopathological changes within the nervous tissue. The acute stage (Days 1-3) was defined by (1) extensive coagulation necrosis, (2) pyknosis of neuronal elements in the gray matter, (3) edema and vacuolation in the white matter, and (4) polymorphonuclear leukocytes. The subacute stage (Days 3-21) was characterized by (1) the appearance of lipid-laden macrophages, (2) liquefaction of the necrotic regions, (3) fibroblastic proliferation, and (4) vascular proliferation with some perivascular inflammatory infiltration (lymphocytes). Lastly, the chronic stage (Days 21-56) was defined by (1) fibrosis (reticulin and collagen formation) and (2) gliosis (reactive astrocytic proliferation) occurring around the fluid-filled necrotic center. Analysis of these data has also included a study of the lesion size versus the dose (temperature for 50 min) of heating. The results demonstrate a significant linear dose-response correlation. The results of this study indicate that the histological appearance and time course of repair of thermal injury in the normal brain tissue are analogous to acute brain necrosis resulting from cerebral infarction, except the thermal damage does not result in significant hemorrhage. PMID:3704114

  8. Chronic impact of traumatic brain injury on outcome and quality of life: a narrative review.

    Science.gov (United States)

    Stocchetti, Nino; Zanier, Elisa R

    2016-01-01

    Traditionally seen as a sudden, brutal event with short-term impairment, traumatic brain injury (TBI) may cause persistent, sometimes life-long, consequences. While mortality after TBI has been reduced, a high proportion of severe TBI survivors require prolonged rehabilitation and may suffer long-term physical, cognitive, and psychological disorders. Additionally, chronic consequences have been identified not only after severe TBI but also in a proportion of cases previously classified as moderate or mild. This burden affects the daily life of survivors and their families; it also has relevant social and economic costs.Outcome evaluation is difficult for several reasons: co-existing extra-cranial injuries (spinal cord damage, for instance) may affect independence and quality of life outside the pure TBI effects; scales may not capture subtle, but important, changes; co-operation from patients may be impossible in the most severe cases. Several instruments have been developed for capturing specific aspects, from generic health status to specific cognitive functions. Even simple instruments, however, have demonstrated variable inter-rater agreement.The possible links between structural traumatic brain damage and functional impairment have been explored both experimentally and in the clinical setting with advanced neuro-imaging techniques. We briefly report on some fundamental findings, which may also offer potential targets for future therapies.Better understanding of damage mechanisms and new approaches to neuroprotection-restoration may offer better outcomes for the millions of survivors of TBI. PMID:27323708

  9. Protection of Effective Component Group from Xiaoshuan Tongluo on Brain Injury after Chronic Hypoperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    TAN Chu-bing; WANG Hong-qing; TIAN Shuo; GAO Mei; XU Wei-ren; CHEN Ruo-yun; DU Guan-hua

    2011-01-01

    Objective To investigate the protective effects of purified effective component group in extract from Xiaoshuan Tongluo(CGXT)formula on chronic brain ischemia in rats.Methods CGXT 75,150,and 300 mg/kg or vehicle were ig administered daily for four weeks to rats with bilateral common carotid arteries ligation(BCCAL).From the day 24 to 28 after BCCAL,Morris water maze was performed to assess the learning and memory impairment of rats.Four weeks after BCCAL,brain gray and white matter damage were assessed.Results In Morris test,the mean escape latency of rats in the CGXT(150 and 300 mg/kg)groups was significantly shorter than that in the vehicle group.CGXT also attenuated the neuronal damage in hippocampus and cortex and reduced the pathological damage in the optic tract and corpus callosum.Conclusion CGXT could improve learning and memory impairment resulted from BCCAL in rats.These results provide the experimental basis for the clinical use of CGXT in stroke treatment and may help in investigation of multimodal therapy strategies in ischemic cerebrovascular diseases including stroke.

  10. Abnormal face identity coding in the middle fusiform gyrus of two brain-damaged prosopagnosic patients.

    OpenAIRE

    Steeves, J.; Dricot, L.; Goltz, H.C.; Sorger, B; Peters, J.; Milner, A D; Goodale, M. A.; Goebel, R.; B Rossion

    2009-01-01

    We report a functional magnetic resonance imaging (fMRI) adaptation study of two well-described patients, DF and PS, who present face identity recognition impairments (prosopagnosia) following brain-damage. Comparing faces to non-face objects elicited activation in all visual areas of the cortical face processing network that were spared subsequent to brain damage. The common brain lesion in the two patients was in the right inferior occipital cortex, in the territory of the right “occipital ...

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

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yankui Guo; Yalu Li; Zhenying Yang

    2011-01-01

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

  12. Hyper-resting brain entropy within chronic smokers and its moderation by Sex

    OpenAIRE

    Zhengjun Li; Zhuo Fang; Nathan Hager; Hengyi Rao; Ze Wang

    2016-01-01

    Cigarette smoking is a chronic relapsing brain disorder, and remains a premier cause of morbidity and mortality. Functional neuroimaging has been used to assess differences in the mean strength of brain activity in smokers’ brains, however less is known about the temporal dynamics within smokers’ brains. Temporal dynamics is a key feature of a dynamic system such as the brain, and may carry information critical to understanding the brain mechanisms underlying cigarette smoking. We measured th...

  13. Diffusion Tensor Imaging Study of White Matter Damage in Chronic Meningitis

    OpenAIRE

    Lin, Wei-Che; Chen, Pei-Chin; Wang, Hung-Chen; Tsai, Nai-Wen; Chou, Kun-Hsien; Chen, Hsiu-Ling; Su, Yu-Jih; Lin, Ching-Po; Li, Shau-Hsuan; Chang, Wen-Neng; Lu, Cheng-Hsien

    2014-01-01

    Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based ...

  14. Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

    2016-08-17

    Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase. PMID:27362436

  15. Analysis of MRI in chronic alcoholics with brain atrophy

    International Nuclear Information System (INIS)

    To quantitatively evaluate by MRI brain atrophy and abnormal parenchymal signal intensity on T2-weighted spin echo image in alcoholics. MRI of 24 alcoholic patients were retrospectively evaluated to measure brain atrophy (cerebral sulcal width, bifrontal horn distance, third ventricular width, fourth ventricular width, ambient cistern width, cerebellopontine angle cistern width, number of cerebellar sulci, and number of vermian sulci) and abnormal high signal lesions of brain parenchyma on T2-weighted spin echo image, and were compared with age matched controls (n=29). The alcoholics and controls were divided into two age groups, younger (30-49 years) and older (50-72 years), and statistical analysis was then performed. Axial and sagittal T1- and T2-weighted spin echo images were obtained using a 0.5 Tesla superconductive system. Statistical significant parameters in the supratentorial region were cerebral sulcal width, distance between lateral ends of frontal horns of both lateral ventricles, and third ventricular width (p < 0.05), and in the infratentorial region were fourth ventricular width, ambient cistern width, cerebellopontine angle cistern width, number of cerebellar sulci, and number of vermian sulci (p < 0.05). In the younger age group, statistical significant parameters were cerebral sulcal width, third ventricular width, ambient cistern width, cerebellopontine angle cistern width, number of cerebellar sulci, and number of vermian sulci (p < 0.05) and in the older group were cerebral sulcal width, bifrontal horn distance, third ventricular width, fourth ventricular width, number of cerebellar sulci, and number of vermian sulci (p < 0.05). Abnormal high signal intensity on T2-weighted spin echo images were seen in 46% of alcoholics (11/24) and in 13% of controls (3/29). High signal lesions in the older group were statistically significant (p < 0.05). Atrophic brain changes and periventricular high signal foci on T2-weighted spin echo image are

  16. Neurotherapy for chronic headache following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    David V Nelson; Mary Lee Esty

    2015-01-01

    Background:Chronic headache following traumatic brain injury (TBI) sustained in military service, while common, is highly challenging to treat with existing pharmacologic and non-pharmacologic interventions, and it may be complicated by co-morbid posttraumatic stress. Recently, a novel form of brainwave-based intervention known as the Flexyx Neurotherapy System (FNS), which involves minute pulses of electromagnetic energy stimulation of brainwave activity, has been suggested as a means to address symptoms of TBI. This study reports on a clinical series of patients with chronic headache following service-connected TBI treated with FNS. Methods: Nine veterans of the wars in Afghanistan and Iraq with moderate to severe chronic headaches following service-connected TBI complicated by posttraumatic stress symptoms were treated in 20 individual FNS sessions at the Brain Wellness and Biofeedback Center of Washington (in Bethesda, Maryland, USA). They periodically completed measures including the Brief Pain Inventory-Headache (BPI-HA), previous week worst and average pain ratings, the Posttraumatic Stress Disorder Checklist-Military version (PCL-M), and an individual treatment session numerical rating scale (NRS) for the degree of cognitive dysfunction. Data analyses included beginning-to-end of treatmentt-test comparisons for the BPI-HA, PCL-M, and cognitive dysfunction NRS. Results: All beginning-to-end of treatmentt-test comparisons for the BPI-HA, PCL-M, and cognitive dysfunction NRS indicated statistically significant decreases. All but one participant experienced a reduction in headaches along with reductions in posttraumatic stress and perceived cognitive dysfunction, with a subset experiencing the virtual elimination of headaches. One participant obtained modest headache relief but no improvements in posttraumatic stress or cognitive dysfunction. Conclusions: FNS may be a potentially efficacious treatment for chronic posttraumatic headache sustained in military

  17. 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.

  18. Bilirubin and its oxidation products damage brain white matter

    OpenAIRE

    Lakovic, Katarina; Ai, Jinglu; D'abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-01-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compound...

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

  20. 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…

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

    NARCIS (Netherlands)

    D.C. Engel (Doortje Caroline)

    2008-01-01

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

  2. 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

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

    Science.gov (United States)

    Lorimer, David

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

  4. Expression of receptor for advanced glycation endproducts and nuclear factor κB in brain hippocampus of rat with chronic fluorosis

    Institute of Scientific and Technical Information of China (English)

    张凯琳

    2014-01-01

    Objective To investigate the expressions of receptor for advanced glycation endproducts(RAGE)and nuclear factorκB(NF-κB)in brain hippocampus of rat with chronic fluorosis,and to reveal the mechanism of brain damage resulted from chronic fluorosis.Methods Sixty clean grade SD rats were randomly divided to three groups(20 rats in each group,10 female and 10 male)fed with different contents of fluoride,control group with normal tap-water(<0.5 mg/L fluoride),

  5. 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.,…

  6. Expression Profile of DNA Damage Signaling Genes in Proton Exposed Mouse Brain

    Science.gov (United States)

    Ramesh, Govindarajan; Wu, Honglu

    Exposure of living systems to radiation results in a wide assortment of lesions, the most signif-icant of is damage to genomic DNA which induce several cellular functions such as cell cycle arrest, repair, apoptosis etc. The radiation induced DNA damage investigation is one of the im-portant area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes particularly, damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR array in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2Gy proton exposed mouse brain tissues as compared with control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed brain tissue undergo severe DNA damage which in turn destabilize the chromatin stability.

  7. Uraemic vascular damage and calcification in children with chronic kidney disease

    OpenAIRE

    Shroff, R

    2009-01-01

    Summary of thesis: Cardiovascular disease is the most common cause of death in patients with chronic kidney disease. Structural and functional vascular abnormalities and arterial calcification begins early in the course of renal decline and can be found even in children, contributing to their high mortality risk. Through clinical and laboratory studies, this thesis sought to investigate the causes of uraemic vascular damage and calcification in children with chronic kidney dise...

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

    OpenAIRE

    Godwin Sokpor; Frederick Kwaku Addai; Richard Kwasi Gyasi; Kwasi Agyei Bugyei; John Ahenkorah; Bismarck Hottor

    2012-01-01

    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 o...

  9. EFFECTS OF CHRONIC STRESS ON THE ACTIVITIES OF SOD, GSH-Px AND MDA LEVEL IN FEMALE RATS' BRAIN

    Institute of Scientific and Technical Information of China (English)

    王莹; 杨东伟; 谢雯; 庞炜; 蒋马莉; 韩太真

    2002-01-01

    Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats' brain. Methods The rats were randomly divided into 4 groups: normal control group (group N), emotional stress group (group E), emotional stress + pregnancy group (group E+P) and regularly drinking group (group R). Emotional stress in rats was induced by training rats with empty drinking bottles. Having been finished the stress procedure, the brain was taken out and homogenized. Then the activities of SOD, GSH-Px and MDA level were measured. Results Compared to group N, both the activities of SOD in brain tissues of group E and group E+P were significantly decreased (P<0.05 and P<0.01, respectively) while the MDA level increased (P<0.05). However, the extent of changes in group E+P was more obvious than that in E. GSH-Px activities in E+P and E were significantly changed. However, the GSH-Px activity in E+P was decreased (P<0.05) while the activity in E increased (P<0.05).Conclusion The chronic emotional stress can reduce the antioxidative system by decreasing the antioxidative enzyme activity and potentiating the lipid peroxidation in the brain. It is also suggested that the combination of emotional stress and pregnancy can augment the oxidative damage in rats' brain.

  10. Clinical peculiarities of the brain damage in the liquidators of the Chernobyl accident

    International Nuclear Information System (INIS)

    Investigation into the features of the brain damage by the liquidators of the Chernobyl accident has become an urgent issue of today due to a number of circumstances. According to the classical concept dominating radiobiology until recently, the brain being composed of highly - differentiated nerve cells, present a radioresistant structure responsive to radiation injury induced by high and very high radiation doses (10000 rem and higher) only. The results of clinical examinations given to the Chernobyl accident recovery workers at Kiev Institute of Neurosurgery, Academy of Medical Sciences of Ukraine, show that even the so - called ''small - dose'' radiation, when consumed continuously, produces neurological sings of brain damage. 6 figs

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

    Science.gov (United States)

    ... R.; et al. Gender differences in moderate drinking effects. Alcohol Research & Health 23:55–64, 1999. (5) Loft, S. ; ... A.; and Sullivan, E. Sex differences in the effects of alcohol on brain structure. American Journal of Psychiatry 158: ...

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

    OpenAIRE

    Engel, Doortje Caroline

    2008-01-01

    textabstractTraumatic brain injury (TBI) is defined as a microscopic or macroscopic injury to the brain caused by external physical forces. Road traffic accidents, falls, sports injuries (i.e. boxing), recreational accidents (i.e. parachute jumping), the use of firearms, assault, child abuse, and several rare causes e.g. the use of nail guns or lawn mowers have all been described as causes of TBI. The pathology of TBI can be classified by mechanism (closed versus penetrating); clinical severi...

  13. A clinical study on closing-in in focal brain-damaged individuals.

    Science.gov (United States)

    De Lucia, Natascia; Grossi, Dario; Trojano, Luigi

    2016-04-15

    In visuo-constructional assessment, brain-damaged individuals may copy figures near to or superimposed on the model, showing the Closing-in (CI). CI has been largely investigated in dementia, and often ascribed to impairments of the attention/executive abilities ("Attraction hypothesis"). Only a few dated studies investigated frequency of CI in brain-damaged individuals, without clarifying the genesis of the phenomenon. We aimed at testing the "Attraction hypothesis" in 27 individuals with focal frontal cortical or sub-cortical brain lesions by a dual-task experimental paradigm. The participants underwent a neuropsychological battery and a copying task to be performed alone (single task condition), or concurrently with a simple or a complex verbal secondary task (dual-task conditions). CI was found in 66% of frontal-damaged individuals, who scored significantly lower than healthy adults on all neuropsychological measures; brain-damaged individuals showing CI performed worse than frontal-damaged individuals without CI on frontal and visuo-constructional measures. In the dual-task condition with the complex secondary task CI was significantly enhanced, with a weaker tendency to self-correction, in individuals with CI compared to individuals without CI. These findings would confirm that the CI in brain-damaged individuals is related to reduction of attentional resources, consistently with the "Attraction hypothesis". PMID:27000246

  14. 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

  15. Contralateral and ipsilateral disorders of visual attention in patients with unilateral brain damage.

    Science.gov (United States)

    Gainotti, G; Giustolisi, L; Nocentini, U

    1990-05-01

    To explain the prevalence of unilateral spatial neglect in patients with right brain damage, Heilman et al have suggested that the attentional neurons of the right parietal lobe might have bilateral receptive fields, whereas the homologous cells of the left hemisphere would have strictly contralateral receptive fields. One implication of this theory is that patients with right brain damage should show a prevalence of disorders of visual attention not only in the half space contralateral to the damaged hemisphere, but also in the ipsilateral one. To check this theory, 50 control subjects, 102 right and 125 left brain-damaged patients were given a drawing completion task in which patients were requested to complete the missing parts of a star, a cube and a house. Omissions of lines lying on the sides of the models contralateral and ipsilateral to the damaged hemisphere were taken separately into account. Results did not confirm the hypothesis, since right brain-damaged patients failed to complete the contralateral sides of the models much more frequently than patients with left brain injury, but no difference was found between the two hemispheric groups when ipsilateral disorders of visual attention were taken into account. Furthermore, no correlation was found between omissions of lines lying on the sides of the models contralateral and ipsilateral to the damaged hemisphere. This finding suggests that contralateral and ipsilateral disorders of visual attention are not due to the same mechanism in right brain-damaged patients. The alternative hypothesis viewing ipsilateral disorders as resulting from a widespread lowering of general attention (and only contralateral neglect reflecting a specific disorder of visual attention) was supported by results obtained on a verbal memory test, used to evaluate the general cognitive and attention level of the patients. Patients with clear-cut ipislateral inattention obtained very low scores on this test, whereas patients with

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

    Science.gov (United States)

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

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population. PMID:26184082

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

    Science.gov (United States)

    Samarghandian, Saeed; Farkhondeh, Tahereh; Samini, Fariborz; Borji, Abasalt

    2016-01-01

    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. PMID:26904286

  18. 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.

  19. Life expectancy of brain impaired, chronically ventilated children.

    Science.gov (United States)

    Gale, Rena; Namestnic, Julia

    2013-04-01

    We present a 5-year survival profile of 42 children and adolescents between 1 to 21 years of age in an immobile minimally conscious state, chronically dependent on supportive ventilation. Data were collected from a 22-bed pediatric unit dedicated to this unique population, within a 350-bed geriatric hospital, between May 2006 and May 2011. The practice of ventilating children even in minimally conscious state stems from the unique cultural, religious, and ethnic background of the population in Israel. The 5-year survival probability was 48% (52% probability of death within 5 years, 26.5% within 2 years). No significant difference was found in the survival profile of patients admitted following hypoxic accidents (20 children) and those admitted with other problems such as genetic/metabolic diseases or brain anomalies (22). The mortality rate of male patients was higher than that of female patients, but the difference was not statistically significant. No difference in 5-year mortality rates was found between children of different ethnic backgrounds. PMID:23498560

  20. 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

  1. Experimental investigations on chronic irradiation damage of the heart

    International Nuclear Information System (INIS)

    Irradiation of rat hearts induced the following clinical phenomena: increasingly severe dyspnea, associated flank respiration and deterioration of the general condition bordering on a prefinal syndrome. Dissection of the sick animals and thoracal x-rays taken regularly revealed extensive pesicardial and pleural effusions. The tissue of the pericardium was thickened and edematous. The most striking histological finding consisted in a focal degeneration and destruction of the myocardium without an increase in collagenous fibres. This damage to the heart muscle was quite severe and seen in all dose groups from 15 to 40 Gy. At the same time there was a reduction of the capillary density as a function of the radiation dose. Clinical symptoms were also observed in animals irradiated with 10 Gy only. All animals irradiated with at least 20 Gy, attained a state where death was imminent. Consequently, the LD-50 must be lower than 20 Gy. The latency period was over a year at 15 Gy but decreased considerably as the dose increased. (orig.)

  2. 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.

  3. Brain damage in hanging: a new CT finding

    International Nuclear Information System (INIS)

    We report a 23-year-old man who attempted suicide by hanging. There have been few reports of involvement of the brain parenchyma shown on CT, all showing ischaemic lesions. This is the first report of multifocal intracerebral haematomas due to hanging seen on CT. (orig.) (orig.)

  4. 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....

  5. Effects of static magnetic field and cadmium on oxidative stress and DNA damage in rat cortex brain and hippocampus.

    Science.gov (United States)

    Amara, Salem; Douki, Thierry; Garrel, Catherine; Favier, Alain; Ben Rhouma, Khémais; Sakly, Mohsen; Abdelmelek, Hafedh

    2011-03-01

    The present study was undertaken to determine the effect of co-exposure to static magnetic field (SMF) and cadmium (Cd) on the antioxidant enzymes activity and DNA integrity in rat brain. Sub-chronic exposure to CdCl (CdCl(2), 40 mg/L, per os) for 30 days resulted in a significant reduction in antioxidant enzyme activity such as the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in frontal cortex and hippocampus. Total GSH were decreased in the frontal cortex of the Cd-exposed group. Cd exposure induced an increase in malondialdehyde (MDA) concentration in the frontal cortex and hippocampus. Moreover, the same exposure increased 8-oxo-7,8-dihydro-2-desoxyguanosine (8-oxodGuo) level in rat brain. Interestingly, the combined effect of SMF (128 mT, 1 hour/day for 30 consecutive days) and CdCl (40 mg/L, per os) decreased the SOD activity and glutathione level in frontal cortex as compared with the Cd group. Moreover, the association between SMF and Cd increased MDA concentration in frontal cortex as compared with Cd-exposed rats. DNA analysis revealed that SMF exposure failed to alter 8-oxodGuo concentration in Cd-exposed rats. Our data showed that Cd exposure altered the antioxidant enzymes activity and induced oxidative DNA lesions in rat brain. The combined effect of SMF and Cd increased oxidative damage in rat brain as compared with Cd-exposed rats. PMID:20837562

  6. Brain damage following prophylactic cranial irradiation in lung cancer survivors.

    Science.gov (United States)

    Simó, Marta; Vaquero, Lucía; Ripollés, Pablo; Jové, Josep; Fuentes, Rafael; Cardenal, Felipe; Rodríguez-Fornells, Antoni; Bruna, Jordi

    2016-03-01

    Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population. PMID:26015269

  7. Propagation of damage in brain tissue: coupling the mechanics of oedema and oxygen delivery.

    Science.gov (United States)

    Lang, Georgina E; Vella, Dominic; Waters, Sarah L; Goriely, Alain

    2015-11-01

    Brain tissue swelling, or oedema, is a dangerous consequence of traumatic brain injury and stroke. In particular, a locally swollen region can cause the injury to propagate further through the brain: swelling causes mechanical compression of the vasculature in the surrounding tissue and so can cut off that tissue's oxygen supply. We use a triphasic mathematical model to investigate this propagation, and couple tissue mechanics with oxygen delivery. Starting from a fully coupled, finite elasticity, model, we show that simplifications can be made that allow us to express the volume of the propagating region of damage analytically in terms of key parameters. Our results show that performing a craniectomy, to alleviate pressure in the brain and allow the tissue to swell outwards, reduces the propagation of damage; this finding agrees with experimental observations. PMID:25822263

  8. 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.

  9. RXPERIMENTAL AND CLINICAL STUDY OF CREATINE KINASE BB ACTIVITY FOR TH E DIAGNOSIS ON BRAIN DAMAGE

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To study the differential diagnosis o n cerebral concussion and mild cerebral contusion value of the brain type creati n e kinase isoenzyme(CK-BB),and evaluate the seriousness of brain damage and prog nosis of the patients with acute head injury.Methods Chromatographic separating and fluorometric quant ifying technique was used to detect the CK-BB activity in the cerebrospinal flu id(CSF) of 117 patients with acute head injury and 12 patients with increased in tracranial pressure and 20 normal people.Results The CSF-CK-BB activity of the patients with acu te head injury was remarkably higher than that of the normal people and the CSF -CK-BB activity increased with the seriousness of brain damage.There was a clo se relationship between CSF-CK-BB activity and prognosis,and higher activity o f CSF-CK-BB indicated poor prognosis.Conclusion CSF-CK -BB activity could be used as a new index to diagnose brain damage and evaluate the seriousness of brain damage and prognosis.

  10. Simplified Radiographic Damage Index for Affected Joints in Chronic Gouty Arthritis.

    Science.gov (United States)

    Son, Chang-Nam; Kim, Tae Eun; Park, Kyungmin; Hwang, Jun Hyun; Kim, Seong-Kyu

    2016-03-01

    The aim of this study was to develop and validate a new radiographic damage scoring method (DAmagE index of GoUt; DAEGU) in chronic gout using plain radiography. Two independent observers scored foot x-rays from 15 patients with chronic gout according to the DAEGU method and the modified Sharp/van der Heijde (SvdH) method. The 10 metatarsophalangeal (MTP) and 2 interphalangeal (IP) joints of the first toes of both feet were scored to assess the degrees of erosion and joint space narrowing (JSN). The intraobserver and interobserver reliabilities were analyzed by calculating the intraclass correlation coefficient (ICC) and minimal detectable change (MDC). The correlation between the DAEGU and SvdH methods was analyzed by calculating the Spearman's rho correlation coefficients and Kappa coefficients. The DAEGU method was found to be highly reproducible (0.945-0.987 for the intraobserver and 0.993-0.996 for the interobserver ICC values). The erosion, JSN, and total scores exhibited strong positive correlations between the DAEGU and SvdH methods and also within each method (r = 0.860-0.969, P < 0.001 for all parameters). The DAEGU and SvdH methods were in very good agreement as determined by Kappa coefficient analysis [0.732 (0.387-1.000) for erosion and 1.000 (1.000-1.000) for JSN]. In conclusion, this study revealed that DAEGU method was a reliable and feasible tool in the assessment of radiographic damage in chronic gout. The DAEGU method may provide a more easy assessment of structural damage in chronic gout in the real clinical practice. PMID:26955246

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

    OpenAIRE

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

    2014-01-01

    Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal T...

  12. DNA DAMAGE INDUCED BY A OZONE IN PERIPHERAL BLOOD LYMPHOCYTES OF ELDERLY PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    OpenAIRE

    Kytikova, Oxana; Gvozdenko, Tatyana; Vitkina, Tatyana

    2015-01-01

    We have assessed DNA damage by using various therapeutic concentrations of ozone in the peripheral blood lymphocytes of elderly patients with chronic obstructive pulmonary disease (in vitro). The results of this work demonstrate that ozone induces DNA damage. It was also noticed, that there is a clear dose-dependent increase in DNA damage.

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

    OpenAIRE

    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

    2015-01-01

    Mild traumatic brain injuries are frequent events in the general population and are associated with a severe neurodegenerative disease, chronic traumatic encephalopathy (CTE). This disease is characterized by abnormal accumulation of protein aggregates, primarily tau proteins, which accumulate in brain areas responsible for mood, fear, stress, and cognition. There is no definitive clinical diagnosis of CTE at the present time, and this new work shows how a tau-sensitive brain imaging agent, [...

  14. Enhancement of rat brain metabolism of a tryptophan load by chronic ethanol administration

    OpenAIRE

    1980-01-01

    We have previously shown that chronic ethanol administration enhances brain 5-hydroxytryptamine synthesis by increasing the availability of circulating tryptophan to the brain secondary to the decreased liver tryptophan pyrrolase activity. We now find that ethanol enhances the brain metabolism of a tryptophan load by the same mechanism. The results are discussed in relation to ethanol preference and the need for further clinical work on the effects of alcoholism on tryptophan metabolism.

  15. EEG Delta Band as a Marker of Brain Damage in Aphasic Patients after Recovery of Language

    Science.gov (United States)

    Spironelli, Chiara; Angrilli, Alessandro

    2009-01-01

    In this study spectral delta percentage was used to assess both brain dysfunction/inhibition and functional linguistic impairment during different phases of word processing. To this aim, EEG delta amplitude was measured in 17 chronic non-fluent aphasic patients while engaged in three linguistic tasks: Orthographic, Phonological and Semantic.…

  16. Hyper-resting brain entropy within chronic smokers and its moderation by Sex.

    Science.gov (United States)

    Li, Zhengjun; Fang, Zhuo; Hager, Nathan; Rao, Hengyi; Wang, Ze

    2016-01-01

    Cigarette smoking is a chronic relapsing brain disorder, and remains a premier cause of morbidity and mortality. Functional neuroimaging has been used to assess differences in the mean strength of brain activity in smokers' brains, however less is known about the temporal dynamics within smokers' brains. Temporal dynamics is a key feature of a dynamic system such as the brain, and may carry information critical to understanding the brain mechanisms underlying cigarette smoking. We measured the temporal dynamics of brain activity using brain entropy (BEN) mapping and compared BEN between chronic non-deprived smokers and non-smoking controls. Because of the known sex differences in neural and behavioral smoking characteristics, comparisons were also made between males and females. Associations between BEN and smoking related clinical measures were assessed in smokers. Our data showed globally higher BEN in chronic smokers compared to controls. The escalated BEN was associated with more years of smoking in the right limbic area and frontal region. Female nonsmokers showed higher BEN than male nonsmokers in prefrontal cortex, insula, and precuneus, but the BEN sex difference in smokers was less pronounced. These findings suggest that BEN mapping may provide a useful tool for probing brain mechanisms related to smoking. PMID:27377552

  17. Hyper-resting brain entropy within chronic smokers and its moderation by Sex

    Science.gov (United States)

    Li, Zhengjun; Fang, Zhuo; Hager, Nathan; Rao, Hengyi; Wang, Ze

    2016-01-01

    Cigarette smoking is a chronic relapsing brain disorder, and remains a premier cause of morbidity and mortality. Functional neuroimaging has been used to assess differences in the mean strength of brain activity in smokers’ brains, however less is known about the temporal dynamics within smokers’ brains. Temporal dynamics is a key feature of a dynamic system such as the brain, and may carry information critical to understanding the brain mechanisms underlying cigarette smoking. We measured the temporal dynamics of brain activity using brain entropy (BEN) mapping and compared BEN between chronic non-deprived smokers and non-smoking controls. Because of the known sex differences in neural and behavioral smoking characteristics, comparisons were also made between males and females. Associations between BEN and smoking related clinical measures were assessed in smokers. Our data showed globally higher BEN in chronic smokers compared to controls. The escalated BEN was associated with more years of smoking in the right limbic area and frontal region. Female nonsmokers showed higher BEN than male nonsmokers in prefrontal cortex, insula, and precuneus, but the BEN sex difference in smokers was less pronounced. These findings suggest that BEN mapping may provide a useful tool for probing brain mechanisms related to smoking. PMID:27377552

  18. Melanocortin MC4 receptor agonists alleviate brain damage in abdominal compartment syndrome in the rat.

    Science.gov (United States)

    Liu, Dong; Zhang, Hong-Guang; Zhao, Zi-Ai; Chang, Ming-Tao; Li, Yang; Yu, Jian; Zhang, Ye; Zhang, Lian-Yang

    2015-02-01

    Intra-abdominal hypertension (IAH) is accompanied by high morbidity and mortality in surgical departments and ICUs. However, its specific pathophysiology is unclear. IAH not only leads to intra-abdominal tissue damage but also causes dysfunction in distal organs, such as the brain. In this study, we explore the protective effects of melanocortin 4 receptor agonists in IAH-induced brain injury. The IAH rat models were induced by hemorrhagic shock/resuscitation (with the mean arterial pressure (MAP) maintained at 30 mm Hg for 90 min followed by the reinfusion of the withdrawn blood with lactated Ringer's solution). Then, air was injected into the peritoneal cavity of the rats to maintain an intra-abdominal pressure of 20 mm Hg for 4 h. The effects of the melanocortin 4 receptor agonist RO27-3225 in alleviating the rats' IAH brain injuries were observed, which indicated that RO27-3225 could reduce brain edema, the expressions of the IL-1β and TNF-α inflammatory cytokines, the blood-brain barrier's permeability and the aquaporin4 (AQP4) and matrix metalloproteinase 9 (MMP9) levels. Moreover, the nicotinic acetylcholine receptor antagonist chlorisondamine and the selective melanocortin 4 receptor antagonist HS024 can negate the protective effects of the RO27-3225. The MC4R agonist can effectively reduce the intracerebral proinflammatory cytokine gene expression and alleviate the brain injury caused by blood-brain barrier damage following IAH. PMID:25616531

  19. Pathophysiology of repetitive head injury in sports. Prevention against catastrophic brain damage

    International Nuclear Information System (INIS)

    The most common head injury in sports is concussion and experiencing multiple concussions in a short period of time sometimes can cause severe brain damage. In this paper, we investigate severe brain damage due to repeated head injury in sports and discuss the pathophysiology of repeated sports injury. The majority of these severe cases are usually male adolescents or young adults that suffer a second head injury before they have recovered from the first head injury. All cases that could be confirmed by brain CT scan after the second injury revealed brain swelling associated with a thin subdural hematoma. We suggested that the existence of subdural hematoma is one of the major causes of brain swelling after repeated head injury in sports. Since repeated concussions occurring within a short period may have a risk for severe brain damage, the diagnosis for initial cerebral concussion should be done appropriately. To prevent catastrophic brain damage, the player who suffered from concussion should not engage in any sports before recovery. The american Academy of Neurology and Colorado Medical Society set a guideline to return to play after cerebral concussion. An international conference on concussion in sports was held at Prague in 2004. The summary and agreement of this meeting was published and the Sports Concussion Assessment Tool (SCAT) was introduced to treat sports-related concussion. In addition, a number of computerized cognitive assessment tests and test batteries have been developed to allow athletes to return to play. It is important that coaches, as well as players and trainers, understand the medical issues involved in concussion. (author)

  20. Radiation-related damage to the developing human brain

    International Nuclear Information System (INIS)

    The authors summarize the significant dose-related effects on brain development which have emerged largely within the last six years of study of prenatally exposed A-bomb survivors. The results are described primarily in terms of the DS86 estimates and differences between these and the older T65DR dose estimates are discussed. The severe mental retardation sample was based on 1598 individuals taken from the PE-86 sample, and the intelligence test scores considered from the same sample involved 1673 children. The authors also discuss some of the recent neurobiological developments that appear relevant to an understanding of the biological bases of dose-related events observed, and suggest future research that may contribute either to further delineation of exposure consequences or to the explanation of the cellular and molecular origins of observed effects. (UK)

  1. 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 possibil

  2. 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…

  3. Repair of potentially lethal radiation damage in human squamous carcinoma cells after chronic hypoxia

    International Nuclear Information System (INIS)

    The purpose of this study was to examine the repair of radiation-induced potentially lethal damage in A431 and CaSki cells after chronic hypoxia. Cells in exponential phase are subjected to hypoxia (4 h of hypoxia. The repair returned to aerobic control level by 3 h of reoxygenation. PLDR of A431 cells reached maximum at about 9 h after irradiation in cells reoxygenated for 10 min after hypoxia. However, the repair is maximum at 6 h in cells reoxygenated for 3 h after hypoxia and in aerobic cells not previously exposed to hypoxia. Reoxygenation after chronic hypoxia did not affect the PLDR capacity and repair kinetics of CaSki cells. The results suggest that radiosensitization by reoxygenation after chronic hypoxia is not related to inhibition of PLDR. 14 refs., 3 figs

  4. A protective effect of musical expertise on cognitive outcome following brain damage?

    Science.gov (United States)

    Omigie, Diana; Samson, Severine

    2014-12-01

    The current review examines the possibility that training-related changes that take place in the brains of musicians may have a beneficial effect on their cognitive outcome and recovery following neurological damage. First, we propose three different mechanisms by which training-related brain changes might result in relatively preserved function in musicians as compared to non-musicians with cerebral lesions. Next, we review the neuropsychological literature examining musical ability in professional musicians following brain damage, specifically of vascular, tumoral and epileptic aetiology. Finally, given that assessment of musician patients can greatly inform our understanding of the influence of premorbid experience on postmorbid recovery, we suggest some basic guidelines for the future evaluation of relevant patients. PMID:25380766

  5. Oxidative stress, progressive damage in the substantia nigra and plasma dopamine oxidation, in rats chronically exposed to ozone.

    Science.gov (United States)

    Santiago-López, D; Bautista-Martínez, J A; Reyes-Hernandez, C I; Aguilar-Martínez, M; Rivas-Arancibia, S

    2010-09-01

    The purpose of our work was to determine the effects of oxidative stress on the neurodegeneration process in the substantia nigra, and to evaluate dopamine-oxidation metabolites in the plasma using a cyclic voltammetry (CV) technique. We have also studied the correlation between the increases in oxidized dopamine-species levels with the severity of lipid-peroxidation in the plasma. Sixty-four male Wistar rats were divided into four experimental groups and received air (Group I, control) or ozone (0.25 ppm) daily by inhalation for 4h for 15 (Group II), 30 (Group III), and 60 (Group IV) days. The brains were processed for immunohistochemical location of dopamine and p53 in the substantia nigra. Plasma collected from these animals was assayed for oxidized dopamine products using CV and lipid-peroxidation levels were measured. Our results indicate that chronic exposure to low O(3) doses causes that the number of dopaminergic neurons decreased, and p53-immunoreactive cells increases until 30 days; which was a function of the time of exposure to ozone. Oxidative stress produces a significant increase in the levels of the dopamine quinones (DAQs) that correlated well (r=0.962) with lipid peroxides in the plasma during the study period. These results suggest that DAQ could be a reliable, peripheral oxidative indicator of nigral dopaminergic damage in the brain. PMID:20541596

  6. Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress.

    Science.gov (United States)

    Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J; Robison, A J

    2015-12-01

    Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry", consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression--the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus--in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 h following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders. PMID:26164345

  7. Chronic P-glycoprotein inhibition increases the brain concentration of escitalopram: potential implications for treating depression.

    Science.gov (United States)

    O'Brien, Fionn E; Moloney, Gerard M; Scott, Karen A; O'Connor, Richard M; Clarke, Gerard; Dinan, Timothy G; Griffin, Brendan T; Cryan, John F

    2015-12-01

    Recent preclinical studies have revealed a functionally important role for the drug efflux pump P-glycoprotein (P-gp) at the blood-brain barrier in limiting brain levels and thus antidepressant-like activity of certain antidepressant drugs. Specifically, acute administration of P-gp inhibitors, such as verapamil and cyclosporin A (CsA), has been shown to augment brain concentrations and functional activity of the antidepressant escitalopram in rodents. However, depression is a chronic disorder and current treatments require prolonged administration to elicit their full therapeutic effect. Thus, it is important to investigate whether acute findings in relation to P-gp inhibition translate to chronic paradigms. To this end, the present study investigates whether chronic treatment with the P-gp inhibitor verapamil and the antidepressant escitalopram results in enhanced brain distribution and antidepressant-like effects of escitalopram. Verapamil (10 mg·kg(-1) i.p.) and escitalopram (0.1 mg·kg(-1) i.p.) were administered once daily for 22 days. On the final day of treatment, brain regions and plasma were collected for analysis of cortical and plasma escitalopram concentrations, and to determine the hippocampal expression of genes previously reported to be altered by chronic antidepressant treatment. Verapamil treatment resulted in a greater than twofold increase in brain levels of escitalopram, without altering plasma levels. Neither gene expression analysis nor behavioral testing revealed an augmentation of responses to escitalopram treatment due to verapamil administration. Taken together, these data demonstrate for the first time that P-gp inhibition can yield elevated brain concentrations of an antidepressant after chronic treatment. The functional relevance of these increased brain levels requires further elaboration. PMID:27022464

  8. Effects of chronic ingestion of tritiated water on prenatal brain development

    International Nuclear Information System (INIS)

    In view of the anticipated increased use of atomic energy in industry, the possible long-term effects of chronic radiation exposure were studied in five generations of rats. Female rats (F0) were given tritiated drinking water (3HOH;3μCi/ml) from adolescence (60 days) until and throughout pregnancy. A separate study showed that the maximum radioactivity in the urine is reached in 30 days, and in the blood in 42 days. In the newborns, the highest specific activity was in the nucleic acid fraction, but total radioactivity was mainly due to the water (body fluids) compartment. No signs of radiation illness or increase in cataract formation in the mothers were observed. The food and water intake and body weight changes before pregnancy were normal. The course and the outcome of pregnancy were also normal. However, 60% of the newborns (F1) exhibited hematomas, edemas, and subdural hemorrhages, which disappeared at 30 days of age. Bollod analysis of the F1 offspring at various ages did not reveal significant differences from the controls, except for a significant decrease in alkaline phosphatase. Newborn body weight and cerebral weight were also normal. On the other hand, cerebral DNA, protein, and protein/DNA were significantly lower. 3HOH administration was then continued throughout weaning, adolescence, and next pregnancies, to give F3, F4, and F5 generations. The newborns in F3--F5 showed no more cerebral damage than those in F1, i.e., there was no cumulative effect of radiation; presumably the maximum radioactivity level was already attained in F1. As the generations progressed, the radiation damage to the developing brain became less pronounced; a possibility of inducible DNA repair has been discussed

  9. Effects of chronic ingestion of tritiated water on prenatal brain development. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Zamenhof, S.; van Marthens, E.

    1979-01-01

    In view of the anticipated increased use of atomic energy in industry, the possible long-term effects of chronic radiation exposure were studied in five generations of rats. Female rats (F/sub 0/) were given tritiated drinking water (/sup 3/HOH;3..mu..Ci/ml) from adolescence (60 days) until and throughout pregnancy. A separate study showed that the maximum radioactivity in the urine is reached in 30 days, and in the blood in 42 days. In the newborns, the highest specific activity was in the nucleic acid fraction, but total radioactivity was mainly due to the water (body fluids) compartment. No signs of radiation illness or increase in cataract formation in the mothers were observed. The food and water intake and body weight changes before pregnancy were normal. The course and the outcome of pregnancy were also normal. However, 60% of the newborns (F/sub 1/) exhibited hematomas, edemas, and subdural hemorrhages, which disappeared at 30 days of age. Bollod analysis of the F/sub 1/ offspring at various ages did not reveal significant differences from the controls, except for a significant decrease in alkaline phosphatase. Newborn body weight and cerebral weight were also normal. On the other hand, cerebral DNA, protein, and protein/DNA were significantly lower. /sup 3/HOH administration was then continued throughout weaning, adolescence, and next pregnancies, to give F/sub 3/, F/sub 4/, and F/sub 5/ generations. The newborns in F/sub 3/--F/sub 5/ showed no more cerebral damage than those in F/sub 1/, i.e., there was no cumulative effect of radiation; presumably the maximum radioactivity level was already attained in F/sub 1/. As the generations progressed, the radiation damage to the developing brain became less pronounced; a possibility of inducible DNA repair has been discussed.

  10. A Chronic Generalized Bi-directional Brain-Machine Interface

    OpenAIRE

    Rouse, Adam; Stanslaski, Scott; Cong, Peng; Jensen, Randy; Afshar, Pedram; Ullestad, Dave; Moran, Dan; Denison, Tim

    2011-01-01

    A bi-directional neural interface (NI) system was designed and built by incorporating a novel neural recording and processing subsystem into a commercially approved neural stimulator. The NI system prototype leverages the system infrastructure from a market-approved neurostimulator to ensure reliable operation in a chronic implantation environment. In addition to providing approved therapy capabilities, the device adds key elements to facilitate chronic clinical research, such as four channel...

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

    International Nuclear Information System (INIS)

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

  12. Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2016-06-01

    Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. PMID:27345710

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

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan Xia; Yi-xin Xia

    2011-01-01

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

  14. Exendin-4 attenuates brain death-induced liver damage in the rat.

    Science.gov (United States)

    Carlessi, Rodrigo; Lemos, Natalia E; Dias, Ana L; Brondani, Leticia A; Oliveira, Jarbas R; Bauer, Andrea C; Leitão, Cristiane B; Crispim, Daisy

    2015-11-01

    The majority of liver grafts destined for transplantation originate from brain dead donors. However, significantly better posttransplantation outcomes are achieved when organs from living donors are used, suggesting that brain death (BD) causes irreversible damage to the liver tissue. Recently, glucagon-like peptide-1 (GLP1) analogues were shown to possess interesting hepatic protection effects in different liver disease models. We hypothesized that donor treatment with the GLP1 analogue exendin-4 (Ex-4) could alleviate BD-induced liver damage. A rat model of BD was employed in order to estimate BD-induced liver damage and Ex-4's potential protective effects. Liver damage was assessed by biochemical determination of circulating hepatic markers. Apoptosis in the hepatic tissue was assessed by immunoblot and immunohistochemistry using an antibody that only recognizes the active form of caspase-3. Gene expression changes in inflammation and stress response genes were monitored by quantitative real-time polymerase chain reaction. Here, we show that Ex-4 administration to the brain dead liver donors significantly reduces levels of circulating aspartate aminotransferase and lactate dehydrogenase. This was accompanied by a remarkable reduction in hepatocyte apoptosis. In this model, BD caused up-regulation of tumor necrosis factor and stress-related genes, confirming previous findings in clinical and animal studies. In conclusion, treatment of brain dead rats with Ex-4 reduced BD-induced liver damage. Further investigation is needed to determine the molecular basis of the observed liver protection. After testing in a randomized clinical trial, the inclusion of GLP1 analogues in organ donor management might help to improve organ quality, maximize organ donation, and possibly increase liver transplantation success rates. PMID:26334443

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

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Andersen, Stine Hasselholt; 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...

  16. Berberine protects against neuronal damage via suppression of glia-mediated inflammation in traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Chien-Cheng Chen

    Full Text Available Traumatic brain injury (TBI triggers a series of neuroinflammatory processes that contribute to evolution of neuronal injury. The present study investigated the neuroprotective effects and anti-inflammatory actions of berberine, an isoquinoline alkaloid, in both in vitro and in vivo TBI models. Mice subjected to controlled cortical impact injury were injected with berberine (10 mg·kg(-1 or vehicle 10 min after injury. In addition to behavioral studies and histology analysis, blood-brain barrier (BBB permeability and brain water content were determined. Expression of PI3K/Akt and Erk signaling and inflammatory mediators were also analyzed. The protective effect of berberine was also investigated in cultured neurons either subjected to stretch injury or exposed to conditioned media with activated microglia. Berberine significantly attenuated functional deficits and brain damage associated with TBI up to day 28 post-injury. Berberine also reduced neuronal death, apoptosis, BBB permeability, and brain edema at day 1 post-injury. These changes coincided with a marked reduction in leukocyte infiltration, microglial activation, matrix metalloproteinase-9 activity, and expression of inflammatory mediators. Berberine had no effect on Akt or Erk 1/2 phosphorylation. In mixed glial cultures, berberine reduced TLR4/MyD88/NF-κB signaling. Berberine also attenuated neuronal death induced by microglial conditioned media; however, it did not directly protect cultured neurons subjected to stretch injury. Moreover, administration of berberine at 3 h post-injury also reduced TBI-induced neuronal damage, apoptosis and inflammation in vivo. Berberine reduces TBI-induced brain damage by limiting the production of inflammatory mediators by glial cells, rather than by a direct neuroprotective effect.

  17. 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.

  18. Changes of brain microstructure in patients with painful chronic pancreatitis assessed by diffusion tensor imaging

    DEFF Research Database (Denmark)

    Frøkjær, Jens Brøndum; Olesen, Søren Schou; Gram, Mikkel;

    Objective In patients with painful chronic pancreatitis (CP) there is increasing evidence of abnormal pain processing in the central nervous system. Using magnetic resonance (MR) diffusion tensor imaging, brain microstructure in areas involved in processing of visceral pain was characterised and...... correlated to patients' clinical pain scores. Conclusion The findings suggest that microstructural changes of the brain accompany pain in CP. The changes are likely to be a consequence of ongoing pain and structural reorganisation of the neuromatrix as also seen in other diseases characterised by chronic...

  19. Altered brain microstructure assessed by diffusion tensor imaging in patients with chronic pancreatitis

    DEFF Research Database (Denmark)

    Frøkjær, Jens Brøndum; Olesen, Søren Schou; Gram, Mikkel;

    2011-01-01

    Objective In patients with painful chronic pancreatitis (CP) there is increasing evidence of abnormal pain processing in the central nervous system. Using magnetic resonance (MR) diffusion tensor imaging, brain microstructure in areas involved in processing of visceral pain was characterised and...... correlated to patients' clinical pain scores. Conclusion The findings suggest that microstructural changes of the brain accompany pain in CP. The changes are likely to be a consequence of ongoing pain and structural reorganisation of the neuromatrix as also seen in other diseases characterised by chronic...

  20. Altered brain microstructure assessed by diffusion tensor imaging in patients with chronic pancreatitis

    DEFF Research Database (Denmark)

    Frøkjær, Jens Brøndum; Olesen, Søren Schou; Gram, Mikkel;

    Objective In patients with painful chronic pancreatitis (CP) there is increasing evidence of abnormal pain processing in the central nervous system. Using magnetic resonance (MR) diffusion tensor imaging, brain microstructure in areas involved in processing of visceral pain was characterised and...... correlated to patients' clinical pain scores. Conclusion The findings suggest that microstructural changes of the brain accompany pain in CP. The changes are likely to be a consequence of ongoing pain and structural reorganisation of the neuromatrix as also seen in other diseases characterised by chronic...

  1. An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment

    International Nuclear Information System (INIS)

    Quantitative autoradiographic procedures were used to examine the effects of chronic nicotine infusion on the number of central nervous system nicotinic cholinergic receptors. Female DBA mice were implanted with jugular cannulas and infused with saline or various doses of nicotine (0.25, 0.5, 1.0 or 2.0 mg/kg/hr) for 10 days. The animals were then sacrificed and the brains were removed and frozen in isopentane. Cryostat sections were collected and prepared for autoradiographic procedures as previously described. Nicotinic cholinergic receptors were labeled with L-[3H]nicotine or alpha-[125I]bungarotoxin; [3H]quinuclidinyl benzilate was used to measure muscarinic cholinergic receptor binding. Chronic nicotine infusion increased the number of sites labeled by [3H]nicotine in most brain areas. However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions. After the highest treatment dose, binding was increased in 67 of 86 regions measured. Septal and thalamic regions were most resistant to change. Nicotinic binding measured by alpha-[125I]bungarotoxin also increased after chronic treatment, but in a less robust fashion. At the highest treatment dose, only 26 of 80 regions were significantly changes. Muscarinic binding was not altered after chronic nicotine treatment. These data suggest that brain regions are not equivalent in the mechanisms that regulate alterations in nicotinic cholinergic receptor binding after chronic nicotine treatment

  2. Nerve cell damage in mammalian brain after exposure to microwaves from GSM mobile phones.

    OpenAIRE

    Salford, Leif; Brun, Arne; Eberhardt, Jacob; Malmgren, Lars; Persson, Bertil R

    2003-01-01

    The possible risks of radio-frequency electromagnetic fields for the human body is a growing concern for our society. We have previously shown that weak pulsed microwaves give rise to a significant leakage of albumin through the blood-brain barrier. In this study we investigated whether a pathologic leakage across the blood-brain barrier might be combined with damage to the neurons. Three groups each of eight rats were exposed for 2 hr to Global System for Mobile Communications (GSM) mobile p...

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

    DEFF Research Database (Denmark)

    Undén, Johan; Strandberg, Karin; Malm, Jan;

    2009-01-01

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

  4. Multiple faces of pain: effects of chronic pain on the brain regulation of facial expression.

    Science.gov (United States)

    Vachon-Presseau, Etienne; Roy, Mathieu; Woo, Choong-Wan; Kunz, Miriam; Martel, Marc-Olivier; Sullivan, Michael J; Jackson, Philip L; Wager, Tor D; Rainville, Pierre

    2016-08-01

    Pain behaviors are shaped by social demands and learning processes, and chronic pain has been previously suggested to affect their meaning. In this study, we combined functional magnetic resonance imaging with in-scanner video recording during thermal pain stimulations and use multilevel mediation analyses to study the brain mediators of pain facial expressions and the perception of pain intensity (self-reports) in healthy individuals and patients with chronic back pain (CBP). Behavioral data showed that the relation between pain expression and pain report was disrupted in CBP. In both patients with CBP and healthy controls, brain activity varying on a trial-by-trial basis with pain facial expressions was mainly located in the primary motor cortex and completely dissociated from the pattern of brain activity varying with pain intensity ratings. Stronger activity was observed in CBP specifically during pain facial expressions in several nonmotor brain regions such as the medial prefrontal cortex, the precuneus, and the medial temporal lobe. In sharp contrast, no moderating effect of chronic pain was observed on brain activity associated with pain intensity ratings. Our results demonstrate that pain facial expressions and pain intensity ratings reflect different aspects of pain processing and support psychosocial models of pain suggesting that distinctive mechanisms are involved in the regulation of pain behaviors in chronic pain. PMID:27411160

  5. Clinical Utility of '99mTc-HMPAO Brain SPECT Findings in Chronic Head Injury

    International Nuclear Information System (INIS)

    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 99mTc-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 99mTc-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 99mTc-HMPAO Brain SPECT in the patients who had suffered from post-traumatic sequelae, which changes were undetectable on Brain CT or MRI.

  6. A reliable method for intracranial electrode implantation and chronic electrical stimulation in the mouse brain

    OpenAIRE

    Jeffrey, Melanie; Lang, Min; Gane, Jonathan; Wu, Chiping; Burnham, W McIntyre; Zhang, Liang

    2013-01-01

    Background Electrical stimulation of brain structures has been widely used in rodent models for kindling or modeling deep brain stimulation used clinically. This requires surgical implantation of intracranial electrodes and subsequent chronic stimulation in individual animals for several weeks. Anchoring screws and dental acrylic have long been used to secure implanted intracranial electrodes in rats. However, such an approach is limited when carried out in mouse models as the thin mouse skul...

  7. Fatal cerebritis and brain abscesses following a nontraumatic subdural hematoma in a chronic hemodialyzed patient.

    Science.gov (United States)

    Mesquita, Maria; Damry, Nasroolla; Gazagnes, Marie D

    2008-10-01

    Staphylococcus aureus is the leading cause of bacteremia in hemodialysis-dependent patients that can lead to metastatic abscesses with poor outcome. We report a case of a 65-year-old chronic hemodialyzed male patient who developed cerebritis and brain abscesses complicating a spontaneous subdural hematoma, following Staphylococcus aureus bacteremia related to infected arteriovenous fistula. In spite of adequate antibiotherapy and several surgical brain drainages, our patient did not survive. Prevention of S. aureus is highly important in hemodialysis patients. PMID:19090864

  8. Brain grafts can restore irradiation-damaged neuronal connections in newborn rats

    International Nuclear Information System (INIS)

    In the present study, rat hippocampal neurones were damaged by neonatal X-ray irradiation and replaced by transplantation of normal, developing neurones of the same type. The grafted neurones (dentate granule cells) are not cholinergic or monoaminergic, but when appropriately located in the host hippocampal region they established specific and highly ordered afferent and efferent connections with the damaged host brain. Moreover, simultaneous demonstration of afferent and efferent transplant pathways showed that serial host-transplant-host connections had formed, restoring the normal neuronal circuitry initially disrupted by the irradiation. (author)

  9. 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. PMID:27590975

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

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

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

  11. Neuropsychology of colour vision: Studies in patients with acquired brain damage, healthy participants, and cases

    OpenAIRE

    Nijboer, T. C. W.

    2007-01-01

    In this thesis, we studied the neuropsychology of low-level sensory and higher-order visual perception in healthy participants, patients with acquired deficits in visual perception, and a man with a selective developmental deficit in colour processing. In neuropsychological literature, sensory disorders as well as higher-order recognition deficits have been reported after acquired brain damage. There is still considerable debate about the link between sensory disorders and higher-order, recog...

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

    OpenAIRE

    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 carci...

  13. Piezosurgery prevents brain tissue damage: an experimental study on a new rat model

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, G.; Foltán, R.; Burian, M.; Horká, E.; Adámek, S.; Hejčl, Aleš; Hanzelka, T.; Šedý, Jiří

    2011-01-01

    Roč. 40, č. 8 (2011), s. 840-844. ISSN 0901-5027 R&D Projects: GA MŠk(CZ) LC554; GA ČR GAP304/10/0320 Grant ostatní: GA MŠk(CZ) 1M0538 Institutional research plan: CEZ:AV0Z50390703 Keywords : piezosurgery * brain * tissue damage Subject RIV: FJ - Surgery incl. Transplants; FH - Neurology (UEM-P) Impact factor: 1.506, year: 2011

  14. Adults with PKU and brain damage : Composition and management of a protein restricted diet

    OpenAIRE

    2007-01-01

    Summary Phenylketonuria (PKU) is an inborn error of metabolism, due to a defective liver enzyme the conversion of the amino acid phenylalanine (phe) to tyrosine is not functioning. PKU was first described in 1934 by the Norwegian doctor and scientist Asbjørn Følling. Without treatment persons with PKU suffer permanent neurological damage and mental retardation. Today newborn screening programmes result in early diagnosis. Dietary treatment is started shortly after birth to prevent brain da...

  15. Frontal lobe syndrome reassessed: comparison of patients with lateral or medial frontal brain damage

    OpenAIRE

    Paradiso, S; Chemerinski, E; Yazici, K.; Tartaro, A.; Robinson, R

    1999-01-01

    Examination of mood and behaviour changes after frontal damage may contribute to understanding the functional role of distinct prefrontal areas in depression and anxiety. Depression and anxiety disorders, symptoms, and behaviour were compared in eight patients with single lateral and eight patients with single medial frontal lesions matched for age, sex, race, education, socioeconomic status, side, and aetiology of lesion 2 weeks and 3 months after brain injury. DSM IV major de...

  16. Emotional and non-emotional facial behaviour in patients with unilateral brain damage.

    OpenAIRE

    Borod, J C; Koff, E.; Lorch, M P; Nicholas, M.; Welkowitz, J

    1988-01-01

    Aspects of emotional facial expression (responsivity, appropriateness, intensity) were examined in brain-damaged adults with right or left hemisphere cerebrovascular lesions and in normal controls. Subjects were videotaped during experimental procedures designed to elicit emotional facial expression and non-emotional facial movement (paralysis, mobility, praxis). On tasks of emotional facial expression, patients with right hemisphere pathology were less responsive and less appropriate than pa...

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

    Institute of Scientific and Technical Information of China (English)

    陈立华; 于嘉; 刘丽旭; 曹美鸿

    2002-01-01

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

  18. Recurrent Moderate Hypoglycemia Ameliorates Brain Damage and Cognitive Dysfunction Induced by Severe Hypoglycemia

    OpenAIRE

    Puente, Erwin C.; Silverstein, Julie; Bree, Adam J.; Musikantow, Daniel R.; Wozniak, David F.; Maloney, Susan; Daphna-Iken, Dorit; Fisher, Simon J.

    2010-01-01

    OBJECTIVE Although intensive glycemic control achieved with insulin therapy increases the incidence of both moderate and severe hypoglycemia, clinical reports of cognitive impairment due to severe hypoglycemia have been highly variable. It was hypothesized that recurrent moderate hypoglycemia preconditions the brain and protects against damage caused by severe hypoglycemia. RESEARCH DESIGN AND METHODS Nine-week-old male Sprague-Dawley rats were subjected to either 3 consecutive days of recurr...

  19. 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.

  20. 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.

  1. Oxidative mitochondrial DNA damage in peripheral blood mononuclear cells is associated with reduced volumes of hippocampus and subcortical gray matter in chronically HIV-infected patients

    Science.gov (United States)

    Kallianpur, Kalpana J.; Gerschenson, Mariana; Mitchell, Brooks I.; LiButti, Daniel E.; Umaki, Tracie M.; Ndhlovu, Lishomwa C.; Nakamoto, Beau K.; Chow, Dominic C.; Shikuma, Cecilia M.

    2016-01-01

    Cross-sectional relationships were examined between regional brain volumes and mitochondrial DNA (mtDNA) 8-hydroxy-2-deoxyguanosine (8-oxo-dG) in peripheral blood mononuclear cells (PBMCs) of 47 HIV patients [mean age 51 years; 81% with HIV RNA ≤50 copies/mL] on combination antiretroviral therapy. The gene-specific DNA damage and repair assay measured mtDNA 8-oxo-dG break frequency. Magnetic resonance imaging was performed at 3 T. Higher mtDNA 8-oxo-dG was associated with lateral ventricular enlargement and with decreased volumes of hippocampus, pallidum, and total subcortical gray matter, suggesting the involvement of systemic mitochondrial-specific oxidative stress in chronic HIV-related structural brain changes and cognitive difficulties. Clarification of the mechanism may provide potential therapeutic targets. PMID:26923169

  2. Alternaria infectoria brain abscess in a child with chronic granulomatous disease

    NARCIS (Netherlands)

    Hipolito, E.; Faria, E.; Alves, A.; de Hoog, G.S.; Anjos, J.; Goncalves, T.; Morais, P.V.; Estevao, H.

    2009-01-01

    In the present report, we describe the first case of a phaeohyphomycotic brain abscess in a 5-year-old boy with chronic granulomatous disease (CGD) admitted to hospital with seizures. A computed tomography (CT) scan revealed a cerebral abscess and the microbiology study showed a dark, melanin-pigmen

  3. 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 crit...

  4. Changes of brain microstructure in patients with painful chronic pancreatitis assessed by diffusion tensor imaging

    DEFF Research Database (Denmark)

    Frøkjær, Jens Brøndum; Olesen, Søren Schou; Gram, Mikkel; Yavarian, Yousef; Drewes, Asbjørn Mohr

    Objective In patients with painful chronic pancreatitis (CP) there is increasing evidence of abnormal pain processing in the central nervous system. Using magnetic resonance (MR) diffusion tensor imaging, brain microstructure in areas involved in processing of visceral pain was characterised and...

  5. Chronic Pain: Where the Body Meets the Brain

    OpenAIRE

    Crofford, Leslie J

    2015-01-01

    Chronic musculoskeletal pain is one of the most intractable clinical problems faced by clinicians and can be devastating for patients. Central pain amplification is perceived pain that cannot be fully explained on the basis of somatic or neuropathic processes and is due to physiologic alterations in pain transmission or descending pain modulatory pathways. In any individual, central pain amplification may complicate nociceptive or neuropathic pain. Furthermore, patients with somatic symptom d...

  6. Windows to the Brain (WttB): Transparent Nanocrystalline Yttria Stabilized Zirconia Cranial Implants for Non-Invasive, Chronic Access to the Brain for Optical Diagnostics and Therapeutics

    OpenAIRE

    Damestani, Yasaman

    2015-01-01

    Windows to the Brain (WttB) platform can improve patient care by enabling the delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically-recurring basis without the need for repeated craniotomies. WttB holds the transformative potential for facilitating diagnosis and treatment of a wide variety of brain pathologies and neurological disorders including cerebral edema, traumatic brain injury, stroke, glioma, and neurodegenerative diseases.We have ...

  7. Chronic Kidney Disease Induced Intestinal Mucosal Barrier Damage Associated with Intestinal Oxidative Stress Injury

    Science.gov (United States)

    Yu, Chao; Wang, Qiang; Zhou, Chunyu; Kang, Xin; Zhao, Shuang; Liu, Shuai; Fu, Huijun; Yu, Zhen; Peng, Ai

    2016-01-01

    Background. To investigate whether intestinal mucosal barrier was damaged or not in chronic kidney disease progression and the status of oxidative stress. Methods. Rats were randomized into two groups: a control group and a uremia group. The uremia rat model was induced by 5/6 kidney resection. In postoperative weeks (POW) 4, 6, 8, and 10, eight rats were randomly selected from each group to prepare samples for assessing systemic inflammation, intestinal mucosal barrier changes, and the status of intestinal oxidative stress. Results. The uremia group presented an increase trend over time in the serum tumor necrosis factor-alpha, interleukin-6 (IL-6) and IL-10, serum D-lactate and diamine oxidase, and intestinal permeability, and these biomarkers were significantly higher than those in control group in POW 8 and/or 10. Chiu's scores in uremia group were also increased over time, especially in POW 8 and 10. Furthermore, the intestinal malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were significantly higher in uremia group when compared with those in control group in POW 8 and/or 10. Conclusions. The advanced chronic kidney disease could induce intestinal mucosal barrier damage and further lead to systemic inflammation. The underlying mechanism may be associated with the intestinal oxidative stress injury. PMID:27493661

  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. 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

  10. SPECT perfusion lung scintigraphy in children with chronic pulmonary damage: Preliminary results of a prospective study

    International Nuclear Information System (INIS)

    The aim of this study was to describe SPECT perfusion lung scintigraphy findings in symptomatic children with chronic pulmonary damage. Material and Method: We studied 111 children (average age:3.9 yr, range:1 month- 15 yr, 61.3% boys) with chronic pulmonary pathology. The most common clinical diagnosis reported in this population were recurrent bronchopneumonia (45.9%), unknown origin chronic pulmonary damage (36.9%), chronic obstructed bronchitis (27.9%), adenovirus bronchopneumonia sequelae (27.9%) and bronchopulmonary dysplasia (14.4%). The SPECT lung perfusion scintigraphy (LS) was performed in a SMV DST XLi two headed gammacamera, 64x64 matrix, 32 steps of 15 sec each, using a HRLE collimator, after i.v. injection of a age-adjusted dose of Tc99m-MAA. The images were reconstructed using a iterative-post filter method and displayed in tomographic slices and 3D form. We took also planar images in frontal and posterior projections to assess the differential perfusion. The studies were separated according to scintigraphy findings and gender. Results: Ninety eight (88.3%) of realized LS were abnormal (59.2% boys). Fifty three (54.1%) of abnormal scans showed bilateral alterations, being this finding significantly (p:0.034) more frequent in boys (63.8% bilateral lesions) than in girls (40.0% bilateral lesions). When unilateral altered scans were analyzed, the right lung was more frequently affected than left lung (73.5% vs 26.5%) (p:0.002). Of whole abnormal group, 19.4% had diffuse perfusion alterations, 46.9% showed focal alterations and 33.7% had a mixed diffuse-focal pattern. In focal alterations group, the majority presented a segmental distribution (83.7%), being the more frequent localizations the right inferior lobe (39.8%), right upper lobe (34.7%) and left inferior lobe (34.7%). Sixteen patients (16,3%) had focal non-segmental alterations, being situated mainly in upper middle of right lung (47.6%). The range of differential perfusion quantification in

  11. Diffusion tensor imaging study of white matter damage in chronic meningitis.

    Directory of Open Access Journals (Sweden)

    Wei-Che Lin

    Full Text Available Tuberculous meningitis (TBM and cryptococcal meningitis (CM are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based diffusion tensor imaging (DTI magnetic resonance imaging. All of the participants underwent complete medical and neurologic examinations, and neuro-psychological testing. Differences in DTI indices correlated with the presence of neuro-psychological rating scores and cerebrospinal fluid (CSF analysis during the initial hospitalization. Patients with CM had more severe cognitive deficits than healthy subjects, especially in TBM. There were changes in WM integrity in several limbic regions, including the para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus pallidus. A decline in WM integrity close to the globus pallidus and anterior cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI parameters directly correlated with worse cognitive performance on follow-up. These correlations suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities. Abnormalities in the limbic system and globus pallidus, with their close relationship to the CSF space, may be specific biomarkers for disease evaluation.

  12. Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury.

    Science.gov (United States)

    Hou, Zonggang; Luo, Wei; Sun, Xuejun; Hao, Shuyu; Zhang, Ying; Xu, Feifan; Wang, Zhongcheng; Liu, Baiyun

    2012-09-01

    Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates events that result in protracted neuronal dysfunction and remodeling. Importantly, antioxidants can protect the brain against oxidative damage and modulate the capacity of the brain to cope with synaptic dysfunction and cognitive impairment. However, no studies have investigated the effects of hydrogen-rich saline on cognitive deficits after TBI. In the present study, rats with fluid percussion injury (FPI) were used to investigate the protective effects of hydrogen-rich saline. The results showed that hydrogen-rich saline reduced the level of malondialdehyde (MDA) and elevated the level of silent information regulator 2 (Sir2). In addition, treatment with hydrogen-rich saline, which elevated the levels of molecules associated with brain-derived neurotropic factor (BDNF)-mediated synaptic plasticity, improved cognitive performance in the Morris water maze after mild TBI. These results suggest that hydrogen-rich saline can protect the brain against the deleterious effects of mild TBI on synaptic plasticity and cognition and that hydrogen-rich saline could be an effective therapeutic strategy for patients with cognitive deficits after TBI. PMID:22742936

  13. Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase

    International Nuclear Information System (INIS)

    Single doses of organophosphorus compounds (OP) which covalently inhibit neuropathy target esterase (NTE) can induce lower-limb paralysis and distal damage in long nerve axons. Clinical signs of neuropathy are evident 3 weeks post-OP dose in humans, cats and chickens. By contrast, clinical neuropathy in mice following acute dosing with OPs or any other toxic compound has never been reported. Moreover, dosing mice with ethyloctylphosphonofluoridate (EOPF) - an extremely potent NTE inhibitor - causes a different (subacute) neurotoxicity with brain oedema. These observations have raised the possibility that mice are intrinsically resistant to neuropathies induced by acute toxic insult, but may incur brain oedema, rather than distal axonal damage, when NTE is inactivated. Here we provide the first report that hind-limb dysfunction and extensive axonal damage can occur in mice 3 weeks after acute dosing with a toxic compound, bromophenylacetylurea. Three weeks after acutely dosing mice with neuropathic OPs no clinical signs were observed, but distal lesions were present in the longest spinal sensory axons. Similar lesions were evident in undosed nestin-cre:NTEfl/fl mice in which NTE had been genetically-deleted from neural tissue. The extent of OP-induced axonal damage in mice was related to the duration of NTE inactivation and, as reported in chickens, was promoted by post-dosing with phenylmethanesulfonylfluoride. However, phenyldipentylphosphinate, another promoting compound in chickens, itself induced in mice lesions different from the neuropathic OP type. Finally, EOPF induced subacute neurotoxicity with brain oedema in both wild-type and nestin-cre:NTEfl/fl mice indicating that the molecular target for this effect is not neural NTE.

  14. 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.; Pritchard, Kirkwood A.; 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...

  15. Effect of acute and chronic cholinesterase inhibition on biogenic amines in rat brain.

    Science.gov (United States)

    Soininen, H; Unni, L; Shillcutt, S

    1990-12-01

    The effects of five cholinesterase inhibitors on forebrain monoamine and their metabolite levels, and on forebrain and plasma cholinesterase (ChE) activity in rat were studied in acute and chronic conditions. Acute tetrahydroaminoacridine (THA) dosing caused lower brain (68%) and higher plasma (90%) ChE inhibition than the other drugs studied and increased levels of brain dihydroxyphenylacetic acid (DOPAC) (236%), homovanillic acid (HVA) (197%) and 5-hydroxyindoleacetic acid (5-HIAA) (130%). Acute physostigmine (PHY) administration caused a 215% increase in brain DOPAC content. Despite high brain ChE inhibition induced by metrifonate (MTF), dichlorvos (DDVP) or naled no changes in brain noradrenaline (NA), dopamine (DA) or serotonin (5-HT) occurred due to treatment with the study drugs in the acute study. In the chronic 10-day study THA or PHY caused no substantial ChE inhibition in brain when measured 18 hours after the last dose, whereas MTF induced 74% ChE inhibition. Long-term treatment with THA or MTF caused no changes in monoamine levels, but PHY treatment resulted in slightly increased 5-HT values. These results suggest that MTF, DDVP and naled seem to act solely by cholinergic mechanisms. However, the central neuropharmacological mechanism of action of THA and PHY may involve changes in cholinergic as well as dopaminergic and serotoninergic systems. PMID:1711162

  16. Abnormal Reactions of Free Radicals and Oxidative Damages in the Bodies of Patients With Chronic Glomerulonephritis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To study the abnormal reactions of a series of free radicals and the oxidative damages induced by free radical abnormal reactions in the bodies of patients with chronic glomerulonephritis. Methods Eighty chronic glomerulonephritis patients (CGNP) and eighty healthy adult volunteers (HAV) were enrolled in a random control study, in which concentrations of nitric oxide (NO) in plasma, lipoperoxides (LPO) in plasma and in erythrocytes, and vitamin C (VC),vitamin E (VE) and beta-carotene (β-CAR) in plasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric assays. Results Compared with the average values of the above biochemical parameters in the HAV group, the average values of NO in plasma, and LPO in plasma and erythrocytes in the CGNP group were significantly increased (P = 0.0001), while those of VC, VE and β-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the CGNP group were significantly decreased (P = 0.0001). Pearson product-moment correlation analysis showed that with increase of the concentration of blood creatinine as well as prolongation of the course of disease in the CGNP, the concentrations of NO in plasma, and LPO in plasma and erythrocytes in the CGNP increased gradually, while the concentrations of VC, VE and β-CAR in plasma as well as the activities of SOD, CAT and GPX in erythrocytes in the CGNP decreased gradually (P = 0.002454 - 0.000001).The relative risk ratio (RR) of the above biochemical parameters reflecting oxidative damages in the bodies of CGNP ranged from 6.061 to 72.429. The reliability coefficient (alpha) that the above biochemical parameters were used to reflect the oxidative damages of the CGNP was 0.8137,standardized item alpha = 0.9728, Hotelling's T-Squared = 1135680.191, F = 53274.6478, P =0.000001. Conclusions The findings irt this study show that in the bodies of CGNP a series of free

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-05-01

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

  18. MRI of the brain in chronic carbon monoxide poisoning

    International Nuclear Information System (INIS)

    We examined 13 patients with CO poisoning by MRI; all of them had been in an explosion in a coal mine 25 years previously. Symmetrical globus pallidus lesions were observed in 12, as was degeneration of the white matter, with focal cortical atrophy. The temporal parietal and occipital lobes were usually affected, the parietooccipital region being the most frequently and extensively damaged. Of the 12 patients with white matter degeneration 7 had definitely asymmetrical cortical and subcortical lesions. There were 6 patients with dilated temporal horns, probably due to atrophy of the hippocampal gyri. (orig./MG)

  19. 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; Laureys, Steven; Boly, Melanie

    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

  20. Brain-peripheral cell crosstalk in white matter damage and repair.

    Science.gov (United States)

    Hayakawa, Kazuhide; Lo, Eng H

    2016-05-01

    White matter damage is an important part of cerebrovascular disease and may be a significant contributing factor in vascular mechanisms of cognitive dysfunction and dementia. It is well accepted that white matter homeostasis involves multifactorial interactions between all cells in the axon-glia-vascular unit. But more recently, it has been proposed that beyond cell-cell signaling within the brain per se, dynamic crosstalk between brain and systemic responses such as circulating immune cells and stem/progenitor cells may also be important. In this review, we explore the hypothesis that peripheral cells contribute to damage and repair after white matter damage. Depending on timing, phenotype and context, monocyte/macrophage can possess both detrimental and beneficial effects on oligodendrogenesis and white matter remodeling. Endothelial progenitor cells (EPCs) can be activated after CNS injury and the response may also influence white matter repair process. These emerging findings support the hypothesis that peripheral-derived cells can be both detrimental or beneficial in white matter pathology in cerebrovascular disease. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26277436

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

    Institute of Scientific and Technical Information of China (English)

    谢秋幼; 孙红宇; 刘晓加

    2001-01-01

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

  2. 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

    2016-06-01

    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

  3. 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.

  4. Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain.

    Science.gov (United States)

    Egorova, Natalia; Gollub, Randy L; Kong, Jian

    2015-01-01

    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. PMID:26594625

  5. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats

    Indian Academy of Sciences (India)

    Ashok Iyyaswamy; Sheeladevi Rathinasamy

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  6. Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

    Directory of Open Access Journals (Sweden)

    Francesca Colciaghi

    Full Text Available Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

  7. 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.

  8. Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function?

    OpenAIRE

    Tyler, Lorraine K.; Wright, Paul; Randall, Billi; Marslen-Wilson, William D.; Stamatakis, Emmanuel A.

    2010-01-01

    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 b...

  9. Congenital brain damage: cognitive development correlates with lesion and electroencephalographic features.

    Science.gov (United States)

    Riva, Daria; Franceschetti, Silvana; Erbetta, Alessandra; Baranello, Giovanni; Esposito, Silvia; Bulgheroni, Sara

    2013-04-01

    The purpose of this study was to assess cognitive development in 26 children with congenital focal brain lesion and unilateral spastic cerebral palsy first diagnosed and followed up for rehabilitation at our institution. Mean intelligence quotients (IQs) were correlated not only to the different features of the cerebral lesions, but also to the different types of electroencephalographic abnormalities. We also examined individual scores. We found that about 70% of the children had values of Full-Scale, Verbal, and Performance IQs within the normal range. No differences were found between left and right injured children. Different Verbal IQ-Performance IQ profiles were observed. Larger lesions and some electroencephalographic features, mainly signal slowing/attenuation as signs of structural brain damage, were significantly associated with lower intellectual abilities. The role of other factors, including genetic and environmental background variability, as well as rehabilitative treatments, on cognitive sequelae in such patients was discussed. PMID:22752481

  10. Salvia officinalis l. (sage) Ameliorates Radiation-Induced Oxidative Brain Damage In Rats

    International Nuclear Information System (INIS)

    The present study was designed to investigate the oxidative stress and the role of antioxidant system in the management of gamma irradiation induced whole brain damage in rats . Also, to elucidate the potential role of Salvia officinalis (sage) in alleviating such negative effects. Rats were subjected to gamma radiation (6 Gy). Sage extract was daily given to rats during 14 days before starting irradiation and continued after radiation exposure for another 14 days. The results revealed that the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and nitric oxide (NO) content were significantly increased, while the activities of superoxide dismutase (SOD) and catalase (CAT) as well as the reduced glutathione (GSH) content were significantly decreased in the brain homogenate of irradiated rats. Additionally, brain acetylcholinesterase (AChE) as well as alkaline phosphatase (ALP), acid phosphatase (ACP) and lactate dehydrogenase (LDH) activities were significantly increased. On the other hand, the results showed that, administration of sage extract to rats was able to ameliorate the mentioned parameters and the values returned close to the normal ones. It could be concluded that sage extract, by its antioxidant constituents, could modulate radiation induced oxidative stress and enzyme activities in the brain.

  11. 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.

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

    Science.gov (United States)

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

    2014-02-01

    Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA). The current study was designed to investigate the protective effects of candesartan (0.15 mg/kg, orally) and glycyrrhizin (30 mg/kg, orally) experimentally-induced ischemic brain damage in C57BL/6 mice (middle cerebral artery occlusion, MCAO) in comparison to the effects of a standard neuroprotective drug (cerebrolysin, 7.5 mg/kg, IP). All drugs were administered 30 min before and 24h after MCAO. Both candesartan and glycyrrhizin ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in behaviour tests, reduction in brain infarction, neuronal degeneration, and leukocyte infiltration. In addition, MCAO induced a significant upregulation in the different elements of the TLR pathway including TLR-2 and TLR-4, Myd88, TRIF and IRF-3 and the downstream effectors TNF-α, IL-1β, IL-6 and NF-kB. All these changes were significantly ameliorated by treatment with candesartan and glycyrrhizin. The results of the current study represent a new indication for both candesartan and glycyrrhizin in the management of ischemic stroke with effects comparable to those of the standard neuroprotective drug cerebrolysin. PMID:24378346

  13. Are Himalayan Sherpas better protected against brain damage associated with extreme altitude climbs?

    Science.gov (United States)

    Garrido, E; Segura, R; Capdevila, A; Pujol, J; Javierre, C; Ventura, J L

    1996-01-01

    1. The potential risk of brain damage when low-landers attempt to climb the highest summits is a well-known fact. However, very little is known about what occurs to Himalayan natives, perfectly adapted to high altitude, when performing the same type of activity. 2. Taking into account their long-life climbing experience at extreme altitudes, we examined seven of the most recognized Sherpas with the aim of performing a comprehensive neurological evaluation based on medical history, physical examination and magnetic resonance brain imaging. We compared them with one group of 21 lowland elite climbers who had ascended to altitudes of over 8000 m, and another control group of 21 healthy individuals who had never been exposed to high altitude. 3. While all of the lowland climbers presented psychoneurological symptoms during or after the expeditions, and 13 of them (61%) showed magnetic resonance abnormalities (signs of mild cortical atrophy and/or periventricular high-intensity signal areas in the white matter), only one Sherpa (14%) showed similar changes in the scans, presenting neurological symptoms at extreme altitude. The neurological examination was normal in all three groups, and no neuroimaging abnormalities were detected in the control group. 4. The significant differences, in both clinical and neuroimaging terms, suggest that Sherpa highlanders have better brain protection when exposed to extreme altitude. Although the key to protection against cerebral hypoxia cannot be established, it is possible that an increase in the usually short period of acclimatization could minimize brain damage in those low-landers who attempt the highest summits without supplementary oxygen. PMID:8697710

  14. Family needs in the chronic phase after severe brain injury in Denmark

    DEFF Research Database (Denmark)

    Doser, Karoline; Norup, Anne

    2014-01-01

    caregiving for the patient was completed. The relatives completed the revised version of the Family Needs Questionnaire, a questionnaire consisting of 37 items related to different needs following brain injury. Results: Significant changes in status were found in employment (z = -3.464, p = 0.001) and co-habitation...... were only met in 41-50% of the total sample. Conclusion: Occupational and co-habitation status of the relatives was significantly affected by brain injury. A high number of relatives reported family needs not satisfied in the chronic phase. This requires an interventional approach for families to get...

  15. 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 is......-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...

  16. Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: an intricate pathway.

    Science.gov (United States)

    Cardin, Romilda; Piciocchi, Marika; Bortolami, Marina; Kotsafti, Andromachi; Barzon, Luisa; Lavezzo, Enrico; Sinigaglia, Alessandro; Rodriguez-Castro, Kryssia Isabel; Rugge, Massimo; Farinati, Fabio

    2014-03-28

    The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an "inflammatory cancer", arising from a context of inflammation, and characterized by inflammation-related mechanisms that favor tumor cell survival, proliferation, and invasion. Molecular mechanisms that link inflammation and neoplasia have been widely investigated, and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species. The latter, in turn, probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation, and ultimately leading to cancer. The relationship amongst chronic liver injury, free radical production, and development of HCC is explored in the present review, particularly in the light of the complex network that involves oxidative DNA damage, cytokine synthesis, telomere dysfunction, and microRNA regulation. PMID:24696595

  17. Chronic and acute alcohol administration induced neurochemical changes in the brain: Comparison of distinct zebrafish populations

    OpenAIRE

    Chatterjee, Diptendu; Shams, Soaleha; Gerlai, Robert

    2014-01-01

    The zebrafish is increasingly utilized in the analysis of the effects of ethanol (alcohol) on brain function and behaviour. We have shown significant population dependent alcohol induced changes in zebrafish behaviour and have started to analyze alterations in dopaminergic and serotoninergic responses. Here, we analyze the effects of alcohol on levels of selected neurochemicals using a 2×3 (chronic x acute) between subject alcohol exposure paradigm randomized for two zebrafish populations, AB...

  18. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury

    OpenAIRE

    John Williamson; Emi Isaki

    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 ro...

  19. Sleep is associated with task-negative brain activity in fibromyalgia participants with comorbid chronic insomnia

    OpenAIRE

    Vatthauer KE; Craggs JG; Robinson ME; Staud R; Berry RB; Perlstein WM; McCrae CS

    2015-01-01

    Karlyn E Vatthauer,1 Jason G Craggs,1 Michael E Robinson,1 Roland Staud,2 Richard B Berry,2 William M Perlstein,1 Christina S McCrae11Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA; 2Department of Medicine, University of Florida, Gainesville, FL, USAAbstract: Patients with chronic pain exhibit altered default mode network (DMN) activity. This preliminary project questioned whether comorbid disease states are associated with further brain alterations....

  20. Sex differences in synaptic plasticity in stress-responsive brain regions following chronic variable stress

    OpenAIRE

    Carvalho-Netto, Eduardo F.; Myers, Brent; Jones, Kenneth; Solomon, Matia B.; Herman, James P.

    2011-01-01

    Increased stress responsiveness is implicated in the etiology of mood and anxiety disorders, including depression and post-traumatic stress disorder. Additionally, stress-related affective disorders have a higher incidence in women than men. Chronic stress in rodents produces numerous neuromorphological changes in a variety of limbic brain regions. Here, we examined the sex-dependent differences in presynaptic innervation of the paraventricular nucleus of the hypothalamus (PVN), prefrontal co...

  1. Proinflammatory cytokine expression contributes to brain injury provoked by chronic monocyte activation.

    OpenAIRE

    Sirén, A. L.; McCarron, R.; Wang, L.; Garcia-Pinto, P.; Ruetzler, C.; Martin, D.; Hallenbeck, J. M.

    2001-01-01

    BACKGROUND: We have proposed that an increased interaction between monocyte/macrophages and blood vessel endothelium predisposes subjects to strokes. The effect of chronic monocyte activation on the development of cerebral infarcts was thus studied in rats after provocation of a modified local Swartzman reaction, in brain vasculature. MATERIALS AND METHODS: Two weeks after an IV bolus of bacillus Calmette-Guérin (BCG), we studied spontaneous superoxide production, integrin expression, endothe...

  2. The Consequences of adolescent chronic unpredictable stress exposure on brain and behavior

    OpenAIRE

    Hollis, Fiona; Isgor, Ceylan; Kabbaj, Mohamed

    2013-01-01

    There is increasing evidence for adolescence as a time period vulnerable to environmental perturbations such as stress. What is unclear is the persistent nature of the effects of stress and how specific these effects are to the type of stressor. In this review, we describe the effects of chronic, unpredictable stress (CUS) exposure during adolescence on adult behavior and brain morphology and function in animal models. We provide evidence for adolescence as a critical window for the effects o...

  3. [The clinical study of the first febrile convulsion in children with brain-damage].

    Science.gov (United States)

    Asoh, M

    1997-05-01

    Forty-nine patients with cerebral palsy, mental retardation, or other congenital neurological disorders who had experienced febrile convulsions and had no previous nonfebrile seizures were presented. They were followed for 1.6 years to 15 years (mean: 6.8 years) after the initial febrile convulsion. The incidence of subsequent epilepsy (two or more afebrile seizures) was 39%, and 80% of them developed epilepsy within 2 years after the first febrile convulsion. The paroxysmal discharges on EEG recorded prior to or after the first febrile convulsion did not predict the occurrence of later epilepsy. Also under 3 years of age, EEG findings led to the same result. There was no definite evidence that administration of anticonvulsive drugs prevented later epilepsy. Pre-existing neurological abnormality was identified as a risk factor for epilepsy, and was an indication of persistent medication. There is no clear prophylactic procedure against long-lasting attacks. Accordingly, medical therapy can be started when epilepsy has developed. Patients with very severe brain damage who could not move except lying comprised only 6% of all cases, and 69% of the epilepsy patients were well controlled. They showed a good prognosis as compared with children with brain-damage in general with epilepsy. PMID:9146028

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

    Science.gov (United States)

    Lampe, Renée; Thienel, Anna; Mitternacht, Jürgen; Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana

    2015-01-01

    Damage to the developing brain may lead to impairment of the hand motor function and negatively impact on patients' quality of life. Development of manual dexterity and finger and hand motor function may be promoted by learning to play the piano. The latter brings together music with the intensive training of hand coordination and fine finger mobility. We investigated if learning to play the piano helped to improve hand motor skills in 18 youths with hand motor disorders resulting from damage during early brain development. Participants trained 35-40 minutes twice a week for 18 months with a professional piano teacher. With the use of a Musical Instrument Digital Interface piano, the uniformity of finger strokes could be objectively assessed from the timing of keystrokes. The analysis showed a significant improvement in the uniformity of keystrokes during the training. Furthermore, the youths showed strong motivation and engagement during the study. This is nevertheless an open study, and further studies remain needed to exclude effects of growth and concomitant therapies on the improvements observed and clarify which patients will more likely benefit from learning to play the piano. PMID:26345312

  5. Vulnerability of premyelinating oligodendrocytes to white-matter damage in neonatal brain injury

    Institute of Scientific and Technical Information of China (English)

    Xiao-Bo Liu; Yan Shen; Jennifer M.Plane; Wenbin Deng

    2013-01-01

    Premature birth is a significant economic and public health burden,and its incidence is rising.Periventricular leukomalacia (PVL) is the predominant form of brain injury in premature infants and the leading cause of cerebral palsy.PVL is characterized by selective white-matter damage with prominent oligodendroglial injury.The maturation-dependent vulnerability of developing and premyelinating oligodendrocytes to excitotoxic,oxidative,and inflammatory forms of injury is a major factor in the pathogenesis of PVL.Recent studies using mouse models of PVL reveal that synapses between axons and developing oligodendrocytes are quickly and profoundly damaged in immature white matter.Axon-glia synapses are highly vulnerable to white-matter injury in the developing brain,and the loss of synapses between axons and premyelinating oligodendrocytes occurs before any cellular loss in the immature white matter.Microglial activation and astrogliosis play important roles in triggering white-matter injury.Impairment of white-matter development and function in the neonatal period contributes critically to functional and behavioral deficits.Preservation of the integrity of the white matter is likely key in the treatment of PVL and subsequent neurological consequences and disabilities.

  6. The problem of aphasia in the assessment of consciousness in brain-damaged patients.

    Science.gov (United States)

    Majerus, Steve; Bruno, Marie-Aurélie; Schnakers, Caroline; Giacino, Joseph T; Laureys, Steven

    2009-01-01

    The assessment of the level and content of consciousness in brain-damaged patients relies to a large extent on behavioral assessment techniques. The limited behavioral repertoire displayed by vegetative and minimally conscious states requires the use of highly sensitive and reliable behavioral assessment methods, allowing the detection of subtle changes in behavior and associated level of consciousness. This situation is further complicated when patients with such disorders of consciousness have underlying deficits in the domain of communication functions, such as aphasia. The present paper examines the consequences of receptive and/or productive aphasia on the already limited behavioral repertoire presented in these patients and discusses a number of behavioral and neuroimaging assessment procedures designed to: (1) detect the presence of aphasia in patients with disorders of consciousness, and (2) reliably assess the level of consciousness of brain-damaged patients while taking into account the existence of receptive and/or expressive language deficits. The combined use of behavioral and neuroimaging assessment techniques appears to be particularly promising for disentangling impaired consciousness and aphasia. PMID:19818894

  7. Dimensions of personality disturbance after focal brain damage: investigation with the Iowa Scales of Personality Change.

    Science.gov (United States)

    Barrash, Joseph; Asp, Erik; Markon, Kristian; Manzel, Kenneth; Anderson, Steven W; Tranel, Daniel

    2011-10-01

    This study employed a multistep, rational-empirical approach to identify dimensions of personality disturbance in brain-damaged individuals: (a) Five dimensions were hypothesized based on empirical literature and conceptual grounds; (b) principal components analysis was performed on the Iowa Scales of Personality Change (ISPC) to determine the pattern of covariance among 30 personality characteristics; (c) when discrepancies existed between principal components analysis results and conceptually based dimensions, empirical findings and clinical considerations were weighed to determine assignment of ISPC scales to dimensions; (d) the fit of data to the refined dimensions was assessed by examination of intercorrelations; (e) differential predictions concerning the relationship of dimensions to ventromedial prefrontal cortex (vmPFC) damage were tested. This process resulted in the specification of five dimensions: Disturbed Social Behavior, Executive/Decision-Making Deficits, Diminished Motivation/Hypo-Emotionality, Irascibility, and Distress. In accord with predictions, the 28 participants with vmPFC lesions, compared to 96 participants with focal lesions elsewhere in the brain, had significantly more Disturbed Social Behavior and Executive/Decision-Making Deficits and tended to have more Diminished Motivation/Hypo-Emotionality. Irascibility was not significantly higher among the vmPFC group, and the groups had very similar levels of Distress. The findings indicate that conceptually distinctive dimensions with differential relationships to vmPFC can be derived from the Iowa Scales of Personality Change. PMID:21500116

  8. Effect of propentofylline on hypoxic-ischaemic brain damage in newborn rat

    Institute of Scientific and Technical Information of China (English)

    XIA Xiao-yan 夏晓艳; SAMESHIMA Hiroshi 鲛岛浩; OTA Arturo 大田Arturo; XIA Yi-xin 夏义欣; IKENOUE Tsuyomu 池ノ上克; TOSHIMORI Kiyotaka 年森清隆; HUANG Xing-hua 黄醒华

    2004-01-01

    Background Studies showed that propentofylline enhances the action of adenosine and protects hippocampal neuronal demage against transient global cerebral ischaemia. Our study was to investigate the effect of propentofylline on hypoxic-ischaemic brain damage in neonatal rat.Methods Seven-day-old Wistar rats were subjected to unilateral common carotid artery ligation and hypoxia in oxygen 8 kPa for two hours at 37℃. Propentofylline (10 mg/kg) was administered intraperitoneally one hour after hypoxia-ischaemia (treated group). Control group rats were received an equivalent volume of saline. The effects of propentofylline were assessed by observing the body mass gain, behavioural alteration and neurohistological changes. The rats were sacrificed at 72 hours after hypoxia-ischaemia, and the brain sections were examined after haematoxylin and eosin staining.Results The propentofylline-treated rats had better body mass gain and better behavioural response than the paired saline-controls did. In the control group, the rats either lost body mass or had little mass gain after the insult, their average body mass gain was 97.3% at 24 h, 100.3% at 48 h, and 114.1% at 72 h of recovery. In propentofylline-treated group, there was a significant improvement of body mass gain at 24 h (100.2%, P<0.05) and 48 h (110.3%, P<0.01) of recovery; the percentage of rats that performed well on behavioural test was significantly higher from 48 h to 72 h of recovery (P<0.05); the incidence of severe brain damage to the cerebral cortex and dentate gyrus was significantly reduced in propentofylline-treated rats (cortex, 93%-70.8%, P<0.01; dentate gyrus 95%-66.7%, P<0.01) as compared with control rats. Conclusions Administration of propentofylline 1 hour after hypoxia-ischaemia significantly attenuates brain damage in both the cerebral cortex and dentate gyrus, and also improves the body mass gain as well as behavioural disturbance in 7-day-old rats.

  9. Pathological and MRI study on experimental heroin-induced brain damage in rats

    International Nuclear Information System (INIS)

    Objective: To study the pathological characteristics of the heroin-induced brain damage in rats, and to assess the diagnostic value of MRI. Methods: A total of 40 adult Wistar rats were studied, 32 rats were used for injecting heroin as heroin group and 8 were used for injecting saline as control group. The heroin dependent rat model was established by administering heroin (ip) in the ascending dosage schedule (0.5 mg/kg), three times a day (at 8:00, 12:00, and 18:00). The control group was established by the same way by injection with saline. The withdrawal scores were evaluated with imp roved criterion in order to estimate the degree of addiction after administering naloxone. Based on the rat model of heroin dependence, the rat model of heroin-induced brain damage was established by the same way with increasing heroin dosage everyday. Two groups were examined by using MRI, light microscope, and electron microscope, respectively in different heroin accumulated dosage (918, 1580, 2686, 3064, 4336, and 4336 mg/kg withdrawal after 2 weeks). Results: There was statistically significant difference (t=9.737, P<0.01) of the withdrawal scores between the heroin dependent group and the saline group (23.0 ± 4.4 and 1.4 ± 0.5, respectively). It suggested that the heroin dependent rat model be established successfully. In different accumulated dosage ( from 1580 mg/kg to 4336 mg/kg), there were degeneration and death of nerve cells in cerebrum and cerebellum of heroin intoxicated rats, and it suggested that the rat model of heroin-induced brain damage was established successfully. The light microscope and electron microscope features of heroin-induced brain damage in rats included: (1) The nerve cells of cerebral cortex degenerated and died. According to the heroin accumulated dosage, there were statistically significant difference of the nerve cell deaths between 4336 mg/kg group and 1580 mg/kg group or control group (P=0.024 and P=0.032, respectively); (2) The main

  10. 1H MRS study of brain metabolic disorder in patients with chronic liver cirrhosis

    International Nuclear Information System (INIS)

    Objective: To study the metabolic alterations in the brain of patients with chronic liver cirrhosis with 1H magnetic resonance spectroscopy (1H MRS) for better understanding the pathophysiology of chronic hepatic encephalopathy (CHE), which will help us in the diagnosis and treatment of this disease. Methods: STEAM 1H MRS and MRI were performed in 30 patients with chronic liver cirrhosis is and 15 healthy volunteers. The height of resonance peaks of different metabolites was measured and the ratios of the other metabolites to Cr were calculated. The authors also studied the correlation between metabolites and the association between globus pallidum signal intensity and the spectroscopic alterations. Results: In patients with severe cirrhosis (in decompensatory period) or CHE, the mean values of mI/Cr and Cho/Cr ratio were significantly lower than those in healthy volunteers or patients with minor cirrhosis (in compensatory period) (P0.05). There was negative correlation between mI/Cr and Glx-α/Cr(r -0.51, n = 44, P1-weighted images, the globus pallidum signal intensity was significantly higher in patients with severe cirrhosis or CHE. mI/Cr, Cho/Cr and Glx-α/Cr correlated significantly with MRI signal changes respectively. Conclusions: Proton MRS can demonstrate brain metabolic changes in patients with chronic liver cirrhosis in vivo noninvasively, thereby helping interpret the pathophysiology of CHE

  11. Chronic ibuprofen administration worsens cognitive outcome following traumatic brain injury in rats.

    Science.gov (United States)

    Browne, Kevin D; Iwata, Akira; Putt, M E; Smith, Douglas H

    2006-10-01

    Traumatic brain injury (TBI) can induce progressive neurodegeneration in association with chronic inflammation. Since chronic treatment with the non-steroidal anti-inflammatory drug (NSAID), ibuprofen, improves functional and histopathologic outcome in a mouse model of Alzheimer's disease (AD), we investigated whether it would also improve long-term outcome following TBI. Anesthetized adult rats were subjected to fluid percussion brain injury. Over the following 4 months the injured animals received ibuprofen per os (formulated in feed) at the approximate doses of 20 mg/kg body wt/day (n=13), 40 mg/kg body wt/day (n=13), or control (feed only, n=12). Sham animals underwent surgery without injury or ibuprofen treatment (n=9). At 4 months post-injury, a Morris water maze task revealed a profound learning dysfunction in all three injured groups compared to the sham group. Surprisingly, the learning ability of injured animals treated with either chronic ibuprofen regimen was significantly worsened compared to non-treated injured animals. However, there was no difference in the extent of progressive atrophy of the cortex or hippocampus between treated and non-treated injured animals. These data may have important implications for TBI patients who are often prescribed NSAIDs for chronic pain. PMID:16764859

  12. 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.

  13. Chronic social isolation affects thigmotaxis and whole-brain serotonin levels in adult zebrafish.

    Science.gov (United States)

    Shams, Soaleha; Chatterjee, Diptendu; Gerlai, Robert

    2015-10-01

    The popularity of the zebrafish has been growing in behavioral brain research. Previously utilized mainly in developmental biology and genetics, the zebrafish has turned out to possess a complex behavioral repertoire. For example, it is a highly social species, and individuals form tight groups, a behavior called shoaling. Social isolation induced changes in brain function and behavior have been demonstrated in a variety of laboratory organisms. However, despite its highly social nature, the zebrafish has rarely been utilized in this research area. Here, we investigate the effects of chronic social isolation (lasting 90 days) on locomotor activity and anxiety-related behaviors in an open tank. We also examine the effect of chronic social isolation on levels of whole-brain serotonin and dopamine and their metabolites. We found that long-term social deprivation surprisingly decreased anxiety-related behavious during open-tank testing but had no effect on locomotor activity. We also found that serotonin levels, decreased significantly in socially isolated fish, but levels of dopamine and metabolites of these neurotransmitters 5HIAA and DOPAC, respectively, remained unchanged. Our results imply that the standard high density housing employed in most zebrafish laboratories may not be the optimal way to keep these fish, and open a new avenue towards the analysis of the biological mechanisms of social behavior and of social deprivation induced changes in brain function using this simple vertebrate model organism. PMID:26119237

  14. DNA DAMAGE IN BUCCAL EPITHELIAL CELLS FROM INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA, CHINA

    Science.gov (United States)

    The purpose of this pilot study was to assess DNA damage in buccal cells from individuals chronically exposed to arsenic via drinking water in Ba Men, Inner Mongolia. Buccal cells were collected from 19 Ba Men residents exposed to arsenic at 527.5 ? 23.7 g/L (mean ? SEM) and ...

  15. Regional alterations of brain biogenic amines in young rats following chronic lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Dubas, T.C.; Stevenson, A.; Singhal, R.L.; Hrdina, P.D.

    1978-02-01

    An examination was made of neurochemical changes that occur in discrete brain regions of rats that have been chronically exposed to low levels of lead from birth, in order to provide further information on the involvement of brain biogenic amines in lead-induced neurotoxicity. Results indicate a relationship between exposure to lead and alterations in the brain levels of various putative neurotransmitters. However, changes in the functional activity of the neurotransmitter may not be adequately reflected in the change of its steady-state levels or may occur even in the absence of any changes in the actual concentrations. Lead may influence central neurotransmitter function by affecting one or several of the processes involved in the synthesis, release and/or disposition of biogenic amines.

  16. Diagnostic usefulness of the oedema-infarct ratio to differentiate acute from chronic myocardial damage using magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Kiyoyasu; Suzuki, Susumu; Kinoshita, Kousuke; Yokouchi, Kazuhiko; Iwata, Hirokazu; Sawada, Ken [Gifu Social Insurance Hospital, Department of Cardiology, Gifu (Japan); Isobe, Satoshi; Ohshima, Satoru; Murohara, Toyoaki [Nagoya University Graduate School of Medicine, Department of Cardiology, Nagoya (Japan); Hirai, Makoto [Nagoya University School of Health Sciences, Department of Nursing, Nagoya (Japan)

    2012-04-15

    To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase (P < 0.05). An analysis of relative cumulative frequency distributions revealed an O/I of 1.4 as a cut-off value for differentiating acute from chronic myocardial damage with the sensitivity, specificity, and accuracy of 85.1%, 82.7% and 83.9%, respectively. The oedema-infarct ratio may be a useful index in differentiating acute from chronic myocardial damage in patients with MI. (orig.)

  17. Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress.

    Science.gov (United States)

    Li, Qin; Bi, Ming Jun; Bi, Wei Kang; Kang, Hai; Yan, Le Jing; Guo, Yun-Liang

    2016-03-01

    Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO-1 and Nrf-2 proteins were found in normal brain tissue. CO poisoning could activate HO-1/Nrf-2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 372-379, 2016

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

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2012-01-01

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

  19. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Microcavitation as a Neuronal Damage Mechanism in Blast Traumatic Brain Injury

    Science.gov (United States)

    Franck, Christian; Estrada, Jonathan

    2015-11-01

    Blast traumatic brain injury (bTBI) is a leading cause of injury in the armed forces. Diffuse axonal injury, the hallmark feature of blunt TBI, has been investigated in direct mechanical loading conditions. However, recent evidence suggests inertial cavitation as a possible bTBI mechanism, particularly in the case of exposure to blasts. Cavitation damage to free surfaces has been well-studied, but bubble interactions within confined 3D environments, in particular their stress and strain signatures are not well understood. The structural damage due to cavitation in living tissues - particularly at the cellular level - are incompletely understood, in part due to the rapid bubble formation and deformation strain rates of up to ~ 105-106 s-1. This project aims to characterize material damage in 2D and 3D cell culture environments by utilizing a novel high-speed red-blue diffraction assisted image correlation method at speeds of up to 106 frames per second. We gratefully acknowledge funding from the Office of Naval Research (POC: Dr. Tim Bentley).

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

    Directory of Open Access Journals (Sweden)

    Jung Hwa Seo

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

  2. If this argument is true: Hashimotos disease causes chronic thyroid damage so in diseased elderly population the thyroid volumes must be low-retrospective US study

    Directory of Open Access Journals (Sweden)

    Betul Tiryaki Bastug

    2016-05-01

    Conclusions: The results have suggested that while aging although disease causes chronic thyroid damage, volume measurements do not change. Because volume reduction due to chronic damage of disease is balanced by volume increase due to aging. [Int J Res Med Sci 2016; 4(5.000: 1433-1437

  3. Rapid reversal by naloxone of the chronic effects of morphine on rat liver and brain tryptophan metabolism.

    OpenAIRE

    Badawy, A. A.; Evans, M.

    1981-01-01

    The chronic morphine-induced inhibition of rat liver tryptophan pyrrolase activity and the resultant increases in tryptophan availability to the brain and brain 5-hydroxytryptamine (5-HT) synthesis are reversed within 10 min after naloxone administration. The possible involvement of hepatic tryptophan metabolism in morphine dependence is briefly discussed.

  4. Heavy metal uranium affects the brain cholinergic system in rat following sub-chronic and chronic exposure

    International Nuclear Information System (INIS)

    Uranium is a heavy metal naturally present in the environment that may be chronically ingested by the population. Previous studies have shown that uranium is present in the brain and alters behaviour, notably locomotor activity, sensorimotor ability, sleep/wake cycle and the memory process, but also metabolism of neurotransmitters. The cholinergic system mediates many cognitive systems, including those disturbed after chronic exposure to uranium i.e., spatial memory, sleep/wake cycle and locomotor activity. The objective of this study was to assess whether these disorders follow uranium-induced alteration of the cholinergic system. In comparison with 40 control rats, 40 rats drank 40 mg/L uranyl nitrate for 1.5 or 9 months. Cortex and hippocampus were removed and gene expression and protein level were analysed to determine potential changes in cholinergic receptors and acetylcholine levels. The expression of genes showed various alterations in the two brain areas after short- and long-term exposure. Nevertheless, protein levels of the choline acetyltransferase enzyme (ChAT), the vesicular transporter of acetylcholine (VAChT) and the nicotinic receptor β2 sub-unit (nAChRβ2) were unmodified in all cases of the experiment and muscarinic receptor type 1 (m1AChR) protein level was disturbed only after 9 months of exposure in the cortex (-30%). Acetylcholine levels were unchanged in the hippocampus after 1.5 and 9 months, but were decreased in the cortex after 1.5 months only (-22%). Acetylcholinesterase (AChE) activity was also unchanged in the hippocampus but decreased in the cortex after 1.5 and 9 months (-16% and -18%, respectively). Taken together, these data indicate that the cholinergic system is a target of uranium exposure in a structure-dependent and time-dependent manner. These cholinergic alterations could participate in behavioural impairments.

  5. Ligularia fischeri extract attenuates liver damage induced by chronic alcohol intake.

    Science.gov (United States)

    Kim, Dongyeop; Kim, Gyeong-Woo; Lee, Seon-Ho; Han, Gi Dong

    2016-08-01

    Context Ligularia fischeri (Ledebour) Turcz. (Compositae) has been used as a leafy vegetable and in traditional medicine to treat hepatic disorder in East Asia. Objective The present study explores the antioxidant activity of LF aqueous extract on EtOH-induced oxidative stress accompanied by hepatotoxicity both in vitro and in vivo. Materials and methods In vitro study using the mouse liver NCTC-1469 cell line was conducted to estimate the cytotoxicity as well as the inhibitory effect of LF extract against alcohol-treated cell damage. In vivo study used an alcohol-fed Wister rat model orally administered EtOH (3.95 g/kg of body weight/d) with or without LF extract (100 or 200 mg/kg body weight) for 6 weeks. Serum and liver tissue were collected to evaluate hepatic injury and antioxidant-related enzyme activity. Results The EC50 value for the DPPH radical scavenging capacity of LF extract was 451.5 μg/mL, whereas the IC50 value of LF extract in terms of EtOH-induced reactive oxygen species (ROS) generation was 98.3 μg/mL without cell cytotoxicity. LF extract (200 mg/kg body weight) significantly reduced the triglyceride content of serum (33%) as well as hepatic lipid peroxidation (36%), whereas SOD activity was elevated three-fold. LF extract suppressed expression of CYP2E1 and TNF-α, and attenuated alcohol-induced abnormal morphological changes. Discussion and conclusion LF extract attenuated liver damage induced by alcoholic oxidative stress through inhibition of ROS generation, down-regulation of CYP2E1, and activation of hepatic antioxidative enzymes. Homeostasis of the antioxidative defence system in the liver by LF extract mitigated hepatic disorder following chronic alcohol intake. PMID:26799831

  6. Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

    Science.gov (United States)

    Piloni, Natacha E; Perazzo, Juan C; Fernandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2016-02-01

    This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(•))/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(•))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation. PMID:26677163

  7. 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

    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......-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...

  8. Comparative study of delayed brain damage in pubescent and adult rhesus monkeys from radiation within the therapeutic range

    International Nuclear Information System (INIS)

    The whole brains of pubescent and fully adult rhesus monkeys were subjected to 6,000 rads of fractionated supervoltage X-irradiation, and the difference of these two age groups in clinical and neuropathological changes after the irradiation was studied. The pubescent monkey was more vulnerable to irradiation than the fully adult monkey, and showed more clinical signs and more focal lesions of delayed brain damage from radiation. (author)

  9. Effects of Chronic Renal Failure on Brain Cytochrome P450 in Rats.

    Science.gov (United States)

    Naud, Judith; Harding, Jessica; Lamarche, Caroline; Beauchemin, Stephanie; Leblond, Francois A; Pichette, Vincent

    2016-08-01

    Chronic renal failure (CRF) impedes renal excretion of drugs and their metabolism by reducing the expression of liver cytochrome P450 (P450). Uremic serum contains factors, such as parathyroid hormone (PTH), that decrease liver P450s. The P450s are also involved in the metabolism of xenobiotics in the brain. This study investigates: 1) the effects of CRF on rat brain P450, 2) the role of PTH in the downregulation of brain P450s in CRF rats, and 3) the effects of PTH on P450s in astrocytes. Protein and mRNA expression of P450s were assessed in the brain of CRF and control (CTL) rats, as well as from CTL or CRF rats that underwent parathyroidectomy (PTX) 1 week before nephrectomy. CYP3A activity was measured using 3-[(3, 4-difluorobenzyl) oxy]-5, 5-dimethyl-4-[4-methylsulfonyl) phenyl] furan-2(5H)-1 metabolism in brain microsomal preparation. CYP3A protein expression was assessed in primary cultured astrocytes incubated with serum obtained from CRF or CTL rats or with PTH. Significant downregulations (≥40%) of CYP1A, CYP2C11, and CYP3A proteins were observed in microsomes from CRF rat brains. CYP3A activity reduction was also observed. CYP3A expression and activity were unaffected in PTX-pretreated CRF rats. Serum of PTX-treated CRF rats had no impact on CYP3A levels in astrocytes compared with that of untreated CRF rats. Finally, PTH addition to normal calf serum induced a reduction in CYP3A protein similar to CRF serum, suggesting that CRF-induced hyperparathyroidism is associated with a significant decrease in P450 drug-metabolizing enzymes in the brain, which may have implications in drug response. PMID:27271372

  10. Studies on atrophy of the brain in chronic alcoholics examined by CT scan

    International Nuclear Information System (INIS)

    A study of atrophy of the brain using CT scan was performed in 113 patients with chronic alcoholism who had history of alcohol abuse over 150 grams in average as amount of absolute ethanol for more than ten years. They had no focal cerebral lesions such as infarction, hemorrhage or tumor, nor clinical neurological deficits. Prominent enlagement of cortical sulci and lateral ventricles was found in chronic alcoholics when compared with age-matched controls. The most remarkable change among 6 indices in all age group was enlargement of cortical sulci. The ratio of lateral ventricle area to intracranical area was more significantly increased compared with the widening of the lateral ventricle determined as a distance between two tips of bilateral frontal horns or intercaudate distance. Forty-eight of 96 patients in whom EEG was examined, showed abnormalities such as dominant slow background activities and sporadic slow bursts, which were found more frequently (25/38, 66%) in patients over 50 years of age. No correlation was found between the occurrence of EEG abnormalities and cerebral atrophy or between the degree of cerebral atrophy and the severity of hepatic dysfunction. It is concluded from our study that atrophy of the brain in chronic alcoholics may be clearly estimated by CT planimetry of the ratio of lateral ventricle area to intracranial area. (J.P.N.)

  11. Chronic brief restraint decreases in vivo binding of benzodiazepine receptor ligand to mouse brain.

    Science.gov (United States)

    Mosaddeghi, M; Burke, T F; Moerschbaecher, J M

    1993-01-01

    This study examines the effects of chronic brief restraint on in vivo benzodiazepine (BZD) receptor binding in mouse brain. Three groups of mice were used. Mice in group 1 were neither restrained nor injected (ACUTE control). Mice in group 2 were restrained for 5-6 s by grabbing the back skin and holding the subject upside-down at a 45 degrees angle as if to be injected (CHRONIC SHAM control) for 7 d. Mice in group 3 (CHRONIC SALINE) received daily single intraperitoneal (ip) injections of saline (5 mL/kg) for 7 d. On d 8 BZD receptors were labeled in vivo by administration of 3 microCi [3H]flumazenil (ip). The levels of ligand bound in vivo to cerebral cortex (CX), cerebellum (CB), brain stem (BS), striatum (ST), hippocampus (HP), and hypothalamus (HY) were determined. Results indicated that the level of binding was significantly (p stress produces a decrease in BZD receptor binding sites. PMID:8385464

  12. Inhaled nitric oxide and neonatal brain damage: experimental and clinical evidences.

    Science.gov (United States)

    Sun, Bo

    2012-04-01

    Inhaled nitric oxide (iNO) has been used not only for pulmonary vasodilation in term neonates with hypoxemic respiratory failure, but also in preterm ones at risk of chronic lung disease (CLD) with variable results in prevention and treatment of CLD and/or brain injury. However, meta analysis of clinical trials does not support that iNO should be used routinely in preterm infants with hypoxic respiratory failure as it has no convincing long-term follow-up data to show its advantages in neurodevelopment. Investigation of extra-pulmonary effects of iNO through nitrosothiol hemoglobin-associated hypoxic vasodilation, as well as its intra- and extra-pulmonary anti-inflammation effect, would have biological and physiological potential in the management of the lung and brain injury of prematurity. The eligibility and safety of iNO in these premature infants at high risk of neurodevelopmental disability require more clinical and follow-up effort to test its pharmacological benefit over harm. PMID:22348510

  13. Pulmonary perfusion scintigraphy in children with chronic pulmonary damage: Preliminary results from application of the SPECT technique

    International Nuclear Information System (INIS)

    The aim was to describe lung perfusion SPECT (LPS) findings in children with chronic pulmonary damage. Material and Method: We revised 106 LPS of children (age:3.9 ± 3.3 yr) with chronic pulmonary damage, performed with a two headed gamma camera. The most common clinical diagnosis were adenovirus bronchopneumonia sequelae (ADV)(29%), unknown origin chronic pulmonary damage (UOPD) (21%), bronchopulmonary dysplasia (BPD)(15%), and chronic obstructed bronchitis (COB)(14%). Severity of pulmonary alterations were evaluated using a Score, which considered extent and type of lung involvement and differential pulmonary perfusion. Pattern of involvement and Score were correlated with diagnosis and gender. Results: Ninety one percent (96/106) of LPS were abnormal (62% boys). Fifty two (54%) showed bilateral alterations, being this finding (p:0.019) more frequent in boys. ADV group showed mainly a mixed bilateral pattern (35%), UOPD a focal unilateral pattern (32%), COB a diffuse unilateral pattern (33%), and BPD a normal pattern (25%). Miscellaneous and UOPD showed the highest score values, and BPD and COB the lowest ones. Conclusion: In this population, LPS is abnormal in high proportion, with some differential characteristics according gender and original diagnosis (au)

  14. Biomarkers of Brain Damage and Postoperative Cognitive Disorders in Orthopedic Patients: An Update

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    Dariusz Tomaszewski

    2015-01-01

    Full Text Available The incidence of postoperative cognitive dysfunction (POCD in orthopedic patients varies from 16% to 45%, although it can be as high as 72%. As a consequence, the hospitalization time of patients who developed POCD was longer, the outcome and quality of life were worsened, and prolonged medical and social assistance were necessary. In this review the short description of such biomarkers of brain damage as the S100B protein, NSE, GFAP, Tau protein, metalloproteinases, ubiquitin C terminal hydrolase, microtubule-associated protein, myelin basic protein, α-II spectrin breakdown products, and microRNA was made. The role of thromboembolic material in the development of cognitive decline was also discussed. Special attention was paid to optimization of surgical and anesthetic procedures in the prevention of postoperative cognitive decline.

  15. Arctigenin Treatment Protects Against Brain Damage Through an Anti-inflammatory and Anti-apoptotic Mechanism After Needle Insertion

    OpenAIRE

    Jie Song; Na Li; Xia Yang; Zhong Gao; Liang Kong; Yingjia Yao; Yanan Jiao; Yuhui Yan; Shaoheng Li; Zhenyu Tao; Guan Lian; Jingxian Yang; Tingguo Kang

    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 ...

  16. 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. PMID:27016924

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

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    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.

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

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    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

  19. Efficacy of Carnosine in Modulating Radiation-Induced Oxidative Damage and Neurotransmitter Alterations in Rat Brain

    International Nuclear Information System (INIS)

    The present study was designed to investigate the role of carnosine (β-alanyl-L-histidine) in alleviating oxidative damage and alteration of neurotransmitters in the brain of rats exposed to gamma radiation. Male albino rats were whole body exposed to a single dose of γ- rays (5 Gy). Carnosine (50 mg/Kg/day) was administered via gavages as follows: a) during 28 successive days, b) during 14 successive days before whole body gamma irradiation and administered distilled water for 14 days after irradiation, c) during 14 successive days before whole body gamma irradiation and during 14 days after irradiation with carnosine. The animals were sacrificed at 1, 7 and 14 days post irradiation. (3 hours after the last dose of carnosine). The results revealed that exposure to γ- rays, (5 Gy(, resulted in significant increases of the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (CO), and advanced oxidation protein products (AOPP), associated with significant decreases of superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) content which indicate oxidative stress. Gamma rays also, induced significant decrease of the serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents as well as significant increase of 5-hydroxy-indole-acetic-acid (5-HIAA) level and monoamine oxidase (MAO) activity which indicated alterations in the metabolism of monoamines. Carnosine has significantly attenuated oxidative stress, and monoamine alterations in the cerebral hemispheres of irradiated rats. Carnosine might preserve the integrity of brain functions.

  20. Laser-induced accurate frontal cortex damage: a new tool for brain study

    Science.gov (United States)

    Flores, Gonzalo; Khotiaintsev, Sergei N.; Sanchez-Huerta, Maria L.; Ibanes, Osvaldo; Hernandez, Adan; Silva, Adriana B.; Calderon, Rafael; Ayala, Griselda; Marroquin, Javier; Svirid, Vladimir; Khotiaintsev, Yuri V.

    1999-01-01

    New laser-based technique for anatomical-functional study of the medial prefrontal cortex (MPFC) of the brain of experimental animals (rats) is presented. The technique is based on making accurate well-controlled lesions to small MPFC and subsequent observing behavioral alterations in the lesioned animals relative to control ones. Laser produces smaller and more accurate lesions in comparison to those obtained by traditional methods, such as: mechanical action, chemical means, and electrical currents. For producing the brain lesions, a 10 W CO2 CW laser is employed for reasons of its sufficiently high power, which is combined with relatively low cost-per-Watt ratio. In our experience, such power rating is sufficient for making MPFC lesions. The laser radiation is applied in a form of pulse series via hollow circular metallic waveguide made of stainless steel. The waveguide is of inner diameter 1.3 mm and 95 mm long. The anesthetized animals are placed in stereotaxic instrument. Via perforations made in the skull bone, the MPFC is exposed to the laser radiation. Several weeks later (after animal recuperation), standard behavioral tests are performed. They reveal behavioral changes, which point to a damage of some small regions of the MPFC. These results correlate with the histological data, which reveal the existence of small and accurate MPFC lesions. The present technique has good prospects for use in anatomical- functional studies of brain by areas. In addition, this technique appears to have considerable promise as a treatment method for some pathologies, e.g. the Parkinson's disease.

  1. Transcriptomic responses in mouse brain exposed to chronic excess of the neurotransmitter glutamate

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    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.

  2. Sleep is associated with task-negative brain activity in fibromyalgia participants with comorbid chronic insomnia

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    Vatthauer KE

    2015-11-01

    Full Text Available Karlyn E Vatthauer,1 Jason G Craggs,1 Michael E Robinson,1 Roland Staud,2 Richard B Berry,2 William M Perlstein,1 Christina S McCrae11Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA; 2Department of Medicine, University of Florida, Gainesville, FL, USAAbstract: Patients with chronic pain exhibit altered default mode network (DMN activity. This preliminary project questioned whether comorbid disease states are associated with further brain alterations. Thirteen women with fibromyalgia (FM only and 26 women with fibromyalgia with comorbid chronic insomnia (FMI underwent a single night of ambulatory polysomnography and completed a sleep diary each morning for 14 days prior to performing a neuroimaging protocol. Novel imaging analyses were utilized to identify regions associated with significantly disordered sleep that were more active in task-negative periods than task-oriented periods in participants with FMI, when compared to participants with FM. It was hypothesized that core DMN areas (ie, cingulate cortex, inferior parietal lobule, medial prefrontal cortex, medial temporal cortex, precuneus would exhibit increased activity during task-negative periods. Analyses revealed that significantly disordered sleep significantly contributed to group differences in the right cingulate gyrus, left lentiform nucleus, left anterior cingulate, left superior gyrus, medial frontal gyrus, right caudate, and the left inferior parietal lobules. Results suggest that FMI may alter some brain areas of the DMN, above and beyond FM. However, future work will need to investigate these results further by controlling for chronic insomnia only before conclusions can be made regarding the effect of FMI comorbidity on the DMN.Keywords: insomnia, fibromyalgia, neuroimaging, task-negative, brain activity, comorbidity

  3. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  4. Facial Affect Recognition Training Through Telepractice: Two Case Studies of Individuals with Chronic Traumatic Brain Injury

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    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.               

  5. Effect of progesterone intervention on the dynamic changes of AQP-4 in hypoxic-ischaemic brain damage.

    Science.gov (United States)

    Li, Xiaojuan; Bai, Ruiying; Zhang, Junhe; Wang, Xiaoyin

    2015-01-01

    To observe the effect of progesterone (PROG) on blood-brain barrier (BBB) permeability, brain tissue water content and dynamic changes of aquaporin-4 (AQP-4) in neonatal rats with hypoxic-ischaemic brain damage (HIBD). 72 neonatal Wistar rats, aged 7 days old, were randomly divided into control, hypoxic-ischaemic (6, 24 and 72 h, and 7 d subgroups) and drug groups (6, 24 and 72 h, and 7 d subgroups). The HIBD animal model was established. BBB was detected via an Evans blue tracer. Brain water content was determined by the dry/wet method. The AQP-4 expression in the cerebral cortex was observed through immunohistochemistry and Western blot. BBB permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the hypoxia-ischaemia group were significantly higher than those of the control group after hypoxia for 6 h (P permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the drug group were significantly lower than those of the hypoxia-ischaemia group after hypoxia for 6, 24 and 72 h (P permeability and BBB expression were positively correlated with the AQP-4 expression. In conclusion, PROG protects the brain of HIBD neonatal rats by alleviating the damage of BBB and cerebral oedema. The protective effect of PROG may be related to the down-regulation of AQP-4 expression in the cerebral cortex of neonatal rats. PMID:26770503

  6. Late radiation damage in bone, bone marrow and brain vasculature, with particular emphasis upon fractionation models

    International Nuclear Information System (INIS)

    X-ray induced changes in rat and human bone and bone marrow vasculature and in rat brain vasculature were measured as a function of time after irradiation and absorbed dose. The absorbed dose in the organ varied from 5 to 25 Gy for single dose irradiations and from 19 to 58 Gy for fractionated irradiations.The number of fractions varied from 3 to 10 for the rats and from 12 to 25 for the human. Blood flow changes were measured using an ''1''2''5I antipyrine or ''8''6RbCl extraction technique. The red blood cell (RBC) volume was examined by ''5''1Cr labelled red cells. Different fractionation models have been compared. Radiation induced reduction of bone and bone marrow blood flow were both time and dose dependent. Reduced blood flow 3 months after irradiation would seem to be an important factor in the subsequent atrophy of bones. With a single dose of 10 Gy the bone marrow blood flow returned to the control level by 7 months after irradiation. In the irradiated bone the RBC volume was about same as that in the control side but in bone marrow the reduction was from 32 to 59%. The dose levels predicted by the nominal standard dose (NSD) formula produced about the same damage to the rat femur seven months after irradiation when the extraction of ''8''6Rb chloride and the dry weight were concerned as the end points. However, the results suggest that the NSB formula underestimates the late radiation damage in bone marrow when a small number of large fractions are used. In the irradiated brains of the rats the blood flow was on average 20.4% higher compared to that in the control group. There was no significant difference in brain blood flow between different fractionation schemes. The value of 0.42 for the exponent of N corresponds to the average value for central nervous system tolerance in the literature. The model used may be sufficiently accurate for clinical work provided the treatment schemes used do not depart too radically from standard practice

  7. Relationship between the repair of radiation-induced DNA damage and recovery from potentially lethal damage in 9L rat brain tumor cells. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    vanAnkeren, S.C.; Wheeler, K.T.

    1984-03-01

    The kinetics of repair of radiation-induced DNA damage and recovery from radiation-induced potentially lethal damage (PLD) for fed plateau-phase 9L/Ro rat brain tumor cells were compared after single doses of gamma-radiation and after combined treatment with 3 micrograms of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)/ml given 16 hr prior to irradiation. DNA damage and repair were assayed using alkaline filter elution, while cell survival was assayed by colony formation. Repair of radiation-induced DNA damage and recovery from radiation-induced PLD followed statistically identical biphasic kinetics; the fast-phase half-times were 4.1 +/- 0.3 (S.D.) min and 4.0 +/- 0.8 min, while the slow-phase half-times were 59.7 +/- 11.2 min and 78.7 +/- 34.1 min, respectively. Treatment with BCNU prior to irradiation resulted in both additional DNA damage and increased cell kill. When DNA damage and cell survival after the combined treatment were corrected for the contribution from BCNU given alone, no inhibition of either repair of radiation-induced DNA damage or of recovery from radiation-induced PLD was observed. However, postirradiation hypertonic treatment inhibited both DNA repair and recovery from radiation-induced PLD. These correlations between the kinetics of the molecular and cellular repair processes support a role for repair of radiation-induced DNA damage in recovery from radiation-induced PLD. The lack of inhibition by BCNU of both repair of radiation-induced DNA damage and of recovery from radiation-induced PLD also demonstrates that these are not the mechanisms by which BCNU enhances radiation-induced cytotoxicity in 9L cells.

  8. The role of Tc-99m HMPAO brain perfusion SPECT in the psychiatric disability evaluation of patients with chronic traumatic brain injury

    International Nuclear Information System (INIS)

    We studied whether brain perfusion SPECT is useful in the psychiatric disability evaluation of patients with chronic traumatic brain injury (TBI). Sixty-nine patients (M:F=58:11, age 39 ± 14 years) who underwent Tc-99m HMPAO brain SPECT, brain MRI and neuropsychological (NP) tests during hospitalization in psychiatric wards for the psychiatric disability evaluation were included; the severity of injury was mild in 31, moderate in 17 and severe in 21. SPECT, MRI, NP tests were performed 6 ∼ 61 months (mean 23 months) post-injury. Diagnostic accuracy of SPECT and MRI to show hypoperfusion or abnormal signal intensity in patients with cognitive impairment represented by NP test results were compared. Forty-two patients were considered to have cognitive impairment on NP tests and 27 not. Brain SPECT showed 71% sensitivity and 85% specificity, while brain MRI showed 62% sensitivity and 93% specificity (p>0.05, McNemar test). SPECT found more cortical lesions and MRI was superior in detecting white matter lesions. sensitivity and specificity of 31 mild TBI patients were 45%, 90% for SPECT and 27%, 100% for MRI (p>0.05, McNemar test). Among 41 patients with normal brain MRI, SEPCT showed 63% sensitivity (50% for mild TBI) and 88% specificity (85% for malingerers). Brain SPECT has a supplementary role to neuropsychological tests in the psychiatric disability evaluation of chronic TBI patients by detecting more cortical lesions than MRI

  9. Relationship between AQP4 expression and structural damage to the blood-brain barrier at early stages of traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    LU Hong; LEI Xiao-yan; HU Hui; HE Zhan-ping

    2013-01-01

    Background Although some studies have reported that aquaporin-4 (AQP4) plays an important role in the brain edema after traumatic brain injury (TBI),little is known about the AQP4 expression in the early stage of TBI,or about the correlation between the structural damage to the blood-brain barrier (BBB) and angioedema.The aim of this project was to investigate the relationship between AQP4 expression and damage to the BBB at early stages of TBI.Methods One hundred and twenty healthy adult Wistar rats were randomly divided into two greups:sham operation group (SO) and TBI group.The TBI group was divided into five sub-groups according to the different time intervals:1,3,6,12,and 24 hours.The brains of the animals were taken out at different time points after TBI to measure brain water content.The cerebral edema and BBB changes in structure were examined with an optical microscopy (OM) and transmission electron microscopy (TEM),and the IgG content and AQP4 protein expression in traumatic brain tissue were determined by means of immunohistochemistry and Western blotting.The data were analyzed with SPSS 13.0statistical software.Results In the SO greup,tissue was negative for IgG,and there were no abnormalities in brain water content or AQP4 expression.In the TBI group,brain water content significantly increased at 6 hours and peaked at 24 hours following injury.IgG expression significantly increased from 1 to 6 hours following injury,and remained at a high level at 24 hours.Pathological observation revealed BBB damage at 1 hour following injury.Angioedema appeared at 1 hour,was gradually aggravated,and became obvious at 6 hours.Intracellular edema occurred at 3 hours,with the presence of large glial cell bodies and mitochondrial swelling.These phenomena were aggravated with time and became obvious at 12 hours.In addition,microglial proliferation was visible at 24 hours.AQP4 protein expression were reduced at 1 hour,lowest at 6 hours,and began to increase at 12 hours

  10. Elastolytic activity and alveolar epithelial type-1 cell damage after chronic LPS inhalation: Effects of dexamethasone and rolipram

    International Nuclear Information System (INIS)

    This study investigated whether a correlation between leukocyte-derived elastolytic activity, alveolar epithelial type-1 cell damage, and leukocyte infiltration of the airways existed in guinea-pigs chronically exposed to inhaled lipopolysaccharide (LPS). The airway pathology of this model, notably the neutrophilia, resembles chronic obstructive pulmonary disease (COPD). The effect of the corticosteroid, dexamethasone, or the phosphodiesterase-4 (PDE4)-inhibitor, rolipram, on these features was studied. Conscious guinea-pigs were exposed for 1 h to single or repeated (nine) doses of LPS (30 μg ml-1). Dexamethasone (20 mg kg-1, ip) or rolipram (1 mg kg-1, ip) was administered 24 and 0.5 h before the first exposure and daily thereafter. Bronchoalveolar lavage fluid (BALF) was removed and elastolytic activity determined as the elastase-like release of Congo Red from impregnated elastin. The presence of the specific epithelial cell type-1 protein (40-42 kDa) RT140 in BALF was identified by Western blotting using a rat monoclonal antibody and semi-quantified by dot-blot analysis. The antibody was found to identify guinea-pig RT140. BALF inflammatory cells, particularly neutrophils and macrophages, and elastolytic activity were increased in chronic LPS-exposed guinea-pigs, the latter by 90%. Chronic LPS exposure also increased (10.5-fold) RT140 levels, indicating significant alveolar epithelial type-1 cell damage. Dexamethasone or rolipram treatment reduced the influx of inflammatory cells, the elastolytic activity (by 40% and 38%, respectively), and RT140 levels (by 50% and 57%, respectively). In conclusion, chronic LPS-exposed guinea-pigs, like COPD, exhibit elastolytic lung damage. This was prevented by a PDE4 inhibitor and supports their development for suppressing this leukocyte-mediated pathology

  11. Cerebral circulation and metabolism in the patients with higher brain dysfunction caused by chronic minor traumatic brain injury. A study by the positron emission tomography in twenty subjects with normal MRI findings

    International Nuclear Information System (INIS)

    . After 9.3 months, FIQ scores of 13 subjects were significantly increased. CMRO2 was significantly increased in the bilateral frontal and temporal lobe, as well as in the right occipital lobe, along with the improvement of FIQ score. It was concluded that higher brain dysfunction caused by chronic MTBI was related to malfunction of neuronal networks based on the generalized decrease of brain oxygen metabolism in all brain regions. Damage to neuronal networks in the bilateral frontal and temporal lobe appeared to play the most important role in higher brain dysfunction. (author)

  12. Resveratrol supplementation protects against chronic nicotine-induced oxidative damage and organ dysfunction in the rat urogenital system

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    Hale Toklu

    2010-01-01

    Full Text Available The protective effect of resveratrol against nicotine induced oxidative damage on urogenital tissues was evaluated by biochemical, histological and functional studies. Wistar Albino rats were injected with either nicotine hydrogen bitartarate (0.6 mg/kg/day, ip or saline. Resveratrol (10 mg/kg, po was administered along with saline or nicotine injections for 28 days. After decapitation, the urinary bladder, corpus cavernosum and kidney tissues were excised. Corpus cavernosum and bladder tissues were used for in vitro contractility studies, or stored at -80 ºC along with kidney tissue for the measurement of malondialdehyde (MDA, glutathione (GSH, and luminol-lucigenin chemiluminescence (CL levels. Tissue samples were also examined histologically. Chronic nicotine administration caused a significant decrease in GSH levels and increases in MDA levels, and luminol-lucigenin CL in kidney, urinary bladder and corpus cavernosum tissues, suggesting oxidative organ damage, which was also verified histologically. In serum samples increased blood urea nitrogen (BUN, creatinine, proinflammatory cytokines (TNF-α and IL-1β, lactate dehydrogenase (LDH activity, oxidative DNA damage (8-OHdG and decreased antioxidant capacity (AOC due to nicotine administration were reversed with resveratrol. Furthermore, chronic nicotine administration impaired the contractile activity of the bladder and corpus cavernosum strips while resveratrol supplementation to nicotine-treated animals reversed these effects in both tissues. Resveratrol treatment to the nicotine group restored the endogenous GSH levels and decreased oxidative damage parameters in all studied tissues. These data suggest that resveratrol supplementation effectively counteracts the deleterious effect of chronic nicotine administration on bladder, corpus cavernosum and kidney functions and attenuates oxidative damage possibly by its antioxidant effects.

  13. Development of brain damage as measured by brain impedance recordings, and changes in heart rate, and blood pressure induced by different stunning and killing methods.

    Science.gov (United States)

    Savenije, B; Lambooij, E; Gerritzen, M A; Korf, J

    2002-04-01

    Poultry are electrically stunned before slaughter to induce unconsciousness and to immobilize the chickens for easier killing. From a welfare point of view, electrical stunning should induce immediate and lasting unconsciousness in the chicken. As an alternative to electroencephalography, which measures brain electrical activity, this study used brain impedance recordings, which measure brain metabolic activity, to determine the onset and development of brain damage. Fifty-six chickens were surgically equipped with brain electrodes and a canula in the wing artery and were subjected to one of seven stunning and killing methods: whole body electrical stunning; head-only electrical stunning at 50, 100 or 150 V; or an i.v. injection with MgCl2. After 30 s, the chickens were exsanguinated. Brain impedance and blood pressure were measured. Extracellular volume was determined from the brain impedance data and heart rate from the blood pressure data. An immediate and progressive reduction in extracellular volume in all chickens was found only with whole body stunning at 150 V. This treatment also caused cardiac fibrillation or arrest in all chickens. With all other electrical stunning treatments, extracellular volume was immediately reduced in some but not all birds, and cardiac fibrillation or arrest was not often found. Ischemic conditions, caused by cessation of the circulation, stimulated this epileptic effect. A stunner setting of 150 V is therefore recommended to ensure immediate and lasting unconsciousness, which is a requirement for humane slaughter. PMID:11989758

  14. Evaluation of the serum catalase and myeloperoxidase activities in chronic arsenic-exposed individuals and concomitant cytogenetic damage

    International Nuclear Information System (INIS)

    Chronic arsenic exposure through contaminated drinking water is a major environmental health issue. Chronic arsenic exposure is known to exert its toxic effects by a variety of mechanisms, of which generation of reactive oxygen species (ROS) is one of the most important. A high level of ROS, in turn, leads to DNA damage that might ultimately culminate in cancer. In order to keep the level of ROS in balance, an array of enzymes is present, of which catalase (CAT) and myeloperoxidase (MPO) are important members. Hence, in this study, we determined the activities of these two enzymes in the sera and chromosomal aberrations (CA) in peripheral blood lymphocytes in individuals exposed and unexposed to arsenic in drinking water. Arsenic in drinking water and in urine was used as a measure of exposure. Our results show that individuals chronically exposed to arsenic have significantly higher CAT and MPO activities and higher incidence of CA. We found moderate positive correlations between CAT and MPO activities, induction of CA and arsenic in urine and water. These results indicate that chronic arsenic exposure causes higher CAT and MPO activities in serum that correlates with induction of genetic damage. We conclude that the serum levels of these enzymes might be used as biomarkers of early arsenic exposure induced disease much before the classical dermatological symptoms of arsenicosis begin to appear.

  15. 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.

  16. Chronic and acute alcohol administration induced neurochemical changes in the brain: comparison of distinct zebrafish populations.

    Science.gov (United States)

    Chatterjee, Diptendu; Shams, Soaleha; Gerlai, Robert

    2014-04-01

    The zebrafish is increasingly utilized in the analysis of the effects of ethanol (alcohol) on brain function and behavior. We have shown significant population-dependent alcohol-induced changes in zebrafish behavior and have started to analyze alterations in dopaminergic and serotoninergic responses. Here, we analyze the effects of alcohol on levels of selected neurochemicals using a 2 × 3 (chronic × acute) between-subject alcohol exposure paradigm randomized for two zebrafish populations, AB and SF. Each fish first received the particular chronic treatment (0 or 0.5 vol/vol% alcohol) and subsequently the acute exposure (0, 0.5 or 1.0% alcohol). We report changes in levels of dopamine, DOPAC, serotonin, 5HIAA, glutamate, GABA, aspartate, glycine and taurine as quantified from whole brain extracts using HPLC. We also analyze monoamine oxidase and tyrosine hydroxylase enzymatic activity. The results demonstrate that compared to SF, AB is more responsive to both acute alcohol exposure and acute alcohol withdrawal at the level of neurochemistry, a finding that correlates well with prior behavioral observations and one which suggests the involvement of genes in the observed alcohol effects. We discuss correlations between the current results and prior behavioral findings, and stress the importance of characterization of zebrafish strains for future behavior genetic and psychopharmacology studies. PMID:24381007

  17. Impaired cerebral autoregulation is associated with brain atrophy and worse functional status in chronic ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Mikio C Aoi

    Full Text Available Dynamic cerebral autoregulation (dCA is impaired following stroke. However, the relationship between dCA, brain atrophy, and functional outcomes following stroke remains unclear. In this study, we aimed to determine whether impairment of dCA is associated with atrophy in specific regions or globally, thereby affecting daily functions in stroke patients.We performed a retrospective analysis of 33 subjects with chronic infarctions in the middle cerebral artery territory, and 109 age-matched non-stroke subjects. dCA was assessed via the phase relationship between arterial blood pressure and cerebral blood flow velocity. Brain tissue volumes were quantified from MRI. Functional status was assessed by gait speed, instrumental activities of daily living (IADL, modified Rankin Scale, and NIH Stroke Score.Compared to the non-stroke group, stroke subjects showed degraded dCA bilaterally, and showed gray matter atrophy in the frontal, parietal and temporal lobes ipsilateral to infarct. In stroke subjects, better dCA was associated with less temporal lobe gray matter atrophy on the infracted side ([Formula: see text] = 0.029, faster gait speed ([Formula: see text] = 0.018 and lower IADL score ([Formula: see text]0.002. Our results indicate that better dynamic cerebral perfusion regulation is associated with less atrophy and better long-term functional status in older adults with chronic ischemic infarctions.

  18. Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage

    OpenAIRE

    YU, LIN-SHENG; FAN, YAN-YAN; YE, GUANGHUA; Li, Junli; FENG, XIANG-PING; Lin, Kezhi; DONG, MIUWU; Wang, Zhenyuan

    2016-01-01

    The present study aimed to investigate the therapeutic effects of curcumin (CU) against brain edema in a rat model of hypoxia-hypercapnia (HH)-induced brain damage (HHBD). Male Sprague-Dawley rats were divided into five groups, including a control group and four treatment groups. The rats in the control group were raised under normal laboratory conditions and were injected with water, whereas the rats in the treatment groups were exposed to a low O2/high CO2 environment simulating HH conditio...

  19. Implicit and Explicit Routes to Recognize the Own Body: Evidence from Brain Damaged Patients

    Science.gov (United States)

    Candini, Michela; Farinelli, Marina; Ferri, Francesca; Avanzi, Stefano; Cevolani, Daniela; Gallese, Vittorio; Northoff, Georg; Frassinetti, Francesca

    2016-01-01

    Much research suggested that recognizing our own body-parts and attributing a body-part to our physical self-likely involve distinct processes. Accordingly, facilitation for self-body-parts was found when an implicit, but not an explicit, self-recognition was required. Here, we assess whether implicit and explicit bodily self-recognition is mediated by different cerebral networks and can be selectively impaired after brain lesion. To this aim, right- (RBD) and left- (LBD) brain damaged patients and age-matched controls were presented with rotated pictures of either self- or other-people hands. In the Implicit task participants were submitted to hand laterality judgments. In the Explicit task they had to judge whether the hand belonged, or not, to them. In the Implicit task, controls and LBD patients, but not RBD patients, showed an advantage for self-body stimuli. In the Explicit task a disadvantage emerged for self-compared to others' body stimuli in controls as well as in patients. Moreover, when we directly compared the performance of patients and controls, we found RBD, but not LBD, patients to be impaired in both the implicit and explicit recognition of self-body-part stimuli. Conversely, no differences were found for others' body-part stimuli. Crucially, 40% RBD patients showed a selective deficit for implicit processing of self-body-part stimuli, whereas 27% of them showed a selective deficit in the explicit recognition of their own body. Additionally, we provide anatomical evidence revealing the neural basis of this dissociation. Based on both behavioral and anatomical data, we suggest that different areas of the right hemisphere underpin implicit and explicit self-body knowledge.

  20. 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

  1. 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.

  2. Melatonin reduces membrane rigidity and oxidative damage in the brain of SAMP8 mice.

    Science.gov (United States)

    García, J J; Piñol-Ripoll, G; Martínez-Ballarín, E; Fuentes-Broto, L; Miana-Mena, F J; Venegas, C; Caballero, B; Escames, G; Coto-Montes, A; Acuña-Castroviejo, D

    2011-11-01

    We evaluated the autophagy-lysosomal pathway and membrane fluidity in brain cells and mitochondrial membranes obtained from senescence-accelerated (SAMP(8)) and senescence-resistant (SAMR(1)) mice at 5 and 10 months of age. Moreover, we studied whether chronic treatment from age 1 to 10 months with melatonin stabilizes membrane fluidity. Fluidity was measured by polarization changes of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene-p-toluene sulfonate. Results showed that in untreated animals at 5 months of age, synaptosomal and mitochondrial fluidity was decreased in SAMP(8) compared to SAMR(1), as was the cathepsin D/B ratio, indicating dysfunction of the autophagy-lysosomal pathway. Moreover, we detected synaptosomal rigidity and programmed cell death capability in both groups at 10 months of age. Mitochondrial fluidity, however, did not show a significant age-dependent change but was lower in SAMP(8) than in SAMR(1) at the 5- and 10-month time points. Melatonin administration prevented rigidity in the mitochondrial membrane and seemed to decrease age-related autophagy-lysosomal alterations. These data suggest that melatonin may act to slow down the aging process because of its ability to enhance membrane fluidity and maintain structural pathways. PMID:20096480

  3. 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. PMID:27245243

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

    Directory of Open Access Journals (Sweden)

    Bárbara B. Garrido-Suárez

    2015-12-01

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

  5. Evaluation of brain CT scan in children with chronic and recurrent headache in kashan in the year 1996

    OpenAIRE

    A. Talebian; M.Kohnavard Aslee; A.R.TabasiH

    2001-01-01

    SummaryBackground and purpose: Since headache is one of the common problems in children and adolescents and only a minority of them have a life threatening intracranial lesions and performing brain CT scan in many of such cases is costly, therefore it was decided to evaluate the findings of brain CT scan of children with chronic and recurrent headache.Materials and Methods: This study was performed on 300 children of 5-15 years of age with a complaint of chronic recurrenthead-ache in kashan i...

  6. Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports

    OpenAIRE

    Naeser, Margaret A.; Saltmarche, Anita; Krengel, Maxine H.; Hamblin, Michael R.; Knight, Jeffrey A.

    2011-01-01

    Objective: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented. Background: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI pati...

  7. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    International Nuclear Information System (INIS)

    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 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl4, 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. Highlights: ► After 30-day chronic CCl4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

  8. Radiation damage to the normal monkey brain. Experimental study induced by interstitial irradiation

    International Nuclear Information System (INIS)

    Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT), magnetic resonance imaging (MRI), and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis. (author)

  9. Alteration in rectification of potassium channels in perinatal hypoxia ischemia brain damage.

    Science.gov (United States)

    Chen, Penghui; Wang, Liyan; Deng, Qiyue; Ruan, Huaizhen; Cai, Wenqin

    2015-01-15

    Oligodendrocyte progenitor cells (OPCs) are susceptible to perinatal hypoxia ischemia brain damage (HIBD), which results in infant cerebral palsy due to the effects on myelination. The origin of OPC vulnerability in HIBD, however, remains controversial. In this study, we defined the HIBD punctate lesions by MRI diffuse excessive high signal intensity (DEHSI) in postnatal 7-day-old rats. The electrophysiological functional properties of OPCs in HIBD were recorded by patch-clamp in acute cerebral cortex slices. The slices were intracellularly injected with Lucifer yellow and immunohistochemically labeled with NG2 antibody to identify local OPCs. Passive membrane properties and K(+) channel functions in OPCs were analyzed to estimate the onset of vulnerability in HIBD. The resting membrane potential, membrane resistance, and membrane capacitance of OPCs were increased in both the gray and white matter of the cerebral cortex. OPCs in both the gray and white matter exhibited voltage-dependent K(+) currents, which consisted of the initiated rectified potassium currents (IA) and the sustained rectified currents (IK). The significant alternation in membrane resistance was influenced by the diversity of potassium channel kinetics. These findings suggest that the rectification of IA and IK channels may play a significant role in OPC vulnerability in HIBD. PMID:25355958

  10. Pilot study: Computer-based virtual anatomical interactivity for rehabilitation of individuals with chronic acquired brain injury

    OpenAIRE

    C. Douglas Simmons, PhD, OTR/L, FAOTA; Sajay Arthanat, PhD, OTR/L, ATP; Vincent J. Macri, BA, MA

    2014-01-01

    Deficiencies in upper-limb motor function and executive functioning can compromise an affected individual’s ability to complete everyday activities. Impaired motor and executive functioning therefore pose a risk to increasing numbers of veterans who have been diagnosed with acquired brain injury. This article reports on changes in upper-limb motor function and executive functioning of 12 adult participants with chronic acquired brain injury using a novel, computer-based, motor and cognitive r...

  11. Mechanism of brain damaging by rapid evacuation decompression of epidural hematoma explored with dynamic brain SPECT imaging

    International Nuclear Information System (INIS)

    Objective: To explore the value of dynamic brain SPECT imaging in clarifying the major mechanism of obstinate brain edema following evacuation of epidural hematoma. Methods: The dynamic brain SPECT imaging was performed on New Zealand rabbit model of epidural hematoma. The changes of their intracellular [Ca2+], and brain tissue water content were measured, and the correlation between them was analyzed. Results: It is showed that the severe hypoperfusion occurred on compressing parietal lobe for 30 min and hyper-reperfusion occurred 10 min after decompression on dynamic brain SPECT imaging and on its time-radioactivity curve. [Ca2+] increased remarkably after being pressed. There was a short-term decreasing following decompression and then increased gradually reaching the peak at 24 h. The correlation between [Ca2+] and brain tissue water content was with magnificent value (r=0.469, P<0.01). Conclusions: These findings indicate there exists severe reperfusion injury, which is the major mechanism of obstinate brain edema after evacuation of epidural hematoma. The dynamic brain SPECT imaging can show the image evidence of reperfusion clearly and non-invasively. (authors)

  12. Exercise Ameliorates Endocrine Pancreas Damage Induced by Chronic Cola Drinking in Rats

    Science.gov (United States)

    Otero-Losada, Matilde; González, Julián; Müller, Angélica; Ottaviano, Graciela; Cao, Gabriel; Azzato, Francisco; Ambrosio, Giuseppe; Milei, José

    2016-01-01

    Purpose This study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats. Methods 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. Results 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). Conclusion 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

  13. 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

    2012-10-01

    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. PMID:22772077

  14. 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

  15. PGC-1α Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases.

    Science.gov (United States)

    Xiong, Shiqin; Patrushev, Nikolay; Forouzandeh, Farshad; Hilenski, Lula; Alexander, R Wayne

    2015-09-01

    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. PMID:26299964

  16. Evaluation of the liver function for patients with chronic liver damage using 99mTc-galactosyl human serum albumin

    International Nuclear Information System (INIS)

    99mTc-Galactosyl human serum albumin (99mTc-GSA) is a new liver imaging radiopharmaceutical which specifically binds to the asialoglycoprotein-receptor on the liver cell membrane. We investigated the usefulness of 99mTc-GSA for evaluation of the liver function in patients with chronic liver damage. We calculated LHL15 for the index of hepatic uptake and HH15 for the index of clearance. In patients with liver cirrhosis, LHL15 value was higher and HH15 value was lower than those of other groups. Both decrease in LHL15 value and increase in HH15 value were correlated with the severity of the liver damage. Significant correlation ws also observed between the prolongation of ICG clearance and both decrease in LHL15 value and increase in HH15 value. In conclusion, these findings indicate that 99mTc-GAS can be a useful agent for evaluation of the liver function in patients with chronic liver damage. (author)

  17. 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.

  18. An Experimental Study on Drugs for Improving Blood Circulation and Removing Blood Stasis in Treating Mild Chronic Hepatic Damage

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Large and small doses of drugs for improving blood circulation and removing blood stasis were used in model rats to treat mild chronic hepatic damage induced by carbon tetrachloride (CCl4). The results show that large dose of Dang Gui (当归 Radix Angelicae Sinensis) and Dan Shen (丹参 Radix Salviae Miltiorrhizae) (drugs for regulating blood flow) and small dose of Yu Jin (郁金 Radix Curcumae) and Niu Xi (牛膝 Radix Achyranthis Bidentatae) (drugs for activating blood flow) can significantly elevate the activity of SOD (P<0.05) and/or lower the T/K ratio, markedly reduce the MDA content (P<0.05 or P<0.01) and significantly decrease the activities of ALT and AST (P<0.05 or P<0.01), demonstrating that these drugs are effective in combating oxygen free radicals (OFR) in chronic liver damage. On the contrary, large dose of Tu Bie Chong (土鳖虫 Eupolyphaga seu Steleophaga) and E Zhu (莪术 Rhizoma Curcumae) (drugs for removing blood stasis) tend to increase the ALT and AST (P<0.05) activities. The results suggest that the synergism of elevation of the SOD activity and reduction of T/K ratio contributes to the action of drugs for improving blood circulation and removing blood stasis in combating the liver damage induced by CCl4.

  19. Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.

    Science.gov (United States)

    Ojo, Joseph O; Mouzon, Benoit; Algamal, Moustafa; Leary, Paige; Lynch, Cillian; Abdullah, Laila; Evans, James; Mullan, Michael; Bachmeier, Corbin; Stewart, William; Crawford, Fiona

    2016-07-01

    Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI. PMID:27251042

  20. Verbal memory in brain damaged patients under different conditions of retrieval aids: a study of frontal, temporal, and diencephalic damaged subjects.

    Science.gov (United States)

    Vogel, C C; Markowitsch, H J; Hempel, U; Hackenberg, P

    1987-04-01

    The performance of 36 patients, divided into six groups, and 13 control subjects was investigated in paired-associate learning. The patients had right or left prefrontal, right or left anterior lateral temporopolar or medial temporal lobe damage, or lesions restricted to diencephalic areas. As tasks, two lists of paired words had to be learned, with the first list presenting only the word pairs, and the second one embedding the word pairs in sentences of a highly imaginable content. Recall consisted of immediate or delayed (48 hrs) free recall of the first list (condition I), of immediate or delayed recall of the second list (with visual imagery as a learning aid; condition II), and of cued recall (in which the sentence form was presented with a blank space where the word to be recalled had been previously; condition III). Control subjects clearly performed best under all conditions, manifesting a ceiling effect for the second and third ones under immediate recall. Among the brain-damaged groups the diencephalic subjects were poorest and gained only little from the aids given for learning and recall. Of the four patients with medial temporal lobe damage, those two with bilateral lesions were nearly as bad as the diencephalic lesioned subjects. The other patients were markedly inferior to the control subjects, but gained considerably under conditions II and III. These statements hold for immediate and delayed recall, though for the delayed recall conditions all groups showed a reduction in performance which amounted to roughly half of the values they had had under immediate recall. It is concluded that increasing the possibilities for depth of information processing assists brain damaged (as well as normal) subjects in verbal learning, but that the advantage of aiding them at the moment of encoding and retrieval is highest for patients with restricted lesions and/or with lesions not invading the two regions most regularly implicated in long-term information

  1. Monitoring stroke progression: in vivo imaging of cortical perfusion, blood–brain barrier permeability and cellular damage in the rat photothrombosis model

    OpenAIRE

    Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon

    2014-01-01

    Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood–brain barrier (BBB), yet the role of disturbed vascular permea...

  2. Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove;

    2016-01-01

    Abstract This data article describes a large, high resolution diffusion MRI data set from fixed rat brain acquired at high field strength. The rat brain samples consist of21adult rat brain hemispheres from animals exposed to chronic mild stress (anhedonic and resilient) and controls. Histology from...... (ALDH1L1). This combination of high field diffusion data and high resolution images from microscopy enables comparison of microstructural parameters derived from diffusion MRIto histological microstructure. The data provided here is used in the article (Jespersen, 2016) [1]....

  3. 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

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

    Science.gov (United States)

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

    2014-05-01

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

  5. Diffuse traumatic brain injury affects chronic corticosterone function in the rat

    Directory of Open Access Journals (Sweden)

    Rachel K Rowe

    2016-07-01

    Full Text Available As many as 20–55% of patients with a history of traumatic brain injury (TBI experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration–deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic–pituitary endocrine (HPE dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT, a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI. At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain, neuropathology (silver stain and activated astrocytes (GFAP in the paraventricular nucleus (PVN of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI.

  6. Diffuse traumatic brain injury affects chronic corticosterone function in the rat.

    Science.gov (United States)

    Rowe, Rachel K; Rumney, Benjamin M; May, Hazel G; Permana, Paska; Adelson, P David; Harman, S Mitchell; Lifshitz, Jonathan; Thomas, Theresa C

    2016-07-01

    As many as 20-55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration-deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic-pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI. PMID:27317610

  7. Efficient neuroplasticity induction in chronic stroke patients by an associative brain-computer interface.

    Science.gov (United States)

    Mrachacz-Kersting, Natalie; Jiang, Ning; Stevenson, Andrew James Thomas; Niazi, Imran Khan; Kostic, Vladimir; Pavlovic, Aleksandra; Radovanovic, Sasa; Djuric-Jovicic, Milica; Agosta, Federica; Dremstrup, Kim; Farina, Dario

    2016-03-01

    Brain-computer interfaces (BCIs) have the potential to improve functionality in chronic stoke patients when applied over a large number of sessions. Here we evaluated the effect and the underlying mechanisms of three BCI training sessions in a double-blind sham-controlled design. The applied BCI is based on Hebbian principles of associativity that hypothesize that neural assemblies activated in a correlated manner will strengthen synaptic connections. Twenty-two chronic stroke patients were divided into two training groups. Movement-related cortical potentials (MRCPs) were detected by electroencephalography during repetitions of foot dorsiflexion. Detection triggered a single electrical stimulation of the common peroneal nerve timed so that the resulting afferent volley arrived at the peak negative phase of the MRCP (BCIassociative group) or randomly (BCInonassociative group). Fugl-Meyer motor assessment (FM), 10-m walking speed, foot and hand tapping frequency, diffusion tensor imaging (DTI) data, and the excitability of the corticospinal tract to the target muscle [tibialis anterior (TA)] were quantified. The TA motor evoked potential (MEP) increased significantly after the BCIassociative intervention, but not for the BCInonassociative group. FM 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. Corticospinal tract integrity on DTI did not correlate with clinical or physiological changes. For the BCI as applied here, the precise coupling between the brain command and the afferent signal was imperative for the behavioral, clinical, and neurophysiological changes reported. This association may become the driving principle for the design of BCI rehabilitation in the future. Indeed, no available BCIs can match this degree of functional improvement with such a short intervention. PMID:26719088

  8. Multimodal deficits in right brain damaged patients with and without neglect and their modulation by sensory stimulation techniques

    OpenAIRE

    Rosenthal, Alisha

    2015-01-01

    Spatial neglect is a neurological disorder most often caused by vascular, right hemispheric brain damage. It is mainly characterized by a failure to attend, orient to or react to stimuli presented in the contralesional hemispace. By definition, neglect is seen as a higher order spatial disorder not merely caused by a sensory (e.g. hemianopia) or motor (e.g. hemiplegia) deficit. This definition includes the aspect of multimodality, which plays a central role in the assessment and therapy of th...

  9. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

    OpenAIRE

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

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600–1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the tr...

  10. 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...

  11. Functional Magnetic Resonance Imaging of Chronic Dysarthric Speech after Childhood Brain Injury: Reliance on a Left-Hemisphere Compensatory Network

    Science.gov (United States)

    Morgan, Angela T.; Masterton, Richard; Pigdon, Lauren; Connelly, Alan; Liegeois, Frederique J.

    2013-01-01

    Severe and persistent speech disorder, dysarthria, may be present for life after brain injury in childhood, yet the neural correlates of this chronic disorder remain elusive. Although abundant literature is available on language reorganization after lesions in childhood, little is known about the capacity of motor speech networks to reorganize…

  12. Differences in 99mTc-HMPAO brain SPET perfusion imaging between Tourette's syndrome and chronic tic disorder in children

    International Nuclear Information System (INIS)

    Early differential diagnosis between Tourette's syndrome and chronic tic disorder is difficult but important because both the outcome and the treatment of these two childhood-onset diseases are distinct. We assessed the sensitivity and specificity of brain single-photon emission tomography (SPET) perfusion imaging in distinguishing the two diseases, and characterized their different cerebral perfusion patterns. Twenty-seven children with Tourette's syndrome and 11 with chronic tic disorder (mean age 9.5 and 8.6 years, respectively) underwent brain SPET with technetium-99m hexamethylpropylene amine oxime (HMPAO). Visual interpretation and semi-quantitative analysis of SPET images were performed. On visual interpretation, 22 of 27 (82%) of the Tourette's syndrome group had lesions characterized by decreased perfusion. The left hemisphere was more frequently involved. None of the children with chronic tic disorder had a visible abnormality. Semi-quantitative analysis showed that, compared with children with chronic tic disorder, children with Tourette's syndrome had significantly lower perfusion in the left lateral temporal area and asymmetric perfusion in the dorsolateral frontal, lateral and medial temporal areas. In conclusion, using the visual approach, brain SPET perfusion imaging is sensitive and specific in differentiating Tourette's syndrome and chronic tic disorder. The perfusion difference between the two groups, demonstrated by semi-quantitative analysis, may be related more to the co-morbidity in Tourette's syndrome than to tics per se. (orig.)

  13. BRAIN DAMAGE AND OXIDATIVE STRESS IN THE PERINATAL PERIOD: MELATONIN AS A NEUROPROTECTIVE NEW DRUG

    Directory of Open Access Journals (Sweden)

    S. Perrone

    2012-08-01

    Full Text Available Prenatal factors represent the main determinants of hypoxicischemic encephalopathy (HIE rather than intra- or post-partum conditions in perinatal period. Oxidative stress (OS plays a key role in perinatal brain damage. The development of therapeutic strategies to improve the outcomes of babies with HIE is still mandatory. Aim: to evaluate the effectiveness of melatonin as a neuroprotective drug. To investigate the influence of Melatonin on the OS biomarkers production in an animal model of cerebral hypoxia-ischemia. Methods: 30 rat pups were subjected to ligation of the right common carotid artery and exposed for 2.5 hours at an hypoxic condition. A group of 15 rats was administered melatonin at a dose of 15 mg/kg 5 minutes after the procedure (Mel GROUP. At the same time 15 rats received placebo (HI GROUP. A group of 5 healthy rats was used as sham operated (S GROUP. Isoprostanes (IsoPs, neuroprostanes (NPs and neurofurans (NFs, all markers of OS were measured at 1, 24 and 48 h from ischemic injury in homogenized cerebral cortex of the two sides, right (hypoxia and ischemia and left (hypoxia. Results: In the HI group were observed: a significant increase of IsoPs on the left side of cortex after 1 h from HI injury (p<0.001; a significant increase of NPs on both sides after 24 h (p<0.05 and a significant increase of NFs on the left (p<0.05 after 24 h. After 48 h in the Mel group was observed a significant increase of IsoPs on the left (p<0.05 and of NPs on both sides of cerebral cortex (p<0.05. Conclusions: Melatonin reduces OS biomarkers in cerebral cortex of HI rats after 24 h from its administration. The drug is no longer effective after 48 h. These results lay the groundwork for future clinical studies in infants.

  14. 1HMR spectroscopy and diffusion tensor technology in heroin-induced brain damage

    International Nuclear Information System (INIS)

    Objective: To study the values of 1HMRS and DTI technology for detecting brain damage in heroin-dependent patients. Methods: The routine MRI, 1HMRS and DTI were performed in 7 heroin abusers and 8 healthy volunteers without the history of drug abuse. The regions of interest (ROI) were selected in the gray matter and white matter of prefrontal lobe in 1HMRS exam, and the ratio of NAA/ Cr, Cho/Cr and Cho/NAA were measured respectively. For the DTI, six ROIs were selected, and the values of fractional anisotropy (FA) and ADC were calculated respectively. The independent samples t test was used for the statistics. Results: No abnormality was found in the routine MRI. The ratio of NAA/Cr decreased in the prefrontal lobe, the values were 1.40 + 0. 16 in gray matter and 1.72 + 0.41 in white matter of the drug group, 1.57±0.09 and 2.08±0.21 in the control group on 1HMRS examiation. The difference between the two groups had statistical significance (t = 2. 183, 2.190, P -4, (7.54±0.22) x 10-4, (7.72±0.30) x 10-4, and (7.50±0.26) x 10-4, (7.15±0.20) x 10-4, (7.19±0.39) x 10-4 mm2/s in control group respectively. The difference between the two groups had statistical significance (t=3.477, 3.507, 2.895, P1HMRS and DTI. (authors)

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  16. Effect of thermal therapy using hot water bottles on brain natriuretic peptide in chronic hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Yoko Uchiyama-Tanaka

    2013-02-01

    Full Text Available Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The author assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with chronic heart failure. Methods: The author evaluated plasma brain natriuretic peptide (BNP levels in 98 hemodialysis patients in a clinic. A total of nine patients whose BNP levels were more than 500 pg/mL agreed to be enrolled in this study and received thermal therapy using hot water bottles. Results: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 ± 448 pg/mL to 680 ± 339 pg/mL, but the difference was not significant (P = 0.0845. The oral temperature changed from 36.44℃± 0.45℃ to 37.04℃ ± 0.48℃ (+0.597℃, P

  17. Changes of Plasma Levels of Brain Natriuretic Peptide in Patients with Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)

    Pei Xiaoyang; Pan Ying; Hu Xuesong; Li Song; Xu Yawei; Yu Xuejing

    2006-01-01

    Objectives To investigate the changes of plasma brain natriuretic peptide (BNP) levels in patients with chronic heart failure (CHF).Methods Plasma BNP concentrations in patients with CHF (n=56) and in normal controls (n=60) were measured with specific radioimmunoassay. Left ventricular ejection fraction in patients with chronic heart failure was measured with 99mTc gated cardiac blood pool scintigraphy. Results The results showed that Plasma BNP concentrations in patients with CHF were significantly higher than normal controls (223±79 ng/L vs 40±15 ng/L, P < 0.01). Plasma BNP concentrations had a significant negative correlation with left ventricular ejection fractions(r=-0.68, P <0.01 ). Conclusions These results indicates that Plasma BNP levels are increased in patients with CHF, and they markedly increased according to the severity of heart failure classified by NYHA classification. The plasma BNP levels may be a biochemical parameter for evaluating the left ventricular function.

  18. Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.

    Science.gov (United States)

    Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

    2016-01-01

    Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; P<0.0001), regardless of the diet. All groups presented similar insulin sensitivity index (ISI = 1.39±0.10 mL·min-1·μUI·kg). Compared to starch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these

  19. Brain SPECT of chronic fatigue syndrome (CFS): a blinded visual analysis

    International Nuclear Information System (INIS)

    Full text: Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterised by profound fatigue and neuropsychiatric dysfunction. Previous studies with cerebral perfusion SPECT (rCBF) scans have yielded conflicting results. Most were performed with inhomogeneous patient populations and the findings were not based on a blinded visual analysis. To address this, HMPAO SPECT on a triple head gamma camera was performed on a group of 59 subjects. This group included 32 subjects (16-61 years, 24F and 8M) with moderate CFS based on the Fukuda criteria not on medication and not depressed and 27 normal volunteers (20-56 years, 16F and 11 M). Two blinded reviewers (RC and GC) separately assessed the SPECT studies. 28 brain structures were scored as either definitely abnormal(1), possibly abnormal(2) or normal(3-5). Abnormal results were only found in the temporal lobes and brainstem. The results (Sensitivity/Specificity) based on scores 1 or 2, show that that abnormal score yielded acceptable specificity but low sensitivity. Scores 1 or 2 improved sensitivity but reduced the specificity. This shows that visual analysis of brain SPECT is not a reliable discriminant test for CFS, although quantitative analysis with statistical parametric mapping (SPM) has demonstrated significant abnormalities. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  20. Brain-computer interfaces in the completely locked-in state and chronic stroke.

    Science.gov (United States)

    Chaudhary, U; Birbaumer, N; Ramos-Murguialday, A

    2016-01-01

    Brain-computer interfaces (BCIs) use brain activity to control external devices, facilitating paralyzed patients to interact with the environment. In this chapter, we discuss the historical perspective of development of BCIs and the current advances of noninvasive BCIs for communication in patients with amyotrophic lateral sclerosis and for restoration of motor impairment after severe stroke. Distinct techniques have been explored to control a BCI in patient population especially electroencephalography (EEG) and more recently near-infrared spectroscopy (NIRS) because of their noninvasive nature and low cost. Previous studies demonstrated successful communication of patients with locked-in state (LIS) using EEG- and invasive electrocorticography-BCI and intracortical recordings when patients still showed residual eye control, but not with patients with complete LIS (ie, complete paralysis). Recently, a NIRS-BCI and classical conditioning procedure was introduced, allowing communication in patients in the complete locked-in state (CLIS). In severe chronic stroke without residual hand function first results indicate a possible superior motor rehabilitation to available treatment using BCI training. Here we present an overview of the available studies and recent results, which open new doors for communication, in the completely paralyzed and rehabilitation in severely affected stroke patients. We also reflect on and describe possible neuronal and learning mechanisms responsible for BCI control and perspective for future BMI research for communication in CLIS and stroke motor recovery. PMID:27590968

  1. Cognitive Gains from Gist Reasoning Training in Adolescents with Chronic-Stage Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Lori G. Cook

    2014-06-01

    Full Text Available Adolescents with traumatic brain injury (TBI typically demonstrate good recovery of previously acquired skills. However, higher-order and later emergent cognitive functions are often impaired and linked to poor outcomes in academic and social/behavioral domains. Few control trials exist that test cognitive treatment effectiveness at chronic recovery stages. The current pilot study compared the effects of two forms of cognitive training, gist reasoning (top-down versus rote memory learning (bottom-up, on ability to abstract meanings, recall facts, and utilize core executive functions (i.e., working memory, inhibition in 20 adolescents (ages 12-20 who were six months or longer post-TBI. Participants completed eight 45-minute sessions over one month. After training, the gist reasoning group (n = 10 exhibited significant improvement in ability to abstract meanings and increased fact recall. This group also showed significant generalizations to untrained executive functions of working memory and inhibition. The memory training group (n = 10 failed to show significant gains in ability to abstract meaning or on other untrained specialized executive functions, although improved fact recall approached significance. These preliminary results suggest that relatively short-term training (6 hours utilizing a top-down reasoning approach is more effective than a bottom-up rote learning approach in achieving gains in higher-order cognitive abilities in adolescents at chronic stages of TBI. These findings need to be replicated in a larger study; nonetheless, the preliminary data suggest that traditional cognitive intervention schedules need to extend to later-stage training opportunities. Chronic-stage, higher-order cognitive trainings may serve to elevate levels of cognitive performance in adolescents with TBI.

  2. 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.

  3. 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).

  4. Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

    Directory of Open Access Journals (Sweden)

    BradleyS.Carter

    2013-08-01

    Full Text Available Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested two hours post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for two weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1 similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2 similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.

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

    Science.gov (United States)

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

    2014-11-01

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

  6. Pomegranate Alleviates Oxidative Damage and Neurotransmitter Alterations in Rats Brain Exposed to Aluminum Chloride and/or Gamma Radiation

    International Nuclear Information System (INIS)

    Aluminum and gamma radiation, both are potent neurotoxins and have been implicated in many human neuro degenerative diseases. The present study was designed to investigate the role of pomegranate in alleviating oxidative damage and alteration of neurotransmitters in the brain of rats exposed to aluminum chloride (AlCl3), and/or gamma radiation (IR). The results revealed that rats whole body exposed to γ- rays, (1 Gy/week up to 4 Gy), and/or administered aluminum chloride (35 mg/kg body weight), via gavages for 4 weeks, resulted in brain tissue damage, featuring by significant increase of the level of thiobarbituric acid reactive substances (TBARS), and advanced oxidation protein products (AOPP), associated with significant decrease of superoxide dismutase (SOD) and catalase (CAT) activities, as well as glutathione (GSH) content indicating occurrence of oxidative stress. A significant decrease of serotonin (5-HT) level associated with a significant increase of 5-hydroxyindole acetic acid (5-HIAA), in addition to a significant decrease in dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents recorded at the 1st, 7th and 14th day post-irradiation, indicating alterations in the metabolism of brain monoamines. On the other hand, the results exhibited that, supplementation of rats with pomegranate, via gavages, at a dose of 3 ml /kg body weight/ day, for 4 weeks along with AlCl3 with or without radiation has significantly ameliorated the changes occurred in the mentioned parameters and the values returned close to the normal ones. It could be concluded that pomegranate, by its antioxidant constituents might antagonize brain oxidative damage and minimize the severity of aluminum (Al), and/or radiation-induced neurotransmitters disorders

  7. Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood- brain barrier damage and brain oedema independently of infarct size

    OpenAIRE

    Dénes Ádám; Ferenczi Szilamér; Kovács Krisztina J.

    2011-01-01

    Abstract Background Systemic inflammation impairs outcome in stroke patients and experimental animals via mechanisms which are poorly understood. Circulating inflammatory mediators can activate cerebrovascular endothelium or glial cells in the brain and impact on ischaemic brain injury. One of the most serious early clinical complications of cerebral ischaemia is brain oedema, which compromises survival in the first 24-48 h. It is not understood whether systemic inflammatory challenges impair...

  8. Chronic intermittent hypoxia-induced deficits in synaptic plasticity and neurocognitive functions: a role for brain-derived neurotrophic factor

    Institute of Scientific and Technical Information of China (English)

    Hui XIE; Wing-ho YUNG

    2012-01-01

    Obstructive sleep apnea (OSA) is well known for its metabolic as well as neurobehavioral consequences.Chronic intermittent hypoxia (IH) is a major component of OSA.In recent years,substantial advances have been made in elucidating the cellular and molecular mechanisms underlying the effect of chronic IH on neurocognitive functions,many of which are based on studies in animal models.A number of hypotheses have been put forward to explain chronic IH-induced neurological dysfunctions.Among these,the roles of oxidative stress and apoptosis-related neural injury are widely accepted.Here,focusing on results derived from animal studies,we highlight a possible role of reduced expression of brain-derived neurotrophic factor (BDNF) in causing impairment in long-term synaptic plasticity and neurocognitive functions during chronic IH.The possible relationship between BDNF and previous findings on this subject will be elucidated.

  9. [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. PMID:27188144

  10. Attenuation of the bacterial load in blood by pretreatment with granulocyte-colony-stimulating factor protects rats from fatal outcome and brain damage during Streptococcus pneumoniae meningitis

    DEFF Research Database (Denmark)

    Brandt, Christian T; Lundgren, Jens D; Lund, Søren Peter;

    2004-01-01

    postinfection did not alter the clinical or histological outcome relative to that for non-G-CSF-treated rats. The magnitude of bacteremia and pretreatment with G-CSF were found to be prognostic factors for both outcome and brain damage. In summary, elevated neutrophil levels prior to the development of...... meningitis result in reduced risks of death and brain damage. This beneficial effect is most likely achieved through improved control of the systemic disease....

  11. Effect of montelukast on the expression of interleukin-18, telomerase reverse transcriptase, and Bcl-2 in the brain tissue of neonatal rats with hypoxic-ischemic brain damage.

    Science.gov (United States)

    Liu, J L; Zhao, X H; Zhang, D L; Zhang, J B; Liu, Z H

    2015-01-01

    The aim of this study was to investigate the effect of montelukast on the expression of interleukin (IL)-18, telomerase reverse transcriptase (TERT), and Bcl-2 in the brain tissue of neonatal rats with hypox-ic-ischemic brain damage (HIBD). To establish the model of HIBD, 8% oxygen was applied to rats after the unilateral carotid artery was ligated. Twenty rats were randomly assigned to the control group, while another 40 were used to establish the HIBD model and were randomly divided equally into model group and treatment group. A 0.1 mg/kg dose of montelukast or an equal volume of saline was intraperitoneally injected to the rats in the treatment group and the model group, respectively. Brain tissue from 4 rats in each group was sampled at 0, 6, 12, 24, and 72 h after brain damage, and immunohistochemistry was used to measure IL-18, TERT and Bcl-2 expressions. IL-18, TERT, and Bcl-2 levels increased after 12 h in both the model group and treatment group, peaked after 48 h, and then decreased. Although not statistically significant, IL-18, TERT, and Bcl-2 expressions after 24, 48, and 96 h were all lower in the treatment group than those in the model group. In conclusion, montelukast has a protective effect on the cerebral tissue of neonatal rats with HIBD, and may mediate an increase of TERT and Bcl-2 levels but not of IL-18. Further study is required to elucidate the mechanism of the protective effect of montelukast on HIBD. PMID:26345821

  12. Implicit short-lived motor representations of space in brain damaged and healthy subjects.

    Science.gov (United States)

    Rossetti, Y

    1998-09-01

    This article reviews experimental evidence for a specific sensorimotor function which can be dissociated from higher level representations of space. It attempts to delineate this function on the basis of results obtained by psychophysical experiments performed with brain damaged and healthy subjects. Eye and hand movement control exhibit automatic features, such that they are incompatible with conscious control. In addition, they rely on a reference frame different from the one used by conscious perception. Neuropsychological cases provide a strong support for this specific motor representation of space, which can be spared in patients with lesions of primary sensory systems who have lost conscious perception of visual, tactile or proprioceptive stimuli. Observation of these patients also showed that their motor behavior can be "attracted" by a goal only under specific conditions, that is, when the response is immediate and when no cognitive representation of this goal is elaborated at the same time. Beyond the issue of the dissociation between an implicit motor representation and more cognitive processing of spatial information, the issue of the interaction between these two systems is thus a matter of interest. It is suggested that the conscious, cognitive representation of a stimulus can contaminate or override the short-lived motor representation, but no reciprocal influence seem to occur. The interaction observed in patients can also be investigated in normals. The literature provides examples of interaction between sensorimotor and cognitive framing of space, which confirm that immediate action is not mediated by the same system as delayed action, and that elaborating a categorial representation of the action goal prevents the expression of the short-lived sensorimotor representation. It is concluded that action can be controlled by a sensory system which is specialized for on-line processing of relevant goal characteristics. The temporal constraints of this

  13. Changes in cerebral blood flow and psychometric indicators in veterans with early forms of chronic brain ischemia

    Directory of Open Access Journals (Sweden)

    Vasilenko Т.М.

    2015-09-01

    Full Text Available The goal is to study the cerebral blood flow and psychometric characteristics in veterans of Afghanistan with early forms of chronic brain ischemia. Material and Methods. The study included 74 veterans of the Afghan war aged from 45 to 55 years: group 1, 28 people with NPNKM; Group 2-28 patients with circulatory encephalopathy stage 1; group 3-18 healthy persons. Doppler examination of cerebral vessels was carried out on the unit «Smart-lite». Reactive and personal anxiety of patients was assessed using the scale of Spielberger, evaluation of the quality of life through the test SAN. Determining the level of neuroticism and psychoticism was conducted by the scale of neuroticism and psy-choticism. Results: The study of cerebral blood flow in the Afghan war veterans showed signs of insolvency of carotid and carotid-basilar anastomoses, hypoperfusion phenomenon with the depletion of autoregulation, violation of the outflow of venous blood at the level of the microvasculature, accompanied by cerebral arteries spasm. More than 40% of patients with early forms of chronic brain ischemia had high personal anxiety, low levels of well-being and activity, with maximum expression of dyscirculatory hypoxia. Conclusion. Readaptation of veterans of Afghanistan is accompanied by the changes in psychometric performance and the formation of the earliest forms of brain chronic ischemia associated with inadequate hemodynamics providing increased functional activity of the brain and the inefficiency of compensatory-adaptive reactions.

  14. Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain.

    Science.gov (United States)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove; Kroenke, Christopher D; Nyengaard, Jens R; Hansen, Brian; Jespersen, Sune Nørhøj

    2016-09-01

    This data article describes a large, high resolution diffusion MRI data set from fixed rat brain acquired at high field strength. The rat brain samples consist of 21 adult rat brain hemispheres from animals exposed to chronic mild stress (anhedonic and resilient) and controls. Histology from amygdala of the same brain hemispheres is also included with three different stains: DiI and Hoechst stained microscopic images (confocal microscopy) and ALDH1L1 antibody based immunohistochemistry. These stains may be used to evaluate neurite density (DiI), nuclear density (Hoechst) and astrocytic density (ALDH1L1). This combination of high field diffusion data and high resolution images from microscopy enables comparison of microstructural parameters derived from diffusion MRI to histological microstructure. The data provided here is used in the article (Jespersen, 2016) [1]. PMID:27508246

  15. Ameliorative effect of polydatin on oxidative stress-mediated testicular damage by chronic arsenic exposure in rats.

    Science.gov (United States)

    Ince, S; Avdatek, F; Demirel, H H; Arslan-Acaroz, D; Goksel, E; Kucukkurt, I

    2016-06-01

    Arsenic causes lipid peroxidation leading to alterations in antioxidant status in organisms. In this study, the reproductive effects of chronic exposure to arsenic and the protective effects of polydatin (PD) were evaluated in 35 Wistar male rats, which were divided equally into five groups. The control group received a normal diet and tap water, arsenic (100 mg l(-1) , approximately 1/50 of oral LD50 ) was given via drinking water to experimental groups except control group, and PD was orally given to the other groups at dose of 50, 100 and 200 mg kg(-1) for 60 days. Arsenic administration decreased sperm motility, glutathione level, superoxide dismutase and catalase activities in testicular tissue of rats. In contrast, malondialdehyde level and DNA damage were found to be high levels in arsenic-treated group. Histopathologically, it was observed that decreased sperm concentration and degeneration of Sertoli cells in testicular tissue. PD administration, partially 200 mg kg(-1) , reversed arsenic-induced lipid peroxidation, DNA damage, antioxidant enzyme activity and cell integrity in testis of rats. These results demonstrate that PD decreases arsenic-induced lipid peroxidation, enhances the antioxidant defence mechanism and regenerates tissue damage in testis of rats. PMID:26302725

  16. Chronic methamphetamine treatment reduces the expression of synaptic plasticity genes and changes their DNA methylation status in the mouse brain.

    Science.gov (United States)

    Cheng, Min-Chih; Hsu, Shih-Hsin; Chen, Chia-Hsiang

    2015-12-10

    Methamphetamine (METH) is a highly addictive psychostimulant that may cause long-lasting synaptic dysfunction and abnormal gene expression. We aimed to explore the differential expression of synaptic plasticity genes in chronic METH-treated mouse brain. We used the RT(2) Profiler PCR Array and the real-time quantitative PCR to characterize differentially expressed synaptic plasticity genes in the frontal cortex and the hippocampus of chronic METH-treated mice compared with normal saline-treated mice. We further used pyrosequencing to assess DNA methylation changes in the CpG region of the five immediate early genes (IEGs) in chronic METH-treated mouse brain. We detected six downregulated genes in the frontal cortex and the hippocampus of chronic METH-treated mice, including five IEGs (Arc, Egr2, Fos, Klf10, and Nr4a1) and one neuronal receptor gene (Grm1), compared with normal saline-treated group, but only four genes (Arc, Egr2, Fos, and Nr4a1) were confirmed to be different. Furthermore, we found several CpG sites of the Arc and the Fos that had significant changes in DNA methylation status in the frontal cortex of chronic METH-treated mice, while the klf10 and the Nr4a1 that had significant changes in the hippocampus. Our results show that chronic administration of METH may lead to significant downregulation of the IEGs expression in both the frontal cortex and the hippocampus, which may partly account for the molecular mechanism of the action of METH. Furthermore, the changes in DNA methylation status of the IEGs in the brain indicate that an epigenetic mechanism-dependent transcriptional regulation may contribute to METH addiction, which warrants additional study. PMID:26496011

  17. Functional outcome following rehabilitation in chronic severe traumatic brain injury patients: A prospective study

    Directory of Open Access Journals (Sweden)

    Anupam Gupta

    2012-01-01

    Full Text Available Objective: The objective was to assess functional outcome of rehabilitation in chronic severe traumatic brain injury (TBI in-patients. Setting: The study was performed at university tertiary research hospital. Study Design: A prospective cross-sectional study Materials and Methods: Forty patients (34 men with mean age of 30.1 years (range 6--60, SD 10.8, severe TBI (Glasgow coma scale 3--8, duration of coma > 6 hours, post-traumatic amnesia> 1 day postinjury were admitted in rehabilitation unit minimum 3 months (mean 7.7±4.6 months, range 3--22 months following injury falling in Glasgow outcome scale (GOS of 3. Functional recovery was assessed using the Barthel Index (BI score and disability rating scores (DRS. Data Analysis: Paired Student′s t-test was used for the assessment of functional recovery using mean BI scores at admission and discharge. The Wilcoxon nonparametric test was used for the assessment of functional recovery by comparing admission and discharge DRS scores. Results: Mean duration of stay was 30.8 days (range 18--91, SD15.6. Significant functional recovery observed in patients comparing BI and DRS scores at admission and discharge (mean BI admission 50.5±25.4, range 0--85 vs. mean discharge BI score 61.1±25.3, range 0--95, P<0.001, mean DRS admission score 7.57±4.1, range 2.5--21.0 vs. mean discharge DRS score 6.36±4.3, range 1.0-21.0, P<0.001. Conclusion: Patients with severe TBI continue to show functional recovery even in chronic phase with rehabilitation. They are left with significant residual physical and cognitive deficits and would require long-term care and assistance from care givers for the daily activities, as suggested by the mean DRS score at discharge.

  18. Tracking Single Units in Chronic, Large Scale, Neural Recordings for Brain Machine Interface Applications

    Directory of Open Access Journals (Sweden)

    Ahmed eEleryan

    2014-07-01

    Full Text Available In the study of population coding in neurobiological systems, tracking unit identity may be critical to assess possible changes in the coding properties of neuronal constituents over prolonged periods of time. Ensuring unit stability is even more critical for reliable neural decoding of motor variables in intra-cortically controlled brain-machine interfaces (BMIs. Variability in intrinsic spike patterns, tuning characteristics, and single-unit identity over chronic use is a major challenge to maintaining this stability, requiring frequent daily calibration of neural decoders in BMI sessions by an experienced human operator. Here, we report on a unit-stability tracking algorithm that efficiently and autonomously identifies putative single-units that are stable across many sessions using a relatively short duration recording interval at the start of each session. The algorithm first builds a database of features extracted from units' average spike waveforms and firing patterns across many days of recording. It then uses these features to decide whether spike occurrences on the same channel on one day belong to the same unit recorded on another day or not. We assessed the overall performance of the algorithm for different choices of features and classifiers trained using human expert judgment, and quantified it as a function of accuracy and execution time. Overall, we found a trade-off between accuracy and execution time with increasing data volumes from chronically implanted rhesus macaques, with an average of 12 seconds processing time per channel at ~90% classification accuracy. Furthermore, 77% of the resulting putative single-units matched those tracked by human experts. These results demonstrate that over the span of a few months of recordings, automated unit tracking can be performed with high accuracy and used to streamline the calibration phase during BMI sessions.

  19. 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. PMID:25129810

  20. A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure

    OpenAIRE

    Enoch, Mary-Anne; Baghal, Basel; Yuan, Qiaoping; Goldman, David

    2013-01-01

    Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the GABAA gene clusters, before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions...

  1. Association of chronic vascular changes with functional outcome after traumatic brain injury in rats.

    Science.gov (United States)

    Hayward, Nick M E A; Immonen, Riikka; Tuunanen, Pasi I; Ndode-Ekane, Xavier Ekolle; Gröhn, Olli; Pitkänen, Asla

    2010-12-01

    We tested the hypothesis that vascular remodeling in the cortex, hippocampus, and thalamus is associated with long-term functional recovery after traumatic brain injury (TBI). We induced TBI with lateral fluid-percussion (LFP) injury in adult rats. Animals were followed-up for 9 months, during which we tested motor performance using a neuroscore test, spatial learning and memory with a Morris water maze, and seizure susceptibility with a pentylenetetrazol (PTZ) test. At 8 months, they underwent structural MRI, and cerebral blood flow (CBF) was assessed by arterial spin labeling (ASL) MRI. Then, rats were perfused for histology to assess the density of blood vessels. In the perilesional cortex, the CBF decreased by 56% (p water maze correlated with enhanced thalamic vessel density (r = -0.81, p < 0.01). Finally, enhanced seizure susceptibility was associated with reduced CBF in the ipsilateral hippocampus (r = 0.78, p < 0.05) and increased vascular density in the thalamus (r = 0.69, p < 0.05). There was little interaction between the behavioral measures. The present study demonstrates that each of the investigated brain areas has a unique pattern of vascular abnormalities. Chronic alterations in CBF could not be attributed to changes in vascular density. Association of thalamic hypervascularity to epileptogenesis warrants further studies. Finally, hippocampal hypoperfusion may predict later seizure susceptibility in the LFP injury model of TBI, which could be of value for pre-clinical antiepileptogenesis trials. PMID:20839948

  2. Transcranial LED therapy for cognitive dysfunction in chronic, mild traumatic brain injury: two case reports

    Science.gov (United States)

    Naeser, Margaret A.; Saltmarche, Anita; Krengel, Maxine H.; Hamblin, Michael R.; Knight, Jeffrey A.

    2010-02-01

    Two chronic, traumatic brain injury (TBI) cases are presented, where cognitive function improved following treatment with transcranial light emitting diodes (LEDs). At age 59, P1 had closed-head injury from a motor vehicle accident (MVA) without loss of consciousness and normal MRI, but unable to return to work as development specialist in internet marketing, due to cognitive dysfunction. At 7 years post-MVA, she began transcranial LED treatments with cluster heads (2.1" diameter with 61 diodes each - 9x633nm, 52x870nm; 12-15mW per diode; total power, 500mW; 22.2 mW/cm2) on bilateral frontal, temporal, parietal, occipital and midline sagittal areas (13.3 J/cm2 at scalp, estimated 0.4 J/cm2 to brain cortex per area). Prior to transcranial LED, focused time on computer was 20 minutes. After 2 months of weekly, transcranial LED treatments, increased to 3 hours on computer. Performs nightly home treatments (now, 5 years, age 72); if stops treating >2 weeks, regresses. P2 (age 52F) had history of closed-head injuries related to sports/military training and recent fall. MRI shows fronto-parietal cortical atrophy. Pre-LED, was not able to work for 6 months and scored below average on attention, memory and executive function. Performed nightly transcranial LED treatments at home (9 months) with similar LED device, on frontal and parietal areas. After 4 months of LED treatments, returned to work as executive consultant, international technology consulting firm. Neuropsychological testing (post- 9 months of transcranial LED) showed significant improvement in memory and executive functioning (range, +1 to +2 SD improvement). Case 2 reported reduction in PTSD symptoms.

  3. L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain.

    Science.gov (United States)

    Ueno, Yuji; Koike, Masato; Shimada, Yoshiaki; Shimura, Hideki; Hira, Kenichiro; Tanaka, Ryota; Uchiyama, Yasuo; Hattori, Nobutaka; Urabe, Takao

    2015-03-01

    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model. PMID:25465043

  4. 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.,…

  5. 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

  6. Brain

    Science.gov (United States)

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  7. Chronic occupational exposure to hexavalent chromium causes DNA damage in electroplating workers

    Directory of Open Access Journals (Sweden)

    Ren Xiao-Bin

    2011-04-01

    Full Text Available Abstract Background Occupational exposure to chromium compounds may result in adverse health effects. This study aims to investigate whether low-level hexavalent chromium (Cr(VI exposure can cause DNA damage in electroplating workers. Methods 157 electroplating workers and 93 control subjects with no history of occupational exposure to chromium were recruited in Hangzhou, China. Chromium levels in erythrocytes were determined by graphite furnace atomic absorption spectrophotometer. DNA damage in peripheral lymphocytes was evaluated with the alkaline comet assay by three parameters: Olive tail moment, tail length and percent of DNA in the comet tail (tail DNA%. Urinary 8-OHdG levels were measured by ELISA. Results Chromium concentration in erythrocytes was about two times higher in electroplating workers (median: 4.41 μg/L than that in control subjects (1.54 μg/L, P P P P Conclusion The findings in this study indicated that there was detectable chromium exposure in electroplating workers. Low-level occupational chromium exposure induced DNA damage.

  8. Brain damage after treatment for acute lymphoblastic leukemia. A report on 34 patients with special regard to MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Biti, G.P.; Magrini, S.M.; Villari, N.; Caramella, D.; Guazzelli, G.; Rosi, A.; Lippi, A.

    1989-01-01

    In 34 patients treated for acute lymphoblastic leukemia (ALL), central nervous system (CNS) damage was assessed by clinical evaluation and brain magnetic resonance imaging (MRI). Twenty-seven of them had been off therapy from 5 to 109 months (median 64 months) while 7 had not completed the maintenance phase of their treatment. All the patients were disease-free when evaluated. None of the 3 patients who showed clinical CNS damage during the follow-up was symptomatic when submitted to MRI, while periventricular hyperintensity in T2-weighted images, suggestive of leukoencephalopathy, was present in 8 of the 34 patients. These subclinical abnormalities appear to be more frequent, transient in nature and treatment-related in patients evaluated shortly after the induction phase. Similar MRI findings seem, on the contrary, to be consequences of the disease on the CNS when appearing in long-term survivors. (orig.).

  9. Biomarkers of Brain Damage: S100B and NSE Concentrations in Cerebrospinal Fluid—A Normative Study

    Science.gov (United States)

    Hajduková, Lenka; Sobek, Ondřej; Prchalová, Darina; Bílková, Zuzana; Koudelková, Martina; Lukášková, Jiřina; Matuchová, Inka

    2015-01-01

    NSE and S100B belong among the so-called structural proteins of the central nervous system (CNS). Lately, this group of structural proteins has been profusely used as specific biomarkers of CNS tissue damage. So far, the majority of the research papers have focused predominantly on the concentrations of these proteins in blood in relation to CNS damage of various origins. Considering the close anatomic and functional relationship between the brain or spinal cord and cerebrospinal fluid (CSF), in case of a CNS injury, a rapid and pronounced increase of the concentrations of structural proteins specifically in CSF takes place. This study inquires into the physiological concentrations of NSE and S100B proteins in CSF, carried out on a sufficiently large group of 601 patients. The detected values can be used for determination of a normal reference range in CSF in a clinical laboratory diagnostics. PMID:26421286

  10. 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.)

  11. MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

    International Nuclear Information System (INIS)

    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.)

  12. Study Suggests Brain Damage in 40 Percent of Ex-NFL Players

    Science.gov (United States)

    ... from the Florida Center for Headache and Sports Neurology, in Port St. Lucie. Traumatic brain injury may ... Dr. Mohan Kottapally, an assistant professor of clinical neurology and neurocritical care at the University of Miami ...

  13. Berberine Protects against Neuronal Damage via Suppression of Glia-Mediated Inflammation in Traumatic Brain Injury

    OpenAIRE

    Chien-Cheng Chen; Tai-Ho Hung; Chao Yu Lee; Liang-Fei Wang; Chun-Hu Wu; Chia-Hua Ke; Szu-Fu Chen

    2014-01-01

    Traumatic brain injury (TBI) triggers a series of neuroinflammatory processes that contribute to evolution of neuronal injury. The present study investigated the neuroprotective effects and anti-inflammatory actions of berberine, an isoquinoline alkaloid, in both in vitro and in vivo TBI models. Mice subjected to controlled cortical impact injury were injected with berberine (10 mg·kg(-1)) or vehicle 10 min after injury. In addition to behavioral studies and histology analysis, blood-brain ba...

  14. Rehabilitation of Executive Functioning in Patients with Frontal Lobe Brain Damage with Goal Management Training

    OpenAIRE

    Brian Levine; Schweizer, Tom A.; Charlene O'Connor; Gary Turner; Tom Manly; Robertson, Ian H.

    2011-01-01

    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 approa...

  15. Chronic Unpredictable Stress Decreases Expression of Brain-Derived Neurotrophic Factor (BDNF) in Mouse Ovaries: Relationship to Oocytes Developmental Potential

    OpenAIRE

    Li-Min Wu; Mei-Hong Hu; Xian-Hong Tong; Hui Han; Ni Shen; Ren-Tao Jin; Wei Wang; Gui-Xiang Zhou; Guo-Ping He; Yu-Sheng Liu

    2012-01-01

    BACKGROUND: Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chroni...

  16. Chronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel

    OpenAIRE

    Stein, Thor D.; Alvarez, Victor E.; McKee, Ann C.

    2014-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive traumatic brain injury experienced in sport and military service. In most instances, the clinical symptoms of the disease begin after a long period of latency ranging from several years to several decades. The initial symptoms are typically insidious, consisting of irritability, impulsivity, aggression, depression, short-term memory loss and heightened suicidality. The ...

  17. Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats

    Institute of Scientific and Technical Information of China (English)

    潘宝龙

    2013-01-01

    Objective To investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in SpragueDawley (SD) rats.Methods Thirty-two male SD rats were randomly and equally divided into 4 groups:control group and high-,middle-,and low-dose exposure groups.The rats in high-,middle-,and low-dose expo-

  18. Withdrawal from Chronic Cocaine Administration Induces Deficits in Brain Reward Function in C57BL/6J Mice

    OpenAIRE

    Stoker, Astrid K.; Markou, Athina

    2011-01-01

    Anhedonia is a major symptom of cocaine withdrawal, whereas euphoria characterizes the effects of acute administration of this drug in humans. These mood states can be measured quantitatively in animals with brain reward thresholds obtained from the intracranial self-stimulation (ICSS) procedure. Studies have previously reported the reward-enhancing effects of acute cocaine administration using the ICSS procedure in mice, but the effects of chronic cocaine administration and withdrawal on bra...

  19. Cardiac cell damage: a primary myocardial disease in streptozotocin-induced chronic diabetes.

    OpenAIRE

    Seager, M. J.; Singal, P. K.; Orchard, R.; Pierce, G. N.; Dhalla, N S

    1984-01-01

    Ultrastructural changes in heart muscle due to chronic diabetes subsequent to a single injection of streptozotocin (65 mg/kg body wt, i.v.) were studied in rats. Presence of diabetes was indicated by hyperglycaemia (plasma glucose, control, 120 +/- 7; diabetic, 448 +/- 21 mg/dl) as well as hypo-insulinaemia (plasma insulin, control, 25.6 +/- 5.2; diabetic, 11.2 +/- 0.5 microU/ml). After 8 weeks of diabetes, the hearts were processed for electron microscopic examination. Cardiac muscle cells i...

  20. Memory and brain-derived neurotrophic factor after subchronic or chronic amphetamine treatment in an animal model of mania.

    Science.gov (United States)

    Fries, Gabriel R; Valvassori, Samira S; Bock, Hugo; Stertz, Laura; Magalhães, Pedro Vieira da Silva; Mariot, Edimilson; Varela, Roger B; Kauer-Sant'Anna, Marcia; Quevedo, João; Kapczinski, Flávio; Saraiva-Pereira, Maria Luiza

    2015-09-01

    Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala. PMID:26026487

  1. Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF in mouse ovaries: relationship to oocytes developmental potential.

    Directory of Open Access Journals (Sweden)

    Li-Min Wu

    Full Text Available BACKGROUND: Brain-derived neurotropic factor (BDNF was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. METHODS: Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. RESULTS: Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn't affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. CONCLUSION: BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress.

  2. Influence of cytokine and cytokine receptor gene polymorphisms on the degree of liver damage in patients with chronic hepatitis C.

    Science.gov (United States)

    Moreira, Sara Tatiana; Silva, Giovanni Faria; de Moraes, Camila Fernanda Verdichio; Grotto, Rejane Maria Tomasini; de Moura Campos Pardini, Maria Inês; Bicalho, Maria da Graça; Moliterno, Ricardo Alberto

    2016-09-01

    Hepatic fibrosis may be the result of repetitive injury to hepatocytes caused by HCV infection and the immune response to it. Cytokines regulate the inflammatory response to injury and modulate hepatic fibrogenesis. Single nucleotide polymorphisms (SNPs) located in cytokine genes may influence the cytokine expression and secretion that may contribute to hepatic fibrogenesis in HCV infection. The aim of this study was to determine the genotype of 22 SNPs found in the genes of 13 cytokines/cytokine receptors to assess the influence of polymorphic variants on the stage of liver damage in Brazilian patients chronically infected with HCV genotype 1 only. 141 unrelated patients were grouped according to their stage of fibrosis: absence of fibrosis or patients in the initial stages of fibrosis (F0-F2, n = 84), patients with advanced stages of fibrosis or cirrhosis (F3-F4, n = 57), without cirrhosis (F0-F3, n = 103), and with cirrhosis (F4, n = 38). The comparison of frequencies in each sub-sample was performed by 2 × 2 contingency tables using the chi-square or Fisher's exact test. Stepwise logistic regression was also used to assess independent associations between cirrhosis or fibrosis with polymorphic variants. The TNFA-308G:A genotype conferred increased risk of fibrosis and cirrhosis. The TNFA-238G:G genotype was associated with protection from cirrhosis. The IL10-819C:T genotype conferred protection from fibrosis and the IL1B-511C:T genotype conferred increased risk of cirrhosis. Some of these genotypes showed results on the borderline of statistical significance in the bivariate analysis. We conclude that gene variants of cytokines/receptors may influence liver damage in patients chronically infected by HCV genotype 1. PMID:27200267

  3. Expression of Glutamatergic Genes in Healthy Humans across 16 Brain Regions; Altered Expression in the Hippocampus after Chronic Exposure to Alcohol or Cocaine

    OpenAIRE

    Enoch, Mary-Anne; Rosser, Alexandra A.; Zhou, Zhifeng; Mash, Deborah C; Yuan, Qiaoping; Goldman, David

    2014-01-01

    We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus.

  4. A Cross-Sectional Investigation of Chronic Exposure to Microcystin in Relationship to Childhood Liver Damage in the Three Gorges Reservoir Region, China

    OpenAIRE

    Li, Yan; Chen, Ji-an; Zhao, Qing; Pu, Chaowen; QIU, ZHIQUN; Zhang, Renping; Shu, Weiqun

    2011-01-01

    Background: Microcystin-producing Microcystis bloom is a severe water problem in the world. Some reports indicate that chronic exposure to microcystin may result in liver damage in adults, but information on effects in children is limited. Objective: We investigated the relationship between microcystin exposure and liver damage in children. Methods: We measured microcystin concentrations in drinking water and aquatic food (carp and duck) from two lakes and four wells. Participants were 1,322 ...

  5. 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. 

  6. Molecular changes associated with chronic liver damage and neoplastic lesions in a murine model of hereditary tyrosinemia type 1.

    Science.gov (United States)

    Angileri, Francesca; Roy, Vincent; Morrow, Geneviève; Scoazec, Jean Yves; Gadot, Nicolas; Orejuela, Diana; Tanguay, Robert M

    2015-12-01

    Hereditary tyrosinemia type 1 (HT1) is the most severe inherited metabolic disease of the tyrosine catabolic pathway, with a progressive hepatic and renal injury and a fatal outcome if untreated. Toxic metabolites accumulating in HT1 have been shown to elicit endoplasmic reticulum (ER) stress response, and to induce chromosomal instability, cell cycle arrest and apoptosis perturbation. Although many studies have concentrated on elucidating these events, the molecular pathways responsible for development of hepatocellular carcinoma (HCC) still remain unclear. In this study the fah knockout murine model (fah(-/-)) was used to investigate the cellular signaling implicated in the pathogenesis of HT1. Fah(-/-) mice were subjected to drug therapy discontinuation (Nitisinone withdrawal), and livers were analyzed at different stages of the disease. Monitoring of mice revealed an increasing degeneration of the overall physiological conditions following drug withdrawal. Histological analysis unveiled diffuse hepatocellular damage, steatosis, oval-like cells proliferation and development of liver cell adenomas. Immunoblotting results revealed a progressive and chronic activation of stress pathways related to cell survival and proliferation, including several stress regulators such as Nrf2, eIF2α, CHOP, HO-1, and some members of the MAPK signaling cascade. Impairment of stress defensive mechanisms was also shown by microarray analysis in fah(-/-) mice following prolonged therapy interruption. These results suggest that a sustained activation of stress pathways in the chronic HT1 progression might play a central role in exacerbating liver degeneration. PMID:26360553

  7. Protective Effect of Topically Applied Polypeptide from Chlamys farreri Against Ultraviolet Radiation-Induced Chronic Skin Damage in Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    迟明亮; 曹鹏利; 于国英; 朱莉; 王跃军; 王春波

    2003-01-01

    Polypeptide from Chlamys farreri (PCF) , a topical polypeptide isolated from Chlamys farreri, was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation. The chronic ultraviolet-irradiated guinea pig model was established, and visible changes in the skin including wrinkling, sagging and erythema were observed. Malondialdehyde (MDA) and antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in the dorsal skin were determined using biochemical methods. The results showed:(1)PCF (5 % and 20%) could greatly protect the dorsal skin of guinea pig against wrinkling, sagging and erythema induced by UV radiation in a concentration-dependent manner.(2)PCF could reduce MDA formation in the dorsal skin caused by UV irradiation, while increasing the activities of SOD and GSH-px.(3)The differences among the PCF groups and UV model group were significant (P<0.05, P<0.01). These results indicated that topical application of PCF provided broad solar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.

  8. Chronic infection with Toxoplasma gondii induces death of submucosal enteric neurons and damage in the colonic mucosa of rats.

    Science.gov (United States)

    Góis, Marcelo Biondaro; Hermes-Uliana, Catchia; Barreto Zago, Maísa Cristina; Zanoni, Jacqueline Nelisis; da Silva, Aristeu Vieira; de Miranda-Neto, Marcílio Hubner; Almeida Araújo, Eduardo José de; Sant'Ana, Débora de Mello Gonçales

    2016-05-01

    Intestinal epithelial secretion is coordinated by the submucosal plexus (SMP). Chemical mediators from SMP regulate the immunobiological response and direct actions against infectious agents. Toxoplasma gondii is a worldwide parasite that causes toxoplasmosis. This study aimed to determine the effects of chronic infection with T. gondii on the morphometry of the mucosa and the submucosal enteric neurons in the proximal colon of rats. Male adult rats were distributed into a control group (n = 10) and an infected group (n = 10). Infected rats received orally 500 oocysts of T. gondii (ME-49). After 36 days, the rats were euthanized and samples of the proximal colon were processed for histology to evaluate mucosal thickness in sections. Whole mounts were stained with methylene blue and subjected to immunohistochemistry to detect vasoactive intestinal polypeptide. The total number of submucosal neurons decreased by 16.20%. Vasoactive intestinal polypeptide-immunoreactive neurons increased by 26.95%. Intraepithelial lymphocytes increased by 62.86% and sulfomucin-producing goblet cells decreased by 22.87%. Crypt depth was greater by 43.02%. It was concluded that chronic infection with T. gondii induced death and hypertrophy in the remaining submucosal enteric neurons and damage to the colonic mucosa of rats. PMID:26902605

  9. Region-specific changes in gene expression in rat brain after chronic treatment with levetiracetam or phenytoin

    Science.gov (United States)

    Hassel, Bjørnar; Taubøll, Erik; Shaw, Renee; Gjerstad, Leif; Dingledine, Ray

    2014-01-01

    Summary Purpose It is commonly assumed that antiepileptic drugs (AEDs) act similarly in the various parts of the brain as long as their molecular targets are present. A few experimental studies on metabolic effects of vigabatrin, levetiracetam, valproate, and lamotrigine have shown that these drugs may act differently in different brain regions. We examined effects of chronic treatment with levetiracetam or phenytoin on mRNA levels to detect regional drug effects in a broad, nonbiased manner. Methods mRNA levels were monitored in three brain regions with oligonucleotide-based microarrays. Results Levetiracetam (150 mg/kg for 90 days) changed the expression of 65 genes in pons/medulla oblongata, two in hippocampus, and one in frontal cortex. Phenytoin (75 mg/kg), in contrast, changed the expression of only three genes in pons/medulla oblongata, but 64 genes in hippocampus, and 327 genes in frontal cortex. Very little overlap between regions or drug treatments was observed with respect to effects on gene expression. Discussion We conclude that chronic treatment with levetiracetam or phenytoin causes region-specific and highly differential effects on gene expression in the brain. Regional effects on gene expression could reflect regional differences in molecular targets of AEDs, and they could influence the clinical profiles of AEDs. PMID:20345932

  10. Chronic exposure to perfluorooctane sulfonate induces behavior defects and neurotoxicity through oxidative damages, in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Na Chen

    Full Text Available Perfluorooctane sulfonate (PFOS is an emerging persistent pollutant which shows multiple adverse health effects. However, the neurotoxicity of PFOS and its mechanisms have not been fully elucidated. Using a combination of in vivo and in vitro methods, the present study provides a detailed description of PFOS-induced neurotoxicity. Results showed that the median lethal concentration of PFOS was 2.03 mM in Caenorhabditis elegans for 48 h exposure. 20 µM PFOS caused decrease of locomotor behaviors including forward movement, body bend and head thrash. Additionally, PFOS exposure reduced chemotaxis index of C. elegans, which indicates the decline of chemotaxis learning ability. Using green fluorescent protein (GFP labelled transgenic strains, we found that PFOS caused down-regulated expression of a chemoreceptor gene, gcy-5, in ASE chemosensory neurons, but did not affect cholinergic neurons and dopaminergic neurons. In SH-SY5Y cells, 48 h exposure to 25 µM and 50 µM PFOS induced cell damage, apoptosis and the reactive oxygen species (ROS generation. PFOS caused significant increases of lipid peroxidation and superoxide dismutase activity, but an actual decrease of glutathione peroxidase activity. Furthermore, antioxidant N-acetylcysteine rescued cells from PFOS-induced apoptosis via blocking ROS. Our results demonstrate that chronic exposure to PFOS can cause obvious neurotoxicity and behavior defects. Oxidative damage and anti-oxidative deficit are crucial mechanisms in neurotoxicity of PFOS.

  11. Filling in the gaps: Anticipatory control of eye movements in chronic mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Mithun Diwakar

    2015-01-01

    Full Text Available A barrier in the diagnosis of mild traumatic brain injury (mTBI stems from the lack of measures that are adequately sensitive in detecting mild head injuries. MRI and CT are typically negative in mTBI patients with persistent symptoms of post-concussive syndrome (PCS, and characteristic difficulties in sustaining attention often go undetected on neuropsychological testing, which can be insensitive to momentary lapses in concentration. Conversely, visual tracking strongly depends on sustained attention over time and is impaired in chronic mTBI patients, especially when tracking an occluded target. This finding suggests deficient internal anticipatory control in mTBI, the neural underpinnings of which are poorly understood. The present study investigated the neuronal bases for deficient anticipatory control during visual tracking in 25 chronic mTBI patients with persistent PCS symptoms and 25 healthy control subjects. The task was performed while undergoing magnetoencephalography (MEG, which allowed us to examine whether neural dysfunction associated with anticipatory control deficits was due to altered alpha, beta, and/or gamma activity. Neuropsychological examinations characterized cognition in both groups. During MEG recordings, subjects tracked a predictably moving target that was either continuously visible or randomly occluded (gap condition. MEG source-imaging analyses tested for group differences in alpha, beta, and gamma frequency bands. The results showed executive functioning, information processing speed, and verbal memory deficits in the mTBI group. Visual tracking was impaired in the mTBI group only in the gap condition. Patients showed greater error than controls before and during target occlusion, and were slower to resynchronize with the target when it reappeared. Impaired tracking concurred with abnormal beta activity, which was suppressed in the parietal cortex, especially the right hemisphere, and enhanced in left caudate and

  12. Diagnostic and prognostic value of asphyxia, Sarnat's clinical classification, and CT-scan in perinatal brain damage

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Toshihide; Wakita, Yoshiharu; Kubonishi, Sakae; Yoshikawa, Seishi (Kochi Prefectural Central Hospital (Japan)); Ito, Toshiyuki; Okada, Yasusuke

    1990-11-01

    A retrospective review was made of 145 babies, excluding those with congenital heart disease or chromosome aberration, admitted for CT scanning. The study was done to determine the diagnostic and prognostic value of CT findings, as well as the presence of asphyxia and the clinical stage based on the Sarnat's classification, in perinatal brain damage. The patients had a minimum follow up of 2 years for the evaluation of neurologic manifestations, such as cerebral palsy, epilepsy and mental retardation. Among babies weighing 2,000 g or more at birth, neonatal asphyxia was significantly correlated with neurologic prognosis. In addition, both clinical stages and CT findings were significantly correlated with neurologic prognosis, irrespective of birth weight. The correlation between clinical stages and CT findings was significant, irrespective of body weight, however, a significant correlation between clinical stages and neonatal asphyxia was restricted to those weighing 2,000 g or more. These findings suggest that the presence of asphyxia, clinical stages and CT findings are complementary in the diagnosis and prognosis evaluation of perinatal brain damage. (N.K.).

  13. Diagnostic and prognostic value of asphyxia, Sarnat's clinical classification, and CT-scan in perinatal brain damage

    International Nuclear Information System (INIS)

    A retrospective review was made of 145 babies, excluding those with congenital heart disease or chromosome aberration, admitted for CT scanning. The study was done to determine the diagnostic and prognostic value of CT findings, as well as the presence of asphyxia and the clinical stage based on the Sarnat's classification, in perinatal brain damage. The patients had a minimum follow up of 2 years for the evaluation of neurologic manifestations, such as cerebral palsy, epilepsy and mental retardation. Among babies weighing 2,000 g or more at birth, neonatal asphyxia was significantly correlated with neurologic prognosis. In addition, both clinical stages and CT findings were significantly correlated with neurologic prognosis, irrespective of birth weight. The correlation between clinical stages and CT findings was significant, irrespective of body weight, however, a significant correlation between clinical stages and neonatal asphyxia was restricted to those weighing 2,000 g or more. These findings suggest that the presence of asphyxia, clinical stages and CT findings are complementary in the diagnosis and prognosis evaluation of perinatal brain damage. (N.K.)

  14. Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites.

    Science.gov (United States)

    Knapp, Darin J; Harper, Kathryn M; Whitman, Buddy A; Zimomra, Zachary; Breese, George R

    2016-01-01

    Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint) or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE) and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C-C motif) ligand 2 (CCL2), interleukin-1-beta (IL-1β), tumor necrosis factor alpha (TNFα) and toll-like receptor 4 (TLR4) mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β) while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally-based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1) receptor inhibition in blocking WCE-induced cytokine mRNAs-the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals. Overall, these

  15. Progressive white matter microstructure damage in male chronic heroin dependent individuals: a DTI and TBSS study.

    Directory of Open Access Journals (Sweden)

    Yingwei Qiu

    Full Text Available BACKGROUND: To investigate the WM microstructure deficits in heroin dependent individuals (HDIs with different length of heroin dependence, and to investigate whether these WM deficits can be related to the duration of heroin use and to decision-making deficits in HDIs. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-six HDIs [including eighteen sHDIs (duration of heroin dependent is less than 10 years and eighteen lHDIs (duration of dependent is between 10:20 years] and sixteen healthy controls participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA, mean diffusivity (MD, axial diffusivity (Da and radial diffusivity (Dr were performed by tract-based spatial statistics (TBSS to localize abnormal WM regions among groups. TBSS demonstrated that sHDIs had significantly lower FA than controls in right orbito-frontal WM, bilateral temporal WM and right parietal WM. The lHDIs had significantly lower FA throughout the brain compared with the controls and sHDIs. The lHDIs had significantly lower Da than controls in bilateral inferior frontaloccipital fasciculus, bilateral splenium of corpus callosum, left inferior longitudinal fasciculus, and had significantly higher Dr than controls in bilateral uncinatus fasciculus, bilateral inferior frontaloccipital fasciculus and bilateral cortical spinal fasciculus. Volume-of-interest (VOI analyses detect the changes of diffusivity indices in the regions with FA abnormalities revealed by control vs sHDIs. In most VOIs, FA reductions were caused by the increase in Dr as well as the decrease in Da. Correlation analysis was used to assess the relationship between FA and behavioral measures in HDIs and controls available. Significantly positively correlations were found between the FA values in the right orbital-frontal WM, right parietal WM and IGT performance. CONCLUSIONS: The extent and severity of WM integrity deficits in HDIs was associated with the length of heroin dependent. Furthermore

  16. 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

  17. Chronic dietary mercury exposure causes oxidative stress, brain lesions, and altered behaviour in Atlantic salmon (Salmo salar) parr

    Energy Technology Data Exchange (ETDEWEB)

    Berntssen, Marc H.G.; Aatland, Aase; Handy, Richard D

    2003-10-08

    Atlantic salmon (Salmo salar L.) parr were fed for 4 months on fish meal based diets supplemented with mercuric chloride (0, 10, or 100 mg Hg kg{sup -1} DW) or methylmercury chloride (0, 5, or 10 mg Hg kg{sup -1} DW) to assess the effects of inorganic (Hg) and organic dietary mercury on brain lipid peroxidation and neurotoxicity. Lipid peroxidative products, endogenous anti oxidant enzymes, brain histopathology, and overall behaviour were measured. Methylmercury accumulated significantly in the brain of fish fed 5 or 10 mg kg{sup -1} by the end of the experiment, and inorganic mercury accumulated significantly in the brain only at 100 mg kg{sup -1} exposure levels. No mortality or growth reduction was observed in any of the exposure groups. Fish fed 5 mg kg{sup -1} methylmercury had a significant increase (2-fold) in the antioxidant enzyme super oxide dismutase (SOD) in the brain. At dietary levels of 10 mg kg{sup -1} methylmercury, a significant increase (7-fold) was observed in lipid peroxidative products (thiobarbituric acid reactive substances, TBARS) and a subsequently decrease (1.5-fold) in anti oxidant enzyme activity (SOD and glutathione peroxidase, GSH-Px). Fish fed 10 mg kg{sup -1} methylmercury also had pathological damage (vacoulation and necrosis), significantly reduced neural enzyme activity (5-fold reduced monoamine oxidase, MAO, activity), and reduced overall post-feeding activity behaviour. Pathological injury started in the brain stem and became more widespread in other areas of the brain at higher exposure levels. Fish fed 100 mg Hg kg{sup -1} inorganic mercury had significant reduced neural MAO activity and pathological changes (astrocyte proliferation) in the brain, however, neural SOD and GSH-Px enzyme activity, lipid peroxidative products (TBARS), and post feeding behaviour did not differ from controls. Compared with other organs, the brain is particular susceptible for dietary methylmercury induced lipid peroxidative stress at relative low

  18. Brain SPECT of chronic fatigue syndrome (CFS): SPM analysis of two age groups

    International Nuclear Information System (INIS)

    Full text: Chronic fatigue syndrome (CFS) is a complex disorder characterised by profound fatigue and neuropsychiatric dysfunction. Previous studies with cerebral perfusion SPECT (rCBF) scans were performed with inhomogeneous patient populations and were not analysed with Statistical Parametric Mapping (SPM). We have used SPM to study subjects with moderate CFS based on the Fukuda criteria, who were not on medication and not depressed, compared to age matched control subjects. An apparent bimodal age distribution has been observed in CFS. Subjects were therefore divided into two age groups: 16-35 or under 35 (17 CFS, 11 control) and 36-61 or over 35 (15 CFS, 15 control). HMPAO brain SPECT was acquired on a 3-head camera. After lower window scatter subtraction, reconstruction with attenuation correction (mu=0.15/cm) and editing of facial activity, scans were spatially normalised (affine + 2x3x2 nonlinear) to SPM's anatomical space. SPM statistical analysis yielded the location, amplitude and corrected p-value of significant focal rCBF deficits. They were: for under 35, left lateral temporal lobe (13%, 0.004), the left insular region (15%, 0.006) and the right lentiform nucleus (15%, 0.01); and for over 35 the left lentiform nucleus (18%, 0.01). Counts at the most significant voxel in the under 35 age group permitted separation of the CFS and control groups with sensitivity 94% and specificity 100%. We are acquiring more controls to better define the age and sex dependence of rCBF in CFS. Analysis of associated clinical variables will be used to investigate the observed differences between the two age groups. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  19. Effects of endurance training on brain structures in chronic schizophrenia patients and healthy controls.

    Science.gov (United States)

    Malchow, Berend; Keeser, Daniel; Keller, Katriona; Hasan, Alkomiet; Rauchmann, Boris-Stephan; Kimura, Hiroshi; Schneider-Axmann, Thomas; Dechent, Peter; Gruber, Oliver; Ertl-Wagner, Birgit; Honer, William G; Hillmer-Vogel, Ursula; Schmitt, Andrea; Wobrock, Thomas; Niklas, Andree; Falkai, Peter

    2016-06-01

    The objective of this longitudinal magnetic resonance (MR) imaging study was to examine the effects of endurance training on hippocampal and grey matter volumes in schizophrenia patients and healthy controls. 20 chronic schizophrenia patients and 21 age- and gender-matched healthy controls underwent 3months of endurance training (30min, 3 times per week). 19 additionally recruited schizophrenia patients played table soccer ("foosball" in the USA) over the same period. MR imaging with 3D-volumetric T1-weighted sequences was performed on a 3T MR scanner at baseline, after 6weeks and after the 3-month intervention and 3 additional training-free months. In addition to voxel-based morphometry (VBM), we performed manual and automatic delineation of the hippocampus and its substructures. Endurance capacity and psychopathological symptoms were measured as secondary endpoints. No significant increases in the volumes of the hippocampus or hippocampal substructures were observed in schizophrenia patients or healthy controls. However, VBM analyses displayed an increased volume of the left superior, middle and inferior anterior temporal gyri compared to baseline in schizophrenia patients after the endurance training, whereas patients playing table soccer showed increased volumes in the motor and anterior cingulate cortices. After the additional training-free period, the differences were no longer present. While endurance capacity improved in exercising patients and healthy controls, psychopathological symptoms did not significantly change. The subtle changes in the left temporal cortex indicate an impact of exercise on brain volumes in schizophrenia. Subsequent studies in larger cohorts are warranted to address the question of response variability of endurance training. PMID:25623601

  20. Clinical pragmatism and the care of brain damaged patients: toward a palliative neuroethics for disorders of consciousness.

    Science.gov (United States)

    Fins, Joseph J

    2005-01-01

    Unraveling the mysteries of consciousness, lost and regained, and perhaps even intervening so as to prompt recovery are advances for which neither the clinical nor the lay community are prepared. These advances will shake existing expectations about severe brain damage and will find an unprepared clinical context, perhaps even one inhospitable to what should clearly be viewed as important advances. This could be the outcome of this line of inquiry, if this exceptionally imaginative research can continue at all. This work faces a restrictive research environment that has the potential to imperil it. Added to the complexity of the scientific challenges that must be overcome is the societal context in which these investigations must occur. Research on human consciousness goes to the heart of our humanity and asks us to grapple with fundamental questions about the self. Added to this is the regulatory complexity of research on subjects who may be unable to provide their own consent because of impaired decision-making capacity, itself a function of altered or impaired consciousness. These factors can lead to a restrictive view of research that can favor risk aversion over discovery. In this paper, I attempt to explain systematically some of these challenges. I suggest that some of the resistance might be tempered if we view the needs of patients with severe brain injury through the prism of palliative care and adopt that field's ethos and methods when caring for and conducting research on individuals with severe brain damage and disorders of consciousness. To make this argument I draw upon the American pragmatic tradition and utilize clinical pragmatism, a method of moral problem-solving that my colleagues and I have developed to address ethical challenges in clinical care and research. PMID:16186050

  1. Radiation-Induced Astrogliosis and Blood-Brain Barrier Damage Can Be Abrogated Using Anti-TNF Treatment

    International Nuclear Information System (INIS)

    Purpose: In this article, we investigate the role of tumor necrosis factor-alpha (TNF) in the initiation of acute damage to the blood-brain barrier (BBB) and brain tissue following radiotherapy (RT) for CNS tumors. Methods and Materials: Intravital microscopy and a closed cranial window technique were used to measure quantitatively BBB permeability to FITC-dextran 4.4-kDa molecules, leukocyte adhesion (Rhodamine-6G) and vessel diameters before and after 20-Gy cranial radiation with and without treatment with anti-TNF. Immunohistochemistry was used to quantify astrogliosis post-RT and immunofluorescence was used to visualize protein expression of TNF and ICAM-1 post-RT. Recombinant TNF (rTNF) was used to elucidate the role of TNF in leukocyte adhesion and vessel diameter. Results: Mice treated with anti-TNF showed significantly lower permeability and leukocyte adhesion at 24 and 48 h post-RT vs. RT-only animals. We observed a significant decrease in arteriole diameters at 48 h post-RT that was inhibited in TNF-treated animals. We also saw a significant increase in activated astrocytes following RT that was significantly lower in the anti-TNF-treated group. In addition, immunofluorescence showed protein expression of TNF and ICAM-1 in the cerebral cortex that was inhibited with anti-TNF treatment. Finally, administration of rTNF induced a decrease in arteriole diameter and a significant increase in leukocyte adhesion in venules and arterioles. Conclusions: TNF plays a significant role in acute changes in BBB permeability, leukocyte adhesion, arteriole diameter, and astrocyte activation following cranial radiation. Treatment with anti-TNF protects the brain's microvascular network from the acute damage following RT.

  2. Disruption of caudate working memory activation in chronic blast-related traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Mary R. Newsome

    2015-01-01

    Full Text Available Mild to moderate traumatic brain injury (TBI due to blast exposure is frequently diagnosed in veterans returning from the wars in Iraq and Afghanistan. However, it is unclear whether neural damage resulting from blast TBI differs from that found in TBI due to blunt-force trauma (e.g., falls and motor vehicle crashes. Little is also known about the effects of blast TBI on neural networks, particularly over the long term. Because impairment in working memory has been linked to blunt-force TBI, the present functional magnetic resonance imaging (fMRI study sought to investigate whether brain activation in response to a working memory task would discriminate blunt-force from blast TBI. Twenty-five veterans (mean age = 29.8 years, standard deviation = 6.01 years, 1 female who incurred TBI due to blast an average of 4.2 years prior to enrollment and 25 civilians (mean age = 27.4 years, standard deviation = 6.68 years, 4 females with TBI due to blunt-force trauma performed the Sternberg Item Recognition Task while undergoing fMRI. The task involved encoding 1, 3, or 5 items in working memory. A group of 25 veterans (mean age = 29.9 years, standard deviation = 5.53 years, 0 females and a group of 25 civilians (mean age = 27.3 years, standard deviation = 5.81 years, 0 females without history of TBI underwent identical imaging procedures and served as controls. Results indicated that the civilian TBI group and both control groups demonstrated a monotonic relationship between working memory set size and activation in the right caudate during encoding, whereas the blast TBI group did not (p < 0.05, corrected for multiple comparisons using False Discovery Rate. Blast TBI was also associated with worse performance on the Sternberg Item Recognition Task relative to the other groups, although no other group differences were found on neuropsychological measures of episodic memory, inhibition, and general processing speed. These results

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

    Institute of Scientific and Technical Information of China (English)

    Zhichun Feng; Jing Liu; Rong Ju

    2013-01-01

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

  4. Organic brain syndrome

    Science.gov (United States)

    OBS; Organic mental disorder (OMS); Chronic organic brain syndrome ... Listed below are disorders associated with OBS. Brain injury caused by ... the brain ( subarachnoid hemorrhage ) Blood clot inside the ...

  5. Organotypic hippocampal slice cultures for studies of brain damage, neuroprotection and neurorepair

    DEFF Research Database (Denmark)

    Noraberg, Jens; Poulsen, Frantz Rom; Blaabjerg, Morten;

    2005-01-01

    ), Alzheimer's disease (AD) and epilepsia. Studies of non-excitotoxic neurotoxic compounds and the experimental use of slice cultures in studies of HIV neurotoxicity, traumatic brain injury (TBI) and neurogenesis are included. For cerebral ischemia, experimental models with oxygen-glucose deprivation (OGD) and......-line biosensor monitoring, and time-lapse fluorescence microscopy are also presented....

  6. Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem

    International Nuclear Information System (INIS)

    Ethanol is one of the most commonly abused substances, and oxidative stress is an important causative factor in ethanol-induced neurotoxicity. Cytochrome P450 2E1 (CYP2E1) is involved in ethanol metabolism in the brain. This study investigates the role of brain CYP2E1 in the susceptibility of certain brain regions to ethanol neurotoxicity. Male Wistar rats were intragastrically treated with ethanol (3.0 g/kg, 30 days). CYP2E1 protein, mRNA expression, and catalytic activity in various brain regions were respectively assessed by immunoblotting, quantitative quantum dot immunohistochemistry, real-time RT-PCR, and LC–MS. The generation of reactive oxygen species (ROS) was analyzed using a laser confocal scanning microscope. The hippocampus, cerebellum, and brainstem were selectively damaged after ethanol treatment, indicated by both lactate dehydrogenase (LDH) activity and histopathological analysis. Ethanol markedly increased the levels of CYP2E1 protein, mRNA expression, and activity in the hippocampus and cerebellum. CYP2E1 protein and activity were significantly increased by ethanol in the brainstem, with no change in mRNA expression. ROS levels induced by ethanol paralleled the enhanced CYP2E1 proteins in the hippocampus, granular layer and white matter of cerebellum as well as brainstem. Brain CYP2E1 activity was positively correlated with the damage to the hippocampus, cerebellum, and brainstem. These results suggest that the selective sensitivity of brain regions to ethanol neurodegeneration may be attributed to the regional and cellular-specific induction of CYP2E1 by ethanol. The inhibition of CYP2E1 levels may attenuate ethanol-induced oxidative stress via ROS generation.

  7. Evaluating the effectiveness of reasoning training in military and civilian chronic traumatic brain injury patients: study protocol

    Directory of Open Access Journals (Sweden)

    Krawczyk Daniel C

    2013-01-01

    Full Text Available Abstract Background Individuals who sustain traumatic brain injuries (TBIs often continue to experience significant impairment of cognitive functions mediated by the prefrontal cortex well into chronic stages of recovery. Traditional brain training programs that focus on improving specific skills fall short of addressing integrative functions that draw upon multiple higher-order processes critical for social and vocational integration. In the current study, we compare the effects of two short-term, intensive, group-based cognitive rehabilitation programs for individuals with chronic TBI. One program emphasizes learning about brain functions and influences on cognition, while the other program adopts a top-down approach to improve abstract reasoning abilities that are largely reliant on the prefrontal cortex. These treatment programs are evaluated in civilian and military veteran TBI populations. Methods/design One hundred individuals are being enrolled in this double-blinded clinical trial (all measures and data analyses will be conducted by blinded raters and analysts. Each individual is randomly assigned to one of two treatment conditions, with each condition run in groups of five to seven individuals. The primary anticipated outcomes are improvement in abstract reasoning and everyday life functioning, measured through behavioral tasks and questionnaires, and attention modulation, as measured by functional neuroimaging. Secondary expected outcomes include improvements in the cognitive processes of working memory, attention, and inhibitory control. Discussion Results of this trial will determine whether cognitive rehabilitation aimed at teaching TBI-relevant information about the brain and cognition versus training in TBI-affected thinking abilities (e.g., memory, attention, and executive functioning can improve outcomes in chronic military and civilian TBI patient populations. It should shed light on the nature of improvements and the

  8. Investigations of subclinical neurogenous damage of persons with chronic occupational exposure to lead and trichlorethylene

    Energy Technology Data Exchange (ETDEWEB)

    Reichenbach, T.

    1980-12-15

    The functions of the peripheral nervous system, for example the maximum and minimum conduction velocities of the ulnar and the radial nerves, were measured in 22 men and 9 women with occupational exposure to lead and in 20 men and 20 women without occupational exposure to lead. The result of the comparison of the obtained measuring values was a decrease of the minimum conduction velocity of the ulnar nerve of the working hand of men exposed to lead. In order to quantify the lead exposure we determined in all test persons the blood lead level, the concentration of free erythrocyteporphyrines in the blood and the hemoglobin concentration. The study reports also about the elcetroneurographic investigations on 7 persons with chronical exposure to trichloroethylene and on 13 comparable persons of a corresponding age group. A correlation between the biochemical and toxicologic parameters and the nervous conduction velocities could be detected neither in the persons exposed to lead nor in those exposed to trichloroethylene. The measured nervous conduction velocities are well comparable with those age-specific indications given in the specialised literature. The dependence of conduction velocity on various parameters as age, temperature, left- or righthandedness and sex is discussed.

  9. Decreased mitochondrial deoxyribonucleic acid and increased oxidative damage in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Hsu-Heng Yen; Kai-Lun Shih; Ta-Tsung Lin; Wei-Wen Su; Maw-Soan Soon; Chin-San Liu

    2012-01-01

    AIM:To determine whether alteration of the mitochondria DNA (mtDNA) copy number and its oxidative damage index (mtDNA△CT) can be detected by analysis of peripheral blood cells in hepatitis C virus (HCV)-infected patients.METHODS:This study enrolled two groups of patients aged 40-60 years:a control group and an HCV-infected group in Department of Gastroenterology and Hepatology in Changhua Christian Hospital.Patients with co-infection with hepatitis B virus or human immunodeficiency virus,autoimmune disease,malignant neoplasia,pregnancy,thyroid disease,or alcohol consumption > 40 g/d were excluded.HCV-infected patients who met the following criteria were included:(1)positive HCV antibodies for > 6 mo; (2) alanine aminotransferase (ALT) levels more than twice the upper limit of normal on at least two occasions during the past 6 mo; and (3) histological fibrosis stage higher than F1.The mtDNA copy number and oxidative damage index of HCV mtDNA (mtDNA△CT) were measured in peripheral blood leukocytes.The association between mtDNA copy number and mtDNA△Cr was further analyzed using clinical data.RESULTS:Forty-seven normal controls (male/female:26/21,mean age 50.51 ± 6.15 years) and 132 HCV-infected patients (male/female:76/61,mean age 51.65± 5.50 years) were included in the study.The genotypes of HCV-infected patients include type 1a (n =3),type 1b (n =83),type 2a (n =32),and type 2b (n =14).Liver fibrosis stages were distributed as follows:F1/F2/F3/F4 =1/61/45/25 and activity scores were A0/A1/A2/A3 =7/45/55/25.There were no age or genderdifferences between the two groups.HCV-infected patients had higher hepatitis activity (aspartate transaminase levels 108.77 ± 60.73 vs 23.19 ± 5.47,P < 0.01;ALT levels 168.69 ± 93.12 vs 23.15 ± 9.45,P < 0.01)and lower platelet count (170.40 ± 58.00 vs 251.24 ±63.42,P < 0.01) than controls.The mtDNA copy number was lower in HCV-infected patients than in controls (173.49 vs 247.93,P < 0.05).The mtDNA△CT was

  10. Functional reorganization of the large-scale brain networks that support high-level cognition following brain damage in aphasia

    Directory of Open Access Journals (Sweden)

    Idan Asher Blank

    2015-05-01

    Full Text Available Over the last decade, a number of large-scale networks in the human cortex that support high-level cognition have been identified. Here, we focus on two of these networks: the fronto-temporal language network (e.g., Fedorenko et al., 2010, and the fronto-parietal “multiple demand (MD” network (e.g., Duncan, 2010. These two networks are clearly distinct from one another: first, their respective regions show distinct functional profiles, with language regions showing selective responses to language stimuli (Fedorenko et al., 2011; Monti et al., 2012 and MD regions showing domain-general responses to cognitive effort across a wide range of tasks (Duncan & Owen, 2001; Fedorenko et al., 2013. Second, during “rest” and cognitive processing, each network shows strong activity synchronization among its constituent regions, whereas regions across the two networks are not synchronized (Blank et al., 2014; Lee et al., 2012; Mantini et al., 2013. In the current study, we examined how these functional characteristics of the two networks were affected following aphasia-inducing strokes. In particular, we asked whether damage to the language network would alter the involvement of the MD network in linguistic processing, and whether such damage would alter the patterns of synchronization across the two networks. Four male individuals with aphasia (age: M=53, having suffered a single left MCA CVA, were scanned in fMRI on two paradigms that enable basic functional characterization of language and MD regions: (i a language localizer task, where they passively read sentences and sequences of pseudowords (Fedorenko et al., 2010; and (ii a spatial working memory task, where they had to remember fewer (easy or more (hard locations in a grid (Fedorenko et al., 2013. Language and MD regions were defined in each individual using the sentences > pseudowords contrast and the hard > easy contrast, respectively. Subjects were also scanned while listening to

  11. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  12. Role of small intestinal bacterial overgrowth in severe small intestinal damage in chronic non-steroidal anti-inflammatory drug users.

    Science.gov (United States)

    Muraki, Motoko; Fujiwara, Yasuhiro; Machida, Hirohisa; Okazaki, Hirotoshi; Sogawa, Mitsue; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Watanabe, Toshio; Arakawa, Tetsuo

    2014-03-01

    OBJECTIVE. Enteric bacteria play a significant role in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal damage. However, the association between small intestinal bacterial overgrowth (SIBO) and NSAID-induced small intestinal damage remains unclear. The aim of the study was to examine the association between SIBO and the presence of NSAID-induced severe small intestinal damage or its symptoms in chronic NSAID users. MATERIALS AND METHODS. Forty-three patients who had been using NSAIDs for over 3 months were enrolled. They were examined by capsule endoscopy and a lactulose hydrogen breath test (LHBT). We defined severe small intestinal damage as the presence of more than four small erosions or large erosions/ulcers. The LHBT result was considered positive if there was an increase in the level of breath hydrogen gas of >20 ppm above baseline. RESULTS. Out of 43 patients, 22 (51%) had severe small intestinal damage. The LHBT was positive in 5 of 21 patients (24%) without severe small intestinal damage and in 13 of 21 patients (59%) with severe small intestinal damage. Multiple logistic regression analysis showed that an LHBT-positive result was significantly associated with increased odds ratio for severe small intestinal damage (OR, 6.54; 95% CI, 1.40-30.50). There was no significant difference in the presence of symptoms between the LHBT-positive and LHBT-negative patients with severe small intestinal damage. CONCLUSION. SIBO might have a role in the development of severe small intestinal damage in chronic NSAID users. PMID:24417613

  13. Alcohol,inflammation,and gut-liver-brain interactions in tissue damage and disease development

    Institute of Scientific and Technical Information of China (English)

    H; Joe; Wang; Samir; Zakhari; M; Katherine; Jung

    2010-01-01

    Chronic inflammation is often associated with alcoholrelated medical conditions. The key inducer of such inflammation, and also the best understood, is gut microflora-derived lipopolysaccharide (LPS). Alcohol can significantly increase the translocation of LPS from the gut. In healthy individuals, the adverse effects of LPS are kept in check by the actions and interactions of multiple organs. The liver plays a central role in detoxifying LPS and producing a balanced cytokine milieu. The central nervous syst...

  14. Brain and Addiction

    Science.gov (United States)

    ... Teens / Drug Facts / Brain and Addiction Brain and Addiction Print Your Brain Your brain is who you ... is taken over and over. What Is Drug Addiction? Addiction is a chronic brain disease that causes ...

  15. Neuropharmacology – Special Issue on Cerebral Ischemia Mechanisms of Ischemic Brain Damage – Review Article

    OpenAIRE

    Doyle, Kristian P.; Simon, Roger P.; Stenzel-Poore, Mary P

    2008-01-01

    Each year in the United States approximately 700,000 individuals are afflicted with a stroke and currently there are almost 2 million survivors of stroke living in the US with prolonged disability. In China 1.5 million people die from stroke each year and in developed nations stroke is the third leading cause of death, only surpassed by heart disease and cancer. Brain injury following stroke results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic...

  16. Protective and damaging effects of stress mediators: central role of the brain

    OpenAIRE

    McEwen, Bruce S.

    2006-01-01

    The mind involves the whole body, and two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Stress is a condition of the mind-body interaction, and a factor in the expression of disease that differs among individuals. It is not just the dramatic stressful events that exact their toll, but rather the many events of daily life that elevate and sustain activities of physiological systems and cause sleep deprivation, overeat...

  17. Central pontine myelinolysis in a chronic alcoholic: A clinical and brain magnetic resonance imaging follow-up

    Directory of Open Access Journals (Sweden)

    Dujmović Irena

    2013-01-01

    Full Text Available Introduction. Central pontine myelinolysis (CPM is a noninflammatory, demyelinating lesion usually localised in the basis pontis. Chronic alcoholism is frequently associated with this condition which may have a variable clinical outcome. Until now, brain magnetic resonance imaging (MRI follow-up in alcoholic CPM cases after alcohol withdrawal has been rarely described. Case report. We reported a 30- year-old male with a 12-year history of alcohol abuse, who presented with inability to stand and walk, nausea, vomiting and somnolence. Neurological examination revealed: impared fixation on lateral gaze, dysarthria, mild spastic quadriparesis, truncal and extremity ataxia, sock-like hypesthesia and moderate decrease in vibration sense in legs. Brain MRI showed a trident-shaped non-enhancing pontine lesion highly suggestive of CPM. After an eight-month alcoholfree follow-up period, the patient’s clinical status significantly improved, while the extent of MRI pontine lesion was merely slightly reduced. Conclusion. The presented case demonstrates that CPM in chronic alcoholics may have a benign clinical course after alcohol withdrawal, which is not necessarily associated with the reduction of lesions on brain MRI. [Projekat Ministarstva nauke Republike Srbije, br. 175031

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

    Science.gov (United States)

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

    2010-01-01

    Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. [2007]: Prog Neuropsychopharmacol Biol Psychiatry 31:1282-1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats. PMID:19634155

  19. Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Hoei-Hansen, Christina E; Krizova, Katerina; Hamerlik, Petra; Skakkebæk, Niels E; Rajpert-De Meyts, Ewa; Bartek, Jiri

    2014-01-01

    were no clear aberrations in the ATM-Chk2-p53 pathway components among the PIGCT cohort; iii) Subsets of PIGCTs showed unusual cytosolic localization of Chk2 and/or ATM. Collectively, these results show that PIGCTs mimic the DDR activation patterns of their gonadal germ cell tumor counterparts, rather......The DNA damage response (DDR) machinery becomes commonly activated in response to oncogenes and during early stages of development of solid malignancies, with an exception of testicular germ cell tumors (TGCTs). The active DDR signaling evokes cell death or senescence but this anti-tumor barrier...... cell tumors (PIGCTs), to address the roles of cell-intrinsic factors including cell of origin, versus local tissue environment, in the constitutive DDR activation in vivo. Immunohistochemical analysis of 7 biomarkers on a series of 21 PIGCTs (germinomas and other subtypes), 20 normal brain specimens...

  20. Minimal Brain Damage/Dysfunction (MBD en de ontwikkeling van de wetenschappelijke kinderstudie in Nederland, ca. 1950–1990

    Directory of Open Access Journals (Sweden)

    Nelleke Bakker

    2014-08-01

    Full Text Available 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 seriously than modern ADHD-children. MBD, moreover, has contributed considerably to the status of the child sciences which focused on the development of remedial teaching and behaviour modification techniques, particularly clinical child psychology and special education studies. In this case the diminishing influence of child psychiatry, as against these rapidly developing academic specialisms, was only temporal. With the help of the media and parent organizations Ritalin’s regime marched in by the late 1980s.

  1. Attenuation of the bacterial load in blood by pretreatment with granulocyte-colony-stimulating factor protects rats from fatal outcome and brain damage during Streptococcus pneumoniae meningitis

    DEFF Research Database (Denmark)

    Brandt, Christian T; Lundgren, Jens D; Lund, Søren Peter;

    2004-01-01

    to the infection compared to that for untreated rats (P = 0.039 by the log rank test). The improved outcome was associated with reduced signs of cerebral cortical damage (P = 0.008). Furthermore, the beneficial effects of G-CSF were associated with reduced bacterial loads in the cerebrospinal fluid...... meningitis result in reduced risks of death and brain damage. This beneficial effect is most likely achieved through improved control of the systemic disease....

  2. Unlearning chronic pain: A randomized controlled trial to investigate changes in intrinsic brain connectivity following Cognitive Behavioral Therapy

    Directory of Open Access Journals (Sweden)

    Marina Shpaner

    2014-01-01

    Full Text Available Chronic pain is a complex physiological and psychological phenomenon. Implicit learning mechanisms contribute to the development of chronic pain and to persistent changes in the central nervous system. We hypothesized that these central abnormalities can be remedied with Cognitive Behavioral Therapy (CBT. Specifically, since regions of the anterior Default Mode Network (DMN are centrally involved in emotional regulation via connections with limbic regions, such as the amygdala, remediation of maladaptive behavioral and cognitive patterns as a result of CBT for chronic pain would manifest itself as a change in the intrinsic functional connectivity (iFC between these prefrontal and limbic regions. Resting-state functional neuroimaging was performed in patients with chronic pain before and after 11-week CBT (n = 19, as well as a matched (ages 19–59, both sexes active control group of patients who received educational materials (n = 19. Participants were randomized prior to the intervention. To investigate the differential impact of treatment on intrinsic functional connectivity (iFC, we compared pre–post differences in iFC between groups. In addition, we performed exploratory whole brain analyses of changes in fractional amplitude of low frequency fluctuations (fALFF. The course of CBT led to significant improvements in clinical measures of pain and self-efficacy for coping with chronic pain. Significant group differences in pre–post changes in both iFC and fALFF were correlated with clinical outcomes. Compared to control patients, iFC between the anterior DMN and the amygdala/periaqueductal gray decreased following CBT, whereas iFC between the basal ganglia network and the right secondary somatosensory cortex increased following CBT. CBT patients also had increased post-therapy fALFF in the bilateral posterior cingulate and the cerebellum. By delineating neuroplasticity associated with CBT-related improvements, these results add to

  3. Total Flavone of Hawthorn Leaf inhibits neuronal apoptosis in brain tissue of rat models of chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Tan Rong-fang; Xia Ai-hua; Wu Xiao-guang; Cao Na-na; Li Meng-meng; Zhang Tian-ge; Wang Yi-ru; Yue Zhi-ling

    2014-01-01

    BACKGROUND: Cerebrovascular disease often causes dysfunction of the brain nerve, and nerve cel apoptosis is the important factor of cerebral nerve dysfunction. The excessive expression of c-fos can block the transduction of intracelular signal so that producing some apoptosis-promoting factors, which involve in nerve cel apoptosis process after ischemia injury of brain. Bcl-2 is an inhibited factor. It might to be the key to treat ischemic cerebrovascular disease by inhibiting or reducing the apoptosis of nerve cels after ischemia injury. OBJECTIVE: To investigate the therapeutic effect and mechanism of the Total Flavone of Hawthorn Leaf on chronic cerebral ischemia rats. METHODS: A total of 72 healthy male Sprague-Dawley rats were randomly divided into sham surgery group, model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model in the model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Total Flavone of Hawthorn Leaf group and ginkgo leaf group respectively received 140 mg/kg Total Flavone of Hawthorn Leaf and 12.3 mg/kg ginkgo leaf intragastricaly for 36 days from 36 days after model induction. Model group and sham surgery group received 3.5 mL/kg physiological saline intragastricaly. RESULTS AND CONCLUSION: Compared with the model group, the expression of c-fos protein significantly deceased in the Total Flavone of Hawthorn Leaf group (P 0.05). These data indicated that the protective effect of Total Flavone of Hawthorn Leaf on chronic cerebral ischemia was associated with its inhibition of neuronal apoptosis. Its mechanism of anti-apoptosis might be associated with up-regulating expression of Bcl-2, down-regulating expression of c-fos and decreasing Ca2+ content in brain.

  4. Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females

    International Nuclear Information System (INIS)

    Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5 Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes

  5. Grafting Genetically Modified Cells to the Damaged Brain: Restorative Effects of NGF Expression

    Science.gov (United States)

    Rosenberg, Michael B.; Friedmann, Theodore; Robertson, Robin C.; Tuszynski, Mark; Wolff, Jon A.; Breakefield, Xandra O.; Gage, Fred H.

    1988-12-01

    Fibroblasts were genetically modified to secrete nerve growth factor (NGF) by infection with a retroviral vector and then implanted into the brains of rats that had surgical lesions of the fimbria-fornix. The grafted cells survived and produced sufficient NGF to prevent the degeneration of cholinergic neurons that would die without treatment. In addition, the protected cholinergic cells sprouted axons that projected in the direction of the cellular source of NGF. These results indicate that a combination of gene transfer and intracerebral grafting may provide an effective treatment for some disorders of the central nervous system.

  6. White matter pathway supporting phonological encoding in speech production: a multi-modal imaging study of brain damage patients.

    Science.gov (United States)

    Han, Zaizhu; Ma, Yujun; Gong, Gaolang; Huang, Ruiwang; Song, Luping; Bi, Yanchao

    2016-01-01

    In speech production, an important step before motor programming is the retrieval and encoding of the phonological elements of target words. It has been proposed that phonological encoding is supported by multiple regions in the left frontal, temporal and parietal regions and their underlying white matter, especially the left arcuate fasciculus (AF) or superior longitudinal fasciculus (SLF). It is unclear, however, whether the effects of AF/SLF are indeed related to phonological encoding for output and whether there are other white matter tracts that also contribute to this process. We comprehensively investigated the anatomical connectivity supporting phonological encoding in production by studying the relationship between the integrity of all major white matter tracts across the entire brain and phonological encoding deficits in a group of 69 patients with brain damage. The integrity of each white matter tract was measured both by the percentage of damaged voxels (structural imaging) and the mean fractional anisotropy value (diffusion tensor imaging). The phonological encoding deficits were assessed by various measures in two oral production tasks that involve phonological encoding: the percentage of nonword (phonological) errors in oral picture naming and the accuracy of word reading aloud with word comprehension ability regressed out. We found that the integrity of the left SLF in both the structural and diffusion tensor imaging measures consistently predicted the severity of phonological encoding impairment in the two phonological production tasks. Such effects of the left SLF on phonological production remained significant when a range of potential confounding factors were considered through partial correlation, including total lesion volume, demographic factors, lesions on phonological-relevant grey matter regions, or effects originating from the phonological perception or semantic processes. Our results therefore conclusively demonstrate the central role of

  7. Correlation between Patent Foramen Ovale, Cerebral "Lesions" and Neuropsychometric Testing in Experienced Sports Divers: Does Diving Damage the Brain?

    Science.gov (United States)

    Balestra, Costantino; Germonpré, Peter

    2016-01-01

    SCUBA diving exposes divers to decompression sickness (DCS). There has been considerable debate whether divers with a Patent Foramen Ovale of the heart have a higher risk of DCS because of the possible right-to-left shunt of venous decompression bubbles into the arterial circulation. Symptomatic neurological DCS has been shown to cause permanent damage to brain and spinal cord tissue; it has been suggested that divers with PFO may be at higher risk of developing subclinical brain lesions because of repeated asymptomatic embolization of decompression-induced nitrogen bubbles. These studies however suffer from several methodological flaws, including self-selection bias. We recruited 200 volunteer divers from a recreational diving population who had never suffered from DCS; we then randomly selected 50 of those for further investigation. The selected divers underwent brain Magnetic Resonance Imaging to detect asymptomatic brain lesions, contrast trans-oesophageal echocardiography for PFO, and extensive neuro-psychometric testing. Neuro-psychometry results were compared with a control group of normal subjects and a separate control group for subjects exposed to neurotoxic solvents. Forty two divers underwent all the tests and are included in this report. Grade 2 Patent Foramen Ovale was found in 16 (38%) of the divers; brain Unidentified Bright Objects (UBO's) were found in 5 (11.9%). There was no association between PFO and the presence of UBO's (P = 0.693) or their size (p = 0.5) in divers. Neuropsychometric testing in divers was significantly worse from controls in two tests, Digit Span Backwards (DSB; p Coordination (EYE) tests. There was no correlation between PFO, number of UBO's and any of the neuro-psychometric tests. We conclude that for uneventful recreational diving, PFO does not appear to influence the presence of UBO's. Diving by itself seems to cause some decrease of short-term memory and higher cognitive function, including visual-motor skills; this

  8. Relationship between chronic pain and brain reorganization after deafferentation: A systematic review of functional MRI findings

    Directory of Open Access Journals (Sweden)

    C.R. Jutzeler

    2015-01-01

    Conclusion: Based solely on advanced functional neuroimaging results, there is only limited evidence for a relationship between chronic pain intensity and reorganization after deafferentation. The review demonstrates the need for additional neuroimaging studies to clarify the relationship between chronic pain and reorganization.

  9. Effects of chronic exposure to benzalkonium chloride in Oncorhynchus mykiss: cholinergic neurotoxicity, oxidative stress, peroxidative damage and genotoxicity.

    Science.gov (United States)

    Antunes, S C; Nunes, B; Rodrigues, S; Nunes, R; Fernandes, J; Correia, A T

    2016-07-01

    Benzalkonium chloride (BAC) is one of the most used conservatives in pharmaceutical preparations. However, its use is limited to a small set of external use formulations, due to its high toxicity. Benzalkonium chloride effects are related to the potential exertion of deleterious effects, mediated via oxidative stress and through interaction with membrane enzymes, leading to cellular damage. To address the ecotoxicity of this specific compound rainbow trouts were chronically exposed to BAC at environmental relevant concentrations (ranging from 0.100 to 1.050mg/L), and the biological response of cholinergic neurotoxicity, modulation of the antioxidant defense, phase II metabolism, lipid peroxidation and genotoxicity was studied. The obtained results showed a dual pattern of antioxidant response, with significant alterations in catalase activity (starting at 0.180mg/L), and lipid peroxidation, for intermediate (0.180 and 0.324mg/L) concentrations. No significant alterations occurred for glutathione-S-transferases activity. An unexpected increased of the acetylcholinesterase activity was also recorded for the individuals exposed to higher concentrations of BAC (starting at 0.180mg/L). Furthermore, exposure to BAC resulted in the establishment of genotoxic alterations, observable (for the specific case of the comet assay results) for all tested BAC concentrations. However, and considering that the oxidative response was not devisable, other mechanisms may be involved in the genotoxic effects reported here. PMID:27280532

  10. Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4-induced chronic liver damage in rats

    Institute of Scientific and Technical Information of China (English)

    Yun-Kyoung Yim; Hyun Lee; Kwon-Eui Hong; Young-Il Kim; Byung-Ryul Lee; Tae-Han Kim; Ji-Young Yi

    2006-01-01

    AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats.METHODS: Rats were injected intraperitoneally with CCl4 (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34(Yanglingquan) 3 times a week for 10 wk. A nonacupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index,biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted.RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes.CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCl4-intoxicated rats.

  11. Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Maren Geissler

    Full Text Available Intraperitoneal transplantation of human umbilical cord blood (hUCB cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury.

  12. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    Directory of Open Access Journals (Sweden)

    Picano Eugenio

    2012-04-01

    Full Text Available Abstract Background According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906, the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Results Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of Conclusions At this point, a systematic assessment of brain (cancer and non-cancer effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed.

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

    Directory of Open Access Journals (Sweden)

    Akbar Anaeigoudari

    2016-03-01

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

  14. Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates.

    Science.gov (United States)

    Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A

    2007-05-01

    To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection. PMID:17413864

  15. Utility of fractional anisotropy imaging analyzed by statistical parametric mapping for detecting minute brain lesions in chronic-stage patients who had mild or moderate traumatic brain injury

    International Nuclear Information System (INIS)

    Diffusion tensor imaging (DTI) has recently evolved as valuable technique to investigate diffuse axonal injury (DAI). This study examined whether fractional anisotropy (FA) images analyzed by statistical parametric mapping (FA-SPM images) are superior to T2*-weighted gradient recalled echo (T2*GRE) images or fluid-attenuated inversion recovery (FLAIR) images for detecting minute lesions in traumatic brain injury (TBI) patients. DTI was performed in 25 patients with cognitive impairments in the chronic stage after mild or moderate TBI. The FA maps obtained from the DTI were individually compared with those from age-matched healthy control subjects using voxel-based analysis and FA-SPM images (p<0.001). Abnormal low-intensity areas on T2*GRE images (T2* lesions) were found in 10 patients (40.0%), abnormal high-intensity areas on FLAIR images in 4 patients (16.0%), and areas with significantly decreased FA on FA-SPM image in 16 patients (64.0%). Nine of 10 patients with T2* lesions had FA-SPM lesions. FA-SPM lesions topographically included most T2* lesions in the white matter and the deep brain structures, but did not include T2* lesions in the cortex/near-cortex or lesions containing substantial hemosiderin regardless of location. All 4 patients with abnormal areas on FLAIR images had FA-SPM lesions. FA-SPM imaging is useful for detecting minute lesions because of DAI in the white matter and the deep brain structures, which may not be visualized on T2*GRE or FLAIR images, and may allow the detection of minute brain lesions in patients with post-traumatic cognitive impairment. (author)

  16. Brain damage in relation to irradiation and chemotherapy of central nervous system

    International Nuclear Information System (INIS)

    Measurements have been made of the concentrations of 3',5'-mono-phosphate, protein and sugar, and of the activities of lactic dehydrogenase (LD), aspartate aminotransferase (AsAT), creatine kinase (CK), and acid phosphatase (AcPhos) in the cerebrospinal fluid (CSF) during 60Co CNS radiotherapy and chemotherapy in eight children with acute lymphoblastic leukaemia (A.L.L.). The CSF white-blood-cell count of the A.L.L. patients did not differ significantly from that of the controls, but protein content rose and sugar content fell during CNS irradiation and chemotherapy (intrathecal methotrexate). LD and AsAT activities were significantly higher during CNS treatment, and a similar tendency was seen for AcPhos and CK activities. The results provide clear biochemical signs of brain injury caused by prophylactic CNS irradiation and chemotherapy. (U.K.)

  17. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    Directory of Open Access Journals (Sweden)

    Borini Paulo

    1999-01-01

    Full Text Available Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28% was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

  18. Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain

    International Nuclear Information System (INIS)

    Recent global events have focused attention on the potential threat of international and domestic chemical terrorism, as well as the possibility of chemical warfare proliferation. Sulphur mustard (SM) is one of the potent chemical warfare agents (CWA), which initiates a cascade of events that converge on the redox mechanisms common to brain injury. The present study was designed to examine the effects of chronic SM exposure on neurobehavioral impairments, mitochondrial oxidative stress in male Swiss Albino mice and its role in inducing apoptotic neuronal cell death. The animals were divided into four groups (control, low, medium and high dose) of 5 animals each. Exposure to SM was given percutaneously daily for 12 weeks. The results demonstrated impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests in a dose dependent manner. There was a significant increase in lipid peroxidation and protein carbonyl content whereas, decrease in the activity of manganese superoxide dismutase (MnSOD), glutathione reductase and glutathione peroxidase suggesting impaired antioxidant defense system. Immunoblotting of cytochrome c, Bcl-2, Bax and activation of caspase-3 suggest induction of apoptosis in a dose dependent manner. Finally, increased p53 expression suggests that it may target the mitochondrial pathway for inducing apoptosis in response to DNA damage signals. In conclusion, chronic SM exposure may have the potential to generate oxidative stress which may trigger the release of cytochrome c as well as caspase-3 activation in neurons leading to cell death by apoptosis in a dose dependent manner which may in the end be responsible for the disruption of cognitive functions in mice.

  19. Knockdown of microRNA-195 contributes to protein phosphatase-2A inactivation in rats with chronic brain hypoperfusion.

    Science.gov (United States)

    Liu, Cheng-Di; Wang, Qin; Zong, De-Kang; Pei, Shuang-Chao; Yan, Yan; Yan, Mei-Ling; Sun, Lin-Lin; Hao, Yang-Yang; Mao, Meng; Xing, Wen-Jing; Ren, Huan; Ai, Jing

    2016-09-01

    Reduction of protein phosphatase-2A (PP2A) activity is a common clinical feature of Alzheimer's disease and vascular dementia. In this study, we observed that chronic brain hypoperfusion induced by bilateral common carotid artery occlusion of rats led to PP2A inactivation based on the increase in tyrosine-307 phosphorylation and leucine-309 demethylation of PP2AC and the depression in PP2ABα. Knockdown of miR-195 using overexpression of its antisense molecule oligonucleotide (pre-AMO-miR-195) delivered by a lentivirus (lenti-pre-AMO-miR-195) increased tyrosine-307 phosphorylation and decreased both PP2ABα expression and leucine-309 methylation; these effects were prevented by the overexpression of miR-195 using lenti-pre-miR-195 and controlled by an increase in methylesterase (PME-1) and a decrease in leucine carboxyl methyltransferase-1. In vitro studies demonstrated that miR-195 regulated PME-1 expression by binding to the Ppme1 gene 3'-untranslated region (3'UTR) domain. Masking the miR-195 binding sites in the amyloid precursor protein (APP) and β-site APP cleaving enzyme 1 genes prevented miR-195-induced leucine carboxyl methyltransferase-1 elevation. We concluded that the miR-195 downregulation in chronic brain hypoperfusion involved PP2A inactivity, which was mediated by the post-transcriptional regulation PME-1, APP, and β-site APP cleaving enzyme 1 expression. PMID:27459928

  20. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    Energy Technology Data Exchange (ETDEWEB)

    Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze [Toxicology Unit, INERIS, Verneuil en Halatte (France)

    2006-07-01

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

  1. Differences in brain structure in patients with distinct sites of chronic pain A voxel-based morphometric analysis

    Institute of Scientific and Technical Information of China (English)

    Cuiping Mao; Longxiao Wei; Qiuli Zhang; Xia Liao; Xiaoli Yang; Ming Zhang

    2013-01-01

    A reduction in gray matter volume is common in patients with chronic back pain, and different types of pain are associated with gray matter abnormalities in distinct brain regions. To examine ences in brain morphology in patients with low back pain or neck and upper back pain, we gated changes in gray matter volume in chronic back pain patients having different sites of pain using voxel-based morphometry. A reduction in cortical gray matter volume was found primarily in the left postcentral gyrus and in the left precuneus and bilateral cuneal cortex of patients with low back pain. In these patients, there was an increase in subcortical gray matter volume in the bilateral putamen and accumbens, right pal idum, right caudate nucleus, and left amygdala. In upper back pain patients, reduced cortical gray matter volume was found in the left precentral and left tral cortices. Our findings suggest that regional gray matter volume abnormalities in low back pain patients are more extensive than in upper back pain patients. Subcortical gray matter volume in-creases are found only in patients with low back pain.

  2. The effects of spinal cord stimulation on the neuronal activity of the brain in patients with chronic neuropathic pain

    International Nuclear Information System (INIS)

    The effects of spinal cord stimulation (SCS) on the neuronal activity of the brain were examined by single photon emission computed tomography (SPECT) in patients with chronic neuropathic pain. Regional cerebral blood flow (CBF) in each cortical area and the thalamus decreased in several patients without SCS. Patients with central pain due to thalamic hemorrhage showed a decrease in rCBF in the thalamus contralateral to the painful side. During the stimulation period in SCS, parietal rCBF decreased on the side contralateral to the pain. In contrast, rCBF increased in the bilateral frontal and anterior cingulate cortex and in the contralateral temporal lobe in half of the patients in whom SCS was effective in relieving pain. The decrease in thalamic rCBF in two patients with central pain was improved by the SCS therapy; however, pain was relieved in only one of them. In the majority of patients in whom SCS was not effective, there was no change in rCBF in various cortical areas, even after SCS. These results suggest that, in patients with chronic neuropathic pain, SCS modulates the neuronal activities of several brain areas that are believed to be associated with pain processing. (author)

  3. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    International Nuclear Information System (INIS)

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

  4. Region-specific up-regulation of oxytocin receptor binding in the brain of mice following chronic nicotine administration.

    Science.gov (United States)

    Zanos, Panos; Georgiou, Polymnia; Metaxas, Athanasios; Kitchen, Ian; Winsky-Sommerer, Raphaelle; Bailey, Alexis

    2015-07-23

    Nicotine addiction is considered to be the main preventable cause of death worldwide. While growing evidence indicates that the neurohypophysial peptide oxytocin can modulate the addictive properties of several abused drugs, the regulation of the oxytocinergic system following nicotine administration has so far received little attention. Here, we examined the effects of long-term nicotine or saline administration on the central oxytocinergic system using [(125)I]OVTA autoradiographic binding in mouse brain. Male, 7-week old C57BL6J mice were treated with either nicotine (7.8 mg/kg daily; rate of 0.5 μl per hour) or saline for a period of 14-days via osmotic minipumps. Chronic nicotine administration induced a marked region-specific upregulation of the oxytocin receptor binding in the amygdala, a brain region involved in stress and emotional regulation. These results provide direct evidence for nicotine-induced neuroadaptations in the oxytocinergic system, which may be involved in the modulation of nicotine-seeking as well as emotional consequence of chronic drug use. PMID:26037668

  5. Differences in supratentorial white matter diffusion after radiotherapy - New biomarker of normal brain tissue damage?

    Energy Technology Data Exchange (ETDEWEB)

    Ravn, Soeren; Jens Broendum Froekaer, Jens [Dept. of Radiology, Aalborg Univ. Hospital, Aalborg (Denmark)], e-mail: sorl@rn.dk; Holmberg, Mats [Dept. of Oncology, Aalborg Univ. Hospital, Aalborg (Denmark); Soerensen, Preben [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark); Carl, Jesper [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark)

    2013-10-15

    Introduction: Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. Material and methods: DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35-71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0-7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on iso curves from Eclipse. Data was analysed by t-test. Estimates are given with 95 % CI. Results: A mean ADC difference of 4.6(0.3;8.9) X 10{sup -5} mm{sup 2}/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60) X 10{sup -5} mm{sup 2}/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(-1.76;5.58) X 10{sup -5} mm{sup 2}/s, p = 0.29; 15 Gy; 5.81(1.53;10.11) X 10{sup -5} mm{sup 2}/s, p = 0.01; 25 Gy; 5.80(2.43;9.18) X 10{sup -5} mm{sup 2}/s, p = 0.002; 35 Gy; 5.93(2.89;8.97) X 10

  6. Interaction of Metabolic Stress with Chronic Mild Stress in Altering Brain Cytokines and Sucrose Preference

    OpenAIRE

    Remus, Jennifer L.; Stewart, Luke T.; Camp, Robert M.; Novak, Colleen M.; Johnson, John D.

    2015-01-01

    There is growing evidence that metabolic stressors increase an organism’s risk of depression. Chronic mild stress is a popular animal model of depression and several serendipitous findings have suggested that food deprivation prior to sucrose testing in this model is necessary to observe anhedonic behaviors. Here, we directly tested this hypothesis by exposing animals to chronic mild stress and used an overnight two bottle sucrose test (food ad libitum) on day 5 and 10, then food and water de...

  7. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    International Nuclear Information System (INIS)

    According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv). At this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed

  8. A clinically relevant model of perinatal global ischemic brain damage in rats.

    Science.gov (United States)

    Yang, Ting; Zhuang, Lei; Terrando, Niccolò; Wu, Xinmin; Jonhson, Mark R; Maze, Mervyn; Ma, Daqing

    2011-04-01

    We have designed a clinically relevant model of perinatal asphyxia providing intrapartum hypoxia in rats. On gestation day 22 SD rats were anesthetized and the uterine horns were exteriorized and placed in a water bath at 37°C for up to 20min. After this, pups were delivered from the uterus and manually stimulated to initiate breathing in an incubator at 37°C for 1 h in air. Brains were harvested and stained with cresyl violet, caspase-3, and TUNEL to detect morphological and apoptotic changes on postnatal days (PND) 1, 3, and 7. Separate cohorts were maintained until PND 50 and tested for learning and memory using Morris water maze (WM). Survival rate was decreased with longer hypoxic time, and 100% mortality was noted when hypoxia time was beyond 18min. Apoptosis was increased with the duration of hypoxia with neuronal loss and cell shrinkage in the CA1 of hippocampus. The time taken for the juveniles to locate the hidden platform during WM was increased in animals subjected to hypoxia. These data demonstrate that perinatal ischemic injury leads to neuronal death in the hippocampus and long-lasting cognitive dysfunction. This model mimics hypoxic ischemic encephalopathy in humans and may be appropriate for investigating therapeutic interventions. PMID:21281606

  9. Planning for selective amygdalohippocampectomy involving less neuronal ifber damage based on brain connectivity using tractography

    Institute of Scientific and Technical Information of China (English)

    Seung-Hak Lee; Mansu Kim; Hyunjin Park

    2015-01-01

    Temporal lobe resection is an important treatment option for epilepsy that involves removal of potentially essential brain regions. Selective amygdalohippocampectomy is a widely performed temporal lobe surgery. We suggest starting the incision for selective amygdalohippocampec-tomy at the inferior temporal gyrus based on diffusion magnetic resonance imaging (MRI) tractography. Diffusion MRI data from 20 normal participants were obtained from Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org). A tractography algorithm was applied to extract neuronal fiber information for the temporal lobe, hippocampus, and amygdala. Fiber information was analyzed in terms of the number of fibers and betweenness centrality. Distances between starting incisions and surgical target regions were also considered to explore the length of the surgical path. Middle temporal and superior temporal gyrus regions have higher connectivity values than the inferior temporal gyrus and thus are not good candi-dates for starting the incision. The distances between inferior temporal gyrus and surgical target regions were shorter than those between middle temporal gyrus and target regions. Thus, the in-ferior temporal gyrus is a good candidate for starting the incision. Starting the incision from the inferior temporal gyrus would spare the important (in terms of betweenness centrality values) middle region and shorten the distance to the target regions of the hippocampus and amygdala.

  10. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  11. [Minimal early-childhood brain damage in the pediatric practice and disability insurance].

    Science.gov (United States)

    Frischknecht, W

    1976-07-01

    In modern practice the pediatrician is called upon daily to take preventive, curative and rehabilitative action in children with cerebro-organic and psychosocial risk factors: 1. Eearly diagnosis of handicaps by POLTIBAC on the occasion of individual vaccinations and infectious diseases. 2. Fitness programs for infants to improve the mother-child relationship and reduce frustrations in children's homes and day nurseries. 3. Psychohygiene and mini-psychotherapy of ambivalent mothers during every pediatric consultation. The pediatrician's second patient is the mother. 4. The self-help mentality in pediatrician, parents and educationists assumes increasing importance as economy cames to rule pediatric practice in view of the cost explosion in the health sector. 5. In the Canton of St. Gall increasing numbers of children with cerebral lesions have been registered with the Disablement Insurance since 1970: in 1972 12%, in 1973 14% and in 1974 19% of first-registered minors. Since 1961 all definitely cerebral motor disorders have been registered with the Disablement Insurance, and since 1971 the infantile psychoorganic syndrome and questionable minimal "dyskinesias" have also been registered. The diagnostic and therapeutic costs for infantile minimal brain lesions according to Disablement Insurance tariffs are computed. PMID:990577

  12. Dental management in dysphagia syndrome patients with previously acquired brain damages

    Directory of Open Access Journals (Sweden)

    Ennio Bramanti

    2012-01-01

    Full Text Available Dysphagia is defined as difficulty in swallowing food (semi-solid or solid, liquid, or both. Difficulty in swallowing affects approximately 7% of population, with risk incidence increasing with age. There are many disorder conditions predisposing to dysphagia such as mechanical strokes or esophageal diseases even if neurological diseases represent the principal one. Cerebrovascular pathology is today the leading cause of death in developing countries, and it occurs most frequently in individuals who are at least 60 years old. Swallowing disorders related to a stroke event are common occurrences. The incidence ranging is estimated from 18% to 81% in the acute phase and with a prevalence of 12% among such patients. Cerebral, cerebellar, or brain stem strokes can influence swallowing physiology while cerebral lesions can interrupt voluntary control of mastication and bolus transport during the oral phase. Among the most frequent complications of dysphagia are increased mortality and pulmonary risks such as aspiration pneumonia, dehydration, malnutrition, and long-term hospitalization. This review article discusses the epidemiology of dysphagia, the normal swallowing process, pathophysiology, signs and symptoms, diagnostics, and dental management of patients affected.

  13. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    Science.gov (United States)

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

  14. The assessment of pragmatics in Iranian patients with right brain damage.

    Directory of Open Access Journals (Sweden)

    Davood Sobhani-Rad

    2014-06-01

    Full Text Available Pragmatics is appropriate use of language across a variety of social contexts that provides accurate interpretation of intentions. The occurrence of the right hemisphere lesions can interfere with pragmatic abilities, and particularly with the processing of nonliteral speech acts.Since the objective of this study was to assess different aspects of pragmatic competence in the right hemisphere damage (RHD patients, 20 Iranian patients with right hemisphere lesions were examined by adult pragmatic profile (APP and a novel checklist was introduced for Persian language speaking individuals. Meanwhile, 40 healthy adult individuals, who were age and gender matched with RHD patients, were considered as the control group. After obtaining video records, all subjects were evaluated for 35 pragmatic skills, including 24 verbal, 5 paralinguistic, and 6 nonverbal aspects, by a two-point scale system.Studying RHD patients and their healthy counterparts revealed that the performance by participants with right hemisphere lesions exhibited a high degree of inappropriate pragmatic abilities compared with controls in all domains. Furthermore, RHD patients showed a trend of increasing difficulty in understanding and producing different pragmatic phenomena, including standard communication acts.Present results indicated that the right hemisphere lesions significantly affected pragmatic abilities in verbal, paralinguistic and nonverbal aspects. Such a pattern of performance, which is in line with deficits previously reported for RHD, proved the unquestioned role of the right hemisphere in processing nonliteral language.

  15. DAPK1 Interaction with NMDA Receptor NR2B Subunits Mediates Brain Damage in Stroke

    Science.gov (United States)

    Tu, Weihong; Xu, Xin; Peng, Lisheng; Zhong, Xiaofen; Zhang, Wenfeng; Soundarapandian, Mangala M.; Balel, Cherine; Wang, Manqi; Jia, Nali; Zhang, Wen; Lew, Frank; Chan, Sic Lung; Chen, Yanfang; Lu, Youming

    2010-01-01

    SUMMARY N-methyl-D-aspartate (NMDA) receptors constitute a major subtype of glutamate receptors at extra-synaptic sites that link multiple intracellular catabolic processes responsible for irreversible neuronal death. Here, we report that cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the NMDA receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly binds with the NMDA receptor NR2B C-terminal tail consisting of amino acid 1292–1304 (NR2BCT). A constitutively active DAPK1 phosphorylates NR2B subunit at Ser-1303 and in turn enhances the NR1/NR2B receptor channel conductance. Genetic deletion of DAPK1 or administration of NR2BCT that uncouples an activated DAPK1 from an NMDA receptor NR2B subunit in vivo in mice blocks injurious Ca2+ influx through NMDA receptor channels at extrasynaptic sites and protects neurons against cerebral ischemic insults. Thus, DAPK1 physically and functionally interacts with the NMDA receptor NR2B subunit at extra-synaptic sites and this interaction acts as a central mediator for stroke damage. PMID:20141836

  16. Chronic treatment with fibrates elevates superoxide dismutase in adult mouse brain microvessels

    OpenAIRE

    Wang, Guangming; Liu, Xiaowei; Guo, Qingmin; Namura, Shobu

    2010-01-01

    Fibrates are activators of peroxisome proliferator-activated receptor (PPAR) α. Pretreatment with fibrates has been shown to protect brain against ischemia in mice. We hypothesized that fibrates elevate superoxide dismutase (SOD) levels in the brain microvessels (BMV). BMV were isolated from male C57BL/6 and PPARα null mice that had been treated with fenofibrate or gemfibrozil for 7 days. To examine the effect of discontinuation of fenofibrate, another animal group treated with fenofibrate wa...

  17. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S.F.; Newport, G.D.; Scallet, A.C.; Gee, K.W.; Paule, M.G.; Brown, R.M.; Slikker, W. Jr. (National Center for Toxicological Research, Jefferson, Arkansas (USA))

    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the (35S)TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of (35S)TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects.

  18. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

    International Nuclear Information System (INIS)

    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects

  19. Effects of alcohol intake on brain structure and function in non-alcohol-dependent drinkers

    OpenAIRE

    Bruin, Eveline Astrid de

    2005-01-01

    About 85% of the adult population in the Netherlands regularly drinks alcohol. Chronic excessive alcohol intake in alcohol-dependent individuals is known to have damaging effects on brain structure and function. Relatives of alcohol-dependent individuals display differences in brain function that are similar to those found in alcoholics, even if they have never been drinking alcohol. This suggests that brain damage in alcohol-dependent individuals is at least partly related to genetic factors...

  20. Magnetic resonance imaging of the brain in chronic dialysis patients. Evaluation of high signal lesions in cerebral subcortical areas

    International Nuclear Information System (INIS)

    This study was aimed to evaluate the incidence of cerebral subcortical high signal lesions (SHS) on T2 weighted images of Magnetic Resonance Imaging in chronic dialysis patients. The incidence of SHS was investigated in three clinically different groups of patients (196 divided into 3 age groups (20-40, 41-60, 61-83 years old). SHS were graded according to size and number. The incidence and severity of SHS increased with advancing age in all groups of patients and were higher in hypertensive and dialysis patients. Patchy confluent SHS were not identified in any patient younger than 60 years old in normal subjects and hypertensive patients. They were present in 9% in patients 41 to 60 years old of dialysis patients. In patients over than 61 years old, patchy confluent SHS were present in 1% of normal subjects, 11% of hypertensive patients, and 30% of dialysis patients. Duration, methods of dialysis therapy or previous history of hypertension in dialysis patients did not affect the incidence of SHS. SHS were mainly located in the territory of anterior, middle carebral and lenticulostriate arteries. In one autopsy case of chronic dialysis patient with severe SHS on magnetic resonance images, microscopic finding at pathological examination showed dilated perivascular space and increased water content in white matter. The results demonstrate a high incidence of severe SHS in chronic dialysis patients, and suggest that the SHS in dialysis patients appear to represent increased water content in perivascular brain tissue. (author)

  1. Use of FDG-PET to detect a chronic odontogenic infection as a possible source of the brain abscess.

    Science.gov (United States)

    Sato, Jun; Kuroshima, Takeshi; Wada, Mayumi; Satoh, Akira; Watanabe, Shiro; Okamoto, Shozo; Shiga, Tohru; Tamaki, Nagara; Kitagawa, Yoshimasa

    2016-05-01

    This study describes the use of (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to detect a chronic odontogenic infection as the possible origin of a brain abscess (BA). A 74-year-old man with esophageal carcinoma was referred to our department to determine the origin of a BA in his oral cavity. He had no acute odontogenic infections. The BA was drained, and bacteria of the Staphylococcus milleri group were detected. Whole body FDG-PET revealed that the only sites of definite uptake of FDG were the esophageal carcinoma and the left upper maxillary region (SUVmax: 4.5). These findings suggested that the BA may have originated from a chronic periodontal infection. Six teeth with progressive chronic periodontal disease were extracted to remove the possible source of BA. These findings excluded the possibility of direct spread of bacteria from the odontogenic infectious lesion to the intracranial cavity. After extraction, there was no relapse of BA. PMID:26497357

  2. Monitoring stroke progression: in vivo imaging of cortical perfusion, blood–brain barrier permeability and cellular damage in the rat photothrombosis model

    Science.gov (United States)

    Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon

    2014-01-01

    Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood–brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood–brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex. PMID:25160672

  3. Monitoring stroke progression: in vivo imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model.

    Science.gov (United States)

    Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon

    2014-11-01

    Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex. PMID:25160672

  4. Inhibition of cytosolic phospholipase A(2) alpha protects against focal ischemic brain damage in mice.

    Science.gov (United States)

    Zhang, Jian; Barasch, Noah; Li, Rung-Chi; Sapirstein, Adam

    2012-08-30

    It is postulated that inhibition of cytosolic phospholipase A(2) alpha (cPLA(2)α) can reduce severity of stroke injury. This is supported by the finding that cPLA(2)α-deficient mice are partially protected from transient, focal cerebral ischemia. The object of this study was to determine the effect of cPLA(2)α inhibition with arachidonyl trifluoromethyl ketone (ATK) on stroke injury in mice. Male C57BL/6 mice were subjected to 1h of focal cerebral ischemia followed by 24 or 72 h of reperfusion. Mice were treated with ATK or vehicle by intermittent intraperitoneal injection or continuous infusion via an implanted infusion pump. ATK injections 1h before and then 1 and 6h after the start of reperfusion significantly reduced infarction volumes in striatum and hemisphere after 24h of reperfusion. ATK did not reduce injury if it was not administered before onset of ischemia or was not administered after 6h of reperfusion. Intermittent doses of ATK failed to reduce infarct volume after 72 h of reperfusion. Continuous infusion with ATK throughout 72h of reperfusion significantly reduced cortical and whole hemispheric infarct volume compared to vehicle treatment. Following ischemia and reperfusion, ATK treatment significantly reduced brain PLA(2) activity. These results are the first to demonstrate a therapeutic effect of cPLA(2)α inhibition on ischemia and reperfusion injury and define a therapeutic time window. cPLA(2)α activity augments injury in the acute and delayed phases of cerebral ischemia and reperfusion injury. We conclude that cPLA(2)α inhibition may be clinically useful if started before initiation of cerebral ischemia. PMID:22819928

  5. Alterations of cerebral blood flow and cerebrovascular reserve in patients with chronic traumatic brain injury accompanying deteriorated intelligence

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate alterations of regional cerbral blood flow (CBF) and cerebrovascular reserve (CVR), and correlation between these alternations and cognitive dysfunctin in patients with chronic traumatic brain injury (TBI) and normal brain MRI findings. Thirty TBI patients and 19 healthy volunteers underwent rest/acetazolaminde brain SPECT using Tc-99m HMPAO. Korean-Wechsler Adult Intelligence scale test was also performed in the patient group. Statistical analysis was performed with statistical parametric mapping software (SPM '97). CBF was diminished in the left hemisphere including Wernicke's area in all patients with lower verbal scale scores. In addition, a reduction in CBF in the right frontal, temporal and parietal cortices was related with depressed scores in information, digital span, arithmetic and similarities. In patients with lower performance scale scores, CBF was mainly diminished in the right hemisphere including superior temporal and supramarginal gyri, premotor, primary somatomotor and a part of prefrontal cortices, left frontal lobe and supramarginal gyrus. CVR was diminished in sixty-four Brodmann's areas compared to control. A reduction in CVR was demonstrated bilaterally in the frontal and temporal lobes in patients with lower scores in both verbal and performance tests, and in addition, both inferior parietal and occipital lobes in information subset. Alterations of CBF and CVR were demonstrated in the symptomatic TBI patients with normal MRI finding. These alterations were correlated with the change of intelligence, of which the complex functions are subserved by multiple interconnected cortical structures.=20

  6. 99mTc-bicisate reliably images CBF in chronic brain diseases but fails to show reflow hyperemia in subacute stroke

    DEFF Research Database (Denmark)

    Lassen, N A; Sperling, B

    normal or elevated flow (luxury perfusion) as sign of spontaneous thrombolysis with reperfusion; in fact, these seven cases comprised all the reperfusion cases in the series. The results validate bicisate as a tracer of CBF in normal humans and in chronic brain diseases. Only in a subgroup of subacute...... 115 cases were collected, and of these 105 were considered technically adequate, comprising 18 normal subjects, 18 senile dementia, eight epilepsy, one brain tumor, eight chronic head trauma, and 52 stroke cases. As expected, bicisate gave better spatial resolution than Xe. Agreement between the...

  7. Gender differences in rat brain serotonin transporter levels after exposure to prenatal stress and/or chronic mild stress in early adulthood

    OpenAIRE

    VERLEYSEN, Alexandra

    2007-01-01

    Prenatal stress and chronic mild stress are great risk factors for developing mood disorders. When the stress response cannot cope with the amount of stress, the brain will undergo longterm changes. These changes can lead to several diseases associated with chronic stress. In these diseases the serotonergic system is a main player, especially in mood disorders. Serotonin is taken up by the serotonin transporter, which is presynaptically localized. In case of depression, seroton...

  8. Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

    Science.gov (United States)

    Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F

    2014-08-22

    Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (pexercise (pexercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate. PMID:24907601

  9. Willed-movement training reduces brain damage and enhances synaptic plasticity related proteins synthesis after focal ischemia.

    Science.gov (United States)

    Nie, Jingjing; Yang, Xiaosu; Tang, Qingping; Shen, Qin; Li, Simin

    2016-01-01

    It has been wildly accepted that willed movement(WM) training promotes neurological rehabilitation in patients with stroke. However, it was not clear whether the effect of WM is better than other forms of exercise. The purpose of this study is to assess different effects of WM and other forms of exercise on rats with focal ischemia. The subjects are all had right middle cerebral artery occlusion (MCAO) surgery and randomly allocated to three groups of training and one control group with no training. Infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) dye, expression of PICK1 and synaptophysin in cerebral cortex and striatum of injured side by western blotting and immunofluorescence performed are analyzed. Exercise has done respectively on rats in each group for 15 days and 30 days. Compared with the control group, the brain damage is reduced in other groups after 15 days exercise. The protein expressions levels of synaptophysin and PICK1 are upregulated after exercise. Concentration of PICK1 protein in WM is greater than other exercise groups, and the expression of synaptophysin in WM and SM groups are higher than EM groups. The number of PICK1 positive cells, synaptophysin and PICK1 co-positive cells are increased by exercise. Synaptophysin is widely distributed in cortex surrounding the injury area in WM and EM. It is indicated in our result that willed-movement training is the most effective intervention in enhancing the PICK1-mediated synaptic plasticity in the area adjacent to the damage region of ischemic rats. PMID:26556240

  10. Chronic intermittent fasting improves cognitive functions and brain structures in mice.

    Directory of Open Access Journals (Sweden)

    Liaoliao Li

    Full Text Available Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day fasting or high fat diet (45% caloric supplied by fat for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice. Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals.

  11. Chemical and radiological effects of chronic ingestion of uranium in the rat brain: biochemical impairment of dopaminergic, serotonergic and cholinergic neuro-transmissions

    International Nuclear Information System (INIS)

    Uranium is an environmental ubiquitous metal-trace element. It has both chemical and radiological toxicity. After chronic ingestion, uranium can distribute in any part of the body and accumulate in the brain. The aims of this study was 1) to determine and estimate the effects of uranium on dopaminergic, serotoninergic and cholinergic systems and 2) to measure the uranium amount in the brain, after chronic exposure by ingestion of depleted (D.U.) or enriched (E.U.) uranium during 1.5 to 18 months at 40 mg.L-1 (40 ppm) in different rat brain areas. At any time of exposure, the results show that both the neurotransmission alterations and the uranium brain accumulation were moderate, area specific, time-evolutive and depended on uranium specific activity. After D.U. exposure, monoamine perturbations are chronic and progressive. On the contrary, monoamine alterations occurred only after long term of E.U. exposure. These mono-aminergic modifications are not always dependent on uranium accumulation in brain areas. Moreover, although the cholinergic system was not affected at both 1.5 and 9 months of D.U. exposure, the alteration of ChE activity after E.U. exposure are both dependent on uranium accumulation in brain areas and on uranium specific activity. After E.U. exposure, cholinergic modification and uranium accumulation in hippocampus could partially explain the short-term memory disturbances which have been previously reported. (author)

  12. MRI of fetal acquired brain lesions

    International Nuclear Information System (INIS)

    Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images

  13. MRI of fetal acquired brain lesions

    Energy Technology Data Exchange (ETDEWEB)

    Prayer, Daniela [Department of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail: daniela.prayer@meduniwien.ac.at; Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Kasprian, Gregor [Department of Radiodiagnostics, Medical University of Vienna (Austria); Witzani, Linde [Department of Radiodiagnostics, Medical University of Vienna (Austria); Helmer, Hanns [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Dietrich, Wolfgang [Department of Neurosurgery, Medical University of Vienna (Austria); Eppel, Wolfgang [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Langer, Martin [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria)

    2006-02-15

    Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images.

  14. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders.

    Science.gov (United States)

    Masliah, E; Díez-Tejedor, E

    2012-04-01

    Neurotrophic factors are considered as part of the therapeutic strategy for neurological disorders like dementia, stroke and traumatic brain injury. Cerebrolysin is a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair. In dementia models, Cerebrolysin decreases β-amyloid deposition and microtubule-associated protein tau phosphorylation by regulating glycogen synthase kinase-3β and cyclin-dependent kinase 5 activity, increases synaptic density and restores neuronal cytoarchitecture. These effects protect integrity of the neuronal circuits and thus result in improved cognitive and behavioral performance. Furthermore, Cerebrolysin enhances neurogenesis in the dentate gyrus, the basis for neuronal replacement therapy in neurodegenerative diseases. Experimental studies in stroke animal models have shown that Cerebrolysin stabilizes the structural integrity of cells by inhibition of calpain and reduces the number of apoptotic cells after ischemic lesion. Cerebrolysin induces restorative processes, decreases infarct volume and edema formation and promotes functional recovery. Stroke-induced neurogenesis in the subventricular zone was also promoted by Cerebrolysin, thus supporting the brain's self-repair after stroke. Both, traumatic brain and spinal cord injury conditions stimulate the expression of natural neurotrophic factors to promote repair and regeneration processes -axonal regeneration, neuronal plasticity and neurogenesis- that is considered to be crucial for the future recovery. Neuroprotective effects of Cerebrolysin on experimentally induced traumatic spinal cord injury have shown that Cerebrolysin prevents apoptosis of lesioned motoneurons and promotes functional recovery. This section summarizes the most relevant data on the pharmacology of Cerebrolysin obtained from in vitro assays (biochemical and cell cultures) and in vivo animal models of acute and chronic neurological disorders. PMID

  15. Dapsone improves functional deficit and diminishes brain damage evaluated by 3-Tesla magnetic resonance image after transient cerebral ischemia and reperfusion in rats.

    Science.gov (United States)

    Diaz-Ruiz, Araceli; Roldan-Valadez, Ernesto; Ortiz-Plata, Alma; Mondragón-Lozano, Rodrigo; Heras-Romero, Yessica; Mendez-Armenta, Marisela; Osorio-Rico, Laura; Nava-Ruiz, Concepción; Ríos, Camilo

    2016-09-01

    Stroke is a frequent cause of death and the first of disability in the world population. We have shown that dapsone acts as an antioxidant, antiinflammatory and antiapoptotic agent after brain Ischemia reperfusion (I/R) in rats; however, its therapeutic efficacy, measured by imaging has not been characterized. In this context, the aim of this study was to evaluate the neuroprotective effect of dapsone by magnetic resonance imaging (MRI) and to correlate imaging markers with motor function and oxidative stress after transient cerebral ischemia and reperfusion (I/R). We used male rats throughout the experiment. Functional deficit after I/R was assessed by using Longa scale. The area of brain tissue damage was measured by histology. The nuclear factor erythroid 2-related factor 2 (Nrf-2) and the amount of reactive oxygen species (ROS) were measured as biomarkers of oxidative stress. Finally, difussion tensor MRI was employed to measure the fractional anisotropy (FA), as a MRI marker of the pathophysiologic brain status. Results showed a better functional recovery and less damaged tissue in animals treated with dapsone vs control group. The values of FA were higher in animals receiving treatment, indicating a better preservation of brain structure. At early stages of the damage, dapsone was able to reduce both oxidative markers (Nrf-2 and ROS). Our findings provide new evidence for the efficacy of dapsone when administered during the acute phase after I/R and that quantitative sequences of MRI are useful for characterizing its potential therapeutic benefits after stroke. PMID:27321157

  16. Model of chronic local irradiation in the brain. Rep. 1. A point of radiation affection

    Energy Technology Data Exchange (ETDEWEB)

    Sataev, M.M. (Uzbekskij Nauchno-Issledovatel' skij Inst. Onkologii i Radiologii, Tashkent (USSR))

    Radionecrosis of tissues was detected after implantation of /sup 90/S-/sup 90/Y sources (0.5-0.2 Gy/h) to the rabbit brain. A repair inflammatory reaction developed around the point of affection which resulted, at a dose of 0.5 Gy/h, in the formation of the connective tissue capsules or gliomesencymal cicatrices, or in the diffuse, hyperplasia of cell elements of neuroglia, membranes and vessels of the brain at doses of 1.4 to 2.0 Gy/h. This is the reason for the appearance of focal epitheliocellular granulomas.

  17. Shared immune and repair markers during experimental toxoplasma chronic brain infection and schizophrenia

    NARCIS (Netherlands)

    J.J. Tomasik (Jakub); T.L. Schultz (Tracey L.); W. Kluge (Wolfgang); R.H. Yolken (Robert H.); S. Bahn (Sabine); V.B. Carruthers (Vern B.)

    2016-01-01

    textabstractChronic 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 m

  18. Protective Effect of Calendula officinalis L. Flowers Against Monosodium Glutamate Induced Oxidative Stress and Excitotoxic Brain Damage in Rats.

    Science.gov (United States)

    Shivasharan, B D; Nagakannan, P; Thippeswamy, B S; Veerapur, V P

    2013-07-01

    Monosodium glutamate (MSG) is a popular flavour enhancer used in food industries; however, excess MSG is neurotoxic. Oxidative stress is well documented in MSG induced neurotoxicity. The compounds having antioxidant and anti-inflammatory properties reportedly possess beneficial effects against various neurotoxic insults. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant and anti-inflammatory activities. Hence, this present study has been designed to evaluate the neuroprotective effect of COE on MSG-induced neurotoxicity in rats. Adult Wistar rats were administered systemically for 7 days with MSG and after one h of MSG injection, rats were treated with COE (100 and 200 mg/kg) orally. At the end the treatment period, animals were assessed for locomotor activity and were sacrificed; brains were isolated for estimation of LPO, GSH, CAT, TT, GST, Nitrite and histopathological studies. MSG caused a significant alteration in animal behavior, oxidative defense (raised levels of LPO, nitrite concentration, depletion of antioxidant levels) and hippocampal neuronal histology. Treatment with COE significantly attenuated behavioral alterations, oxidative stress, and hippocampal damage in MSG-treated animals. Hence, this study demonstrates that COE protects against MSG-induced neurotoxicity in rats. The antioxidant and anti-inflammatory properties of COE may be responsible for its observed neuroprotective action. PMID:24426226

  19. New light on white matter damage of the premature brain: a neonatologist’s point of view

    Directory of Open Access Journals (Sweden)

    Maria Antonietta Marcialis

    2014-06-01

    Full Text Available Periventricular leucomalacia (PVL is traditionally considered a multifactorial lesion related to three main mechanisms: ischemia, inflammation and excitotoxicity. For years it was believed that hypoperfusion, associated with the peculiar vascular anatomy of the premature brain (border zones, was the conditio sine qua non in the pathogenesis of PVL. More recently this theory has been questioned. Many studies have stressed the importance of the association between inflammation/infection and white matter injury and have supported the multi hit hypothesis according to which several (genetic, hormonal, immune and nutritional factors may team up in a multi-hit fashion. The emerging concept is that the fetal white cell activation together with the interaction between the innate and adaptive immune system play a main role in white matter damage. Currently there are increasing evidence that PVL is a disease of connectivity. In this article we review the news in the basics of pathogenesis, the incidence, the definition and the diagnosis of PVL. Furthermore, recent follow-up studies and neuroprotective therapies are mentioned. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  20. Hyperbaric oxygen preconditioning ameliorates hypoxia-ischemia brain damage by activating Nrf2 expression in vivo and in vitro.

    Science.gov (United States)

    Zhai, Xiao; Lin, Han; Chen, Yu; Chen, Xiao; Shi, Jiazi; Chen, Ouyang; Li, Jiasi; Sun, Xuejun

    2016-01-01

    The present study aimed to investigate whether hyperbaric oxygen preconditioning (HBO-PC) could ameliorate hypoxia-ischemia brain damage (HIBD) by an increase of Nrf2 expression. P7 Sprague-Dawley rats (aged 7 d, n = 195) were used in two in vivo experiments, including BO-PC exposure experiments in non-HIBD models and treatment experiments in HIBD models. 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl Staining, and TUNEL staining were performed. And expressions of Nrf2, HO-1, and GSTs were measured. For in vitro studies, oxygen-glucose deprivation cells were established. Morphological and apoptotic staining and gene silencing of Nrf2 by siRNA transfection were investigated. For exposure experiments, HBO-PC for longer time increased the expression of Nrf2 significantly. And for treatment experiments, HBO-PC treatment significantly decreased infarction area, lessened neuronal injury, reduced apoptosis, and increased both the expression of Nrf2 and activities of its downstream proteins. Cytology tests confirmed effects of HBO-PC treatments. Besides, Nrf2 siRNA significantly reduced protective effects of HBO-PC. These observations demonstrated that an up-regulation of Nrf2 by HBO-PC might play an important role in the generation of tolerance against HIBD. PMID:26729624

  1. Brain inflammation in a chronic epilepsy model : Evolving pattern of the translocator protein during epileptogenesis

    NARCIS (Netherlands)

    Amhaoul, Halima; Hamaide, Julie; Bertoglio, Daniele; Reichel, Stephanie Nadine; Verhaeghe, Jeroen; Geerts, Elly; Dam, van Debby; De Deyn, Peter Paul; Kumar-Singh, Samir; Katsifis, Andrew; Van der Linden, Annemie; Staelens, Steven; Dedeurwaerdere, Stefanie

    2015-01-01

    Aims: A hallmark in the neuropathology of temporal lobe epilepsy is brain inflammation which has been suggested as both a biomarker and a new mechanistic target for treatments. The translocator protein (TSPO), due to its high upregulation under neuroinflammatory conditions and the availability of se

  2. Findings of bedside swallowing assessment and brain computerized tomography in patients with chronic cerebral infarction, and their outcome

    International Nuclear Information System (INIS)

    To estimate the usefulness of the bedside swallowing assessment proposed by Smithard et al and neuroimaging findings characteristic for dysphagia, we studied the outcome of 102 patients with chronic cerebral infarction after assessment of swallowing by this test with brain computerized tomography (CT). All patients had a variety of motor disturbance and were admitted on a long-term medicare basis. They were divided into two groups according to the findings: the positive group (n=33), who showed any of the listed types of difficulty in swallowing water, and the negative group (n=69). Followed up to 2.2 years, their outcomes were studied. CT findings were studied on type of infarction, number and laterality of infarction, grade of periventricular lucency (PVL), presence of ventricular dilatation (VD), and severity of cortical atrophy (CA). The mean age was 76.4 years at registration and 61 were men. The frequency of severe dementia and disturbed ADL were significantly higher in the positive group. Eighteen patients died during the observation period and 15 of those were in the positive group, indicating higher, annual death rate (29.9% vs 2.2% in the negative group). All of the 15 patients in the positive group died of pneumonia. CT findings showed high incidence of multiple infarction, bilateral hemispheric lesion, severe PVL, VD, and severe CA in the positive group. These findings indicated that this evaluation method was useful in screening swallow function for patients with cerebral infarction in the chronic phase. Furthermore, CT findings suggested that severe white matter lesion, VD, and severe CA as well as multiple infarction seen in bilateral hemisphere was related to dysphagia, probably due to multiple factors involving pyramidal- and extrapyramidal-tracts with higher brain function. (author)

  3. Findings of bedside swallowing assessment and brain computerized tomography in patients with chronic cerebral infarction, and their outcome

    Energy Technology Data Exchange (ETDEWEB)

    Iwamoto, Toshihiko; Koshibu, Junko; Kikawada, Masayuki; Yoneda, Youichi; Uno, Masanobu; Takasaki, Masaru [Tokyo Medical Coll. (Japan); Imamura, Toshiharu

    2001-09-01

    To estimate the usefulness of the bedside swallowing assessment proposed by Smithard et al and neuroimaging findings characteristic for dysphagia, we studied the outcome of 102 patients with chronic cerebral infarction after assessment of swallowing by this test with brain computerized tomography (CT). All patients had a variety of motor disturbance and were admitted on a long-term medicare basis. They were divided into two groups according to the findings: the positive group (n=33), who showed any of the listed types of difficulty in swallowing water, and the negative group (n=69). Followed up to 2.2 years, their outcomes were studied. CT findings were studied on type of infarction, number and laterality of infarction, grade of periventricular lucency (PVL), presence of ventricular dilatation (VD), and severity of cortical atrophy (CA). The mean age was 76.4 years at registration and 61 were men. The frequency of severe dementia and disturbed ADL were significantly higher in the positive group. Eighteen patients died during the observation period and 15 of those were in the positive group, indicating higher, annual death rate (29.9% vs 2.2% in the negative group). All of the 15 patients in the positive group died of pneumonia. CT findings showed high incidence of multiple infarction, bilateral hemispheric lesion, severe PVL, VD, and severe CA in the positive group. These findings indicated that this evaluation method was useful in screening swallow function for patients with cerebral infarction in the chronic phase. Furthermore, CT findings suggested that severe white matter lesion, VD, and severe CA as well as multiple infarction seen in bilateral hemisphere was related to dysphagia, probably due to multiple factors involving pyramidal- and extrapyramidal-tracts with higher brain function. (author)

  4. Chronic vitamin C deficiency promotes redox imbalance in the brain but does not alter sodium-dependent vitamin C transporter 2 expression

    DEFF Research Database (Denmark)

    Paidi, Maya Devi; Schjoldager, Janne Gram; Lykkesfeldt, Jens;

    2014-01-01

    Vitamin C (VitC) has several roles in the brain acting both as a specific and non-specific antioxidant. The brain upholds a very high VitC concentration and is able to preferentially retain VitC even during deficiency. The accumulation of brain VitC levels much higher than in blood is primarily...... achieved by the sodium dependent VitC transporter (SVCT2). This study investigated the effects of chronic pre-and postnatal VitC deficiency as well as the effects of postnatal VitC repletion, on brain SVCT2 expression and markers of oxidative stress in young guinea pigs. Biochemical analyses demonstrated...... significantly decreased total VitC and an increased percentage of dehydroascorbic acid, as well as increased lipid oxidation (malondialdehyde), in the brains of VitC deficient animals (p < 0.0001) compared to controls. VitC repleted animals were not significantly different from controls. No significant changes...

  5. Brain glucose metabolic changes associated with chronic spontaneous Pain due to brachial plexus avulsion:a preliminary positron emission tomography study

    Institute of Scientific and Technical Information of China (English)

    CHEN Fu-yong; TAO Wei; CHENG Xin; WANG Hong-yan; HU Yong-sheng; ZHANG Xiao-hua; LI Yong-jie

    2008-01-01

    Background Previous brain imaging studies suggested that the brain activity underlying the perception of chronic pain maV differ from that underlying acute pain.To investigate the brain regions involved in chronic spontaneous pain due to brachial plexus avulsion(BPA),fluorine-18fluorodeoxygIucose (19F-FDG) positron emission tomography (PET) scanning was applied to determine the glucose metabolic changes in patients with pain due to BPA.Methods Six right-handed patients with chronic spontaneous pain due to left-BPA and twelve right-handed age-and sex-matched healthy control subjects participated in the 18F-FDG PET study.The patients were rated by visual analog scale (VAS) during scanning and Hamilton depression scale and Hamilton anxiety scale after scanning.Statistical parametric mapping 2 (SPM2) was applied for data analysis.Results Compared with healthy subjects,the patients had significant glucose metabolism decreases in the right thalamus and S I(P<0.001,uncorrected),and significant glucose metabolism increases in the right orbitofrontaI cortex (OFC) (BA11),left rostral insula cortex and left dorsolateral prefrontal codex (DLPFC) (BA10/46) (P<0.001,uncorrected).Conclusion These findings suggest that the brain areas involved in emotion.aRention and internal modulation of pain may be related to the chronic spontaneous pain due to BPA.

  6. Comorbidity Factors and Brain Mechanisms Linking Chronic Stress and Systemic Illness

    OpenAIRE

    Vanja Duric; Sarah Clayton; Mai Lan Leong; Li-Lian Yuan

    2016-01-01

    Neuropsychiatric symptoms and mental illness are commonly present in patients with chronic systemic diseases. Mood disorders, such as depression, are present in up to 50% of these patients, resulting in impaired physical recovery and more intricate treatment regimen. Stress associated with both physical and emotional aspects of systemic illness is thought to elicit detrimental effects to initiate comorbid mental disorders. However, clinical reports also indicate that the relationship between ...

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

    OpenAIRE

    Bárbara B. Garrido-Suárez; Gabino Garrido-Garrido; Marian Castro Labrada; Addis Bellma Menéndez; Roberto Menéndez Soto del Valle; René Delgado-Hernández

    2015-01-01

    Context: Ovarian hormone deficiency observed in menopausal women increases the production of reactive oxygen species, which could be implicated in central sensitization subjacent in chronic functional pain syndromes. Aims: To examine the hyperalgesic state induced by ovariectomy in adult rats and its relation to some oxidative stress outcomes. Methods: The female Wistar rats were divided into normal, sham ovariectomized (OVX) and OVX groups, which were tested for mechanical and therma...

  8. Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression

    Science.gov (United States)

    Haenisch, Britta; Bilkei-Gorzo, Andras; Caron, Marc G.; Bönisch, Heinz

    2009-01-01

    Diverse factors such as changes in neurotrophins and brain plasticity have been proposed to be involved in the actions of antidepressant drugs (ADs). However, in mouse models of depression based on chronic stress, it is still unclear whether simultaneous changes in behavior and neurotrophin expression occur and whether these changes can be corrected or prevented comparably by chronic administration of ADs or genetic manipulations that produce antidepressant-like effects such as the knockout (KO) of the norepinephrine transporter (NET) gene. Here we show that chronic restraint or social defeat stress induce comparable effects on behavior and changes in the expression of neurotrophins in depression-related brain regions. Chronic stress caused down-regulation of BDNF, NGF and NT-3 in hippocampus and cerebral cortex and up-regulation of these targets in striatal regions. In wild-type mice, these effects could be prevented by concomitant chronic administration of five pharmacologically diverse ADs. In contrast, NETKO mice were resistant to stress-induced depressive-like changes in behavior and brain neurotrophin expression. Thus, the resistance of the NETKO mice to the stress-induced depression-associated behaviors and biochemical changes highlight the importance of noradrenergic pathways in the maintenance of mood. In addition, these mice represent a useful model to study depression-resistant behaviors, and they might help to provide deeper insights into the identification of downstream targets involved in the mechanisms of antidepressants. PMID:19694905

  9. Differences in {sup 99m}Tc-HMPAO brain SPET perfusion imaging between Tourette's syndrome and chronic tic disorder in children

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, N.-T.; Lee, B.-F. [Dept. of Nuclear Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Taiwan); Chang, Y.-C. [Dept. of Pediatrics, Kaohsiung Chang Kang Children' s Hospital, Kaohsiung, Taiwan (Taiwan); Huang, C.-C. [Dept. of Pediatrics, College of Medicine, National Cheng Kung University, Tainan (Taiwan); Wang, S.-T. [Dept. of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Taiwan)

    2001-02-01

    Early differential diagnosis between Tourette's syndrome and chronic tic disorder is difficult but important because both the outcome and the treatment of these two childhood-onset diseases are distinct. We assessed the sensitivity and specificity of brain single-photon emission tomography (SPET) perfusion imaging in distinguishing the two diseases, and characterized their different cerebral perfusion patterns. Twenty-seven children with Tourette's syndrome and 11 with chronic tic disorder (mean age 9.5 and 8.6 years, respectively) underwent brain SPET with technetium-99m hexamethylpropylene amine oxime (HMPAO). Visual interpretation and semi-quantitative analysis of SPET images were performed. On visual interpretation, 22 of 27 (82%) of the Tourette's syndrome group had lesions characterized by decreased perfusion. The left hemisphere was more frequently involved. None of the children with chronic tic disorder had a visible abnormality. Semi-quantitative analysis showed that, compared with children with chronic tic disorder, children with Tourette's syndrome had significantly lower perfusion in the left lateral temporal area and asymmetric perfusion in the dorsolateral frontal, lateral and medial temporal areas. In conclusion, using the visual approach, brain SPET perfusion imaging is sensitive and specific in differentiating Tourette's syndrome and chronic tic disorder. The perfusion difference between the two groups, demonstrated by semi-quantitative analysis, may be related more to the co-morbidity in Tourette's syndrome than to tics per se. (orig.)

  10. Study on clinical value of determination of plasma brain natriuretic peptide levels in patients with chronic congestive heart failure

    International Nuclear Information System (INIS)

    Objective: To evaluate the clinical value of determination of plasma brain natriuretic peptide (BNP) levels in patients with chronic congestive heart failure(CHF). Methods: The levels of plasma BNP were measured with fluorescence immunoassay in 341 patients with chronic CHF and 55 controls. Left ventricular ejection fraction (LVEF), left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD) were determined with color doppler ultrasonography in CHF patients. Results: Plasma levels of BNP were significantly increased in patients with CHF as compared with those in controls (P<0.01). There were also significant differences in plasma levels of CHF patients of different clinical stages (P<0.01). There was obvious correlation between plasma levels of BNP and the values of LVEF, LVESD and LVEDD (r was-0.62, +0.54 and +0.60 respectively, P<0.01). Conclusion: Plasma level of BNP is a sensitive indicator for assessment of ventricle function in CHF patients. (authors)

  11. Integrated Semiconductor Optical Sensors for Chronic, Minimally-Invasive Imaging of Brain Function

    OpenAIRE

    Lee, Thomas T.; Levi, Ofer; Cang, Jianhua; Kaneko, Megumi; Stryker, Michael P.; Smith, Stephen J; Shenoy, Krishna V.; Harris, James S.

    2006-01-01

    Intrinsic Optical Signal (IOS) imaging is a widely accepted technique for imaging brain activity. We propose an integrated device consisting of interleaved arrays of gallium arsenide (GaAs) based semiconductor light sources and detectors operating at telecommunications wavelengths in the near-infrared. Such a device will allow for long-term, minimally invasive monitoring of neural activity in freely behaving subjects, and will enable the use of structured illumination patterns to improve syst...

  12. Pilot study: Computer-based virtual anatomical interactivity for rehabilitation of individuals with chronic acquired brain injury

    Directory of Open Access Journals (Sweden)

    C. Douglas Simmons, PhD, OTR/L, FAOTA

    2014-06-01

    Full Text Available Deficiencies in upper-limb motor function and executive functioning can compromise an affected individual’s ability to complete everyday activities. Impaired motor and executive functioning therefore pose a risk to increasing numbers of veterans who have been diagnosed with acquired brain injury. This article reports on changes in upper-limb motor function and executive functioning of 12 adult participants with chronic acquired brain injury using a novel, computer-based, motor and cognitive rehabilitation program called PreMotor Exercise Games (PEGs. Manual muscle, goniometric range of motion, and dynamometer assessments were used to determine motor functioning while the Executive Function Performance Test measured cognitive functioning. A three-level repeated measures design was conducted to determine changes pre- and postintervention. Participants demonstrated significant improvement in shoulder (p = 0.01 and wrist (p = 0.01 range of motion and clinically relevant improvement for elbow range of motion. Participants demonstrated clinically relevant improvement in shoulder, elbow, and wrist strength. Finally, participants demonstrated significant improvement in executive functioning (p < 0.05. Using PEGs as a modality for both motor and cognitive intervention is a potentially beneficial adjunct to rehabilitation and warrants further study.

  13. Behavioral effects and CRF expression in brain structures of high- and low-anxiety rats after chronic restraint stress.

    Science.gov (United States)

    Wisłowska-Stanek, Aleksandra; Lehner, Małgorzata; Skórzewska, Anna; Krząścik, Paweł; Płaźnik, Adam

    2016-09-01

    The aim of our study was to investigate the influence of chronic restraint stress (5 weeks, 3h/day) on behavior and central corticotropin-releasing factor (CRF) expression in rats selected for high (HR) and low anxiety (LR). The conditioned freezing response was used as a discriminating variable. Moreover, we assessed the influence of acute restraint on CRF expression in the brain in HR and LR rats. We found that chronic restraint induced symptoms of anhedonia (decreased consumption of 1% sucrose solution) in HR rats. In addition, HR restraint rats showed an increased learned helplessness behavior (immobility time in the Porsolt test) as well as neophobia in the open field test vs. LR restraint and HR control rats. These behavioral changes were accompanied by a decreased expression of CRF in the paraventricular nucleus of the hypothalamus (pPVN) and the dentate gyrus of the hippocampus (DG) compared to the HR control and LR restraint rat groups, respectively. The acute restraint condition increased the expression of CRF in the pPVN of HR rats compared to the HR control group, and enhanced the expression of CRF in the CA1 area and DG of LR restraint animals compared to the HR restraint and LR control rats, respectively. The present results indicate that chronic restraint stress in high anxiety rats attenuated CRF expression in the pPVN and DG, which was probably due to detrimental actions on the hippocampus-hypothalamus-pituitary-adrenal gland feedback mechanism, thus modulating the stress response and inducing anhedonia and depressive-like symptoms. PMID:27150225

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

    Directory of Open Access Journals (Sweden)

    Haelewyn Benoit

    2011-04-01

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

  15. Experimental hypoxic-ischemic brain damage comparison research of apparent diffusion coefficients, proton MR-spectroscopy and pathologic study

    International Nuclear Information System (INIS)

    Objective: To compare the apparent diffusion coefficients (ADC), proton MR spectroscopy (1H-MRS) and pathologic changes in young pigs subjected to acute hypoxic-ischemic brain damage (HIBD). Methods: Thirty 7-day-old neonatal pigs were divided into sham-operation group (n=5) and hypoxic-ischemic group (n=25). HI group was divided into five small groups. ADC value, NAA/Cho, NAA/Cr, Lac/NAA, Lac/Cho and Lac/Cr were calculated on cessation of the insult, 3, 6, 12 and 24 h after resuscitation in subcortical white matter, periventricular white matter and basal ganglia. Immediately after MR examinations, injury of the brains was evaluated by hematoxylin-eosin-stained and histopathologic study. Results: The hypoxic-ischemic piglets showed ADC (3.69±1.45) reduction, NAA/Cho (0.712± 0.080) and NAA/Cr(1.040±0.137) decrease, Lac/NAA(1.798±0.139), Lac/Cho(1.280±0.167) and Lac/Cr(1.876±0.357)increase on cessation of the insult; transient ADC, Lac/NAA, Lac/Cho and Lac/Cr recovery, NAA/Cho progressive decrease (P0.05) flora 3 h to 12 h after resuscitation; secondary ADC (4.06±1.25)reduction, Lac/NAA (1.221±0.128), Lac/Cho (0.716±0.088) and Lac/Cr (1.212±0.177) increase 24 hours after resuscitation. Corresponding pathologic study revealed astrocytes gradually swelled and collapsed after resuscitation, while neurons changed mildly. The control piglets showed normal ADC, H-MRS and pathologic investigations. Conclusions: ADC value and 1H-MRS can sensitively detect lesions of early HIBD. NAA/Cho has the highest correlation with the pathological changes of early HIBD and is superior to ADC value and the other metabolite ratios in evaluating early HIBD. (authors)

  16. Early (N170/M170 face-sensitivity despite right lateral occipital brain damage in acquired prosopagnosia

    Directory of Open Access Journals (Sweden)

    Esther eAlonso Prieto

    2011-12-01

    Full Text Available Compared to objects, pictures of faces elicit a larger early electromagnetic response at occipito-temporal sites on the human scalp, with an onset of 130 ms and a peak at about 170 ms. This N170 face effect is larger in the right than the left hemisphere and has been associated with the early categorization of the stimulus as a face. Here we tested whether this effect can be observed in the absence of some of the visual areas showing a preferential response to faces as typically identified in neuroimaging. Event related potentials were recorded in response to faces, cars and their phase-scrambled versions in a well-known brain-damaged case of prosopagnosia (PS. Despite the patient’s right inferior occipital gyrus lesion encompassing the most posterior cortical area showing preferential response to faces (occipital face area, OFA, we identified an early face-sensitive component over the right occipito-temporal hemisphere of the patient that was identified as the N170. A second experiment supported this conclusion, showing the typical N170 increase of latency and amplitude in response to inverted faces. In contrast, there was no N170 in the left hemisphere, where PS has a lesion to the middle fusiform gyrus and shows no evidence of face-preferential response in neuroimaging (no left fusiform face area, or lFFA. These results were replicated by a magneto-encephalographic (MEG investigation of the patient, disclosing a M170 component only in the right hemisphere. These observations indicate that face preferential activation in the inferior occipital cortex is not necessary to elicit early visual responses associated with face perception (N170/M170 on the human scalp. These results further suggest that when the right inferior occipital cortex is damaged, the integrity of the middle fusiform gyrus and/or the superior temporal sulcus – two areas showing face preferential responses in the patient’s right hemisphere - might be necessary to generate

  17. Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

    OpenAIRE

    Yang, L.; Hei, M.Y.; Dai, J.J.; Hu, N.; Xiang, X.Y.

    2016-01-01

    The timing and mechanisms of protection by hyperbaric oxygenation (HBO) in hypoxic-ischemic brain damage (HIBD) have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders) were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI) and continued once a da...

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

    International Nuclear Information System (INIS)

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

  19. Oxidative stress during aging and in Alzheimer's disease : a comparative study of oxidative damage and antioxidant enzymatic activities in mouse models and human brain tissue

    OpenAIRE

    Schüssel, Katrin

    2005-01-01

    The hypothesis that oxidative stress plays a role in the pathogenesis of Alzheimer’s disease (AD) was tested by studying oxidative damage, acitvities of antioxidant enzymes and levels of reactive oxygen species (ROS) in several models. To this end, mouse models transgenic for mutant presenilin (PS1M146L) as well as mutant amyloid precursor protein (APP) and human post mortem brain tissue from sporadic AD patients and age-matched controls were studied. Aging leads to an upregulation of antioxi...

  20. Opposing Effects of Pigment Epithelium-Derived Factor on Breast Cancer Cell versus Neuronal Survival: Implication for Brain Metastasis and Metastasis-Induced Brain Damage

    OpenAIRE

    Fitzgerald, Daniel P.; Subramanian, Preeti; Deshpande, Monika; Graves, Christian; Gordon, Ira; Qian, Yongzhen; Snitkovsky, Yeva; Liewehr, David J.; Steinberg, Seth M.; Paltán-Ortiz, José D.; Herman, Mary M.; Camphausen, Kevin; Palmieri, Diane; BECERRA, S. PATRICIA; Steeg, Patricia S

    2012-01-01

    Brain metastases are a significant cause of cancer patient morbidity and mortality, yet preventative and therapeutic options remain an unmet need. The cytokine PEDF is downregulated in resected human brain metastases of breast cancer compared to primary breast tumors, suggesting that restoring its expression might limit metastatic spread. Here we show that outgrowth of large experimental brain metastases from human 231-BR or murine 4T1-BR breast cancer cells was suppressed by PEDF expression,...

  1. Prevention by eliprodil (SL 82.0715) of traumatic brain damage in the rat. Existence of a large (18 h) therapeutic window.

    Science.gov (United States)

    Toulmond, S; Serrano, A; Benavides, J; Scatton, B

    1993-08-20

    The neuroprotective potential of eliprodil (SL 82.0715), an N-methyl-D-aspartate (NMDA) receptor antagonist acting at the polyamine modulatory site, in brain trauma was examined in a rat model of lateral fluid-percussion brain injury. The volume of the lesion was assessed histologically by measuring, at 7 days post-injury, the area of brain damage at 10 coronal planes. Eliprodil (10 mg/kg i.p.) when given 15 min, 6 h and 24 h after fluid percussion (1.6 atm) and then b.i.d. for the following 6 days, reduced by 60% the volume of cortical damage. A similar neuroprotection was obtained when the first administration of eliprodil was delayed by up to 12 h after the brain insult. Moreover, when the treatment with this compound was started at 18 h post-injury, cortical damage was still significantly reduced by 33%. Autoradiographic studies showed that eliprodil treatment (10 mg/kg, i.p.), initiated 15 min after the trauma, also caused a marked reduction of the loss of the neuronal marker omega 1-2 (central benzodiazepine) binding sites and of the increase in the glial/macrophage marker peripheral type benzodiazepine binding sites in the cerebral cortex. In contrast, dizocilpine (a blocker of the cationic channel coupled to the NMDA receptor) when administered 6 h and 24 h after fluid percussion and then b.i.d. for the following 6 days induced a non significant reduction of the volume of the lesion at the highest tolerated dose (0.6 mg/kg i.p.). These results demonstrate the neuroprotective activity of eliprodil in experimental brain trauma using neuropathology as an endpoint and indicate that there is a very large time window for therapeutic intervention, consistent with the delayed nature of the neuronal loss, in this condition. PMID:8402196

  2. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    Koppen, A. van; Papazova, D.A.; Oosterhuis, N.R.; Gremmels, H.; Giles, R.H.; Fledderus, J.O.; Joles, J.A.; Verhaar, M.C.

    2015-01-01

    Introduction: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  3. Regulation of endogenous neural stem/progenitor cells for neural repair - factors that promote neurogenesis and gliogenesis in the normal and damaged brain

    Directory of Open Access Journals (Sweden)

    Kimberly eChristie

    2013-01-01

    Full Text Available Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ of the lateral ventricles and the subgranular zone (SGZ of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioural outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem /precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation.

  4. Right Hemisphere Brain Damage

    Science.gov (United States)

    ... or focusing on what is said or seen. Perception: Visual perception deficits causing a person to have difficulty perceiving ... recalling previously learned information and learning new information. Social communication (pragmatics): Difficulty interpreting abstract language such as ...

  5. Chronic visual dysfunction after blast-induced mild traumatic brain injury

    OpenAIRE

    M. Teresa Magone, MD; Ellen Kwon, OD; Soo Y. Shin, MD

    2014-01-01

    The purpose of this study was to investigate the long-term visual dysfunction in patients after blast-induced mild traumatic brain injury (mbTBI) using a retrospective case series of 31 patients with mbTBI (>12 mo prior) without eye injuries. Time since mbTBI was 50.5 +/– 19.8 mo. Age at the time of injury was 30.0 +/– 8.3 yr. Mean corrected visual acuity was 20/20. Of the patients, 71% (n = 22) experienced loss of consciousness; 68% (n = 15) of patients in this subgroup were dismounted durin...

  6. Chronic restraint stress in rats causes sustained increase in urinary corticosterone excretion without affecting cerebral or systemic oxidatively generated DNA/RNA damage

    DEFF Research Database (Denmark)

    Jorgensen, Anders; Maigaard, Katrine; Wörtwein, Gitta;

    2013-01-01

    of nucleic acid damage from oxidation were affected by stress. In contrast, cerebral DNA repair enzymes exhibited a general trend towards an induction, which was significant for hippocampal Nudt1. The results and their implications for stress sensitivity and resilience are discussed.......Increased oxidatively generated damage to nucleic acids (DNA/RNA) may be a common mechanism underlying accelerated aging in psychological stress states and mental disorders. In the present study, we measured the urinary excretion of corticosterone and markers of systemic oxidative stress on nucleic...... acids, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, in rats subjected to chronic restraint stress. To reliably collect 24h urine samples, the full 3-week restraint stress paradigm was performed in metabolism cages. We further determined frontal...

  7. Phosphodiesterase inhibition rescues chronic cognitive deficits induced by traumatic brain injury.

    Science.gov (United States)

    Titus, David J; Sakurai, Atsushi; Kang, Yuan; Furones, Concepcion; Jergova, Stanislava; Santos, Rosmery; Sick, Thomas J; Atkins, Coleen M

    2013-03-20

    Traumatic brain injury (TBI) modulates several cell signaling pathways in the hippocampus critical for memory formation. Previous studies have found that the cAMP-protein kinase A signaling pathway is downregulated after TBI and that treatment with a phosphodiesterase (PDE) 4 inhibitor rolipram rescues the decrease in cAMP. In the present study, we examined the effect of rolipram on TBI-induced cognitive impairments. At 2 weeks after moderate fluid-percussion brain injury or sham surgery, adult male Sprague Dawley rats received vehicle or rolipram (0.03 mg/kg) 30 min before water maze acquisition or cue and contextual fear conditioning. TBI animals treated with rolipram showed a significant improvement in water maze acquisition and retention of both cue and contextual fear conditioning compared with vehicle-treated TBI animals. Cue and contextual fear conditioning significantly increased phosphorylated CREB levels in the hippocampus of sham animals, but not in TBI animals. This deficit in CREB activation during learning was rescued in TBI animals treated with rolipram. Hippocampal long-term potentiation was reduced in TBI animals, and this was also rescued with rolipram treatment. These results indicate that the PDE4 inhibitor rolipram rescues cognitive impairments after TBI, and this may be mediated through increased CREB activation during learning. PMID:23516287

  8. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

    DEFF Research Database (Denmark)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders;

    2010-01-01

    Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core ...... of the dorsal hippocampus correlated with chronic antidepressant treatment emphasizing a role for BDNF in the mechanisms underlying antidepressant activity....

  9. 8-Hydroxy-2'-deoxyguanosine (8-OH-dG): A biomarker of oxidative damage in yellow bullheads chronically exposed to low-level radiation

    International Nuclear Information System (INIS)

    8-hydroxy-2'-deoxyguanosine (8-OH-dG), an oxidation product of the nucleotide deoxyguanosine (dG) was used as a biomarker to assess oxidative damage in brain and gill tissues of yellow bullhead catfish (Ameiurus natalis; n = 18) inhabiting an abandoned reactor reservoir contaminated with low levels of d137Cs (Pond B, Savannah River Site, SC). DNA was isolated by chloroform-isoamyl extraction, enzymatically digested with Nuclease P1/Calf Intestinal Phosphatase, and analyzed by HPLC with electrochemical detection.Length, weight, age, condition and muscle 137Cs activity of each fish were also determined. Concentrations of 8-OH-dG were greater in brain than in gill tissues. 8-OH-dG in gill tissues decreased as condition of fish increased, but as age increased, the effect of condition declined. Brain 8-OH-dG concentration was not related to age or condition of fish, but was greater in females and the interaction between gender and 137Cs was significant. Brain 8-OH-dG was positively associated with muscle 137Cs concentration among females, but was unrelated to 137Cs concentration in males. At lower 137Cs concentrations, females tended to have fewer oxidative DNA adducts in brian than did males. Deposition of somatic lipids into eggs may provide females some anti-oxidant benefit by diminishing the contribution of lipid peroxidation to DNA damage. 8-OH-dG is a sensitive biomarker of low-level radiation exposure, however, its application in fish requires consideration of factors such as gender, age, body-condition, and the tissue type sampled

  10. Rat behaviour reactions and brain synaptic membrane lipids under the chronical gamma-irradiation

    International Nuclear Information System (INIS)

    The effects of low level chronical ionising irradiation (12.9 cGy/day on the sensory attention to the stimuli of different modalities (somatosensor, visual, odor) of Wistar rats were studied. Analysis of animals behaviour was made after they had received the different doses of irradiation: 4, 6, 8, 10, 15 and 20 Gy. It was founded, that the attention and exploratory activity of rats is significantly decreased up to 20-30% after 4-6 Gy. The irradiation doses 8 Gy did not change animal behaviour as compared to control animals, but doses 10, 15 and 20 Gy decreased the exploratory activity as well as sensory attention of rats to 3-5-times as compared to previous dose. Such a wave-like way of behaviour reflects the functioning of an adaptive mechanism. Biochemical data indicated that after 5 months of the irradiation (dose 20 Gy) the level of phospholipids, lysophosphatidylcholine, phosphatdylethanolamine, phosphatidylcholine, cholesterol were decreased

  11. Effects of alcohol intake on brain structure and function in non-alcohol-dependent drinkers

    NARCIS (Netherlands)

    Bruin, Eveline Astrid de

    2005-01-01

    About 85% of the adult population in the Netherlands regularly drinks alcohol. Chronic excessive alcohol intake in alcohol-dependent individuals is known to have damaging effects on brain structure and function. Relatives of alcohol-dependent individuals display differences in brain function that ar

  12. Clinical Management of a Patient with Chronic Recurrent Vertigo Following a Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Eric G. Johnson

    2009-01-01

    Full Text Available Vertigo, was provoked and right torsional up-beat nystagmus was observed in a 47-year-old patient when she was placed into the right Hallpike-Dix test position using infrared goggle technology. The clinical diagnosis was benign paroxysmal positional vertigo (BPPV, specifically right posterior canalithiasis, resulting from a mild traumatic brain injury (TBI suffered approximately six-months earlier. Previous medical consultations did not include vestibular system examination, and Meclizine was prescribed to suppress her chief complaint of vertigo. Ultimately, the patient was successfully managed by performing two canalith repositioning maneuvers during a single clinical session. The patient reported 100% resolution of symptoms upon reexamination the following day, and the Hallpike-Dix test was negative. Continued symptom resolution was subjectively reported 10 days postintervention via telephone consultation. This case report supports previous publications concerning the presence of BPPV following TBI and the need for inclusion of vestibular system examination during medical consultation.

  13. Cerebral perfusion and neuropsychological follow up in mild traumatic brain injury: acute versus chronic disturbances?

    Science.gov (United States)

    Metting, Zwany; Spikman, Jacoba M; Rödiger, Lars A; van der Naalt, Joukje

    2014-04-01

    In a subgroup of patients with mild traumatic brain injury (TBI) residual symptoms, interfering with outcome and return to work, are found. With neuropsychological assessment cognitive deficits can be demonstrated although the pathological underpinnings of these cognitive deficits are not fully understood. As the admission computed tomography (CT) often is normal, perfusion CT imaging may be a useful indicator of brain dysfunction in the acute phase after injury in these patients. In the present study, directly after admission perfusion CT imaging was performed in mild TBI patients with follow-up neuropsychological assessment in those with complaints and a normal non-contrast CT. Neuropsychological tests comprised the 15 Words test Immediate Recall, Trailmaking test part B, Zoo Map test and the FEEST, which were dichotomized into normal and abnormal. Perfusion CT results of patients with normal neuropsychological test scores were compared to those with abnormal test scores. In total eighteen patients were included. Those with an abnormal score on the Zoo Map test had a significant lower CBV in the right frontal and the bilateral parieto-temporal white matter. Patients with an abnormal score on the FEEST had a significant higher MTT in the bilateral frontal white matter and a significant decreased CBF in the left parieto-temporal grey matter. No significant relation between the perfusion CT parameters and the 15 Words test and the Trailmaking test part B was present. In conclusion, impairments in executive functioning and emotion perception assessed with neuropsychological tests during follow up were related to differences in cerebral perfusion at admission in mild TBI. The pathophysiological concept of these findings is discussed. PMID:24556319

  14. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    CharlesW.Wilkinson

    2012-02-01

    Full Text Available Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP to be unrelated to injury severity. Growth hormone deficiency (GHD and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI, an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and

  15. Differential effects of passive immunization with nicotine-specific antibodies on the acute and chronic distribution of nicotine to brain in rats.

    Science.gov (United States)

    Pentel, P R; Dufek, M B; Roiko, S A; Lesage, M G; Keyler, D E

    2006-05-01

    Vaccination against nicotine blocks or attenuates nicotine-related behaviors relevant to addiction in rats. Passive immunization with nicotine-specific antibodies is an alternative to vaccination with the potential advantages of allowing control of antibody dose and affinity. In the current study, the effects of two antibodies on the distribution of nicotine to brain were evaluated during chronic nicotine administration in rats; the monoclonal antibody Nic311 (K(d) = 60 nM) and nicotine-specific antiserum (K(d) = 1.6 nM). Nicotine was administered via repeated i.v. bolus doses over 2 days and antibody was administered during the first day. Neither antibody appreciably reduced the chronic accumulation of nicotine in brain, despite high protein binding of nicotine in serum (98.9%) and a 73% reduction in the unbound serum nicotine concentration with the highest Nic311 dose. However, both antibodies substantially reduced the early distribution of nicotine to brain 5 min after a dose. The higher affinity antibody was no more effective than Nic311. The highest Nic311 dose produced serum antibody levels 10 times higher than those reported with vaccination. The efficacy of Nic311 was dose-related, with the highest dose producing a 76% decrease in the early distribution of nicotine to brain. These findings, along with previous data, suggest that the primary effect of passive immunization is to slow, rather than prevent, the distribution of nicotine to brain. In the setting of chronic nicotine dosing, antibodies with a moderate affinity for nicotine produced substantial effects on the early distribution of nicotine to brain and were as effective as higher affinity antibodies. PMID:16407464

  16. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)

    2015-09-15

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  17. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    International Nuclear Information System (INIS)

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  18. Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord.

    Science.gov (United States)

    Sufianov, A A; Shapkin, A G; Sufianova, G Z; Elishev, V G; Barashin, D A; Berdichevskii, V B; Churkin, S V

    2014-08-01

    Changes in functional and metabolic activities of the brain were evaluated by EEG and positron-emission/computer tomography with 18F-fluorodeoxyglucose in patients with neuropathic pain syndrome previous to and 3 months after implantation of a system for chronic epidural spinal cord stimulation. In most cases, the use of a nerve stimulator was followed by alleviation of neuropathic pain and partial normalization of functional and metabolic activities of brain structures responsible for pain perception, emotiogenic, behavioral, and autonomic responses. PMID:25113605

  19. Alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy

    Czech Academy of Sciences Publication Activity Database

    Alleva, R.; Nasole, E.; Di Donato, F.; Borghi, B.; Neužil, Jiří; Tomasetti, M.

    2005-01-01

    Roč. 333, č. 2 (2005), s. 404-410. ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514 Keywords : alpha-lipoic acid * chronic wound * ROS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  20. Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury.

    Science.gov (United States)

    Kreber, Lisa A; Griesbach, Grace S; Ashley, Mark J

    2016-09-01

    This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093