Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

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De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

2018-01-01

Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury.

Science.gov (United States)

De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Hellyer, Peter J; Jolly, Amy E; Patel, Maneesh C; Cole, James H; Leech, Robert; Sharp, David J

2018-01-01

Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of

Vasomotor origin of intracranial pressure waves in hydrocephalic infants

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Barritault, L; Rimbert, J N; Hirsch, J F; Pierr-Kahn, A; Lacombe, J; Zouaoui, A; Mises, J; Gabersek, V

1980-12-01

By measuring cerebral blood volume (CBV) and intracranial pressure (ICP) variations at the same running time during sleep, it has been demonstrated that the ICP wave which appears during the REM sleep in hydrocephalic infants is produced by intracerebral vaso-dilatation. Nine infants with stabilized hydrocephalus were investigated by non-invasive means: REM phases were distinguished with the usual polysomnographic electrodes. Intracranial pressure was measured with a fontanel palpation transducer and CBV variations were obtained by recording /sup 99/sup(m)Tc activity at the head level after in vivo labelling of red cells with /sup 99/sup(m)Tc-pertechnetate. The time activity curves, obtained from regions of interest and selected on the sequential radioisotope images, show that an increased ICP wave, occurring during the REM period, is related to a simultaneous increase in the blood volume, limited to the cerebral sector and not to the area of the external carotid artery.

Vascular impairment as a pathological mechanism underlying long-lasting cognitive dysfunction after pediatric traumatic brain injury.

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Ichkova, Aleksandra; Rodriguez-Grande, Beatriz; Bar, Claire; Villega, Frederic; Konsman, Jan Pieter; Badaut, Jerome

2017-12-01

Traumatic brain injury (TBI) is the leading cause of death and disability in children. Indeed, the acute mechanical injury often evolves to a chronic brain disorder with long-term cognitive, emotional and social dysfunction even in the case of mild TBI. Contrary to the commonly held idea that children show better recovery from injuries than adults, pediatric TBI patients actually have worse outcome than adults for the same injury severity. Acute trauma to the young brain likely interferes with the fine-tuned developmental processes and may give rise to long-lasting consequences on brain's function. This review will focus on cerebrovascular dysfunction as an important early event that may lead to long-term phenotypic changes in the brain after pediatric TBI. These, in turn may be associated with accelerated brain aging and cognitive dysfunction. Finally, since no effective treatments are currently available, understanding the unique pathophysiological mechanisms of pediatric TBI is crucial for the development of new therapeutic options. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

2009-01-01

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

Olfactory Dysfunctions and Decreased Nitric Oxide Production in the Brain of Human P301L Tau Transgenic Mice.

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Hu, Yang; Ding, Wenting; Zhu, Xiaonan; Chen, Ruzhu; Wang, Xuelan

2016-04-01

Different patterns of olfactory dysfunction have been found in both patients and mouse models of Alzheimer's Disease. However, the underlying mechanism of the dysfunction remained unknown. Deficits of nitric oxide production in brain can cause olfactory dysfunction by preventing the formation of olfactory memory. The aim of this study was to investigate the behavioral changes in olfaction and alterations in metabolites of nitric oxide, nitrate/nitrite concentration, in the brain of human P301L tau transgenic mice. The tau mice showed impairments in olfaction and increased abnormal phosphorylation of Tau protein at AT8 in different brain areas, especially in olfactory bulb. We now report that these olfactory deficits and Tau pathological changes were accompanied by decreased nitrate/nitrite concentration in the brain, especially in the olfactory bulb, and reduced expression of nNOS in the brain of tau mice. These findings provided evidence of olfactory dysfunctions correlated with decreased nitric oxide production in the brain of tau mice.

Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

Science.gov (United States)

Musolino, Patricia L; Gong, Yi; Snyder, Juliet M T; Jimenez, Sandra; Lok, Josephine; Lo, Eng H; Moser, Ann B; Grabowski, Eric F; Frosch, Matthew P; Eichler, Florian S

2015-11-01

See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

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Andreas Üllen

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

Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

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Haider Raza

2015-02-01

Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

Cyclophilin D Promotes Brain Mitochondrial F1FO ATP Synthase Dysfunction in Aging Mice.

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Gauba, Esha; Guo, Lan; Du, Heng

2017-01-01

Brain aging is the known strongest risk factor for Alzheimer's disease (AD). In recent years, mitochondrial deficits have been proposed to be a common mechanism linking brain aging to AD. Therefore, to elucidate the causative mechanisms of mitochondrial dysfunction in aging brains is of paramount importance for our understanding of the pathogenesis of AD, in particular its sporadic form. Cyclophilin D (CypD) is a specific mitochondrial protein. Recent studies have shown that F1FO ATP synthase oligomycin sensitivity conferring protein (OSCP) is a binding partner of CypD. The interaction of CypD with OSCP modulates F1FO ATP synthase function and mediates mitochondrial permeability transition pore (mPTP) opening. Here, we have found that increased CypD expression, enhanced CypD/OSCP interaction, and selective loss of OSCP are prominent brain mitochondrial changes in aging mice. Along with these changes, brain mitochondria from the aging mice demonstrated decreased F1FO ATP synthase activity and defective F1FO complex coupling. In contrast, CypD deficient mice exhibited substantially mitigated brain mitochondrial F1FO ATP synthase dysfunction with relatively preserved mitochondrial function during aging. Interestingly, the aging-related OSCP loss was also dramatically attenuated by CypD depletion. Therefore, the simplest interpretation of this study is that CypD promotes F1FO ATP synthase dysfunction and the resultant mitochondrial deficits in aging brains. In addition, in view of CypD and F1FO ATP synthase alterations seen in AD brains, the results further suggest that CypD-mediated F1FO ATP synthase deregulation is a shared mechanism linking mitochondrial deficits in brain aging and AD.

Adolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain Structure and Substance Use

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Duncan B. Clark

2017-11-01

Full Text Available During adolescence, problems reflecting cognitive, behavioral and affective dysregulation, such as inattention and emotional dyscontrol, have been observed to be associated with substance use disorder (SUD risks and outcomes. Prior studies have typically been with small samples, and have typically not included comprehensive measurement of executive dysfunction domains. The relationships of executive dysfunction in daily life with performance based testing of cognitive skills and structural brain characteristics, thought to be the basis for executive functioning, have not been definitively determined. The aims of this study were to determine the relationships between executive dysfunction in daily life, measured by the Behavior Rating Inventory of Executive Function (BRIEF, cognitive skills and structural brain characteristics, and SUD risks, including a global SUD risk indicator, sleep quality, and risky alcohol and cannabis use. In addition to bivariate relationships, multivariate models were tested. The subjects (n = 817; ages 12 through 21 were participants in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA study. The results indicated that executive dysfunction was significantly related to SUD risks, poor sleep quality, risky alcohol use and cannabis use, and was not significantly related to cognitive skills or structural brain characteristics. In multivariate models, the relationship between poor sleep quality and risky substance use was mediated by executive dysfunction. While these cross-sectional relationships need to be further examined in longitudinal analyses, the results suggest that poor sleep quality and executive dysfunction may be viable preventive intervention targets to reduce adolescent substance use.

Platelet activation and dysfunction in a large-animal model of traumatic brain injury and hemorrhage

DEFF Research Database (Denmark)

Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S

2013-01-01

Traumatic brain injury (TBI) and hemorrhage are the leading causes of trauma-related mortality. Both TBI and hemorrhage are associated with coagulation disturbances, including platelet dysfunction. We hypothesized that platelet dysfunction could be detected early after injury...

Memory deficits in long-term survivors of childhood brain tumors may primarily reflect general cognitive dysfunctions

DEFF Research Database (Denmark)

Reimers, Tonny Solveig; Mortensen, Erik Lykke; Schmiegelow, Kjeld

2007-01-01

To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction.......To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction....

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

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Corrigan, Neva M.; Shaw, Dennis. W. W.; Richards, Todd L.; Estes, Annette M.; Friedman, Seth D.; Petropoulos, Helen; Artru, Alan A.; Dager, Stephen R.

2012-01-01

Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ([superscript 1]HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally…

Inter-relationship between CSF dynamics and CSF to-and-fro movement in the cervical region as assessed by MR velocity imaging with phase encoding in hydrocephalic and normal patients

International Nuclear Information System (INIS)

Kudo, Sumio; Wachi, Akihiko; Sato, Kiyoshi; Sumie, Hirotoshi.

1992-01-01

The to-and-fro velocity of cerebrospinal fluid (CSF) at C-1 and C-2 spinal-cord levels was measured by means of MR velocity-imaging technique, and the correlation of changes in velocity and various biophysical factors influencing the intracranial pressure environment were analyzed. Eight hydrocephalic patients, male and female, of different ages (both infants and adults), and 11 normal volunteers with a similar age range were investigated. The to-and-fro CSF movement was measured by means of phase-shift techniques with a bipolar gradient pulse. The cerebrospinal opening pressure was also recorded in 6 of the 8 hydrocephalic patients, either through a ventricular catheter reservoir or a spinal catheter inserted in the lumbosacral subarachnoid space; the CSF pulse amplitude, the pressure volume index (PVI), and the CSF outflow resistance (Ro) were also evaluated during the procedure. CSF flowed towards caudally in the early systolic phase of a cardiac stroke, but the flow direction was reversed in the early diastolic phase when the maximum flow rate was reached. Although such a flow pattern was commonly observed in all normal and hydrocephalic subjects, whatever the age, there was a marked difference in flow rate between the infants and the pediatric-adults groups, -i.e., it was 5-10 mm/sec for the former and 10-20 mm/sec for the latter. An abnormally high flow rate (33.0 mm/sec) was observed in the hydrocephalic patients when there was a malfunction of the ventriculoperitoneal shunt. A close correlation was found to exist among the changes in the CSF flow velocity, the CSF pressure amplitude, and the CSF outflow resistance (Ro), but not in the PVI. The measurement of the CSF flow velocity by MR velocity imaging appears to have an important role not only in the investigation of CSF dynamics, but also in the diagnosis and treatment of such pathologies as hydrocephalus and ventriculoperitoneal shunt malfunction. (author)

Contribution of thrombin-reactive brain pericytes to blood-brain barrier dysfunction in an in vivo mouse model of obesity-associated diabetes and an in vitro rat model.

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Takashi Machida

Full Text Available Diabetic complications are characterized by the dysfunction of pericytes located around microvascular endothelial cells. The blood-brain barrier (BBB exhibits hyperpermeability with progression of diabetes. Therefore, brain pericytes at the BBB may be involved in diabetic complications of the central nervous system (CNS. We hypothesized that brain pericytes respond to increased brain thrombin levels in diabetes, leading to BBB dysfunction and diabetic CNS complications. Mice were fed a high-fat diet (HFD for 2 or 8 weeks to induce obesity. Transport of i.v.-administered sodium fluorescein and 125I-thrombin across the BBB were measured. We evaluated brain endothelial permeability and expression of tight junction proteins in the presence of thrombin-treated brain pericytes using a BBB model of co-cultured rat brain endothelial cells and pericytes. Mice fed a HFD for 8 weeks showed both increased weight gain and impaired glucose tolerance. In parallel, the brain influx rate of sodium fluorescein was significantly greater than that in mice fed a normal diet. HFD feeding inhibited the decline in brain thrombin levels occurring during 6 weeks of feeding. In the HFD fed mice, plasma thrombin levels were significantly increased, by up to 22%. 125I-thrombin was transported across the BBB in normal mice after i.v. injection, with uptake further enhanced by co-injection of unlabeled thrombin. Thrombin-treated brain pericytes increased brain endothelial permeability and caused decreased expression of zona occludens-1 (ZO-1 and occludin and morphological disorganization of ZO-1. Thrombin also increased mRNA expression of interleukin-1β and 6 and tumor necrosis factor-α in brain pericytes. Thrombin can be transported from circulating blood through the BBB, maintaining constant levels in the brain, where it can stimulate pericytes to induce BBB dysfunction. Thus, the brain pericyte-thrombin interaction may play a key role in causing BBB dysfunction in

Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.

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Chen, Jianhuai; Chen, Yun; Gao, Qingqiang; Chen, Guotao; Dai, Yutian; Yao, Zhijian; Lu, Qing

2018-05-01

Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.

Pituitary dysfunction following traumatic brain injury: clinical perspectives

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Tanriverdi, Fatih; Kelestimur, Fahrettin

2015-01-01

Traumatic brain injury (TBI) is a well recognized public health problem worldwide. TBI has previously been considered as a rare cause of hypopituitarism, but an increased prevalence of neuroendocrine dysfunction in patients with TBI has been reported during the last 15 years in most of the retrospective and prospective studies. Based on data in the current literature, approximately 15%–20% of TBI patients develop chronic hypopituitarism, which clearly suggests that TBI-induced hypopituitarism is frequent in contrast with previous assumptions. This review summarizes the current data on TBI-induced hypopituitarism and briefly discusses some clinical perspectives on post-traumatic anterior pituitary hormone deficiency. PMID:26251600

The consequence of spatial visual processing dysfunction caused by traumatic brain injury (TBI).

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Padula, William V; Capo-Aponte, Jose E; Padula, William V; Singman, Eric L; Jenness, Jonathan

2017-01-01

A bi-modal visual processing model is supported by research to affect dysfunction following a traumatic brain injury (TBI). TBI causes dysfunction of visual processing affecting binocularity, spatial orientation, posture and balance. Research demonstrates that prescription of prisms influence the plasticity between spatial visual processing and motor-sensory systems improving visual processing and reducing symptoms following a TBI. The rationale demonstrates that visual processing underlies the functional aspects of binocularity, balance and posture. The bi-modal visual process maintains plasticity for efficiency. Compromise causes Post Trauma Vision Syndrome (PTVS) and Visual Midline Shift Syndrome (VMSS). Rehabilitation through use of lenses, prisms and sectoral occlusion has inter-professional implications in rehabilitation affecting the plasticity of the bi-modal visual process, thereby improving binocularity, spatial orientation, posture and balance Main outcomes: This review provides an opportunity to create a new perspective of the consequences of TBI on visual processing and the symptoms that are often caused by trauma. It also serves to provide a perspective of visual processing dysfunction that has potential for developing new approaches of rehabilitation. Understanding vision as a bi-modal process facilitates a new perspective of visual processing and the potentials for rehabilitation following a concussion, brain injury or other neurological events.

Maternal separation as a model of brain-gut axis dysfunction.

LENUS (Irish Health Repository)

O'Mahony, Siobhain M

2011-03-01

Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. Maternal separation in rodents is a well-studied model of early life stress. However, stress during this critical period also induces alterations in many systems throughout the body. Thus, a variety of other disorders that are associated with adverse early life events are often comorbid with psychiatric illnesses, suggesting a common underlying aetiology. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is thought to involve a dysfunctional interaction between the brain and the gut. Essential aspects of the brain-gut axis include spinal pathways, the hypothalamic pituitary adrenal axis, the immune system, as well as the enteric microbiota. Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS.

Executive dysfunction, brain aging, and political leadership.

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Fisher, Mark; Franklin, David L; Post, Jerrold M

2014-01-01

Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function.

2-Chlorohexadecanoic acid induces ER stress and mitochondrial dysfunction in brain microvascular endothelial cells

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Eva Bernhart

2018-05-01

Full Text Available Peripheral leukocytes induce blood-brain barrier (BBB dysfunction through the release of cytotoxic mediators. These include hypochlorous acid (HOCl that is formed via the myeloperoxidase-H2O2-chloride system of activated phagocytes. HOCl targets the endogenous pool of ether phospholipids (plasmalogens generating chlorinated inflammatory mediators like e.g. 2-chlorohexadecanal and its conversion product 2-chlorohexadecanoic acid (2-ClHA. In the cerebrovasculature these compounds inflict damage to brain microvascular endothelial cells (BMVEC that form the morphological basis of the BBB. To follow subcellular trafficking of 2-ClHA we synthesized a ‘clickable’ alkyne derivative (2-ClHyA that phenocopied the biological activity of the parent compound. Confocal and superresolution structured illumination microscopy revealed accumulation of 2-ClHyA in the endoplasmic reticulum (ER and mitochondria of human BMVEC (hCMEC/D3 cell line. 2-ClHA and its alkyne analogue interfered with protein palmitoylation, induced ER-stress markers, reduced the ER ATP content, and activated transcription and secretion of interleukin (IL−6 as well as IL-8. 2-ClHA disrupted the mitochondrial membrane potential and induced procaspase-3 and PARP cleavage. The protein kinase R-like ER kinase (PERK inhibitor GSK2606414 suppressed 2-ClHA-mediated activating transcription factor 4 synthesis and IL-6/8 secretion, but showed no effect on endothelial barrier dysfunction and cleavage of procaspase-3. Our data indicate that 2-ClHA induces potent lipotoxic responses in brain endothelial cells and could have implications in inflammation-induced BBB dysfunction.

High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature.

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Li, Wei; Maloney, Ronald E; Aw, Tak Yee

2015-08-01

We previously demonstrated that in normal glucose (5mM), methylglyoxal (MG, a model of carbonyl stress) induced brain microvascular endothelial cell (IHEC) dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC). Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER) was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia); moreover, barrier function remained disrupted 6h after cell transfer to normal glucose media (acute glycemic fluctuation). Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH) synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal) levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG-occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG-occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature

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Wei Li

2015-08-01

Full Text Available We previously demonstrated that in normal glucose (5 mM, methylglyoxal (MG, a model of carbonyl stress induced brain microvascular endothelial cell (IHEC dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC. Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia; moreover, barrier function remained disrupted 6 h after cell transfer to normal glucose media (acute glycemic fluctuation. Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG–occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG–occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes.

Brain imaging and cognitive dysfunctions in Huntington's disease

Science.gov (United States)

Montoya, Alonso; Price, Bruce H.; Menear, Matthew; Lepage, Martin

2006-01-01

Recent decades have seen tremendous growth in our understanding of the cognitive dysfunctions observed in Huntington's disease (HD). Advances in neuroimaging have contributed greatly to this growth. We reviewed the role that structural and functional neuroimaging techniques have played in elucidating the cerebral bases of the cognitive deficits associated with HD. We conducted a computer-based search using PubMed and PsycINFO databases to retrieve studies of patients with HD published between 1965 and December 2004 that reported measures on cognitive tasks and used neuroimaging techniques. Structural neuroimaging has provided important evidence of morphological brain changes in HD. Striatal and cortical atrophy are the most common findings, and they correlate with cognitive deficits in attention, working memory and executive functions. Functional studies have also demonstrated correlations between striatal dysfunction and cognitive performance. Striatal hypoperfusion and decreased glucose utilization correlate with executive dysfunction. Hypometabolism also occurs throughout the cerebral cortex and correlates with performance on recognition memory, language and perceptual tests. Measures of presynaptic and postsynaptic dopamine biochemistry have also correlated with measurements of episodic memory, speed of processing and executive functioning. Aided by the results of numerous neuroimaging studies, it is becoming increasingly clear that cognitive deficits in HD involve abnormal connectivity between the basal ganglia and cortical areas. In the future, neuroimaging techniques may shed the most light on the pathophysiology of HD by defining neurodegenerative disease phenotypes as a valuable tool for knowing when patients become “symptomatic,” having been in a gene-positive presymptomatic state, and as a biomarker in following the disease, thereby providing a prospect for improved patient care. PMID:16496032

Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection.

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Kumar, Ajay; Deep, Amar; Gupta, Rakesh K; Atam, Virendra; Mohindra, Samir

2017-09-01

This study examined correlates of the brain's neurocognitive performance among clinically and biochemically normal adult patient with hepatitis C virus (HCV). We hypothesized that anti-HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using diffusion tensor tractrography (DTT) metrics. Anti-HCV positive patient ( n  = 40), and healthy controls ( n  = 31), fulfilling inclusion criteria (incidentally detected anti-HCV positive) and able to provide informed consent were screened and recruited for the study. All these subjects and controls underwent subjective assessment of their quality of life related symptoms, neuropsychometric tests (NPT) and magnetic resonance imaging. The patients were subjected to neuroimaging as well as psychological testing. There was no significant difference in basic laboratory parameters in these two groups. Independent t -test reveals significantly lower neuropsychological functioning as compared to healthy control. A significantly decreased FA values and myoinsitol were observed in HCV subjects on sensory, inferior longitudinal fascicules, and STR fiber bundles as compared to healthy control. Bivariate correlation analysis reveals that neuropsychological scores are significantly positive. Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.

ROLE OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF IN THE DIAGNOSIS OF COGNTIVE DYSFUNCTION IN PATIENTS WITH TYPE 2 DIABETES

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Irina Vladimirovna Gatskikh

2016-02-01

Full Text Available One of the heavy progressive vascular complications of type 2 diabetes is a central nervous system, manifesting cognitive dysfunction due to metabolic changes. Goal. Defining the role of brain-derived neurotrophic factor (BDNF in the diagnosis of cognitive dysfunction in patients with type 2 diabetes. Materials and methods. The study involved 83 patients with type 2 diabetes at the age of 40 - 70 years. Complex examination included clinical and laboratory examination, neuropsychological testing. To screen for cognitive impairment used the Montreal Cognitive Assessment Scale (MOS test. To identify early markers of cognitive impairment was determined the level of brain-derived neurotrophic factor (BDNF. Results. The study found a negative correlation between the level of BDNF and the HbA1c (r = - 0,494, p = 0.01, fasting glucose (r = - 0,499, p = 0.01, and a positive relationship between the level of BDNF and cognitive function in patients with type 2 diabetes. Conclusion. In patients with type 2 diabetes revealed cognitive dysfunction in the form of reduced memory, attention, optical-dimensional activity that correlated with chronic hyperglycemia. The role of brain-derived neurotrophic factor (BDNF in the complex diagnosis of cognitive dysfunction in patients with type 2 diabetes. With an increase in HbA1c in patients with type 2 diabetes reduces the level of BDNF in the blood plasma, and a decline in cognitive function. Recommended use of BDNF as an additional marker of cognitive dysfunction in patients with type 2 diabetes.

Combined Therapy of Iron Chelator and Antioxidant Completely Restores Brain Dysfunction Induced by Iron Toxicity

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Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

2014-01-01

Background Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. Methodology Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. Conclusion In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload. PMID:24400127

Incidence and treatment of visual dysfunction in traumatic brain injury.

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Schlageter, K; Gray, B; Hall, K; Shaw, R; Sammet, R

1993-01-01

The incidence of visual dysfunction and effectiveness of visual exercises in acute traumatically brain injured inpatients in a rehabilitation programme were studied. Vision evaluation norms were established on 23 hospital staff. The evaluation was then administered to 51 inpatients within days after admission. An additional 21 patients were unable to participate, usually due to decreased cognition or agitation. Thirty of 51 (59%) scored impaired in one or more of the following: pursuits, saccades, ocular posturing, stereopsis, extra-ocular movements, and near/far eso-exotropia. For patients having dysfunction in pursuits or saccades, a 2-week baseline was followed by vision exercises. During the baseline interval patients were evaluated by an optometrist to verify therapists' findings. Six patients who participated in several weeks of treatment were evaluated at 2-week intervals by an independent rater. Progress is graphically illustrated. Conclusions were that the suitability of an inpatient vision programme, from our experience, is questionable. However, an initial evaluation proved valuable for informing staff of patients' visual status and for referral to an optometrist/ophthalmologist for further treatment.

Neuropsychological factors related to returning to work in patients with higher brain dysfunction.

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Kai, Akiko; Hashimoto, Manabu; Okazaki, Tetsuya; Hachisuka, Kenji

2008-12-01

We conducted neuropsychological tests of patients with higher brain dysfunction to examine the characteristics of barriers to employment. We tested 92 patients with higher brain dysfunction (average age of 36.3 +/- 13.8 years old, ranging between 16 and 63 years old, with an average post-injury period of 35.6 +/- 67.8 months) who were hospitalized at the university hospital between February 2002 and June 2007 for further neuropsychological evaluation, conducting the Wechsler Adult Intelligence Scale-Revised (WAIS-R), Wechsler Memory Scale-Revised (WMS-R), the Rivermead Behavioral Memory Test (RBMT), Frontal Assessment Battery (FAB) and Behavioral Assessment of Dysexecutive Syndrome (BADS). The outcomes after discharge were classified between competitive employment, sheltered employment and non-employment, and the three groups were compared using one-way analysis of variance and the Scheffe test. The WAIS-R subtests were mutually compared based on the standard values of significant differences described in the WAIS-R manual. Verbal performance and full scale Intelligence Quotient (IQ) of WAIS-R were 87.7 +/- 15.6 (mean +/- standard deviation), 78.5 +/- 18.1 and 81.0 +/- 17.2, respectively, and verbal memory, visual memory, general memory, attention/concentration and delayed recall were 74.6 +/- 20.0, 76.6 +/- 21.4, 72.0 +/- 20.4, 89.0 +/- 16.5 and 65.2 +/- 20.8, respectively. The competitive employment group showed significantly higher scores in performance IQ and full IQ on the WAIS-R and verbal memory, visual memory, general memory and delayed recall on the WMS-R and RBMT than the non-employment group. The sheltered employment group showed a significantly higher score in delayed recall than the non-employment group. No difference was observed in the FAB or BADS between the three groups. In the subtests of the WAIS-R, the score for Digit Symbol-Coding was significantly lower than almost all the other subtests. For patients with higher brain dysfunction, IQ (full

WAIS Digit Span-Based Indicators of Malingered Neurocognitive Dysfunction: Classification Accuracy in Traumatic Brain Injury

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Heinly, Matthew T.; Greve, Kevin W.; Bianchini, Kevin J.; Love, Jeffrey M.; Brennan, Adrianne

2005-01-01

The present study determined specificity and sensitivity to malingered neurocognitive dysfunction (MND) in traumatic brain injury (TBI) for several Wechsler Adult Intelligence Scale (WAIS) Digit Span scores. TBI patients (n = 344) were categorized into one of five groups: no incentive, incentive only, suspect, probable MND, and definite MND.…

Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

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Murrin L Charles

2011-03-01

Full Text Available Abstract Background Methamphetamine (METH, an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial cell activation. Here we hypothesized that METH-induced interference of glucose uptake and transport at the endothelium can disrupt the energy requirement of the blood-brain barrier (BBB function and integrity. We undertake this study because there is no report of METH effects on glucose uptake and transport across the blood-brain barrier (BBB to date. Results In this study, we demonstrate that METH-induced disruption of glucose uptake by endothelium lead to BBB dysfunction. Our data indicate that a low concentration of METH (20 μM increased the expression of glucose transporter protein-1 (GLUT1 in primary human brain endothelial cell (hBEC, main component of BBB without affecting the glucose uptake. A high concentration of 200 μM of METH decreased both the glucose uptake and GLUT1 protein levels in hBEC culture. Transcription process appeared to regulate the changes in METH-induced GLUT1 expression. METH-induced decrease in GLUT1 protein level was associated with reduction in BBB tight junction protein occludin and zonula occludens-1. Functional assessment of the trans-endothelial electrical resistance of the cell monolayers and permeability of dye tracers in animal model validated the pharmacokinetics and molecular findings that inhibition of glucose uptake by GLUT1 inhibitor cytochalasin B (CB aggravated the METH-induced disruption of the BBB integrity. Application of acetyl-L-carnitine suppressed the effects of METH on glucose uptake and BBB function. Conclusion Our findings suggest that impairment of GLUT1 at the brain endothelium by METH may contribute to energy-associated disruption of tight junction assembly and loss of BBB integrity.

Cognitive dysfunction in patients with brain metastases: influences on caregiver resilience and coping.

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Saria, Marlon Garzo; Courchesne, Natasia; Evangelista, Lorraine; Carter, Joshua; MacManus, Daniel A; Gorman, Mary Kay; Nyamathi, Adeline M; Phillips, Linda R; Piccioni, David; Kesari, Santosh; Maliski, Sally

2017-04-01

Neurologic deficits that may be manifested as cognitive impairment contribute to the challenges faced by caregivers of patients with brain metastases. To better address their needs, we examined how caregivers respond to these challenges and explore the relationship between the patient's cognitive impairment and caregiver resilience and coping. We conducted a descriptive, cross-sectional study using self-reported data from 56 caregivers of patients with brain metastases. Study participants from a comprehensive cancer center were asked to complete a series of instruments that measured their perception of the patient's cognitive dysfunction (revised memory and behavior problems checklist, RMBC), their own personal resilience (Resilience Scale, RS), and their utilization of a broad range of coping responses (COPE inventory and Emotional-Approach Coping scale). Caregivers reported that memory-related problems occurred more frequently in the patients they cared for compared to depression and disruptive behavior (mean scores 3.52 vs 2.34 vs. 1.32, respectively). Coping strategies most frequently used by caregivers were acceptance (3.28), planning (3.08), and positive reinterpretation and growth (2.95). Most caregivers scored moderate to high on the RS (77%). The coping strategy acceptance correlated significantly with the memory and disruptive behavior subscales of the RMBC. Given the protective effect of problem-focused coping and the high rate of caregivers utilizing less effective coping strategies in instances of worsening cognitive dysfunction, healthcare professionals need to systematically assess the coping strategies of caregivers and deliver a more personalized approach to enhance effective coping among caregivers of patients with brain metastases.

Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

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Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

2013-01-01

Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

Predictors of Memory and Processing Speed Dysfunctions after Traumatic Brain Injury

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William Winardi

2014-01-01

Full Text Available Background. The aims of this study were to evaluate the predictive value of admission Glasgow Coma Scale (GCS scores, duration of unconsciousness, neurosurgical intervention, and countercoup lesion on the impairment of memory and processing speed functions six months after a traumatic brain injury (TBI based on a structural equation modeling. Methods. Thirty TBI patients recruited from Neurosurgical Department at the Kaohsiung Medical University Hospital were administered the Wechsler Memory Scale-III (WMS-III and the Wechsler Adult Intelligence Scale-III processing speed index to evaluate the memory and processing speed functions. Results. The study showed that GCS scores accounted for 40% of the variance in memory/processing speed. No significant predictive effects were found for the other three variables. GCS classification at the time of TBI seems to correspond moderately to the severity of memory/processing speed dysfunctions. Conclusions. The present study demonstrated that admission GCS score is a robust predictor of memory/processing speed dysfunctions after TBI. The results should be replicated with a large sample of patients with TBI, or be extended by examining other potential clinical predictors.

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

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Kabasawa, Hidehiro; Ogawa, Tetsuo; Iida, Akihiko; Matsubara, Michitaka [Nagoya City Rehabilitation and Sports Center (Japan)

2002-06-01

Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerebral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with {sup 15}O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO{sub 2} in all regions. Then we compared rCBF, OEF, and CMRO{sub 2} between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO{sub 2} along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO{sub 2} of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of ''relative luxury perfusion''. Comparison of rCBF, OEF and CMRO{sub 2} between normal group and impaired group revealed that CMRO{sub 2} of the impaired group was significantly lower than that of the

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)

Kabasawa, Hidehiro; Ogawa, Tetsuo; Iida, Akihiko; Matsubara, Michitaka

2002-01-01

Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerebral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with 15 O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO 2 in all regions. Then we compared rCBF, OEF, and CMRO 2 between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO 2 along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO 2 of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of ''relative luxury perfusion''. Comparison of rCBF, OEF and CMRO 2 between normal group and impaired group revealed that CMRO 2 of the impaired group was significantly lower than that of the normal group in the bilateral frontal, temporal, and occipital

Brain natriuretic peptide as noninvasive marker of the severity of right ventricular dysfunction in chronic thromboembolic pulmonary hypertension

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Reesink, Herre J.; Tulevski, Igor I.; Marcus, J. Tim; Boomsma, Frans; Kloek, Jaap J.; Vonk Noordegraaf, Anton; Bresser, Paul

2007-01-01

BACKGROUND: Right ventricular (RV) dysfunction is associated with increased morbidity and mortality in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo pulmonary endarterectomy (PEA). We studied whether plasma brain natriuretic peptide (BNP) levels can be used to

Brain natriuretic peptide and right heart dysfunction after heart transplantation.

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Talha, Samy; Charloux, Anne; Piquard, François; Geny, Bernard

2017-06-01

Heart transplantation (HT) should normalize cardiac endocrine function, but brain natriuretic peptide (BNP) levels remain elevated after HT, even in the absence of left ventricular hemodynamic disturbance or allograft rejection. Right ventricle (RV) abnormalities are common in HT recipients (HTx), as a result of engraftment process, tricuspid insufficiency, and/or repeated inflammation due to iterative endomyocardial biopsies. RV function follow-up is vital for patient management as RV dysfunction is a recognized cause of in-hospital death and is responsible for a worse prognosis. Interestingly, few and controversial data are available concerning the relationship between plasma BNP levels and RV functional impairment in HTx. This suggests that infra-clinical modifications, such as subtle immune system disorders or hypoxic conditions, might influence BNP expression. Nevertheless, due to other altered circulating molecular forms of BNP, a lack of specificity of BNP assays is described in heart failure patients. This phenomenon could exist in HT population and could explain elevated BNP plasmatic levels despite a normal RV function. In clinical practice, intra-individual change in BNP over time, rather than absolute BNP values, might be more helpful in detecting right cardiac dysfunction in HTx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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Bakker, Nelleke

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

[Obsessive-compulsive disorder, a new model of basal ganglia dysfunction? Elements from deep brain stimulation studies].

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Haynes, W I A; Millet, B; Mallet, L

2012-01-01

Deep brain stimulation was first developed for movement disorders but is now being offered as a therapeutic alternative in severe psychiatric disorders after the failure of conventional therapies. One of such pathologies is obsessive-compulsive disorder. This disorder which associates intrusive thoughts (obsessions) and repetitive irrepressible rituals (compulsions) is characterized by a dysfunction of a cortico-subcortical loop. After having reviewed the pathophysiological evidence to show why deep brain stimulation was an interesting path to take for severe and resistant cases of obsessive-compulsive disorder, we will present the results of the different clinical trials. Finally, we will provide possible mechanisms for the effects of deep brain stimulation in this pathology. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Pituitary and/or hypothalamic dysfunction following moderate to severe traumatic brain injury: Current perspectives

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Zeeshan Javed

2015-01-01

Full Text Available There is an increasing deliberation regarding hypopituitarism following traumatic brain injury (TBI and recent data have suggested that pituitary dysfunction is very common among survivors of patients having moderate-severe TBI which may evolve or resolve over time. Due to high prevalence of pituitary dysfunction after moderate-severe TBI and its association with increased morbidity and poor recovery and the fact that it can be easily treated with hormone replacement, it has been suggested that early detection and treatment is necessary to prevent long-term neurological consequences. The cause of pituitary dysfunction after TBI is still not well understood, but evidence suggests few possible primary and secondary causes. Results of recent studies focusing on the incidence of hypopituitarism in the acute and chronic phases after TBI are varied in terms of severity and time of occurrence. Although the literature available does not show consistent values and there is difference in study parameters and diagnostic tests used, it is clear that pituitary dysfunction is very common after moderate to severe TBI and patients should be carefully monitored. The exact timing of development cannot be predicted but has suggested regular assessment of pituitary function up to 1 year after TBI. In this narrative review, we aim to explore the current evidence available regarding the incidence of pituitary dysfunction in acute and chronic phase post-TBI and recommendations for screening and follow-up in these patients. We will also focus light over areas in this field worthy of further investigation.

Remote Traumatic Brain Injury Is Associated with Motor Dysfunction in Older Military Veterans.

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Gardner, Raquel C; Peltz, Carrie B; Kenney, Kimbra; Covinsky, Kenneth E; Diaz-Arrastia, Ramon; Yaffe, Kristine

2017-09-01

Traumatic brain injury (TBI) has been identified as a risk factor for Parkinson's disease (PD). Motor dysfunction among TBI-exposed elders without PD has not been well characterized. We sought to determine whether remote TBI is a risk factor for motor dysfunction on exam and functionally relevant motor dysfunction in day-to-day life among independently living elders without PD. This is a cross-sectional cohort study of independently living retired military veterans aged 50 or older with (n = 78) and without (n = 85) prior TBI-all without diagnosed PD. To characterize multidimensional aspects of motor function on exam, the Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination was performed by a board-certified neurologist and used to calculate a modified UPDRS (mUPDRS) global motor score and four domain scores (tremor, rigidity, bradykinesia, and posture/gait). Functionally relevant motor dysfunction was assessed via self-report of falls within the past year. In analyses adjusted for demographics and comorbidities that differed between groups, compared with veterans without TBI, those with moderate-to-severe TBI were more likely to have fallen in past year (33% vs. 14%, risk ratio 2.5 [95% confidence interval 1.1-5.4]), had higher (worse) mUPDRS global motor (p = .03) and posture/gait scores (p = .02), but not higher tremor (p = .70), rigidity (p = .21), or bradykinesia scores (p = .22). Mild TBI was not associated with worse motor function. Remote moderate-to-severe TBI is a risk factor for motor dysfunction-defined as recent falls and impaired posture/gait-among older veterans. TBI-exposed older adults may be ideal candidates for aggressive fall-screening and prevention strategies. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pituitary dysfunction following traumatic brain injury or subarachnoid haemorrhage - in "Endocrine Management in the Intensive Care Unit".

LENUS (Irish Health Repository)

Hannon, M J

2012-02-01

Traumatic brain injury and subarachnoid haemorrhage are important causes of morbidity and mortality in the developed world. There is a large body of evidence that demonstrates that both conditions may adversely affect pituitary function in both the acute and chronic phases of recovery. Diagnosis of hypopituitarism and accurate treatment of pituitary disorders offers the opportunity to improve mortality and outcome in both traumatic brain injury and subarachnoid haemorrhage. In this article, we will review the history and pathophysiology of pituitary function in the acute phase following traumatic brain injury and subarachnoid haemorrhage, and we will discuss in detail three key aspects of pituitary dysfunction which occur in the early course of TBI; acute cortisol deficiency, diabetes insipidus and SIAD.

Brain networks during free viewing of complex erotic movie: new insights on psychogenic erectile dysfunction.

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Nicoletta Cera

Full Text Available Psychogenic erectile dysfunction (ED is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp. Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC, using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN, default-mode network (DMN, fronto-parietal network (FPN and salience network (SN were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other's actions. Moreover, the between group differences in the SN nodes

Brain networks during free viewing of complex erotic movie: new insights on psychogenic erectile dysfunction.

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Cera, Nicoletta; Di Pierro, Ezio Domenico; Ferretti, Antonio; Tartaro, Armando; Romani, Gian Luca; Perrucci, Mauro Gianni

2014-01-01

Psychogenic erectile dysfunction (ED) is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp). Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA) and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC), using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN), default-mode network (DMN), fronto-parietal network (FPN) and salience network (SN) were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other's actions. Moreover, the between group differences in the SN nodes suggested a

Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation

International Nuclear Information System (INIS)

Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio

2001-01-01

Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis. (author)

Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.

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Ortiz, M Del Carmen; Lores-Arnaiz, Silvia; Albertoni Borghese, M Florencia; Balonga, Sabrina; Lavagna, Agustina; Filipuzzi, Ana Laura; Cicerchia, Daniela; Majowicz, Monica; Bustamante, Juanita

2013-12-01

Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.

Cerebral energy metabolism during induced mitochondrial dysfunction

DEFF Research Database (Denmark)

Nielsen, T H; Bindslev, TT; Pedersen, S M

2013-01-01

In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

Restoration of dietary-fat induced blood–brain barrier dysfunction by anti-inflammatory lipid-modulating agents

Directory of Open Access Journals (Sweden)

Pallebage-Gamarallage Menuka

2012-09-01

Full Text Available Abstract Background Several studies have identified use of non-steroidal-anti-inflammatory drugs and statins for prevention of dementia, but their efficacy in slowing progression is not well understood. Cerebrovascular disturbances are common pathological feature of Alzheimer’s disease. We previously reported chronic ingestion of saturated fatty acids (SFA compromises blood–brain barrier (BBB integrity resulting in cerebral extravasation of plasma proteins and inflammation. However, the SFA-induced parenchymal accumulation of plasma proteins could be prevented by co-administration of some cholesterol lowering agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of this study was to explore lipid-lowering agents could reverse BBB disturbances induced by chronic ingestion of SFA’s. Methods Wild-type mice were fed an SFA diet for 12 weeks to induce BBB dysfunction, and then randomised to receive atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for 2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG and amyloid-β enriched apolipoprotein (apo-B lipoproteins within brain parenchyme were quantified utilising immunofluorescence microscopy. Results Atorvastatin treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a water-soluble statin was less effective than atorvastatin (lipid-soluble. Statin effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG and apo B as effectively as atorvastatin. Our findings are consistent with the drug effects being independent of plasma lipid homeostasis. Conclusion Our findings suggest that BBB dysfunction induced by chronic ingestion of SFA is reversible with timely introduction and sustained treatment with agents that suppress inflammation.

Cerebral amyloid angiopathy-related inflammation presenting with steroid-responsive higher brain dysfunction: case report and review of the literature

Directory of Open Access Journals (Sweden)

Maeda Yasushi

2011-09-01

Full Text Available Abstract A 56-year-old man noticed discomfort in his left lower limb, followed by convulsion and numbness in the same area. Magnetic resonance imaging (MRI showed white matter lesions in the right parietal lobe accompanied by leptomeningeal or leptomeningeal and cortical post-contrast enhancement along the parietal sulci. The patient also exhibited higher brain dysfunction corresponding with the lesions on MRI. Histological pathology disclosed β-amyloid in the blood vessels and perivascular inflammation, which highlights the diagnosis of cerebral amyloid angiopathy (CAA-related inflammation. Pulse steroid therapy was so effective that clinical and radiological findings immediately improved. CAA-related inflammation is a rare disease, defined by the deposition of amyloid proteins within the leptomeningeal and cortical arteries associated with vasculitis or perivasculitis. Here we report a patient with CAA-related inflammation who showed higher brain dysfunction that improved with steroid therapy. In cases with atypical radiological lesions like our case, cerebral biopsy with histological confirmation remains necessary for an accurate diagnosis.

Insulin Protects against Brain Oxidative Stress with an Apparent Effect on Episodic Memory in Doxorubicin-Induced Cognitive Dysfunction in Wistar Rats.

Science.gov (United States)

Ramalingayya, Grandhi Venkata; Sonawane, Vishwajeet; Cheruku, Sri Pragnya; Kishore, Anoop; Nayak, Pawan G; Kumar, Nitesh; Shenoy, Rekha S; Nandakumar, Krishnadas

2017-01-01

The present study was aimed at assessing the protective effect of insulin against doxorubicin (DOX)-induced cognitive dysfunction in Wistar rats. Cognitive function for episodic memory was assessed by a novel object recognition task (NORT) in male Wistar rats. Oxidative stress markers-SOD, catalase, glutathione, and lipid peroxidation-in the hippocampus and frontal cortex were assessed using colorimetric methods. Doxorubicin treatment (2.5 mg/kg, i.p., every 5 days for 50 days) reduced recognition and discriminative indices in NORT with increased oxidative stress in the brain. A nonhypoglycemic dose of insulin (0.5 IU/kg, i.p.) significantly reduced brain oxidative stress (MDA) induced by doxorubicin with an increase in the antioxidant defense systems (SOD, catalase, and GSH). Rats treated with combined insulin and DOX spent comparatively more time with the novel object when compared to the non-novel objects; however, the observed difference was not statistically significant. An apparent improvement (p insulin reduces brain oxidative stress and apparently improves doxorubicin-induced cognitive dysfunction in Wistar rats.

Symptoms of gonadal dysfunction are more predictive of hypopituitarism than nonspecific symptoms in screening for pituitary dysfunction following moderate or severe traumatic brain injury.

Science.gov (United States)

Cuesta, Martín; Hannon, Mark J; Crowley, Rachel K; Behan, Lucy Ann; Tormey, William; Rawluk, Daniel; Delargy, Mark; Agha, Amar; Thompson, Christopher J

2016-01-01

The economic and logistic burden of screening for hypopituitarism following moderate/severe traumatic brain injury (TBI) is considerable. A key recommendation in published guidelines is to prioritize for screening those patients with symptoms suggestive of pituitary dysfunction. The purpose of this study was to evaluate the utility of targeted screening for hypopituitarism in long-term survivors after moderate/severe TBI using referrals on the basis of symptoms. In group 1 (G1), consecutive, unselected patients were screened from the Irish National Neurosurgery Centre, whereas in group 2 (G2) patients were targeted based on the presence of symptoms suggestive of pituitary dysfunction. A total of 137 patients (113 male) were systematically screened (G1) and compared to 112 patients (77 male) referred for pituitary evaluation on the basis of suggestive symptoms (G2). The rate of GH, ACTH, gonadotrophin (GT), TSH and ADH deficiency was compared among groups. Patients referred with menstrual dysfunction had more GH (50% vs 11%, P = 0·001), ACTH (60% vs 14%, P hypopituitarism than those consecutively screened. Symptoms of hypogonadism are sufficiently predictive of hypopituitarism to justify screening for hypopituitarism after moderate/severe TBI. Nonspecific symptoms of hypopituitarism are no more predictive than unselected screening. © 2015 John Wiley & Sons Ltd.

Cognitive dysfunction, MRI findings and manganese levels in alcoholics

Energy Technology Data Exchange (ETDEWEB)

Itoh, Tsutomu; Nakane, Yoshibumi [Nagasaki Univ. (Japan). School of Medicine; Takahashi, Katsurou; Shimanaga, Masaki [National Nagasaki Medical Center, Omura (Japan)

2002-12-01

Alcoholic patients have been known to have brain atrophy and cognitive dysfunction. However, recent studies have reported bilateral signal hyperintensities of the globus pallidus on T1-weighted magnetic resonance imaging (MRI) in liver failure, findings that are typically associated with manganese intoxication. The present study compared brain atrophy on T1-weighted MRI, signal intensity ratios of the globus pallidus on T1-weighted MRI, whole blood manganese levels, and Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ parameters between alcoholics with and without liver cirrhosis, to investigate cognitive dysfunction, MRI findings and manganese levels in alcoholics. Pallidal hyperintensity was visually identified in 80% of alcoholic patients with liver cirrhosis. In addition, a significant correlation was seen between pallidal signal intensity (P.S.I.) ratio and blood manganese level. However, no significant correlations were found between pallidal signal intensity ratio and any of the WAIS-R parameters. These findings suggest that no direct connection exists between cognitive dysfunction and pallidal hyperintensity in alcoholic patients with liver cirrhosis. We confirmed that brain MRI in alcoholics could detect pallidal signal hyperintensity, suggesting severe liver dysfunction. In addition to diagnosis, brain MRI is useful for therapeutic psychoeducation to alcoholic patients with liver cirrhosis, visualizing the severe liver dysfunction. (author)

Cognitive dysfunction, MRI findings and manganese levels in alcoholics

International Nuclear Information System (INIS)

Itoh, Tsutomu; Nakane, Yoshibumi

2002-01-01

Alcoholic patients have been known to have brain atrophy and cognitive dysfunction. However, recent studies have reported bilateral signal hyperintensities of the globus pallidus on T1-weighted magnetic resonance imaging (MRI) in liver failure, findings that are typically associated with manganese intoxication. The present study compared brain atrophy on T1-weighted MRI, signal intensity ratios of the globus pallidus on T1-weighted MRI, whole blood manganese levels, and Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ parameters between alcoholics with and without liver cirrhosis, to investigate cognitive dysfunction, MRI findings and manganese levels in alcoholics. Pallidal hyperintensity was visually identified in 80% of alcoholic patients with liver cirrhosis. In addition, a significant correlation was seen between pallidal signal intensity (P.S.I.) ratio and blood manganese level. However, no significant correlations were found between pallidal signal intensity ratio and any of the WAIS-R parameters. These findings suggest that no direct connection exists between cognitive dysfunction and pallidal hyperintensity in alcoholic patients with liver cirrhosis. We confirmed that brain MRI in alcoholics could detect pallidal signal hyperintensity, suggesting severe liver dysfunction. In addition to diagnosis, brain MRI is useful for therapeutic psychoeducation to alcoholic patients with liver cirrhosis, visualizing the severe liver dysfunction. (author)

Stachys sieboldii (Labiatae, Chorogi) Protects against Learning and Memory Dysfunction Associated with Ischemic Brain Injury.

Science.gov (United States)

Harada, Shinichi; Tsujita, Tsukasa; Ono, Akiko; Miyagi, Kei; Mori, Takaharu; Tokuyama, Shogo

2015-01-01

Stachys sieboldii (Labiatae; Chinese artichoke, a tuber), "chorogi" in Japanese, has been extensively used in folk medicine, and has a number of pharmacological properties, including antioxidative activity. However, few studies have examined the neuroprotective effects of S. sieboldii tuber extract (chorogi extract), and it remains unknown whether the extract can alleviate learning and memory dysfunction associated with vascular dementia or Alzheimer's disease. Therefore, in this study, we investigated the neuroprotective effects of chorogi extract, and examined its protection against learning and memory dysfunction using Ginkgo biloba leaf extract (ginkgo extract) as a positive control. Mice were subjected to bilateral carotid artery occlusion (BCAO) for 30 min. Oral administration of chorogi extract or ginkgo extract significantly reduced post-ischemic glucose intolerance on day 1 and neuronal damage including memory impairment on day 3 after BCAO, compared with the vehicle-treated group. Neither herbal medicine affected locomotor activity. Furthermore, neither significantly alleviated scopolamine-induced learning and memory impairment. In primary neurons, neuronal survival rate was significantly reduced by hydrogen peroxide treatment. This hydrogen peroxide-induced neurotoxicity was significantly suppressed by chorogi extract and ginkgo extract. Taken together, our findings suggest that chorogi extract as well as ginkgo extract can protect against learning and memory dysfunction associated with ischemic brain injury through an antioxidative mechanism.

Effect of chronic forced swimming stress on whole brain radiation induced cognitive dysfunction and related mechanism

International Nuclear Information System (INIS)

Zhang Yuan; Sun Rui; Zhu Yaqun; Zhang Liyuan; Ji Jianfeng; Li Kun; Tian Ye

2014-01-01

Objective: To explore whether chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction and possible mechanism. Methods: Thirty-nine one month old male Sprague-Dawley rats were randomized into sham control group(C), swimming group(C-S), radiation group(R), and radiation plus swimming group(R-S). Radiation groups were given a single dose of 20 Gy on whole-brain. Rats in the swimming groups were trained with swimming of 15 min/d, 5 d/w. Rat behavior was performed 3 months after radiation in an order of free activity in an open field and the Morris water maze test including the place navigation and spatial probe tests. Then, the protein expressions of BDNF, P-ERK, T-ERK, P-CREB and T-CREB in the rat hippocampus tissue were assayed by Western blot. Results: On the day 2, in the place navigation test of Morris water maze, the latency of swimming group was significantly shorter than that of sham group, the latency of sham group was significantly shorter than that of radiation group, and the latency of radiation swimming group was significantly shorter than that of radiation group(P 0.05). Western blot assay showed that the expressions of BDNF and its downstream signals including P-ERK and P-CREB were markedly reduced by radiation (P < 0.05), but this reduction was attenuated by the chronic forced swimming stress. Conclusion: The chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction by up-regulating the expressions of BDNF and its downstream signal molecules of P-ERK and P-CREB in hippocampus. (authors)

MR elastography of hydrocephalus

Science.gov (United States)

Pattison, Adam J.; Lollis, S. Scott; Perrinez, Phillip R.; Weaver, John B.; Paulsen, Keith D.

2009-02-01

Hydrocephalus occurs due to a blockage in the transmission of cerebrospinal fluid (CSF) in either the ventricles or subarachnoid space. Characteristics of this condition include increased intracranial pressure, which can result in neurologic deterioration [1]. Magnetic resonance elastography (MRE) is an imaging technique that estimates the mechanical properties of tissue in vivo. While some investigations of brain tissue have been performed using MRE [2,3,4,5], the effects due to changes in interstitial pressure and fluid content on the mechanical properties of the brain remain unknown. The purpose of this work is to assess the potential of MRE to differentiate between the reconstructed properties of normal and hydrocephalic brains. MRE data was acquired in 18 female feline subjects, 12 of which received kaolin injections resulting in an acute form of hydrocephalus. In each animal, four MRE scans were performed during the process including one pre-injection and three post-injection scans. The elastic parameters were obtained using a subzone-based reconstruction algorithm that solves Navier's equations for linearly elastic materials [6]. The remaining cats were used as controls, injected with saline instead of kaolin. To determine the state of hydrocephalus, ventricular volume was estimated from segmenting anatomical images. The mean ventricular volume of hydrocephalic cats significantly increased (P ~ 0.5) for the control cats. Also, there was an observable increase in the recorded elastic shear modulus of brain tissue in the normal and hydrocephalic acquisitions. Results suggest that MRE is able to detect changes in the mechanical properties of brain tissue resulting from kaolin-induced hydrocephalus, indicating the need for further study.

Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload : correlation between plasma neurohormones and right ventricular dysfunction

NARCIS (Netherlands)

Tulevski, I.I.; Groenink, M; van der Wall, EE; van Veldhuisen, DJ; Boomsma, F; Hirsch, A; Lemkes, JS; Mulder, BJM; Stoker, J

Objective-To evaluate the role of plasma neurohormones in the diagnosis of asymptomatic or minimally symptomatic right ventricular dysfunction. Setting-Tertiary cardiovascular referral centre. Methods-Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were

Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction

NARCIS (Netherlands)

Tulevski, I. I.; Groenink, M.; van der Wall, E. E.; van Veldhuisen, D. J.; Boomsma, F.; Stoker, J.; Hirsch, A.; Lemkes, J. S.; Mulder, B. J.

2001-01-01

OBJECTIVE: To evaluate the role of plasma neurohormones in the diagnosis of asymptomatic or minimally symptomatic right ventricular dysfunction. SETTING: Tertiary cardiovascular referral centre. METHODS: Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were

Frontal brain dysfunction in alcoholism with and without antisocial personality disorder

Directory of Open Access Journals (Sweden)

Marlene Oscar-Berman

2009-05-01

Full Text Available Marlene Oscar-Berman1,2, Mary M Valmas1,2, Kayle s Sawyer1,2, Shalene M Kirkley1, David A Gansler3, Diane Merritt1,2, Ashley Couture11Department of Veterans Affairs Healthcare System, Boston Campus, Boston, MA, USA; 2Boston University School of Medicine, Boston, MA, USA; 3Suffolk University, Boston, MA, USAAbstract: Alcoholism and antisocial personality disorder (ASPD often are comorbid conditions. Alcoholics, as well as nonalcoholic individuals with ASPD, exhibit behaviors associated with prefrontal brain dysfunction such as increased impulsivity and emotional dysregulation. These behaviors can influence drinking motives and patterns of consumption. Because few studies have investigated the combined association between ASPD and alcoholism on neuropsychological functioning, this study examined the influence of ASPD symptoms and alcoholism on tests sensitive to frontal brain deficits. The participants were 345 men and women. Of them, 144 were abstinent alcoholics (66 with ASPD symptoms, and 201 were nonalcoholic control participants (24 with ASPD symptoms. Performances among the groups were examined with Trails A and B tests, the Wisconsin Card Sorting Test, the Controlled Oral Word Association Test, the Ruff Figural Fluency Test, and Performance subtests of the Wechsler Adult Intelligence Scale. Measures of affect also were obtained. Multiple regression analyses showed that alcoholism, specific drinking variables (amount and duration of heavy drinking, and ASPD were significant predictors of frontal system and affective abnormalities. These effects were different for men and women. The findings suggested that the combination of alcoholism and ASPD leads to greater deficits than the sum of each.  Keywords: alcoholism, antisocial personality disorder (ASPD, frontal brain system, neuropsychological deficits, reward system

Is cerebral glucose metabolism related to blood–brain barrier dysfunction and intrathecal IgG synthesis in Alzheimer disease?

Science.gov (United States)

Chiaravalloti, Agostino; Fiorentini, Alessandro; Francesco, Ursini; Martorana, Alessandro; Koch, Giacomo; Belli, Lorena; Torniolo, Sofia; Di Pietro, Barbara; Motta, Caterina; Schillaci, Orazio

2016-01-01

Abstract The aim of this study was to investigate the relationships between blood–brain barrier (BBB) dysfunction, intrathecal IgG synthesis, and brain glucose consumption as detectable by means of serum/cerebrospinal fluid (CSF) albumin index (Qalb) and IgG index [(CSF IgG/serum IgG) × Serum albumin/CSF albumin)] and 2-deoxy-2-(18F) fluoro-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in a selected population affected by Alzheimer disease (AD). The study included 134 newly diagnosed AD patients according to the NINCDS-ADRDA criteria. The mean (±SD) age of the patients was 70 (±6) years; 60 were male and 64 were female. Mini mental State Examination was equal to 18.9 (±7.2). All patients underwent a CSF assay and magnetic resonance before 18F-FDG PET scanning. The relationships were evaluated by means of statistical parametric mapping (SPM8). We found a significant negative correlation between the increase of Qalb and 18F-FDG uptake in the Brodmann Area 42 and 22 that corresponds to the left superior temporal gyrus, with higher Qalb values being related to a reduced glucose consumption in these areas. No significant relationships have been found between brain glucose consumption and IgG index. The results of our study suggest that BBB dysfunction is related to reduction of cortical activity in the left temporal cortex in AD subjects. PMID:27631200

Molecular mechanisms of cognitive dysfunction following traumatic brain injury

Science.gov (United States)

Walker, Kendall R.; Tesco, Giuseppina

2013-01-01

Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration. PMID:23847533

Molecular mechanisms of cognitive dysfunction following traumatic brain injury.

Science.gov (United States)

Walker, Kendall R; Tesco, Giuseppina

2013-01-01

Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.

Trillium tschonoskii maxim saponin mitigates D-galactose-induced brain aging of rats through rescuing dysfunctional autophagy mediated by Rheb-mTOR signal pathway.

Science.gov (United States)

Wang, Lingjie; Du, Junlong; Zhao, Fangyu; Chen, Zonghai; Chang, Jingru; Qin, Furong; Wang, Zili; Wang, Fengjie; Chen, Xianbing; Chen, Ning

2018-02-01

During the expansion of aging population, the study correlated with brain aging is one of the important research topics. Developing novel and effective strategies for delaying brain aging is highly desired. Brain aging is characteristics of impaired cognitive capacity due to dysfunctional autophagy regulated by Rheb-mTOR signal pathway in hippocampal tissues. In the present study, we have established a rat model with brain aging through subcutaneous injection of D-galactose (D-gal). Upon the intervention of Trillium tschonoskii Maxim (TTM) saponin, one of bioactive components from local natural herbs in China, the learning and memory capacity of D-gal-induced aging rats was evaluated through Morris water maze test, and the regulation of Rheb-mTOR signal pathway and functional status of autophagy in hippocampal tissues of D-gal-induced aging rats was explored by Western blot. TTM saponin revealed an obvious function to improve learning and memory capacity of D-gal-induced aging rats through up-regulating Rheb and down-regulating mTOR, thereby rescuing dysfunctional autophagy to execute anti-aging role. Meanwhile, this study confirmed the function of TTM saponin for preventing and treating brain aging, and provided a reference for the development and utilization of natural products in health promotion and aging-associated disease treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cardiovascular dysfunction in infants with neonatal encephalopathy.

LENUS (Irish Health Repository)

Armstrong, Katey

2012-04-01

Severe perinatal asphyxia with hypoxic ischaemic encephalopathy occurs in approximately 1-2\\/1000 live births and is an important cause of cerebral palsy and associated neurological disabilities in children. Multiorgan dysfunction commonly occurs as part of the asphyxial episode, with cardiovascular dysfunction occurring in up to a third of infants. This narrative paper attempts to review the literature on the importance of early recognition of cardiac dysfunction using echocardiography and biomarkers such as troponin and brain type natriuretic peptide. These tools may allow accurate assessment of cardiac dysfunction and guide therapy to improve outcome.

Placement of Ommaya reservoir following endoscopic third ventriculostomy in pediatric hydrocephalic patients: a critical reappraisal.

Science.gov (United States)

Xiao, Bo; Roth, Jonathan; Udayakumaran, Suhas; Beni-Adani, Liana; Constantini, Shlomi

2011-05-01

Endoscopic third ventriculostomy (ETV) has become standard for obstructive hydrocephalus. Even a successful ETV can obstruct, leading to recurrence of symptoms and even death. A possible solution to this problem is leaving an Ommaya reservoir (OR) following the ETV. OR can be tapped in an emergency and for diagnostic purposes. No specific complications have been attributed to OR in this setting. We present our experience with OR in children undergoing ETV for hydrocephalus. A retrospective study was conducted in hydrocephalic children that underwent ETV with OR insertion over 13 years (1997-2010) from a single institution. Data were collected from charts and follow-ups. Twelve patients (from 200 patients who had an ETV) underwent placement of OR with ETV. OR was reserved for a subgroup of patients in whom we anticipated complications-in children that presented with acute hydrocephalus and were in deteriorating condition, for pathologies believed to have a low predicted ETV success rate, or when the surgeon felt that the ETV procedure was suboptimal. OR was tapped in eight patients. Complications occurred in four patients: two cases of subdural effusion, one case of chronic subdural hematoma, and one CSF leak. Four ORs were removed due to complications, and four were converted to shunts. OR should be considered in selected patients undergoing ETV. Despite its obvious advantages, OR may be associated with a relatively high risk of extraaxial fluid collections. This association requires further investigation.

Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

Science.gov (United States)

Wu, Xiang; Chen, Huixin; Huang, Chunhui; Gu, Xinmei; Wang, Jialing; Xu, Dilin; Yu, Xin; Shuai, Chu; Chen, Liping; Li, Shun; Xu, Yiguo; Gao, Tao; Ye, Mingrui; Su, Wei; Liu, Haixiong; Zhang, Jinrong; Wang, Chuang; Chen, Junping; Wang, Qinwen; Cui, Wei

2017-06-01

Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

Ameliorative effects of oleanolic acid on fluoride induced metabolic and oxidative dysfunctions in rat brain: Experimental and biochemical studies.

Science.gov (United States)

Sarkar, Chaitali; Pal, Sudipta; Das, Niranjan; Dinda, Biswanath

2014-04-01

Beneficial effects of oleanolic acid on fluoride-induced oxidative stress and certain metabolic dysfunctions were studied in four regions of rat brain. Male Wistar rats were treated with sodium fluoride at a dose of 20 mg/kg b.w./day (orally) for 30 days. Results indicate marked reduction in acidic, basic and neutral protein contents due to fluoride toxicity in cerebrum, cerebellum, pons and medulla. DNA, RNA contents significantly decreased in those regions after fluoride exposure. Activities of proteolytic enzymes (such as cathepsin, trypsin and pronase) were inhibited by fluoride, whereas transaminase enzyme (GOT and GPT) activities increased significantly in brain tissue. Fluoride appreciably elevated brain malondialdehyde level, free amino acid nitrogen, NO content and free OH radical generation. Additionally, fluoride perturbed GSH content and markedly reduced SOD, GPx, GR and CAT activities in brain tissues. Oral supplementation of oleanolic acid (a plant triterpenoid), at a dose of 5mg/kgb.w./day for last 14 days of fluoride treatment appreciably ameliorated fluoride-induced alteration of brain metabolic functions. Appreciable counteractive effects of oleanolic acid against fluoride-induced changes in protein and nucleic acid contents, proteolytic enzyme activities and other oxidative stress parameters indicate that oleanolic acid has potential antioxidative effects against fluoride-induced oxidative brain damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tert-butylhydroquinone alleviates early brain injury and cognitive dysfunction after experimental subarachnoid hemorrhage: role of Keap1/Nrf2/ARE pathway.

Directory of Open Access Journals (Sweden)

Zhong Wang

Full Text Available Tert-butylhydroquinone (tBHQ, an Nrf2 activator, has demonstrated neuroprotection against brain trauma and ischemic stroke in vivo. However, little work has been done with respect to its effect on early brain injury (EBI after subarachnoid hemorrhage (SAH. At the same time, as an oral medication, it may have extensive clinical applications for the treatment of SAH-induced cognitive dysfunction. This study was undertaken to evaluate the influence of tBHQ on EBI, secondary deficits of learning and memory, and the Keap1/Nrf2/ARE pathway in a rat SAH model. SD rats were divided into four groups: (1 Control group (n=40; (2 SAH group (n=40; (3 SAH+vehicle group (n=40; and (4 SAH+tBHQ group (n=40. All SAH animals were subjected to injection of autologous blood into the prechiasmatic cistern once in 20 s. In SAH+tBHQ group, tBHQ was administered via oral gavage at a dose of 12.5 mg/kg at 2 h, 12 h, 24 h, and 36 h after SAH. In the first set of experiments, brain samples were extracted and evaluated 48 h after SAH. In the second set of experiments, changes in cognition and memory were investigated in a Morris water maze. Results shows that administration of tBHQ after SAH significantly ameliorated EBI-related problems, such as brain edema, blood-brain barrier (BBB impairment, clinical behavior deficits, cortical apoptosis, and neurodegeneration. Learning deficits induced by SAH was markedly alleviated after tBHQ therapy. Treatment with tBHQ markedly up-regulated the expression of Keap1, Nrf2, HO-1, NQO1, and GSTα1 after SAH. In conclusion, the administration of tBHQ abated the development of EBI and cognitive dysfunction in this SAH model. Its action was probably mediated by activation of the Keap1/Nrf2/ARE pathway.

Iron assessment to protect the developing brain.

Science.gov (United States)

Georgieff, Michael K

2017-12-01

Iron deficiency (ID) before the age of 3 y can lead to long-term neurological deficits despite prompt diagnosis of ID anemia (IDA) by screening of hemoglobin concentrations followed by iron treatment. Furthermore, pre- or nonanemic ID alters neurobehavioral function and is 3 times more common than IDA in toddlers. Given the global prevalence of ID and the enormous societal cost of developmental disabilities across the life span, better methods are needed to detect the risk of inadequate concentrations of iron for brain development (i.e., brain tissue ID) before dysfunction occurs and to monitor its amelioration after diagnosis and treatment. The current screening and treatment strategy for IDA fails to achieve this goal for 3 reasons. First, anemia is the final state in iron depletion. Thus, the developing brain is already iron deficient when IDA is diagnosed owing to the prioritization of available iron to red blood cells over all other tissues during negative iron balance in development. Second, brain ID, independently of IDA, is responsible for long-term neurological deficits. Thus, starting iron treatment after the onset of IDA is less effective than prevention. Multiple studies in humans and animal models show that post hoc treatment strategies do not reliably prevent ID-induced neurological deficits. Third, most currently used indexes of ID are population statistical cutoffs for either hematologic or iron status but are not bioindicators of brain ID and brain dysfunction in children. Furthermore, their relation to brain iron status is not known. To protect the developing brain, there is a need to generate serum measures that index brain dysfunction in the preanemic stage of ID, assess the ability of standard iron indicators to detect ID-induced brain dysfunction, and evaluate the efficacy of early iron treatment in preventing ID-induced brain dysfunction. © 2017 American Society for Nutrition.

Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus.

Science.gov (United States)

Barraclough, M; Elliott, R; McKie, S; Parker, B; Bruce, I N

2015-10-01

Cognitive dysfunction is a common aspect of systemic lupus erythematosus (SLE) and is increasingly reported as a problem by patients. In many cases the exact cause is unclear. Limited correlations between specific autoantibodies or structural brain abnormalities and cognitive dysfunction in SLE have been reported. It may be that the most appropriate biomarkers have yet to be found. Functional magnetic resonance imaging (fMRI) is a technique used in many other conditions and provides sensitive measures of brain functionality during cognitive tasks. It is now beginning to be employed in SLE studies. These studies have shown that patients with SLE often perform similarly to healthy controls in terms of behavioural measures on cognitive tasks. However, SLE patients appear to employ compensatory brain mechanisms, such as increased response in fronto-parietal regions, to maintain adequate cognitive performance. As there have been only a few studies using fMRI in SLE to investigate cognitive dysfunction, many questions remain unanswered. Further research could, however, help to identify biomarkers for cognitive dysfunction in SLE. © The Author(s) 2015.

Magnetic resonance imaging of blood brain/nerve barrier dysfunction and leukocyte infiltration: closely related or discordant?

Directory of Open Access Journals (Sweden)

Gesa eWeise

2012-12-01

Full Text Available Unlike other organs the nervous system is secluded from the rest of the organism by the blood brain (BBB or blood nerve barrier (BNB preventing passive influx of fluids from the circulation. Similarly, leukocyte entry to the nervous system is tightly controlled. Breakdown of these barriers and cellular inflammation are hallmarks of inflammatory as well as ischemic neurological diseases and thus represent potential therapeutic targets. The spatiotemporal relationship between BBB/BNB disruption and leukocyte infiltration has been a matter of debate. We here review contrast-enhanced magnetic resonance imaging (MRI as a non-invasive tool to depict barrier dysfunction and its relation to macrophage infiltration in the central and peripheral nervous system under pathological conditions. Novel experimental contrast agents like Gadofluorine M (Gf allow more sensitive assessment of BBB dysfunction than conventional Gadolinium (Gd-DTPA-enhanced MRI. In addition, Gf facilitates visualization of functional and transient alterations of the BBB remote from lesions. Cellular contrast agents such as superparamagnetic iron oxide particles (SPIO and perfluorocarbons (PFC enable assessment of leukocyte (mainly macrophage infiltration by MR technology. Combined use of these MR contrast agents disclosed that leukocytes can enter the nervous system independent from a disturbance of the BBB, and vice versa, a dysfunctional BBB/BNB by itself is not sufficient to attract inflammatory cells from the circulation. We will illustrate these basic imaging findings in animal models of multiple sclerosis (MS, cerebral ischemia and traumatic nerve injury and review corresponding findings in patients.

A study on the mechanism by which MDMA protects against dopaminergic dysfunction after minimal traumatic brain injury (mTBI) in mice.

Science.gov (United States)

Edut, S; Rubovitch, V; Rehavi, M; Schreiber, S; Pick, C G

2014-12-01

Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI). Experimental mTBI was induced using a concussive head trauma device. One hour before injury, animals were subjected to MDMA. Administration of MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels that were observed in mTBI mice. This normalization was also able to lower the elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived neurotrophic factor (BDNF) levels did not change following injury alone, but in mice subjected to MDMA and mTBI, significant elevations were observed. In the behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was administered prior to injury. Altered catecholamine synthesis and high D2 receptor levels contribute to cognitive dysfunction, and strategies to normalize TH signaling and D2 levels may provide relief for the deficits observed after injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing regular dopamine system activity. While the beneficial effect we observe was due to a dangerous recreational drug, understanding the alterations in dopamine and the mechanism of dysfunction at a cellular level can lead to legal therapies and potential candidates for clinical use.

Nuclear medicine imaging technique in the erectile dysfunction evaluation: a mini-review

International Nuclear Information System (INIS)

Ribeiro, Camila Godinho; Moura, Regina; Neves, Rosane de Figueiredo; Spinosa, Jean Pierre; Bernardo-Filho, Mario

2007-01-01

Functional imaging with positron emission tomography and single photon emission computed tomography is capable of visualizing subtle changes in physiological function in vivo. Erectile dysfunction (ED) diminishes quality of life for affected men and their partners. Identification of neural substrates may provide information regarding the pathophysiology of types of sexual dysfunction originating in the brain. The aim of this work is to verify the approaches of the nuclear medicine techniques in the evaluation of the erectile function/dysfunction. A search using the words ED and nuclear medicine, ED and scintigraphy, ED and SPECT and ED and PET was done in the PubMed. The number of citations in each subject was determined. Neuroimaging techniques offer insight into brain regions involved in sexual arousal and inhibition. To tackle problems such as hyposexual disorders or ED caused by brain disorders, it is crucial to understand how the human brain controls sexual arousal and penile erection. (author)

Nuclear medicine imaging technique in the erectile dysfunction evaluation: a mini-review

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Camila Godinho; Moura, Regina; Neves, Rosane de Figueiredo [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Lab. de Radiofarmacia Experimental]. E-mail: cacagr@yahoo.com.br; Spinosa, Jean Pierre [Hopital de Zone, Morges (Switzerland). Dept. of Gynecology and Obstetrics; Bernardo-Filho, Mario [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil). Coordenadoria de Pesquisa

2007-09-15

Functional imaging with positron emission tomography and single photon emission computed tomography is capable of visualizing subtle changes in physiological function in vivo. Erectile dysfunction (ED) diminishes quality of life for affected men and their partners. Identification of neural substrates may provide information regarding the pathophysiology of types of sexual dysfunction originating in the brain. The aim of this work is to verify the approaches of the nuclear medicine techniques in the evaluation of the erectile function/dysfunction. A search using the words ED and nuclear medicine, ED and scintigraphy, ED and SPECT and ED and PET was done in the PubMed. The number of citations in each subject was determined. Neuroimaging techniques offer insight into brain regions involved in sexual arousal and inhibition. To tackle problems such as hyposexual disorders or ED caused by brain disorders, it is crucial to understand how the human brain controls sexual arousal and penile erection. (author)

Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity.

Science.gov (United States)

Oktar, Süleyman; Ilhan, Selçuk; Meydan, Sedat; Aydin, Mehmet; Yönden, Zafer; Gökçe, Ahmet

2010-01-01

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.

Complications of ventriculoperitoneal shunt in hydrocephalic children

African Journals Online (AJOL)

on the right inguinal and lumber regions were found. His laboratory ... bowel loops with air–fluid levels and left renal agenesis. The peritoneal ... computed tomography of the brain to assess change in ventricular size .... Laparoscopic versus.

Gadolinium-based Contrast Agent Accumulates in the Brain Even in Subjects without Severe Renal Dysfunction: Evaluation of Autopsy Brain Specimens with Inductively Coupled Plasma Mass Spectroscopy.

Science.gov (United States)

Kanda, Tomonori; Fukusato, Toshio; Matsuda, Megumi; Toyoda, Keiko; Oba, Hiroshi; Kotoku, Jun'ichi; Haruyama, Takahiro; Kitajima, Kazuhiro; Furui, Shigeru

2015-07-01

To use inductively coupled plasma mass spectroscopy (ICP-MS) to evaluate gadolinium accumulation in brain tissues, including the dentate nucleus (DN) and globus pallidus (GP), in subjects who received a gadolinium-based contrast agent (GBCA). Institutional review board approval was obtained for this study. Written informed consent for postmortem investigation was obtained either from the subject prior to his or her death or afterward from the subject's relatives. Brain tissues obtained at autopsy in five subjects who received a linear GBCA (GBCA group) and five subjects with no history of GBCA administration (non-GBCA group) were examined with ICP-MS. Formalin-fixed DN tissue, the inner segment of the GP, cerebellar white matter, the frontal lobe cortex, and frontal lobe white matter were obtained, and their gadolinium concentrations were measured. None of the subjects had received a diagnosis of severely compromised renal function (estimated glomerular filtration rate brain regions. Gadolinium was detected in all specimens in the GBCA agent group (mean, 0.25 µg per gram of brain tissue ± 0.44 [standard deviation]), with significantly higher concentrations in each region (P = .004 vs the non-GBCA group for all regions). In the GBCA group, the DN and GP showed significantly higher gadolinium concentrations (mean, 0.44 µg/g ± 0.63) than other regions (0.12 µg/g ± 0.16) (P = .029). Even in subjects without severe renal dysfunction, GBCA administration causes gadolinium accumulation in the brain, especially in the DN and GP.

SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats.

Science.gov (United States)

Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Kerdphoo, Sasiwan; Jaiwongkam, Thidarat; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-10-15

Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks. At week 13, the HFD-fed rats were divided into four subgroups (n=8/subgroup) to receive either a vehicle, vildagliptin (3mg/kg/day) dapagliflozin (1mg/kg/day) or combined drugs for four weeks. ND rats were given a vehicle for four weeks. Metabolic parameters and brain function were investigated. The results demonstrated that HFD rats developed obese-insulin resistance and cognitive decline. Dapagliflozin had greater efficacy on improved peripheral insulin sensitivity and reduced weight gain than vildagliptin. Single therapy resulted in equally improved brain mitochondrial function, insulin signaling, apoptosis and prevented cognitive decline. However, only dapagliflozin improved hippocampal synaptic plasticity. A combination of the drugs had greater efficacy in improving brain insulin sensitivity and reducing brain oxidative stress than the single drug therapy. These findings suggested that dapagliflozin and vildagliptin equally prevented cognitive decline in the obese-insulin resistance, possibly through some similar mechanisms. Dapagliflozin had greater efficacy than vildagliptin for preserving synaptic plasticity, thus combined drugs could be the best therapeutic approach for neuroprotection in the obese-insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Subjective cognitive dysfunction in rehabilitation outpatients with musculoskeletal disorders or chronic pain

NARCIS (Netherlands)

Schrier, Ernst; Geertzen, Jan H.; Dijkstra, Pieter U.

BACKGROUND: Rehabilitation patients, without brain damage, sometimes complain about poor concentration and problems with their memory. The magnitude and associations, of this cognitive dysfunction, with different factors is unclear. AIM: To determine the magnitude of cognitive dysfunction in

Prefrontal Cortex Dysfunction in Fragile X Mice Depends on the Continued Absence of Fragile X Mental Retardation Protein in the Adult Brain.

Science.gov (United States)

Siegel, Jennifer J; Chitwood, Raymond A; Ding, James M; Payne, Clayton; Taylor, William; Gray, Richard; Zemelman, Boris V; Johnston, Daniel

2017-08-02

Fragile X Syndrome (FX) is generally considered a developmental disorder, arising from a mutation that disrupts the transcription of Fragile X Mental Retardation Protein (FMRP). However, FMRP regulates the transcription of other proteins and participates in an unknown number of protein-protein interactions throughout life. In addition to known developmental issues, it is thus likely that some dysfunction is also due to the ongoing absence of FMRP. Dissociating dysfunction due to developmental dysregulation from dysfunction due to the continued absence of FMRP is necessary to understand the different roles of FMRP and to treat patients effectively throughout life. We show here that FX model mice display substantial deficits in a PFC-dependent task. We then use conditional knock-out mice to eliminate FMRP only in the PFC alone of adult mice. We observe an increase in the proportion of nonlearners and a delay in the onset of learning in both FX and conditional knock-out mice. The results suggest that these deficits (1) are due to the absence of FMRP in the PFC alone and (2) are not the result of developmental dysregulation. Furthermore, PFC-associated deficits are rescued by initiating production of FMRP in adult conditional restoration mice, suggesting that PFC dysfunction may persist as long as FMRP is absent and therefore can be rescued after development. The data suggest that it is possible to dissociate the roles of FMRP in neural function from developmental dysregulation, and that PFC function can be restored in the adult FX brain. SIGNIFICANCE STATEMENT The absence of Fragile X Mental Retardation Protein (FMRP) from birth results in developmental disabilities and lifelong impairments. We show here that in mouse models PFC dysfunction in Fragile X Syndrome (FX) can be attributed to the continued absence of FMRP from the PFC, independent of FMRP status during development. Furthermore, initiation of FMRP production in the PFC of adult FX animals rescues PFC

Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

Directory of Open Access Journals (Sweden)

Ryuji Sakakibara

2011-01-01

Full Text Available Bladder dysfunction (urinary urgency/frequency, bowel dysfunction (constipation, and sexual dysfunction (erectile dysfunction (also called “pelvic organ” dysfunctions are common nonmotor disorders in Parkinson's disease (PD. In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

Bladder, bowel, and sexual dysfunction in Parkinson's disease.

Science.gov (United States)

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and "prokinetic" drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

Neuron-specific regulation of class I PI3K catalytic subunits and their dysfunction in brain disorders

Directory of Open Access Journals (Sweden)

Christina eGross

2014-02-01

Full Text Available The PI3K complex plays important roles in virtually all cells of the body. The enzymatic activity of PI3K to phosphorylate phosphoinositides in the membrane is mediated by a group of catalytic and regulatory subunits. Among those, the class I catalytic subunits, p110α, p110β, p110γ and p110δ, have recently drawn attention in the neuroscience field due to their specific dysregulation in diverse brain disorders. While in non-neuronal cells these catalytic subunits may have partially redundant functions, there is increasing evidence that in neurons their roles are more specialized, and confined to distinct receptor-dependent pathways. This review will summarize the emerging role of class I PI3K catalytic subunits in neurotransmitter-regulated neuronal signaling, and their dysfunction in a variety of neurological diseases, including fragile X syndrome, schizophrenia and epilepsy. We will discuss recent literature describing the use of PI3K subunit-selective inhibitors to rescue brain disease-associated phenotypes in in vitro and animal models. These studies give rise to the exciting prospect that these drugs, originally designed for cancer treatment, may be repurposed as therapeutic drugs for brain disorders in the future.

Frontal brain asymmetry in adult attention-deficit/hyperactivity disorder (ADHD): extending the motivational dysfunction hypothesis.

Science.gov (United States)

Keune, Philipp M; Wiedemann, Eva; Schneidt, Alexander; Schönenberg, Michael

2015-04-01

Attention-deficit/hyperactivity disorder (ADHD) involves motivational dysfunction, characterized by excessive behavioral approach tendencies. Frontal brain asymmetry in the alpha band (8-13 Hz) in resting-state electroencephalogram (EEG) represents a neural correlate of global motivational tendencies, and abnormal asymmetry, indicating elevated approach motivation, was observed in pediatric and adult patients. To date, the relation between ADHD symptoms, depression and alpha asymmetry, its temporal metric properties and putative gender-specificity remain to be explored. Adult ADHD patients (n=52) participated in two resting-state EEG recordings, two weeks apart. Asymmetry measures were aggregated across recordings to increase trait specificity. Putative region-specific associations between asymmetry, ADHD symptoms and depression, its gender-specificity and test-retest reliability were examined. ADHD symptoms were associated with approach-related asymmetry (stronger relative right-frontal alpha power). Approach-related asymmetry was pronounced in females, and also associated with depression. The latter association was mediated by ADHD symptoms. Test-retest reliability was sufficient. The association between reliably assessable alpha asymmetry and ADHD symptoms supports the motivational dysfunction hypothesis. ADHD symptoms mediating an atypical association between asymmetry and depression may be attributed to depression arising secondary to ADHD. Gender-specific findings require replication. Frontal alpha asymmetry may represent a new reliable marker of ADHD symptoms. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

ABCD1 dysfunction alters white matter microvascular perfusion

DEFF Research Database (Denmark)

Lauer, Arne; Da, Xiao; Hansen, Mikkel Bo

2017-01-01

Cerebral X-linked adrenoleukodystrophy is a devastating neurodegenerative disorder caused by mutations in the ABCD1 gene, which lead to a rapidly progressive cerebral inflammatory demyelination in up to 60% of affected males. Selective brain endothelial dysfunction and increased permeability...... of the blood–brain barrier suggest that white matter microvascular dysfunction contributes to the conversion to cerebral disease. Applying a vascular model to conventional dynamic susceptibility contrast magnetic reson- ance perfusion imaging, we demonstrate that lack of ABCD1 function causes increased...... capillary flow heterogeneity in asymptom- atic hemizygotes predominantly in the white matter regions and developmental stages with the highest probability for conversion to cerebral disease. In subjects with ongoing inflammatory demyelination we observed a sequence of increased capillary flow hetero...

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance

Science.gov (United States)

Tan, Chin Lik; Alavi, Seyed Alireza; Baldeweg, Stephanie E; Belli, Antonio; Carson, Alan; Feeney, Claire; Goldstone, Anthony P; Greenwood, Richard; Menon, David K; Simpson, Helen L; Toogood, Andrew A; Gurnell, Mark; Hutchinson, Peter J

2017-01-01

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines. PMID:28860331

Brain-Heart Interaction: Cardiac Complications After Stroke.

Science.gov (United States)

Chen, Zhili; Venkat, Poornima; Seyfried, Don; Chopp, Michael; Yan, Tao; Chen, Jieli

2017-08-04

Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction; clinical biomarkers and manifestations of cardiac complications; and underlying mechanisms of brain-heart interaction after stroke, such as the hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic and parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, and systemic inflammation, are discussed. © 2017 American Heart Association, Inc.

Dysfunctional involvement of emotion and reward brain regions on social decision making in excess weight adolescents.

Science.gov (United States)

Verdejo-García, Antonio; Verdejo-Román, Juan; Rio-Valle, Jacqueline S; Lacomba, Juan A; Lagos, Francisco M; Soriano-Mas, Carles

2015-01-01

Obese adolescents suffer negative social experiences, but no studies have examined whether obesity is associated with dysfunction of the social brain or whether social brain abnormalities relate to disadvantageous traits and social decisions. We aimed at mapping functional activation differences in the brain circuitry of social decision making in adolescents with excess versus normal weight, and at examining whether these separate patterns correlate with reward/punishment sensitivity, disordered eating features, and behavioral decisions. In this fMRI study, 80 adolescents aged 12 to 18 years old were classified in two groups based on age adjusted body mass index (BMI) percentiles: normal weight (n = 44, BMI percentiles 5th-84th) and excess weight (n = 36, BMI percentile ≥ 85th). Participants were scanned while performing a social decision-making task (ultimatum game) in which they chose to "accept" or "reject" offers to split monetary stakes made by another peer. Offers varied in fairness (Fair vs. Unfair) but in all cases "accepting" meant both players win the money, whereas "rejecting" meant both lose it. We showed that adolescents with excess weight compared to controls display significantly decreased activation of anterior insula, anterior cingulate, and midbrain during decisions about Unfair versus Fair offers. Moreover, excess weight subjects show lower sensitivity to reward and more maturity fears, which correlate with insula activation. Indeed, blunted insula activation accounted for the relationship between maturity fears and acceptance of unfair offers. Excess weight adolescents have diminished activation of brain regions essential for affective tracking of social decision making, which accounts for the association between maturity fears and social decisions. © 2014 Wiley Periodicals, Inc.

Congenital hydrocephalus following X-irradiation of pregnant rats on an early gestational day

International Nuclear Information System (INIS)

Takeuchi, I.K.; Takeuchi, Y.K.

1986-01-01

When pregnant rats were X-irradiated at a dose of 100 R on gestational day 9.5, a considerable number of postnatally-viable hydrocephalic offspring resulted, all of which were accompanied with bilateral micro- or anophthalmia. Histological studies revealed that the cerebral aqueduct of the congenital hydrocephalic brain was severely stenosed, and the subcommissural organ was reduced in size and displaced at some distance from the anterior end of the cerebral aqueduct. From embryological studies, it was considered that the maldevelopment of the subcommissural organ in the X-irradiated fetus might cause a reduction in the amount of its secretions which function as a cushion preventing complete closure of the cerebral aqueduct during fetal life, resulting in stenosis of the cerebral aqueduct

Hypopituitarism after acute brain injury.

Science.gov (United States)

Urban, Randall J

2006-07-01

Acute brain injury has many causes, but the most common is trauma. There are 1.5-2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding 10 billion dollars. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30-40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7-21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.

Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction.

Science.gov (United States)

Reis, Patricia A; Alexandre, Pedro C B; D'Avila, Joana C; Siqueira, Luciana D; Antunes, Barbara; Estato, Vanessa; Tibiriça, Eduardo V; Verdonk, Franck; Sharshar, Tarek; Chrétien, Fabrice; Castro-Faria-Neto, Hugo C; Bozza, Fernando A

2017-02-01

Acute brain dysfunction is a frequent condition in sepsis patients and is associated with increased mortality and long-term neurocognitive consequences. Impaired memory and executive function are common findings in sepsis survivors. Although neuroinflammation and blood-brain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. Experimental sepsis was induced in Swiss Webster mice by intraperitoneal injection of cecal material (5mg/kg, 500μL). Control groups (n=5/group each experiment) received 500μL of saline. Support therapy recover (saline 0.9%, 1mL and imipenem 30mg/kg) were applied (6, 24 and 48h post injection, n=5-10/group, each experiment), together or not with additive orally treatment with statins (atorvastatin/simvastatin 20mg/kg b.w.). Survival rate was monitored at 6, 24 and 48h. In a setting of experiments, animals were euthanized at 6 and 24h after induction for biochemical, immunohistochemistry and intravital analysis. Statins did not prevented mortality in septic mice, however survivors presented lower clinical score. At another setting of experiments, after 15days, mice survivors from fecal supernatant peritoneal sepsis presented cognitive dysfunction for contextual hippocampal and aversive amygdala-dependent memories, which was prevented by atorvastatin/simvastatin treatment. Systemic and brain tissue levels of proinflammatory cytokines/chemokines and activation of microglial were lower in septic mice treated with statins. Brain lipid peroxidation and myeloperoxidase levels were also reduced by statins treatment. Intravital examination of the brain vessels of septic animals revealed decreased functional capillary density and increased rolling and adhesion of leukocytes, and blood flow impairment, which were reversed by treatment with statins. In addition, treatment with statins restored the cholinergic vasodilator response

Abnormal brain structure as a potential biomarker for venous erectile dysfunction: evidence from multimodal MRI and machine learning.

Science.gov (United States)

Li, Lingli; Fan, Wenliang; Li, Jun; Li, Quanlin; Wang, Jin; Fan, Yang; Ye, Tianhe; Guo, Jialun; Li, Sen; Zhang, Youpeng; Cheng, Yongbiao; Tang, Yong; Zeng, Hanqing; Yang, Lian; Zhu, Zhaohui

2018-03-29

To investigate the cerebral structural changes related to venous erectile dysfunction (VED) and the relationship of these changes to clinical symptoms and disorder duration and distinguish patients with VED from healthy controls using a machine learning classification. 45 VED patients and 50 healthy controls were included. Voxel-based morphometry (VBM), tract-based spatial statistics (TBSS) and correlation analyses of VED patients and clinical variables were performed. The machine learning classification method was adopted to confirm its effectiveness in distinguishing VED patients from healthy controls. Compared to healthy control subjects, VED patients showed significantly decreased cortical volumes in the left postcentral gyrus and precentral gyrus, while only the right middle temporal gyrus showed a significant increase in cortical volume. Increased axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) values were observed in widespread brain regions. Certain regions of these alterations related to VED patients showed significant correlations with clinical symptoms and disorder durations. Machine learning analyses discriminated patients from controls with overall accuracy 96.7%, sensitivity 93.3% and specificity 99.0%. Cortical volume and white matter (WM) microstructural changes were observed in VED patients, and showed significant correlations with clinical symptoms and dysfunction durations. Various DTI-derived indices of some brain regions could be regarded as reliable discriminating features between VED patients and healthy control subjects, as shown by machine learning analyses. • Multimodal magnetic resonance imaging helps clinicians to assess patients with VED. • VED patients show cerebral structural alterations related to their clinical symptoms. • Machine learning analyses discriminated VED patients from controls with an excellent performance. • Machine learning classification provided a preliminary demonstration of DTI

Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

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Brandi D Freeman

2016-03-01

Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

Cocaine users with comorbid Cluster B personality disorders show dysfunctional brain activation and connectivity in the emotional regulation networks during negative emotion maintenance and reappraisal.

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Albein-Urios, Natalia; Verdejo-Román, Juan; Soriano-Mas, Carles; Asensio, Samuel; Martínez-González, José Miguel; Verdejo-García, Antonio

2013-12-01

Cocaine dependence often co-occurs with Cluster B personality disorders. Since both disorders are characterized by emotion regulation deficits, we predicted that cocaine comorbid patients would exhibit dysfunctional patterns of brain activation and connectivity during reappraisal of negative emotions. We recruited 18 cocaine users with comorbid Cluster B personality disorders, 17 cocaine users without comorbidities and 21 controls to be scanned using functional magnetic resonance imaging (fMRI) during performance on a reappraisal task in which they had to maintain or suppress the emotions induced by negative affective stimuli. We followed region of interest (ROI) and whole-brain approaches to investigate brain activations and connectivity associated with negative emotion experience and reappraisal. Results showed that cocaine users with comorbid personality disorders had reduced activation of the subgenual anterior cingulate cortex during negative emotion maintenance and increased activation of the lateral orbitofrontal cortex and the amygdala during reappraisal. Amygdala activation correlated with impulsivity and antisocial beliefs in the comorbid group. Connectivity analyses showed that in the cocaine comorbid group the subgenual cingulate was less efficiently connected with the amygdala and the fusiform gyri and more efficiently connected with the anterior insula during maintenance, whereas during reappraisal the left orbitofrontal cortex was more efficiently connected with the amygdala and the right orbitofrontal cortex was less efficiently connected with the dorsal striatum. We conclude that cocaine users with comorbid Cluster B personality disorders have distinctive patterns of brain activation and connectivity during maintenance and reappraisal of negative emotions, which correlate with impulsivity and dysfunctional beliefs. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Focusing on symptoms rather than diagnoses in brain dysfunction: conscious and nonconscious expression in impulsiveness and decision-making.

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Palomo, T; Beninger, R J; Kostrzewa, R M; Archer, T

2008-08-01

Symptoms and syndromes in neuropathology, whether expressed in conscious or nonconscious behaviour, remain imbedded in often complex diagnostic categories. Symptom-based strategies for studying brain disease states are driven by assessments of presenting symptoms, signs, assay results, neuroimages and biomarkers. In the present account, symptom-based strategies are contrasted with existing diagnostic classifications. Topics include brain areas and regional circuitry underlying decision-making and impulsiveness, and motor and learned expressions of explicit and implicit processes. In three self-report studies on young adult and adolescent healthy individuals, it was observed that linear regression analyses between positive and negative affect, self-esteem, four different types of situational motivation: intrinsic, identified regulation, extrinsic regulation and amotivation, and impulsiveness predicted significant associations between impulsiveness with negative affect and lack of motivation (i.e., amotivation) and internal locus of control, on the one hand, and non-impulsiveness with positive affect, self-esteem, and high motivation (i.e., intrinsic motivation and identified regulation), on the other. Although presymptomatic, these cognitive-affective characterizations illustrate individuals' choice behaviour in appraisals of situations, events and proclivities essentially of distal perspective. Neuropathological expressions provide the proximal realities of symptoms and syndromes with underlying dysfunctionality of brain regions, circuits and molecular mechanisms.

Is cerebral glucose metabolism related to blood-brain barrier dysfunction and intrathecal IgG synthesis in Alzheimer disease?: A 18F-FDG PET/CT study.

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Chiaravalloti, Agostino; Fiorentini, Alessandro; Ursini, Francesco; Martorana, Alessandro; Koch, Giacomo; Belli, Lorena; Toniolo, Sofia; Di Pietro, Barbara; Motta, Caterina; Schillaci, Orazio

2016-09-01

The aim of this study was to investigate the relationships between blood-brain barrier (BBB) dysfunction, intrathecal IgG synthesis, and brain glucose consumption as detectable by means of serum/cerebrospinal fluid (CSF) albumin index (Qalb) and IgG index [(CSF IgG/serum IgG) × Serum albumin/CSF albumin)] and 2-deoxy-2-(F) fluoro-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in a selected population affected by Alzheimer disease (AD). The study included 134 newly diagnosed AD patients according to the NINCDS-ADRDA criteria. The mean (±SD) age of the patients was 70 (±6) years; 60 were male and 64 were female. Mini mental State Examination was equal to 18.9 (±7.2). All patients underwent a CSF assay and magnetic resonance before F-FDG PET scanning. The relationships were evaluated by means of statistical parametric mapping (SPM8). We found a significant negative correlation between the increase of Qalb and F-FDG uptake in the Brodmann Area 42 and 22 that corresponds to the left superior temporal gyrus, with higher Qalb values being related to a reduced glucose consumption in these areas. No significant relationships have been found between brain glucose consumption and IgG index. The results of our study suggest that BBB dysfunction is related to reduction of cortical activity in the left temporal cortex in AD subjects.

Cognitive dysfunction in Multiple Sclerosis

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Joana eGuimarães

2012-05-01

Full Text Available In Multiple Sclerosis (MS prevalence studies of community and clinical samples, indicate that 45–60% of patients are cognitively impaired. These cognitive dysfunctions have been traditionally described as heterogeneous, but more recent studies suggest that there is a specific pattern of MS-related cognitive dysfunctions. With the advent of disease-modifying medications for MS and emphasis on early intervention and treatment, detection of cognitive impairment at its earliest stage becomes particularly important. In this review the authors address: the cognitive domains most commonly impaired in MS (memory, attention, executive functions, speed of information processing and visual spatial abilities; the physiopathological mechanism implied in MS cognitive dysfunction and correlated brain MRI features; the importance of neuropsychological assessment of MS patients in different stages of the disease and the influence of its course on cognitive performance; the most used tests and batteries for neuropsychological assessment; therapeutic strategies to improve cognitive abilities.

Bridging disparate symptoms of schizophrenia: a Triple network dysfunction theory

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Tereza eNekovarova

2014-05-01

Full Text Available Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. Yet, the etiology of this disorder has yet to be fully understood.Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of triple brain network model of the dysfunctional switching between default mode and central executive network related to the aberrant activity of salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of SELF (self-awareness and self-representation and theory of mind (ToM dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of SELF and ToM in schizophrenia together with neuroimaging data elucidating the triple brain network model as a common neuronal substrate of this dysfunction.

Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease.

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Kanae Iijima-Ando

2009-12-01

Full Text Available The amyloid-beta 42 (Abeta42 is thought to play a central role in the pathogenesis of Alzheimer's disease (AD. However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. In contrast, organization of microtubule or global axonal transport was not significantly altered at this stage. Abeta42-induced behavioral defects were exacerbated by genetic reductions in mitochondrial transport, and were modulated by cAMP levels and PKA activity. Levels of putative PKA substrate phosphoproteins were reduced in the Abeta42 fly brains. Importantly, perturbations in mitochondrial transport in neurons were sufficient to disrupt PKA signaling and induce late-onset behavioral deficits, suggesting a mechanism whereby mitochondrial mislocalization contributes to Abeta42-induced neuronal dysfunction. These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Abeta42 in vivo.

CD40-CD40 Ligand Pathway is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis.

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Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall'Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

2015-03-26

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40-CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40-CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40-CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40-CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis.

Brain imaging and schizophrenia

International Nuclear Information System (INIS)

Martinot, J.L.; Dao-Castellana, M.H.

1991-01-01

Brain structures and brain function have been investigated by the new brain imaging techniques for more than ten years. In Psychiatry, these techniques could afford a new understanding of mental diseases. In schizophrenic patients, CAT scanner and RMI pointed out statistically significant ventricular enlargments which are presently considered as evidence for abnormalities in brain maturation. Functional imaging techniques reported metabolic dysfunctions in the cortical associative areas which are probably linked to the cognitive features of schizophrenics [fr

Unravelling and Exploiting Astrocyte Dysfunction in Huntington's Disease

DEFF Research Database (Denmark)

Khakh, Baljit S.; Beaumont, Vahri; Cachope, Roger

2017-01-01

Astrocytes are abundant within mature neural circuits and are involved in brain disorders. Here, we summarize our current understanding of astrocytes and Huntington's disease (HD), with a focus on correlative and causative dysfunctions of ion homeostasis, calcium signaling, and neurotransmitter...

Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease.

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Gu, Xue-Mei; Huang, Han-Chang; Jiang, Zhao-Feng

2012-10-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathology of AD includes amyloid-β (Aβ) deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau, as well as neuronal loss in specific brain regions. Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease. Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ, accumulation of which might interfere with the homeostasis of cellular metabolism. Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis. Mitochondrial dysfunction might contribute to Aβ neurotoxicity. In this review, we summarize the pathways of Aβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.

Further Commentary on Mitochondrial Dysfunction in Autism Spectrum Disorder: Assessment and Treatment Considerations

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Dager, Stephen R.; Corrigan, Neva M.; Estes, Annette; Shaw, Dennis W. W.

2012-01-01

The authors respond to a recent letter (Rossignol and Frye 2011) critical of their paper, "Proton magnetic resonance spectroscopy and MRI reveal no evidence for brain mitochondrial dysfunction in children with autism spectrum disorder" (Corrigan et al. 2011). Further considerations regarding the assessment of mitochondrial dysfunction in autism…

Piracetam improves mitochondrial dysfunction following oxidative stress

Science.gov (United States)

Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

2005-01-01

Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. Piracetam treatment at concentrations between 100 and 1000 μM improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 μM) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. Piracetam treatment (100–500 mg kg−1 daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients. PMID:16284628

Both oophorectomy and obesity impaired solely hippocampal-dependent memory via increased hippocampal dysfunction.

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Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2018-04-17

Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.

Postoperative cognitive dysfunction : Involvement of neuroinflammation and neuronal functioning

NARCIS (Netherlands)

Hovens, Iris B.; Schoemaker, Regien G.; van der Zee, Eddy A.; Absalom, Anthony R.; Heineman, Erik; van Leeuwen, Barbara L.

Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway.

Relationship of mechanical impact magnitude to neurologic dysfunction severity in a rat traumatic brain injury model.

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Tsung-Hsun Hsieh

Full Text Available Traumatic brain injury (TBI is a major brain injury type commonly caused by traffic accidents, falls, violence, or sports injuries. To obtain mechanistic insights about TBI, experimental animal models such as weight-drop-induced TBI in rats have been developed to mimic closed-head injury in humans. However, the relationship between the mechanical impact level and neurological severity following weight-drop-induced TBI remains uncertain. In this study, we comprehensively investigated the relationship between physical impact and graded severity at various weight-drop heights.The acceleration, impact force, and displacement during the impact were accurately measured using an accelerometer, a pressure sensor, and a high-speed camera, respectively. In addition, the longitudinal changes in neurological deficits and balance function were investigated at 1, 4, and 7 days post TBI lesion. The inflammatory expression markers tested by Western blot analysis, including glial fibrillary acidic protein, beta-amyloid precursor protein, and bone marrow tyrosine kinase gene in chromosome X, in the frontal cortex, hippocampus, and corpus callosum were investigated at 1 and 7 days post-lesion.Gradations in impact pressure produced progressive degrees of injury severity in the neurological score and balance function. Western blot analysis demonstrated that all inflammatory expression markers were increased at 1 and 7 days post-impact injury when compared to the sham control rats. The severity of neurologic dysfunction and induction in inflammatory markers strongly correlated with the graded mechanical impact levels.We conclude that the weight-drop-induced TBI model can produce graded brain injury and induction of neurobehavioral deficits and may have translational relevance to developing therapeutic strategies for TBI.

Caregiver ratings of long-term executive dysfunction and attention problems after early childhood traumatic brain injury: family functioning is important.

Science.gov (United States)

Kurowski, Brad G; Taylor, H Gerry; Yeates, Keith Owen; Walz, Nicolay C; Stancin, Terry; Wade, Shari L

2011-09-01

To evaluate the relationship of family and parenting factors to long-term executive dysfunction and attention problems after early childhood traumatic brain injury (TBI). We hypothesized that the magnitude of executive dysfunction and attention problems would be moderated by family and parenting factors. A multicenter, prospective cohort study that included an orthopedic injury (OI) reference group. Three tertiary academic children's hospital medical centers and one general medical center. Children, ages 3-7 years, hospitalized for OI, moderate TBI, or severe TBI. METHODS AND OUTCOME MEASUREMENTS: Parental ratings of family functioning and parenting styles were obtained 18 months after the injury occurred. The main outcome measurements, which were parental ratings of children's executive function and attention, were performed at least 24 months after the injury occurred (mean, 39 months; range, 25-63 months). Group comparisons were conducted with use of t-tests, χ(2) analysis, analysis of variance, and Pearson and Spearman correlations. Regression analysis was used to examine associations of the outcomes with family functioning and parenting styles and to test moderating effects of these factors on group differences. Participants with severe TBI demonstrated increased executive dysfunction and attention problems compared with those who sustained moderate TBI or OI. Lower levels of family dysfunction were associated with better executive function and attention across groups but did not moderate group differences. However, attention deficits after severe TBI were exacerbated under conditions of more permissive parenting relative to attention deficits after OIs. Executive function and attention problems persisted on a long-term basis (>24 months) after early childhood TBI, and positive global family functioning and nonpermissive parenting were associated with better outcomes. Better characterization of the optimal family environment for recovery from early childhood

Thermodynamic laws apply to brain function.

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Salerian, Alen J

2010-02-01

Thermodynamic laws and complex system dynamics govern brain function. Thus, any change in brain homeostasis by an alteration in brain temperature, neurotransmission or content may cause region-specific brain dysfunction. This is the premise for the Salerian Theory of Brain built upon a new paradigm for neuropsychiatric disorders: the governing influence of neuroanatomy, neurophysiology, thermodynamic laws. The principles of region-specific brain function thermodynamics are reviewed. The clinical and supporting evidence including the paradoxical effects of various agents that alter brain homeostasis is demonstrated.

Brain dysfunctions in Wistar rats exposed to municipal landfill leachates

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Chibuisi G. Alimba

2015-12-01

Full Text Available Brain damage induced by Olusosun and Aba-Eku municipal landfill leachates was investigated in Wistar rats. Male rats were orally exposed to 1–25% concentrations of the leachates for 30 days. Catalase (CAT and superoxide dismutase (SOD activities, and malondialdehyde (MDA concentrations in the brain and serum of rats were evaluated; body and brain weight gain and histopathology were examined. There was significant (p < 0.05 decrease in body weight gain and SOD activity but increase in absolute and relative brain weight gain, MDA concentration and CAT activity in both brain and serum of treated rats. The biochemical parameters, which were more altered in the brain than serum, corroborated the neurologic lesions; neurodegeneration of purkinje cells with loss of dendrites, perineural vacuolations of the neuronal cytoplasm (spongiosis and neuronal necrosis in the brain. The concentrations of Cr, Cu, Pb, As, Cd, Mn, Ni, sulphates, ammonia, chloride and phosphate in the leachate samples were above standard permissible limits. The interactions of the neurotoxic constituents of the leachates induced the observed brain damage in the rats via oxidative damage. This suggests health risk in wildlife and human populations.

A Case of Primary Central Nervous System Lymphoma Located at Brain Stem in a Child.

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Kim, Jinho; Kim, Young Zoon

2016-10-01

Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis.

ANP, BNP and D-dimer predict right ventricular dysfunction in patients with acute pulmonary embolism

DEFF Research Database (Denmark)

Borgwardt, Henrik Gutte; Mortensen, Jann; Jensen, Claus V

2010-01-01

The aim of this study was to predict right ventricular dysfunction (RVD) using plasma concentration of D-dimer, pro-atrial natriuretic peptide (pro-ANP), brain natriuretic peptide (BNP), endothelin-1 (ET-1) and cardiac troponin I (TNI) in patients with pulmonary embolism (PE).......The aim of this study was to predict right ventricular dysfunction (RVD) using plasma concentration of D-dimer, pro-atrial natriuretic peptide (pro-ANP), brain natriuretic peptide (BNP), endothelin-1 (ET-1) and cardiac troponin I (TNI) in patients with pulmonary embolism (PE)....

Auditory sensory ("echoic") memory dysfunction in schizophrenia.

Science.gov (United States)

Strous, R D; Cowan, N; Ritter, W; Javitt, D C

1995-10-01

Studies of working memory dysfunction in schizophrenia have focused largely on prefrontal components. This study investigated the integrity of auditory sensory ("echoic") memory, a component that shows little dependence on prefrontal functioning. Echoic memory was investigated in 20 schizophrenic subjects and 20 age- and IQ-matched normal comparison subjects with the use of nondelayed and delayed tone matching. Schizophrenic subjects were markedly impaired in their ability to match two tones after an extremely brief delay between them (300 msec) but were unimpaired when there was no delay between tones. Working memory dysfunction in schizophrenia affects brain regions outside the prefrontal cortex as well as within.

CD40–CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis

Science.gov (United States)

Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall’Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

2015-01-01

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40–CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40–CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40–CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40–CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis. PMID:25822797

Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

International Nuclear Information System (INIS)

Welzel, Grit; Fleckenstein, Katharina; Schaefer, Joerg; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Mai, Sabine K.; Wenz, Frederik

2008-01-01

Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy, prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects

Visual Dysfunction and Associated Co-morbidities as Predictors of Mild Traumatic Brain Injury Seen Among Veterans in Non-VA Facilities: Implications for Clinical Practice.

Science.gov (United States)

Urosevich, Thomas G; Boscarino, Joseph J; Hoffman, Stuart N; Kirchner, H Lester; Figley, Charles R; Adams, Richard E; Withey, Carrie A; Boscarino, Joseph A

2018-05-24

Traumatic brain injury (TBI) and post-traumatic stress disorder are considered the signature injuries of the Iraq and Afghanistan conflicts. With the extensive use of improvised explosive devices by the enemy, the concussive effects from blast have a greater potential to cause mild TBI (mTBI) in military Service Members. These mTBI can be associated with other physical and psychological health problems, including mTBI-induced visual processing and eye movement dysfunctions. Our study assessed if any visual dysfunctions existed in those surveyed in non-Veterans Administration (VA) facilities who had suffered mTBI (concussive effect), in addition to the presence of concussion-related co-morbidities. As part of a larger study involving veterans from different service eras, we surveyed 235 Veterans who had served during the Iraq and/or Afghanistan conflict era. Data for the study were collected using diagnostic telephone interviews of these veterans who were outpatients of the Geisinger Health System. We assess visual dysfunction in this sample and compare visual dysfunctions of those who had suffered a mTBI (concussive effect), as well as co-morbidities, with those in the cohort who had not suffered concussion effects. Of those veterans who experienced visual dysfunctions, our results reflected that the visual symptoms were significant for concussion with the subjects surveyed, even though all had experienced a mTBI event greater than five years ago. Although we did find an association with concussion and visual symptoms, the association for concussion was strongest with the finding of greater than or equal to three current TBI symptoms, therefore we found this to be the best predictor of previous concussion among the veterans. Veterans from the Iraq/Afghanistan era who had suffered concussive blast effects (mTBI) can present with covert visual dysfunction as well as additional physical and psychological health problems. The primary eye care providers, especially

Psychological adaptation to life-threatening injury in dyads: the role of dysfunctional disclosure of trauma

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Laura Pielmaier

2011-12-01

Full Text Available Certain modes of trauma disclosure have been found to be associated with more severe symptoms of posttraumatic stress (PTS in different trauma populations: the reluctance to disclose trauma-related thoughts and feelings, a strong urge to talk about it, and physical as well as emotional reactions during disclosure. Although social-contextual influences gain more and more interest in trauma research, no study has yet investigated these “dysfunctional disclosure tendencies” and their association with PTS from an interpersonal perspective.(1 To replicate previous findings on dysfunctional disclosure tendencies in patients with life-threatening injury and their significant others and (2 to study interpersonal associations between dysfunctional disclosure style and PTS at a dyadic level.PTS symptom severity and self-reports on dysfunctional disclosure tendencies were assessed in N=70 dyads comprising one individual with severe traumatic brain injury and a significant other (“proxy” 3 months after injury.Regression analyses predicting PTS symptom severity revealed dysfunctional disclosure tendencies to have incremental validity above and beyond sex, age, and trauma severity within the individual (both patient and proxy, with moderate effect sizes. The interaction between patient's and proxy's disclosure style explained additional portions of the variance in patients’ PTS symptom severity.Findings suggest that dysfunctional disclosure tendencies are related to poorer psychological adaptation to severe traumatic brain injury. This intrapersonal association may be exacerbated by dysfunctional disclosure tendencies on the part of a significant other. Although the results require replication in other trauma samples without brain injury to further generalize the findings beyond the observed population, the study contributes to the expanding literature on the crucial role of interpersonal relationships in trauma recovery.For the abstract or full

Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus.

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Brooks, W M; Jung, R E; Ford, C C; Greinel, E J; Sibbitt, W L

1999-01-01

To determine the relationship between neurochemical markers of brain injury and brain dysfunction associated with systemic lupus erythematosus (SLE). Patients with SLE (n = 12) were studied using magnetic resonance spectroscopic imaging at 1.5 Tesla to determine neurochemistry and a neurocognitive testing battery to determine brain dysfunction. N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) concentrations were measured in white (WM) and gray (GM) matter and expressed as the ratios NAA/Cho, NAA/Cre, and Cho/Cre. Neurocognitive testing results were expressed as a composite z score. Disease activity was quantified by SLE Disease Activity Index (SLEDAI) and disease injury by Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology Damage Index. Neurochemical measures of brain injury were correlated with neurocognitive testing z scores: NAA/Cho in WM (r = 0.77, p = 0.003) and GM (r = 0.67, p = 0.017); WM Cho/Cre also correlated with total z score (r = -0.74, p = 0.006). Neurometabolite ratios and SLICC were correlated: GM NAA/Cho (r = -0.70, p = 0.011 ) and NAA/Cre (r = -0.71, p = 0.01) and WM Cho/Cre (r = 0.66, p = 0.02). Correlations between neurometabolite ratios and SLEDAI did not reach significance. Brain function is closely correlated with brain injury assessed noninvasively by proton magnetic resonance spectroscopy. This important finding further supports the use of magnetic resonance spectroscopy to evaluate brain injury in SLE.

Mitochondrial dysfunction in obesity.

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de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

2018-01-01

Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence and Pattern of Executive Dysfunction in School Age Children with Congenital Heart Disease

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Sanz, Jacqueline H.; Berl, Madison M.; Armour, Anna C.; Wang, Jichuan; Cheng, Yao I.; Donofrio, Mary T.

2016-01-01

Objective Executive Function, a set of cognitive skills important to social and academic outcomes, is a specific area of cognitive weakness in children with congenital heart disease (CHD). We evaluated the prevalence and profile of executive dysfunction in a heterogeneous sample of school aged children with CHD, examined whether children with executive dysfunction are receiving school services and support, and identified risk factors for executive dysfunction at school age. Design 91 school aged patients completed questionnaires, including the Behavior Rating Inventory of Executive Function (BRIEF) and a medical history questionnaire. An age and gender matched control sample was drawn from a normativedatabase. Results CHD patients had a higher rate of parent reported executive dysfunction (OR=4.37, p0.05). Gender, premature birth (≤37 weeks), and CHD with aortic obstruction were predictive of executive dysfunction, especially for behavior regulation skills. Conclusions School aged children with CHD have an increased prevalence of executive dysfunction, especially problems with working memory and flexibility, and are underserved by the school system. The increased risk for executive dysfunction in those with CHD and prematurity or CHD with aortic obstruction suggests an etiology of delayed brain development in the fetal and neonatal periods, while male gender may increase susceptibility to brain injury. This study highlights the need for regular neurodevelopmental follow up in children with CHD, and a need to better understand mechanisms that contribute to adverse neurodevelopmental outcomes. PMID:27863079

Prevalence and pattern of executive dysfunction in school age children with congenital heart disease.

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Sanz, Jacqueline H; Berl, Madison M; Armour, Anna C; Wang, Jichuan; Cheng, Yao I; Donofrio, Mary T

2017-03-01

Executive function, a set of cognitive skills important to social and academic outcomes, is a specific area of cognitive weakness in children with congenital heart disease (CHD). We evaluated the prevalence and profile of executive dysfunction in a heterogeneous sample of school aged children with CHD, examined whether children with executive dysfunction are receiving school services and support, and identified risk factors for executive dysfunction at school age. Ninety-one school aged patients completed questionnaires, including the Behavior Rating Inventory of Executive Function (BRIEF) and a medical history questionnaire. An age- and gender- matched control sample was drawn from a normative database. Children with CHD had a higher rate of parent reported executive dysfunction (OR = 4.37, P  .05). Gender, premature birth (≤37 weeks), and CHD with aortic obstruction were predictive of executive dysfunction, especially for behavior regulation skills. School aged children with CHD have an increased prevalence of executive dysfunction, especially problems with working memory and flexibility, and are underserved by the school system. The increased risk for executive dysfunction in those with CHD and prematurity or CHD with aortic obstruction suggests an etiology of delayed brain development in the fetal and neonatal periods, while male gender may increase susceptibility to brain injury. This study highlights the need for regular neurodevelopmental follow up in children with CHD, and a need to better understand mechanisms that contribute to adverse neurodevelopmental outcomes. © 2016 Wiley Periodicals, Inc.

Neural Oscillations and Synchrony in Brain Dysfunction and Neuropsychiatric Disorders: It's About Time.

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Mathalon, Daniel H; Sohal, Vikaas S

2015-08-01

Neural oscillations are rhythmic fluctuations over time in the activity or excitability of single neurons, local neuronal populations or "assemblies," and/or multiple regionally distributed neuronal assemblies. Synchronized oscillations among large numbers of neurons are evident in electrocorticographic, electroencephalographic, magnetoencephalographic, and local field potential recordings and are generally understood to depend on inhibition that paces assemblies of excitatory neurons to produce alternating temporal windows of reduced and increased excitability. Synchronization of neural oscillations is supported by the extensive networks of local and long-range feedforward and feedback bidirectional connections between neurons. Here, we review some of the major methods and measures used to characterize neural oscillations, with a focus on gamma oscillations. Distinctions are drawn between stimulus-independent oscillations recorded during resting states or intervals between task events, stimulus-induced oscillations that are time locked but not phase locked to stimuli, and stimulus-evoked oscillations that are both time and phase locked to stimuli. Synchrony of oscillations between recording sites, and between the amplitudes and phases of oscillations of different frequencies (cross-frequency coupling), is described and illustrated. Molecular mechanisms underlying gamma oscillations are also reviewed. Ultimately, understanding the temporal organization of neuronal network activity, including interactions between neural oscillations, is critical for elucidating brain dysfunction in neuropsychiatric disorders.

Treatment approaches for interoceptive dysfunctions in drug addiction.

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Paulus, Martin P; Stewart, Jennifer L; Haase, Lori

2013-10-18

There is emerging evidence that individuals with drug addiction have dysfunctions in brain systems that are important for interoceptive processing, which include, among others, the insular and the anterior cingulate cortices. These individuals may not be expending sufficient neural resources to process perturbations of the interoceptive state but may exert over-activation of these systems when processing drug-related stimuli. As a consequence, insufficient detection and processing of interoceptive state changes may result in inadequate anticipation and preparation to adapt to environmental challenges, e.g., adapt to abstinence in the presence of withdrawal symptoms. Here, we integrate interoceptive dysfunction in drug-addicted individuals, with the neural basis for meditation and exercise to develop a heuristic to target the interoceptive system as potential treatments for drug addiction. First, it is suggested that mindfulness-based approaches can modulate both interoceptive function and insular activation patterns. Second, there is an emerging literature showing that the regulation of physical exercise in the brain involves the insula and anterior cingulate cortex and that intense physical exercise is associated with a insula changes that may provide a window to attenuate the increased interoceptive response to drug-related stimuli. It is concluded that the conceptual framework of interoceptive dysfunctions in drug addiction and the experimental findings in meditation and exercise provide a useful approach to develop new interventions for drug addiction.

Treatment Approaches for Interoceptive Dysfunctions in Drug Addiction

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Martin P Paulus

2013-10-01

Full Text Available There is emerging evidence that individuals with drug addiction have dysfunctions in brain systems that are important for interoceptive processing, which include, among others, the insular and the anterior cingulate cortices. These individuals may not be expending sufficient neural resources to process perturbations of the interoceptive state but may exert over-activation of these systems when processing drug-related stimuli. As a consequence, insufficient detection and processing of interoceptive state changes may result in inadequate anticipation and preparation to adapt to environmental challenges, e.g. adapt to abstinence in the presence of withdrawal symptoms. Here, we integrate interoceptive dysfunction in drug-addicted individuals, with the neural basis for meditation and exercise to develop a heuristic to target the interoceptive system as potential treatments for drug addiction. First, it is suggested that mindfulness-based approaches can modulate both interoceptive function and insular activation patterns. Second, there is an emerging literature that the regulation of physical exercise in the brain involves the insula and anterior cingulate cortex and that intense physical exercise is associated with a state-dependent activation difference in the insula that may provide a window to attenuate the increased interoceptive response drug related stimuli. It is concluded that the conceptual framework of interoceptive dysfunctions in drug addiction and the experimental findings in meditation and exercise provide a useful approach to develop new interventions for drug addiction.

Brain ultrasonographic findings of late-onset circulatory dysfunction due to adrenal insufficiency in preterm infants

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Shin, Su Mi; Chai, Jee Won [Dept. of Radiology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul (Korea, Republic of)

2016-07-15

The aim of this study was to characterize the brain ultrasonographic findings of late-onset circulatory dysfunction (LCD) due to adrenal insufficiency (AI) in preterm infants. Among the 257 preterm infants born at <33 weeks of gestation between December 2009 and February 2014 at our institution, 35 preterm infants were diagnosed with AI. Brain ultrasonographic findings were retrospectively analyzed before and after LCD in 14 preterm infants, after exclusion of the other 21 infants with AI due to the following causes: death (n=2), early AI (n=5), sepsis (n=1), and patent ductus arteriosus (n=13). Fourteen of 257 infants (5.4%) were diagnosed with LCD due to AI. The age at LCD was a median of 18.5 days (range, 9 to 32 days). The last ultrasonographic findings before LCD occurred showed grade 1 periventricular echogenicity (PVE) in all 14 patients and germinal matrix hemorrhage (GMH) with focal cystic change in one patient. Ultrasonographic findings after LCD demonstrated no significant change in grade 1 PVE and no new lesions in eight (57%), grade 1 PVE with newly appearing GMH in three (21%), and increased PVE in three (21%) infants. Five infants (36%) showed new development (n=4) or increased size (n=1) of GMH. Two of three infants (14%) with increased PVE developed cystic periventricular leukomalacia (PVL) and rapid progression to macrocystic encephalomalacia. LCD due to AI may be associated with the late development of GMH, increased PVE after LCD, and cystic PVL with rapid progression to macrocystic encephalomalacia.

Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

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Bock, J; Breuer, S; Poeggel, G; Braun, K

2017-03-01

In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

Alleviation of Kainic Acid-Induced Brain Barrier Dysfunction by 4-O-Methylhonokiol in In Vitro and In Vivo Models

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Jin-Yi Han

2015-01-01

Full Text Available This experiment was designed to investigate whether 4-O-methylhonokiol (MH, a principal ingredient of Magnolia (M. officinalis bark, alleviated acute intraperitoneal (i.p. kainic acid- (KA- induced brain blood barrier dysfunction (BBBD via pathological examination and cytological analyses of the brain tissues of mice. KA (10–30 mg/kg time- and dose-dependently increased the water content of brain tissues and induced edema and encephalopathy. However, pretreatment with MH (5 and 20 mg/kg, i.p. significantly reduced the water content of the brain compared to that observed in the KA control group. Furthermore, MH significantly and dose-dependently reversed the remarkable variations in evan’s blue dye (EBD staining and malondialdehyde (MDA levels that were induced by KA (10 mg/kg, i.p.. MH also decreased the elevated seizure scores that were induced by KA (10 mg/kg, i.p. in mice in a manner similar to scavengers such as DMTU and trolox. Additionally, MH significantly scavenged intracellular ROS and Ca2+ within hippocampal cells. The tight junction seals mediated by claudin (Cld-5 were also found to be modulated by MH. MH efficiently reduced 1,1-diphenyl-2-picrylhydrazyl (DPPH (IC50, 52.4 mM and •OH with an electron spin resonance (ESR signal rate constant of 4×109 M-1·S-1, which is close to the reactivity of the vitamin E analog trolox. Taken together, these results suggest that MH may enhance radical scavenging in lipid and hydrophobic environments, which may be important for the physiological activity of the barrier.

Usefulness of near-infrared spectroscopy to detect brain dysfunction in children with autism spectrum disorder when inferring the mental state of others.

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Iwanaga, Ryoichiro; Tanaka, Goro; Nakane, Hideyuki; Honda, Sumihisa; Imamura, Akira; Ozawa, Hiroki

2013-05-01

The purpose of this study was to examine the usefulness of near-infrared spectroscopy (NIRS) for identifying abnormalities in prefrontal brain activity in children with autism spectrum disorders (ASD) as they inferred the mental states of others. The subjects were 16 children with ASD aged between 8 and 14 years and 16 age-matched healthy control children. Oxygenated hemoglobin concentration was measured in the subject's prefrontal brain region on NIRS during tasks expressing a person's mental state (MS task) and expressing an object's characteristics (OC task). There was a significant main effect of group (ASD vs control), with the control group having more activity than the ASD group. But there was no significant main effect of task (MS task vs OC task) or hemisphere (right vs left). Significant interactions of task and group were found, with the control group showing more activity than the ASD group during the MS task relative to the OC task. NIRS showed that there was lower activity in the prefrontal brain area when children with ASD performed MS tasks. Therefore, clinicians might be able to use NIRS and these tasks for conveniently detecting brain dysfunction in children with ASD related to inferring mental states, in the clinical setting. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Brain Imaging of Human Sexual Response: Recent Developments and Future Directions.

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Ruesink, Gerben B; Georgiadis, Janniko R

2017-01-01

The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Stable patterns of brain activation have been established for different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From this solid basis, connectivity studies of the human sexual response have begun to add a deeper understanding of the brain network function and structure involved. The study of "sexual" brain connectivity is still very young. Yet, by approaching the brain as a connected organ, the essence of brain function is captured much more accurately, increasing the likelihood of finding useful biomarkers and targets for intervention in sexual dysfunction.

COGNITIVE DYSFUNCTIONS IN DIABETIC POLYNEUROPATHY

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Mirena Valkova

2011-12-01

Full Text Available Introduction: The objective of our study was to examine cognitive status, short – term memory, delayed recall and the retention of visual information in diabetics with polyneuropathy and to establish the impacts of some risk factors on cognitive performance.Contingent and methods: We assessed 47 diabetic patients with polyneuropathy, using the Mini Mental State Examination, 10 words test, the Benton visual retention test and the Hamilton scale.Results: Global cognitive dysfunction, decline in verbal memory and visual retention and tendency for depressive mood were observed. We found statistically significant interaction of ageing, sex, severity of pain, duration and late onset of diabetes mellitus (DM on cognitive functioning. Therapy association on cognition was not found.Conclusions: Our study confirms the hypothesis of global cognitive dysfunction, associated with diabetic polyneuropathy. The interactions of sex and pain severity require further study. We arise a hypothesis of asymmetrical brain injury in diabetics.

Hydrocephalus in mice following X-irradiation at early gestational stage. Possibly due to persistent deceleration of cell proliferation

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Aolad, H.M.; Inouye, Minoru; Darmanto, W.; Hayasaka, Shizu; Murata, Yoshiharu [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

2000-09-01

The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telecephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus. (author)

Hydrocephalus in mice following X-irradiation at early gestational stage. Possibly due to persistent deceleration of cell proliferation

International Nuclear Information System (INIS)

Aolad, H.M.; Inouye, Minoru; Darmanto, W.; Hayasaka, Shizu; Murata, Yoshiharu

2000-01-01

The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telecephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus. (author)

Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

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Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

2018-04-01

Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain.

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Karri, Venkatanaidu; Schuhmacher, Marta; Kumar, Vikas

2016-12-01

Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na + - K + ATP-ase pump (Cd, MeHg), biological Ca +2 (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals. Copyright © 2016 Elsevier B.V. All rights reserved.

Metabolic Syndrome, Insulin Resistance and Cognitive Dysfunction: Does your metabolic profile affect your brain?

DEFF Research Database (Denmark)

Neergaard, Jesper S; Møller, Katrine Dragsbæk; Christiansen, Claus

2017-01-01

with 44% (9%-91%) larger probability of developing cognitive dysfunction. In addition subjects above the HOMA-IR threshold (HOMA-IR > 2.6) had 47% (9%-99%) larger odds of cognitive dysfunction. The associations could indicate that a significant proportion of dementia cases in women is likely...

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice.

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Paul, Rajib; Borah, Anupom

2017-12-20

There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.

Impaired Pituitary Axes Following Traumatic Brain Injury

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Robert A. Scranton

2015-07-01

Full Text Available Pituitary dysfunction following traumatic brain injury (TBI is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed.

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

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Li, Xue-Yuan; Men, Wei-Wei; Zhu, Hua; Lei, Jian-Feng; Zuo, Fu-Xing; Wang, Zhan-Jing; Zhu, Zhao-Hui; Bao, Xin-Jie; Wang, Ren-Zhi

2016-10-18

Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18 F-labed fluorodeoxyglucose ( 18 F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

Genetic loci for ventricular dilatation in the LEW/Jms rat with fetal-onset hydrocephalus are influenced by gender and genetic background

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Mayorga David A

2005-06-01

Full Text Available Abstract Background The LEW/Jms rat strain has inherited hydrocephalus, with more males affected than females and an overall expression rate of 28%. This study aimed to determine chromosomal positions for genetic loci causing the hydrocephalus. Methods An F1 backcross was made to the parental LEW/Jms strain from a cross with non-hydrocephalic Fischer 344 rats. BC1 rats were generated for two specific crosses: the first with a male LEW/Jms rat as parent and grandparent, [(F × L × L], designated B group, and the second with a female LEW/Jms rat as the parent and grandparent [L × (L × F], designated C group. All hydrocephalic and a similar number of non-hydrocephalic rats from these two groups were genotyped with microsatellite markers and the data was analyzed separately for each sex by MAPMAKER. Results The frequency of hydrocephalus was not significantly different between the two groups (18.2 and 19.9 %, but there was a significant excess of males in the B group. The mean severity of hydrocephalus, measured as the ventricle-to-brain width ratio, was ranked as B group Conclusion Phenotypic expression of hydrocephalus in Lew/Jms, although not X-linked, has a strong male bias. One, and possibly two chromosomal regions are associated with the hydrocephalus.

Mitochondrial dysfunction precedes depression of AMPK/AKT signaling in insulin resistance induced by high glucose in primary cortical neurons.

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Peng, Yunhua; Liu, Jing; Shi, Le; Tang, Ying; Gao, Dan; Long, Jiangang; Liu, Jiankang

2016-06-01

Recent studies have demonstrated brain insulin signaling impairment and mitochondrial dysfunction in diabetes. Hyperinsulinemia and hyperlipidemia arising from diabetes have been linked to neuronal insulin resistance, and hyperglycemia induces peripheral sensory neuronal impairment and mitochondrial dysfunction. However, how brain glucose at diabetic conditions elicits cortical neuronal insulin signaling impairment and mitochondrial dysfunction remains unknown. In the present study, we cultured primary cortical neurons with high glucose levels and investigated the neuronal mitochondrial function and insulin response. We found that mitochondrial function was declined in presence of 10 mmol/L glucose, prior to the depression of AKT signaling in primary cortical neurons. We further demonstrated that the cerebral cortex of db/db mice exhibited both insulin resistance and loss of mitochondrial complex components. Moreover, we found that adenosine monophosphate-activated protein kinase (AMPK) inactivation is involved in high glucose-induced mitochondrial dysfunction and insulin resistance in primary cortical neurons and neuroblastoma cells, as well as in cerebral cortex of db/db mice, and all these impairments can be rescued by mitochondrial activator, resveratrol. Taken together, our results extend the finding that high glucose (≥10 mmol/L) comparable to diabetic brain extracellular glucose level leads to neuronal mitochondrial dysfunction and resultant insulin resistance, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. We found that high glucose (≥10 mmol/L), comparable to diabetic brain extracellular glucose level, leads to neuronal mitochondrial dysfunction and resultant insulin resistance in an AMPK-dependent manner, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central

Noradrenergic dysfunction in Alzheimer’s disease

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Mary eGannon

2015-06-01

Full Text Available The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer’s disease (AD patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located is a predominant site where AD-related pathology begins. Mounting evidence indicate that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed.

Background Noise Contributes to Organic Solvent Induced Brain Dysfunction

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O’neil W. Guthrie

2016-01-01

Full Text Available Occupational exposure to complex blends of organic solvents is believed to alter brain functions among workers. However, work environments that contain organic solvents are also polluted with background noise which raises the issue of whether or not the noise contributed to brain alterations. The purpose of the current study was to determine whether or not repeated exposure to low intensity noise with and without exposure to a complex blend of organic solvents would alter brain activity. Female Fischer344 rats served as subjects in these experiments. Asynchronous volume conductance between the midbrain and cortex was evaluated with a slow vertex recording technique. Subtoxic solvent exposure, by itself, had no statistically significant effects. However, background noise significantly suppressed brain activity and this suppression was exacerbated with solvent exposure. Furthermore, combined exposure produced significantly slow neurotransmission. These abnormal neurophysiologic findings occurred in the absence of hearing loss and detectable damage to sensory cells. The observations from the current experiment raise concern for all occupations where workers are repeatedly exposed to background noise or noise combined with organic solvents. Noise levels and solvent concentrations that are currently considered safe may not actually be safe and existing safety regulations have failed to recognize the neurotoxic potential of combined exposures.

Background Noise Contributes to Organic Solvent Induced Brain Dysfunction

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Guthrie, O'neil W.; Wong, Brian A.; McInturf, Shawn M.; Reboulet, James E.; Ortiz, Pedro A.; Mattie, David R.

2016-01-01

Occupational exposure to complex blends of organic solvents is believed to alter brain functions among workers. However, work environments that contain organic solvents are also polluted with background noise which raises the issue of whether or not the noise contributed to brain alterations. The purpose of the current study was to determine whether or not repeated exposure to low intensity noise with and without exposure to a complex blend of organic solvents would alter brain activity. Female Fischer344 rats served as subjects in these experiments. Asynchronous volume conductance between the midbrain and cortex was evaluated with a slow vertex recording technique. Subtoxic solvent exposure, by itself, had no statistically significant effects. However, background noise significantly suppressed brain activity and this suppression was exacerbated with solvent exposure. Furthermore, combined exposure produced significantly slow neurotransmission. These abnormal neurophysiologic findings occurred in the absence of hearing loss and detectable damage to sensory cells. The observations from the current experiment raise concern for all occupations where workers are repeatedly exposed to background noise or noise combined with organic solvents. Noise levels and solvent concentrations that are currently considered safe may not actually be safe and existing safety regulations have failed to recognize the neurotoxic potential of combined exposures. PMID:26885406

Background Noise Contributes to Organic Solvent Induced Brain Dysfunction.

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Guthrie, O'neil W; Wong, Brian A; McInturf, Shawn M; Reboulet, James E; Ortiz, Pedro A; Mattie, David R

2016-01-01

Occupational exposure to complex blends of organic solvents is believed to alter brain functions among workers. However, work environments that contain organic solvents are also polluted with background noise which raises the issue of whether or not the noise contributed to brain alterations. The purpose of the current study was to determine whether or not repeated exposure to low intensity noise with and without exposure to a complex blend of organic solvents would alter brain activity. Female Fischer344 rats served as subjects in these experiments. Asynchronous volume conductance between the midbrain and cortex was evaluated with a slow vertex recording technique. Subtoxic solvent exposure, by itself, had no statistically significant effects. However, background noise significantly suppressed brain activity and this suppression was exacerbated with solvent exposure. Furthermore, combined exposure produced significantly slow neurotransmission. These abnormal neurophysiologic findings occurred in the absence of hearing loss and detectable damage to sensory cells. The observations from the current experiment raise concern for all occupations where workers are repeatedly exposed to background noise or noise combined with organic solvents. Noise levels and solvent concentrations that are currently considered safe may not actually be safe and existing safety regulations have failed to recognize the neurotoxic potential of combined exposures.

Possible contributions of a novel form of synaptic plasticity in Aplysia to reward, memory, and their dysfunctions in mammalian brain.

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Hawkins, Robert D

2013-09-18

Recent studies in Aplysia have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate- and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in mammals, where it may contribute to reward, memory, and their dysfunctions in several psychiatric disorders. In Aplysia, spontaneous release is enhanced by activation of presynaptic serotonin receptors, but presynaptic D1 dopamine receptors or nicotinic acetylcholine receptors could play a similar role in mammals. Those receptors enhance spontaneous release of glutamate in hippocampus, entorhinal cortex, prefrontal cortex, ventral tegmental area, and nucleus accumbens. In all of those brain areas, glutamate can activate postsynaptic receptors to elevate Ca(2+) and engage mechanisms of early-phase long-term potentiation (LTP), including AMPA receptor insertion, and of late-phase LTP, including protein synthesis and growth. Thus, presynaptic receptors and spontaneous release may contribute to postsynaptic mechanisms of plasticity in brain regions involved in reward and memory, and could play roles in disorders that affect plasticity in those regions, including addiction, Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD).

Cognitive Dysfunctions in Epileptic Syndromes

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Semih Ayta

2014-05-01

Full Text Available Some children with epilepsy display a low level of intelligence, learning disabilities, attention deficit hyperactivity disorder, mood disorders and anxiety. Besides specific learning disabilities like reading, writing, arithmetics, learning problems may involve other major areas of intellectual functions such as speech and language, attention, memory, fine motor coordination. Even in the presence of common pathology that leads to epilepsy and mental dysfunctions, seizures cause additional cognitive problems. Age at seizure onset, type of seizures and epileptic syndromes are some variables that determine the effect of epilepsy on cognition. As recurrent seizures may have some negative impact on the developing brain, the use of antiepileptic drugs should be considered not only to aim reducing seizures but also to prevent possible seizure-induced cortical dysfunctions. Epilepsy is a disorder requiring a complicated psychological adjustment for the patients and indeed is a disease that affects the whole family. Thus, the management of epilepsy must include educational, psychotherapeutic and behavioral interventions as well as drug treatment.

Cerebral Dysfunctions Related to Perinatal Organic Damage: Clinical-Neuropathologic Correlations.

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Towbin, Abraham

1978-01-01

Recent neuropathology studies identify hypoxia as the main cause of perinatal cerebral damage. Cerebral lesions present at birth, with transition to chronic scar lesions, are correlated to mental retardation, cerebral palsy, epilepsy, and minimal brain dysfunction. Gestation age and severity of hypoxic exposure essentially determine the cerebral…

Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome.

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Mitsumoto, H; Schwartzman, M J; Estes, M L; Chou, S M; La Franchise, E F; De Camilli, P; Solimena, M

1991-04-01

Two women with typical stiff-man syndrome (SMS) developed increasingly frequent attacks of muscle spasms with severe paroxysmal autonomic dysfunctions such as transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary dilation, and arterial hypertension. Autoantibodies to GABA-ergic neurons were identified in the serum of both patients and in the cerebrospinal fluid of one. Both died suddenly and unexpectedly. General autopsy did not reveal the cause of death. Neuropathological studies revealed perivascular gliosis in the spinal cord and brain stem of one patient and lymphocytic perivascular infiltration in the spinal cord, brain stem, and basal ganglia of the other. The occurrence of a chronic inflammatory reaction in one of the two patients supports the idea that an autoimmune disease against GABA-ergic neurons may be involved in SMS. A review of the literature indicates that functional impairment in SMS is severe and prognosis is unpredictable because of the potential for sudden and unexpected death. Both muscular abnormalities and autonomic dysfunctions may result from autoimmunity directed against GABA-ergic neurons.

Blood brain barrier permeability of (−-epigallocatechin gallate, its proliferation-enhancing activity of human neuroblastoma SH-SY5Y cells, and its preventive effect on age-related cognitive dysfunction in mice

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Monira Pervin

2017-03-01

Conclusion: Cognitive dysfunction in mice is suppressed after ingesting GTCs when a low concentration of EGCG is incorporated into the brain parenchyma via the BBB. Nerve cell proliferation/differentiation was enhanced by a low concentration of EGCG. Furthermore, the additive effect of EGC and GA suggests that EGCG sustains a preventive effect after the hydrolysis to EGC and GA.

CSF dynamics in children

International Nuclear Information System (INIS)

Oi, Shizuo; Shose, Yoshiteru; Yamada, Hiroshi; Ijichi, Akihiro; Matsumoto, Satoshi.

1986-01-01

Cerebrospinal fluid (CSF) dynamics in infants and children is still obscure. This paper aims to analyze the characteristics of CSF dynamics in the younger age group and to clarify the changes both in the acute/chronic hydrocephalic status and in the post-shunt condition on the basis of our experience with 118 cases of metrizamide CT cisternography. In order to pursue the CSF passive movements, the exact regional CT numbers were obtained by means of the ROI method in each case at 3, 6, and 24 hours after metrizamide injection. The results revealed that, in the normal CSF dynamics in both the major and minor pathways in children, it took more than 24 hours until the regional metrizamide was completely cleared up. In the acute hydrocephalic state, the ventricular reflux and stasis of the contrast was remarkable, and stagnation in the Sylvian fissure continued more than 24 hours. In the minor pathway, the contrast moved into the brain parenchyma, with there obviously being more in the subependymal layer and the adjacent white matter, and lasted more than 24 hours. On the other hand, these phenomena were very much less prominent in the chronic phase of hydrocephalus. This fact may suggest the hypothesis that a reconstituted active major or minor fluid pathway does not play an important role in the compensation of the acute high-pressure progressive hydrocephalic state. The CSF dynamics in a shunted hydrocephalus are obviously improved when in stasis or when stagnated inside or outside of the ventricular system. The timing of the metrizamide clear-up was within 24 hours after achieving a high accumulation of the contrast in the lateral ventricle where the shunt is placed. The contrast movement in the brain parenchyma as the minor pathway was significantly less in a shunted hydrocephalus, and there was almost none in cases of slit-like ventricles. (author)

The mirror neuron system and the consequences of its dysfunction.

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Iacoboni, Marco; Dapretto, Mirella

2006-12-01

The discovery of premotor and parietal cells known as mirror neurons in the macaque brain that fire not only when the animal is in action, but also when it observes others carrying out the same actions provides a plausible neurophysiological mechanism for a variety of important social behaviours, from imitation to empathy. Recent data also show that dysfunction of the mirror neuron system in humans might be a core deficit in autism, a socially isolating condition. Here, we review the neurophysiology of the mirror neuron system and its role in social cognition and discuss the clinical implications of mirror neuron dysfunction.

Immune responses at brain barriers and implications for brain development and neurological function in later life

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Helen B. Stolp

2013-08-01

Full Text Available For a long time the brain has been considered an immune-privileged site due to a muted inflammatory response and the presence of protective brain barriers. It is now recognised that neuroinflammation may play an important role in almost all neurological disorders and that the brain barriers may be contributing through either normal immune signalling, or disruption of their basic physiological mechanisms. The distinction between normal function and dysfunction at the barriers is difficult to dissect, partly due to a lack of understanding of normal barrier function and partly because of physiological changes that occur as part of normal development and ageing. Brain barriers consist of a number of interacting structural and physiological elements including tight junctions between adjacent barrier cells and an array of influx and efflux transporters. Despite these protective mechanisms, the capacity for immune-surveillance of the brain is maintained, and there is evidence of inflammatory signalling at the brain barriers that may be an important part of the body’s response to damage or infection. This signalling system appears to change both with normal ageing, and during disease. Changes may affect diapedesis of immune cells and active molecular transfer, or cause rearrangement of the tight junctions and an increase in passive permeability across barrier interfaces. Here we review the many elements that contribute to brain barrier functions and how they respond to inflammation, particularly during development and aging. The implications of inflammation–induced barrier dysfunction for brain development and subsequent neurological function are also discussed.

High incidence of hydrocephalus following prenatal exposure to X-irradiation at early gestational stage in mice

International Nuclear Information System (INIS)

Aolad, H.; Inouye, Minoru; Hayasaka, Shizu; Darmanto, W.; Murata, Yoshiharu

1998-01-01

Hydrocephalus is one of the severe brain anomalies. Several causes of congenital hydrocephalus have been reported and, it is known that radiation is one of those. The current study was designed to obtain postnatally viable hydrocephalic offspring at a high incidence following X-radiation. This finding will be helpful to elucidate the mechanism of congenital hydrocephalus caused by X-radiation. Twenty pregnant Slc:ICR mice, 5 in each group, were exposed to X-irradiation at a dose of 1.0 Gy on gestational days 7 (G7), G8, G9 or G10. The incidence of hydrocephalus was high in the group exposed on G7. An additional 21 pregnant mice were then exposed to a dose of 1.2 Gy, 1.3 Gy, 1.4 Gy or 1.5 Gy X-radiation on G7. The highest incidence of hydrocephalic offspring was found following exposure to 1.4 Gy X-radiation. (author)

Using game authoring platforms to develop screen-based simulated functional assessments in persons with executive dysfunction following traumatic brain injury.

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Martínez-Pernía, David; Núñez-Huasaf, Javier; Del Blanco, Ángel; Ruiz-Tagle, Amparo; Velásquez, Juan; Gomez, Mariela; Robert Blesius, Carl; Ibañez, Agustin; Fernández-Manjón, Baltasar; Slachevsky, Andrea

2017-10-01

The assessment of functional status is a critical component of clinical neuropsychological evaluations used for both diagnostic and therapeutic purposes in patients with cognitive brain disorders. There are, however, no widely adopted neuropsychological tests that are both ecologically valid and easily administered in daily clinical practice. This discrepancy is a roadblock to the widespread adoption of functional assessments. In this paper, we propose a novel approach using a serious game authoring platform (eAdventure) for creating screen-based simulated functional assessments. We created a naturalistic functional task that consisted of preparing a cup of tea (SBS-COT) and applied the assessment in a convenience sample of eight dyads of therapists/patients with mild executive dysfunction after traumatic brain injury. We had three main aims. First, we performed a comprehensive review of executive function assessment in activities of daily living. Second, we were interested in measuring the feasibility of this technology with respect to staffing, economic and technical requirements. Third, a serious game was administered to patients to study the feasibility of this technology in the clinical context (pre-screening test). In addition, quantitative (Technology Acceptance Model (TAM) questionnaires) and qualitative (semistructured interviews) evaluations were applied to obtain user input. Our results suggest that the staffing, economic and technical requirements of the SBS-COT are feasible. The outcomes of the pre-screening test provide evidence that this technology is useful in the functional assessment of patients with executive dysfunction. In relation to subjective data, the TAM questionnaire showed good user acceptability from a professional perspective. Interview analyses with professionals and patients showed positive experiences related to the use of the SBS-COT. Our work indicates that the use of these types of authoring platforms could have positive long

Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder.

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Tripp, Adam; Oh, Hyunjung; Guilloux, Jean-Philippe; Martinowich, Keri; Lewis, David A; Sibille, Etienne

2012-11-01

The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results. Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex. These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis

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

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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.

Attenuating brain edema, hippocampal oxidative stress, and cognitive dysfunction in rats using hyperbaric oxygen preconditioning during simulated high-altitude exposure.

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Lin, Hung; Chang, Ching-Ping; Lin, Hung-Jung; Lin, Mao-Tsun; Tsai, Cheng-Chia

2012-05-01

We assessed whether hyperbaric oxygen preconditioning (HBO2P) in rats induced heat shock protein (HSP)-70 and whether HSP-70 antibody (Ab) preconditioning attenuates high altitude exposure (HAE)-induced brain edema, hippocampal oxidative stress, and cognitive dysfunction. Rats were randomly divided into five groups: the non-HBO2P + non-HAE group, the HBO2P + non-HAE group, the non-HBO2P + HAE group, the HBO2P + HAE group, and the HBO2P + HSP-70 Abs + HAE group. The HBO2P groups were given 100% O2 at 2.0 absolute atmospheres for 1 hour per day for 5 consecutive days. The HAE groups were exposed to simulated HAE (9.7% O2 at 0.47 absolute atmospheres of 6,000 m) in a hypobaric chamber for 3 days. Polyclonal rabbit anti-mouse HSP-70-neutralizing Abs were intravenously injected 24 hours before the HAE experiments. Immediately after returning to normal atmosphere, the rats were given cognitive performance tests, overdosed with a general anesthetic, and then their brains were excised en bloc for water content measurements and biochemical evaluation and analysis. Non-HBO2P group rats displayed cognitive deficits, brain edema, and hippocampal oxidative stress (evidenced by increased toxic oxidizing radicals [e.g., nitric oxide metabolites and hydroxyl radicals], increased pro-oxidant enzymes [e.g., malondialdehyde and oxidized glutathione] but decreased antioxidant enzymes [e.g., reduced glutathione, glutathione peroxide, glutathione reductase, and superoxide dismutase]) in HAE. HBO2P induced HSP-70 overexpression in the hippocampus and significantly attenuated HAE-induced brain edema, cognitive deficits, and hippocampal oxidative stress. The beneficial effects of HBO2P were significantly reduced by HSP-70 Ab preconditioning. Our results suggest that high-altitude cerebral edema, cognitive deficit, and hippocampal oxidative stress can be prevented by HSP-70-mediated HBO2P in rats.

Blood-brain barrier dysfunction following traumatic brain injury: correlation of K(trans) (DCE-MRI) and SUVR (99mTc-DTPA SPECT) but not serum S100B.

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Winter, Craig; Bell, Christopher; Whyte, Timothy; Cardinal, John; Macfarlane, David; Rose, Stephen

2015-07-01

Damage to the blood-brain barrier (BBB) is an important secondary mechanism that occurs following traumatic brain injury (TBI) and may provide a potential therapeutic target to improve patient outcome. For such a progress to be realised, an accurate assessment of BBB compromise needs to be established. Fourteen patients with TBI were prospectively recruited. Post-traumatic BBB dysfunction was assessed using dynamic contrast-enhanced MRI (DCE-MRI), single-photon emission computerised tomography (SPECT) and serum S100B levels. A statistically significant correlation between standardised uptake value ratio (SUVR) calculated from 99mTc-DTPA SPECT and K(trans) (a volume transfer constant) from DCE-MRI was found for those eight patients who had concurrent scans. The positive correlation persisted when the data were corrected for patient age, number of days following trauma and both parameters combined. We found no statistically significant correlation between either of the imaging modalities and concurrent serum S100B levels. The correlation of SPECT with DCE-MRI suggests that either scan may be used to assess post-traumatic BBB damage. We could not support serum S100B to be an accurate measure of BBB damage when sampled a number of days following injury but the small number of patients, the heterogeneity in TBI patients and the delay following injury makes any firm conclusions regarding S100B and BBB difficult.

Paediatrics brain imaging in epilepsy: common presenting symptoms and spectrum of abnormalities detected on MRI

International Nuclear Information System (INIS)

Ali, A.; Akram, F.; Khan, G.; Hussain, S.

2017-01-01

Epilepsy, a common neurological disorder can present at any age and has a number of aetiologies with underlying brain disease being the most common aetiology. Brain imaging becomes important and mandatory in the work up for epilepsy in localization and lateralization of the seizure focus. Methods: This cross-sectional study was conducted in the department of Radiology Ayub Medical Teaching Institution Abbottabad from 1st March 2015 to 31st March 2016. A total of 209 children aged 28 days to 14 years were included in the study who presented with seizures to clinicians. Information obtained from history, clinical examination and investigations especially MRI brains were recorded in a prescribed pro forma. The data was analysed in SPSS 20. Results: MRI examination was unremarkable in 44.01% (n=92) and mild generalized brain atrophy was noted in 12.91% (n=27). Arachnoid cysts, mild unilateral brain atrophy and hydrocephalous due to aqueduct stenosis were recorded in 3.82% (n=8) of each group. Neoplastic lesions were the second most common abnormal MRI finding and constituted 5.74% (n=12). Leukodystrophy was diagnosed in 4.78% (n=10). MRI examination showed ring enhancing lesions (tuberculomas) and AVM in 1.43% (n=3) of each group. Perinatal ischemia and intracranial infection, (focal or generalized) were recorded in 2.87% (n=6) of each group. A 0.95 % (n=2) of children in each group had agenesis of corpus callosum and cavernoma. The radiological MRI diagnosis of Raussmussen encephalitis was made in 3.34% (n=7). Single case, each of mesial temporal sclerosis, subdural haemorrhage, infarct and craniopharyngioma was recorded making 0.47 % of the total patients in each case. Conclusion: MRI examination was abnormal in significant number of patients (55.86%), so therefore if properly utilized, in a good clinical context, this can identify most of the structural brain abnormalities in paediatric patients presenting with seizures. (author)

Functional neuroanatomy in depressed patients with sexual dysfunction: blood oxygenation level dependent functional MR imaging

International Nuclear Information System (INIS)

Yang, Jong Chul

2004-01-01

To demonstrate the functional neuroanatomy associated with sexual arousal visually evoked in depressed males who have underlying sexual dysfunction using Blood Oxygenation Level Dependent-based fMRI. Ten healthy volunteers (age range 21-55: mean 32.5 years), and 10 depressed subjects (age range 23-51: mean 34.4 years, mean Beck Depression Inventory score of 39.6 ± 5.9, mean Hamilton Rating Scale Depression (HAMD)-17 score of 33.5 ± 6.0) with sexual arousal dysfunction viewed erotic and neutral video films during functional magnetic resonance imaging (fMRI) with 1.5 T MR scanner (GE Signa Horizon). The fMRI data were obtained from 7 oblique planes using gradient-echo EPI (flip angle/TR/TE=90 .deg. /6000 ms/50 ms). The visual stimulation paradigm began with 60 sec of black screen, 150 sec of neutral stimulation with a documentary video film, 30 sec of black screen, 150 sec of sexual stimulation with an erotic video film followed by 30 sec of black screen. The brain activation maps and their quantification were analyzed by SPM99 program. There was a significant difference of brain activation between two groups during visual sexual stimulation. In depressed subjects, the level of activation during the visually evoked sexual arousal was significantly less than that of healthy volunteers, especially in the cerebrocortical areas of the hypothalamus, thalamus, caudate nucleus, and inferior and superior temporal gyri. On the other hand, the cerebral activation patterns during the neutral condition in both groups showed no significant differences (ρ < 0.01). This study is the first demonstration of the functional neuroanatomy of the brain associated with sexual dysfunction in depressed patients using fMRI. In order to validate our physiological neuroscience results, further studies that would include patients with other disorders and sexual dysfunction, and depressed patients without sexual dysfunction and their treatment response are needed

Functional neuroanatomy in depressed patients with sexual dysfunction: blood oxygenation level dependent functional MR imaging

Energy Technology Data Exchange (ETDEWEB)

Yang, Jong Chul [Chonnam National Univ. Hospital, Kwangju (Korea, Republic of)

2004-06-15

To demonstrate the functional neuroanatomy associated with sexual arousal visually evoked in depressed males who have underlying sexual dysfunction using Blood Oxygenation Level Dependent-based fMRI. Ten healthy volunteers (age range 21-55: mean 32.5 years), and 10 depressed subjects (age range 23-51: mean 34.4 years, mean Beck Depression Inventory score of 39.6 {+-} 5.9, mean Hamilton Rating Scale Depression (HAMD)-17 score of 33.5 {+-} 6.0) with sexual arousal dysfunction viewed erotic and neutral video films during functional magnetic resonance imaging (fMRI) with 1.5 T MR scanner (GE Signa Horizon). The fMRI data were obtained from 7 oblique planes using gradient-echo EPI (flip angle/TR/TE=90 .deg. /6000 ms/50 ms). The visual stimulation paradigm began with 60 sec of black screen, 150 sec of neutral stimulation with a documentary video film, 30 sec of black screen, 150 sec of sexual stimulation with an erotic video film followed by 30 sec of black screen. The brain activation maps and their quantification were analyzed by SPM99 program. There was a significant difference of brain activation between two groups during visual sexual stimulation. In depressed subjects, the level of activation during the visually evoked sexual arousal was significantly less than that of healthy volunteers, especially in the cerebrocortical areas of the hypothalamus, thalamus, caudate nucleus, and inferior and superior temporal gyri. On the other hand, the cerebral activation patterns during the neutral condition in both groups showed no significant differences ({rho} < 0.01). This study is the first demonstration of the functional neuroanatomy of the brain associated with sexual dysfunction in depressed patients using fMRI. In order to validate our physiological neuroscience results, further studies that would include patients with other disorders and sexual dysfunction, and depressed patients without sexual dysfunction and their treatment response are needed.

MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

Science.gov (United States)

Andersen, Stine Linding; Carlé, Allan; Karmisholt, Jesper; Pedersen, Inge Bülow; Andersen, Stig

2017-07-01

Fetal programming is a long-standing, but still evolving, concept that links exposures during pregnancy to the later development of disease in the offspring. A fetal programming effect has been considered within different endocrine axes and in relation to different maternal endocrine diseases. In this critical review, we describe and discuss the hypothesis of fetal programming by maternal thyroid dysfunction in the context of fetal brain development and neurodevelopmental disorders in the offspring. Thyroid hormones are important regulators of early brain development, and evidence from experimental and observational human studies have demonstrated structural and functional abnormalities in the brain caused by the lack or excess of thyroid hormone during fetal brain development. The hypothesis that such abnormalities introduced during early fetal brain development increase susceptibility for the later onset of neurodevelopmental disorders in the offspring is biologically plausible. However, epidemiological studies on the association between maternal thyroid dysfunction and long-term child outcomes are observational in design, and are challenged by important methodological aspects. © 2017 European Society of Endocrinology.

Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction.

Science.gov (United States)

Stanyer, Lee; Jorgensen, Wenche; Hori, Osamu; Clark, John B; Heales, Simon J R

2008-09-01

The accumulation of oxidatively modified proteins has been shown to be a characteristic feature of many neurodegenerative disorders and its regulation requires efficient proteolytic processing. One component of the mitochondrial proteolytic system is Lon, an ATP-dependent protease that has been shown to degrade oxidatively modified aconitase in vitro and may thus play a role in defending against the accumulation of oxidized matrix proteins in mitochondria. Using an assay system that allowed us to distinguish between basal and ATP-stimulated Lon protease activity, we have shown in isolated non-synaptic rat brain mitochondria that Lon protease is highly susceptible to oxidative inactivation by peroxynitrite (ONOO(-)). This susceptibility was more pronounced with regard to ATP-stimulated activity, which was inhibited by 75% in the presence of a bolus addition of 1mM ONOO(-), whereas basal unstimulated activity was inhibited by 45%. Treatment of mitochondria with a range of peroxynitrite concentrations (10-1000 microM) revealed that a decline in Lon protease activity preceded electron transport chain (ETC) dysfunction (complex I, II-III and IV) and that ATP-stimulated activity was approximately fivefold more sensitive than basal Lon protease activity. Furthermore, supplementation of mitochondrial matrix extracts with reduced glutathione, following ONOO(-) exposure, resulted in partial restoration of basal and ATP-stimulated activity, thus suggesting possible redox regulation of this enzyme complex. Taken together these findings suggest that Lon protease may be particularly vulnerable to inactivation in conditions associated with GSH depletion and elevated oxidative stress.

Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

Energy Technology Data Exchange (ETDEWEB)

Sharma, Bhupesh, E-mail: drbhupeshresearch@gmail.com; Sharma, P.M.

2013-11-15

Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment of learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good potential

Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

International Nuclear Information System (INIS)

Sharma, Bhupesh; Sharma, P.M.

2013-01-01

Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment of learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good potential in

Psychopathology of Time in Brain Disease and Schizophrenia

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John Cutting

1990-01-01

Full Text Available The literature on disturbance of time-sense in brain disease and schizophrenia is reviewed and the subjective experience of altered time-sense reported by 45 out of 350 personally interviewed schizophrenics is analyzed. A review of the literature on the effect of brain damage revealed that some phenomena (déjà vu, reduplication of time, altered tempo to events were linked with right hemisphere dysfunction, one phenomenon (incorrect sequencing of events was linked with left anterior brain damage, and others (disrupted “biological clock”, disturbed serise of rate of flow of current or past events could arise from subcortical as well as focal cortical damage. The sparse literature on disturbed time-sense in schizophrenia suggested that there was a shared psychopathology in this respect with right hemisphere dysfunction. The phenomena encountered in the 45 schizophrenics are described and classified.

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

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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.

The role of mitochondrial dysfunction in the progression of Alzheimer’s disease

DEFF Research Database (Denmark)

Desler, Claus; Lillenes, Meryl S.; Tønjum, Tone

2018-01-01

The current molecular understanding of Alzheimer’s disease (AD) has still not resulted in successful interventions. Mitochondrial dysfunction of the AD brain is currently emerging as a hallmark of this disease. One mitochondrial function often affected in AD is oxidative phosphorylation responsible...

Brain dysfunction in psychosis

International Nuclear Information System (INIS)

Warkentin, S.

1991-01-01

The present investigation focused on the questions whether previously reported functional brain abnormalities in schizophrenia could be related to the clinical state of the patient (i.e. the degree of psychosis) at time of study, and whether similar findings in patients with schizophrenia, could be made in patients with cycloid psychosis. To this effect, patients were investigated with regional cerebral blood flow measurements and clinical rating on repeated occasions during their most extreme fluctuations during a psychotic episode, i.e. while they were in an exacerbated state and during clinical remission. A subgroup of schizophrenic patients were investigated before and after neuroleptic treatment and during mental activation with a word fluency test. The schizophrenic group has a normal mean hemispheric blood flow irrespective of clinical state and treatment. During exacerbation a highly significant positive correlation was seen between the frontal-occipital (F/O) ratio and the degree of psychosis, suggesting that the more psychotic the patients was, the higher was the ratio. During remission, the F/O ratio decreased. Schizophrenic patients did not activate their prefrontal cortex during exacerbation, but showed a normal frontal response to the word fluency test during remission. The regional cerebral blood flow of the cycloid patients differed clearly from that of the schizophrenic patients. During exacerbation they had elevated mean hemispheric flow levels, and a decreased F/O ration, while rCBF was normal during remission. The findings suggest that variability in the degree of psychosis can be an important factor underlying the heterogeneity of rCBF findings in schizophrenia. (au)

Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

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Valérie Wolff

2015-01-01

Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury.

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Newell, Elizabeth A; Todd, Brittany P; Mahoney, Jolonda; Pieper, Andrew A; Ferguson, Polly J; Bassuk, Alexander G

2018-01-01

Diffuse activation of interleukin-1 inflammatory cytokine signaling after traumatic brain injury (TBI) elicits progressive neurodegeneration and neuropsychiatric dysfunction, and thus represents a potential opportunity for therapeutic intervention. Although interleukin (IL)-1α and IL-1β both activate the common type 1 IL-1 receptor (IL-1RI), they manifest distinct injury-specific roles in some models of neurodegeneration. Despite its potential relevance to treating patients with TBI, however, the individual contributions of IL-1α and IL-1β to TBI-pathology have not been previously investigated. To address this need, we applied genetic and pharmacologic approaches in mice to dissect the individual contributions of IL-1α, IL-β, and IL-1RI signaling to the pathophysiology of fluid percussion-mediated TBI, a model of mixed focal and diffuse TBI. IL-1RI ablation conferred a greater protective effect on brain cytokine expression and cognitive function after TBI than did individual IL-1α or IL-1β ablation. This protective effect was recapitulated by treatment with the drug anakinra, a recombinant naturally occurring IL-1RI antagonist. Our data thus suggest that broad targeting of IL-1RI signaling is more likely to reduce neuroinflammation and preserve cognitive function after TBI than are approaches that individually target IL-1α or IL-1β signaling.

A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model

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McNamara Laurie K

2007-09-01

Full Text Available Abstract Background An accumulating body of evidence is consistent with the hypothesis that excessive or prolonged increases in proinflammatory cytokine production by activated glia is a contributor to the progression of pathophysiology that is causally linked to synaptic dysfunction and hippocampal behavior deficits in neurodegenerative diseases such as Alzheimer's disease (AD. This raises the opportunity for the development of new classes of potentially disease-modifying therapeutics. A logical candidate CNS target is p38α MAPK, a well-established drug discovery molecular target for altering proinflammatory cytokine cascades in peripheral tissue disorders. Activated p38 MAPK is seen in human AD brain tissue and in AD-relevant animal models, and cell culture studies strongly implicate p38 MAPK in the increased production of proinflammatory cytokines by glia activated with human amyloid-beta (Aβ and other disease-relevant stressors. However, the vast majority of small molecule drugs do not have sufficient penetrance of the blood-brain barrier to allow their use as in vivo research tools or as therapeutics for neurodegenerative disorders. The goal of this study was to test the hypothesis that brain p38α MAPK is a potential in vivo target for orally bioavailable, small molecules capable of suppressing excessive cytokine production by activated glia back towards homeostasis, allowing an improvement in neurologic outcomes. Methods A novel synthetic small molecule based on a molecular scaffold used previously was designed, synthesized, and subjected to analyses to demonstrate its potential in vivo bioavailability, metabolic stability, safety and brain uptake. Testing for in vivo efficacy used an AD-relevant mouse model. Results A novel, CNS-penetrant, non-toxic, orally bioavailable, small molecule inhibitor of p38α MAPK (MW01-2-069A-SRM was developed. Oral administration of the compound at a low dose (2.5 mg/kg resulted in attenuation of

Eyeball Pressure Stimulation Unveils Subtle Autonomic Cardiovascular Dysfunction in Persons with a History of Mild Traumatic Brain Injury.

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Hilz, Max J; Aurnhammer, Felix; Flanagan, Steven R; Intravooth, Tassanai; Wang, Ruihao; Hösl, Katharina M; Pauli, Elisabeth; Koehn, Julia

2015-11-15

After mild traumatic brain injury (mTBI), patients have increased long-term mortality rates, persisting even beyond 13 years. Pathophysiology is unclear. Yet, central autonomic network dysfunction may contribute to cardiovascular dysregulation and increased mortality. Purely parasympathetic cardiovascular challenge by eyeball pressure stimulation (EP), might unveil subtle autonomic dysfunction in post-mTBI patients. We investigated whether mild EP shows autonomic cardiovascular dysregulation in post-mTBI patients. In 24 patients (34 ± 12 years; 5-86 months post-injury) and 27 controls (30 ± 11 years), we monitored respiration, electrocardiographic RR intervals (RRI), systolic and diastolic blood pressure (BPsys, BPdia) before and during 2 min of 30 mm Hg EP, applied by an ophthalmologic ocular pressure device (Okulopressor(®)). We calculated spectral powers of RRI in the mainly sympathetic low frequency (LF; 0.04-0.15 Hz) and parasympathetic high frequency (HF; 0.15-0.5 Hz) ranges, and of BP in the sympathetic LF range, the RRI-LF/HF ratio as index of the sympathetic-parasympathetic balance, normalized (nu) RRI-LF- and HF-powers, and LF- and HF-powers after natural logarithmic transformation (ln). Parameters before and during EP in post-mTBI patients and controls were compared by repeated measurement analysis of variance with post hoc analysis (p < 0.05). During EP, BPsys and BPdia increased in post-mTBI patients. Only in controls but not in post-mTBI patients, EP increased RRI-HFnu-powers and decreased RRI-LF-powers, RRI-LFnu-powers, BPsys-LF-powers, BPsys-lnLF-powers and BPdia-lnLF-powers. RRI-LF/HF ratios slightly increased in post-mTBI patients but slightly decreased in controls upon EP. Even with only mild EP, our controls showed normal EP responses and shifted sympathetic-parasympathetic balance towards parasympathetic predominance. In contrast, our post-mTBI patients could not increase parasympathetic heart rate modulation but

I-123 iomazenil single photon emission computed tomography for detecting loss of neuronal integrity in patients with traumatic brain injury

OpenAIRE

Abiko, Kagari; Ikoma, Katsunori; Shiga, Tohru; Katoh, Chietsugu; Hirata, Kenji; Kuge, Yuji; Kobayashi, Kentaro; Tamaki, Nagara

2017-01-01

Background Traumatic brain injury (TBI) causes brain dysfunction in many patients. Using C-11 flumazenil (FMZ) positron emission tomography (PET), we have detected and reported the loss of neuronal integrity, leading to brain dysfunction in TBI patients. Similarly to FMZ PET, I-123 iomazenil (IMZ) single photon emission computed tomography (SPECT) is widely used to determine the distribution of the benzodiazepine receptor (BZR) in the brain cortex. The purpose of this study is to examine whet...

Recurrent venous thromboembolism in patients with pulmonary embolism and right ventricular dysfunction: a post-hoc analysis of the Hokusai-VTE study

NARCIS (Netherlands)

Brekelmans, Marjolein P. A.; Ageno, Walter; Beenen, Ludo F.; Brenner, Benjamin; Buller, Harry R.; Chen, Cathy Z.; Cohen, Alexander T.; Grosso, Michael A.; Meyer, Guy; Raskob, Gary; Segers, Annelise; Vanassche, Thomas; Verhamme, Peter; Wells, Philip S.; Zhang, George; Weitz, Jeffrey I.

2016-01-01

In patients with pulmonary embolism, right ventricular dysfunction is associated with early mortality. The Hokusai-VTE study used N-terminal pro-brain natriuretic peptide (NT-proBNP) and right to left ventricular diameter ratio on CT as indicators of right ventricular dysfunction and reported that

Minor Neurological Dysfunction in Children with Autism Spectrum Disorder

Science.gov (United States)

de Jong, Marianne; Punt, Marja; de Groot, Erik; Minderaa, Ruud B; Hadders-Algra, Mijna

2011-01-01

Aim: The aim of this study was to improve the understanding of brain function in children with autism spectrum disorder (ASD) in relation to minor neurological dysfunctions (MNDs). Method: We studied MNDs in 122 children (93 males, 29 females; mean age 8y 1mo, SD 2y 6mo) who, among a total cohort of 705 children (513 males, 192 females; mean age…

Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain

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Praetorius Jeppe

2010-11-01

Full Text Available Abstract Background The water channel protein aquaporin-4 (AQP4 is reported to be of possible major importance for accessory cerebrospinal fluid (CSF circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus. Methods Hydrocephalus was induced in adult rats (~8 weeks by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4. Results Lateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells. Conclusions AQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF

A new glaucoma hypothesis: a role of glymphatic system dysfunction.

Science.gov (United States)

Wostyn, Peter; Van Dam, Debby; Audenaert, Kurt; Killer, Hanspeter Esriel; De Deyn, Peter Paul; De Groot, Veva

2015-06-29

In a recent review article titled "A new look at cerebrospinal fluid circulation", Brinker et al. comprehensively described novel insights from molecular and cellular biology as well as neuroimaging research, which indicate that cerebrospinal fluid (CSF) physiology is much more complex than previously believed. The glymphatic system is a recently defined brain-wide paravascular pathway for CSF and interstitial fluid exchange that facilitates efficient clearance of interstitial solutes, including amyloid-β, from the brain. Although further studies are needed to substantiate the functional significance of the glymphatic concept, one implication is that glymphatic pathway dysfunction may contribute to the deficient amyloid-β clearance in Alzheimer's disease. In this paper, we review several lines of evidence suggesting that the glymphatic system may also have potential clinical relevance for the understanding of glaucoma. As a clinically acceptable MRI-based approach to evaluate glymphatic pathway function in humans has recently been developed, a unique opportunity now exists to investigate whether suppression of the glymphatic system contributes to the development of glaucoma. The observation of a dysfunctional glymphatic system in patients with glaucoma would provide support for the hypothesis recently proposed by our group that CSF circulatory dysfunction may play a contributory role in the pathogenesis of glaucomatous damage. This would suggest a new hypothesis for glaucoma, which, just like Alzheimer's disease, might be considered then as an imbalance between production and clearance of neurotoxins, including amyloid-β.

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

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Xue-Yuan Li

2016-10-01

Full Text Available Alzheimer’s disease (AD is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1 transgenic (Tg mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr. Morris water maze (MWM was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD. By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD. Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer’s cognition after cognitive decline, at least in animals.

Visceral Afferent Pathways and Functional Brain Imaging

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Stuart W.G. Derbyshire

2003-01-01

Full Text Available The application of functional imaging to study painful sensations has generated considerable interest regarding insight into brain dysfunction that may be responsible for functional pain such as that suffered in patients with irritable bowel syndrome (IBS. This review provides a brief introduction to the development of brain science as it relates to pain processing and a snapshot of recent functional imaging results with somatic and visceral pain. Particular emphasis is placed on current hypotheses regarding dysfunction of the brain-gut axis in IBS patients. There are clear and interpretable differences in brain activation following somatic as compared with visceral noxious sensation. Noxious visceral distension, particularly of the lower gastrointestinal tract, activates regions associated with unpleasant affect and autonomic responses. Noxious somatic sensation, in contrast, activates regions associated with cognition and skeletomotor responses. Differences between IBS patients and control subjects, however, were far less clear and interpretable. While this is in part due to the newness of this field, it also reflects weaknesses inherent within the current understanding of IBS. Future use of functional imaging to examine IBS and other functional disorders will be more likely to succeed by describing clear theoretical and clinical endpoints.

Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

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Pradip P Dalwadi

2017-01-01

Full Text Available Introduction: Traumatic brain injury (TBI is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population. Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality. Subjects and Methods: Forty-nine TBI patients (41 men and 8 women were included in this study. Pituitary functions were evaluated within 24 h of admission. Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3 and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality. Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening

Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm.

Science.gov (United States)

Meyer, Jeffrey H; McMain, Shelley; Kennedy, Sidney H; Korman, Lorne; Brown, Gregory M; DaSilva, Jean N; Wilson, Alan A; Blak, Thomas; Eynan-Harvey, Rahel; Goulding, Verdell S; Houle, Sylvain; Links, Paul

2003-01-01

Dysfunctional attitudes are negatively biased assumptions and beliefs regarding oneself, the world, and the future. In healthy subjects, increasing serotonin (5-HT) agonism with a single dose of d-fenfluramine lowered dysfunctional attitudes. To investigate whether the converse, a low level of 5-HT agonism, could account for the higher levels of dysfunctional attitudes observed in patients with major depression or with self-injurious behavior, cortex 5-HT(2) receptor binding potential and dysfunctional attitudes were measured in patients with major depressive disorder, patients with a history of self-injurious behavior, and healthy comparison subjects (5-HT(2) receptor density increases during 5-HT depletion). Twenty-nine healthy subjects were recruited to evaluate the effect of d-fenfluramine or of clonidine (control condition) on dysfunctional attitudes. Dysfunctional attitudes were assessed with the Dysfunctional Attitude Scale 1 hour before and 1 hour after drug administration. In a second experiment, dysfunctional attitudes and 5-HT(2) binding potential were measured in 22 patients with a major depressive episode secondary to major depressive disorder, 18 patients with a history of self-injurious behavior occurring outside of a depressive episode, and another 29 age-matched healthy subjects. Cortex 5-HT(2) binding potential was measured with [(18)F]setoperone positron emission tomography. In the first experiment, dysfunctional attitudes decreased after administration of d-fenfluramine. In the second experiment, in the depressed group, dysfunctional attitudes were positively associated with cortex 5-HT(2) binding potential, especially in Brodmann's area 9 (after adjustment for age). Depressed subjects with extremely dysfunctional attitudes had higher 5-HT(2) binding potential, compared to healthy subjects, particularly in Brodmann's area 9. Low levels of 5-HT agonism in the brain cortex may explain the severely pessimistic, dysfunctional attitudes associated

Brain imaging research in autism spectrum disorders: in search of neuropathology and health across the lifespan.

Science.gov (United States)

Lainhart, Janet E

2015-03-01

Advances in brain imaging research in autism spectrum disorders (ASD) are rapidly occurring, and the amount of neuroimaging research has dramatically increased over the past 5 years. In this review, advances during the past 12 months and longitudinal studies are highlighted. Cross-sectional neuroimaging research provides evidence that the neural underpinnings of the behavioral signs of ASD involve not only dysfunctional integration of information across distributed brain networks but also basic dysfunction in primary cortices.Longitudinal studies of ASD show abnormally enlarged brain volumes and increased rates of brain growth during early childhood in only a small minority of ASD children. There is evidence of disordered development of white matter microstructure and amygdala growth, and at 2 years of age, network inefficiencies in posterior cerebral regions.From older childhood into adulthood, atypical age-variant and age-invariant changes in the trajectories of total and regional brain volumes and cortical thickness are apparent at the group level. There is evidence of abnormalities in posterior lobes and posterior brain networks during the first 2 years of life in ASD and, even in older children and adults, dysfunction in primary cortical areas.

Ginsenoside Re Ameliorates Brain Insulin Resistance and Cognitive Dysfunction in High Fat Diet-Induced C57BL/6 Mice.

Science.gov (United States)

Kim, Jong Min; Park, Chang Hyeon; Park, Seon Kyeong; Seung, Tae Wan; Kang, Jin Yong; Ha, Jeong Su; Lee, Du Sang; Lee, Uk; Kim, Dae-Ok; Heo, Ho Jin

2017-04-05

The ameliorating effects of ginsenoside Re (G Re) on high fat diet (HFD)-induced insulin resistance in C57BL/6 mice were investigated to assess its physiological function. In the results of behavioral tests, G Re improved cognitive dysfunction in diabetic mice using Y-maze, passive avoidance, and Morris water maze tests. G Re also significantly recovered hyperglycemia and fasting blood glucose level. In the results of serum analysis, G Re decreased triglyceride (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDLC), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) and increased the ratio of high-density lipoprotein cholesterol (HDLC). G Re regulated acetylcholine (ACh), acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), and oxidized glutathione (GSH)/total GSH by regulating the c-Jun N-terminal protein kinase (JNK) pathway. These findings suggest that G Re could be used to improve HFD-induced insulin resistance condition by ameliorating hyperglycemia via protecting the cholinergic and antioxidant systems in the mouse brains.

Abnormalities in gray and white matter volumes associated with explicit memory dysfunction in patients with generalized anxiety disorder.

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Moon, Chung-Man; Jeong, Gwang-Woo

2017-03-01

Background The neuroanatomical abnormalities associated with behavioral dysfunction on explicit memory in patients generalized anxiety disorder (GAD) have not yet been clearly identified. Purpose To investigate the regional gray matter (GM) and white matter (WM) volume alterations over the whole brain in patients with GAD, as well as the correlation between the brain structural abnormality and explicit memory dysfunction. Material and Methods Twenty patients with GAD and 20 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted magnetic resonance imaging (MRI). The participants performed the explicit memory tasks with the neutral and anxiety-inducing words. Results Patients with GAD showed significantly reduced GM volumes in the midbrain (MB), thalamus, hippocampus (Hip), insula, and superior temporal gyrus (STG); and reduced WM volumes in the MB, anterior limb of the internal capsule (ALIC), dorsolateral prefrontal cortex (DLPFC), and precentral gyrus (PrG). It is important to note that the GM volume of the Hip and the WM volume of the DLPFC were positively correlated with the recognition accuracy (%) in the explicit memory tasks with neutral and anxiety-inducing words, respectively. On the other hand, the WM volume of the PrG was negatively correlated with the reaction time in the same memory tasks. Conclusion This study demonstrated the regional volume changes on whole-brain GM and WM and the correlation between the brain structural alteration and explicit memory dysfunction in GAD patients. These findings would be helpful to understand the association between the brain structure abnormality and the functional deficit in the explicit memory in GAD.

Synthesis of new technetium brain radiotracers

International Nuclear Information System (INIS)

Ben Dhieb, Fatma

2012-01-01

The scintigraphic diagnosis is a major mean for detecting neuro degenerative diseases at early stage; this requires specific radiotracers to a particular class of brain receptors. Our goal was the synthesis of radiotracers, cytectrenes derivatives, which are specific to the 5-HT1A receptor, whose dysfunction is an indicator of neuro degeneration. The study of their biodistribution revealed for only one of them, a good brain retention and a retrieval adequate for diagnosis.

Proton MRS of the peritumoral brain.

Science.gov (United States)

Chernov, Mikhail F; Kubo, Osami; Hayashi, Motohiro; Izawa, Masahiro; Maruyama, Takashi; Usukura, Masao; Ono, Yuko; Hori, Tomokatsu; Takakura, Kintomo

2005-02-15

Long-echo (TR: 2000 ms, TE: 136 ms) proton MRS of the cerebral tissue in the vicinity to intracranial lesion was done in 15 patients, mainly with parenchymal brain tumors. Significant decrease of N-acetylaspartate (NAA) (Plactate (Plactate in the lesion (Plactate in the lesion compared to perilesional brain (Plactate in the lesion is associated with lower relative NAA content in the perilesional brain tissue, independently on the presence or absence of any other factor, including brain edema (Plactate diffused from the tumor, or other metabolites secreted by lactate-producing neoplasm, should be considered as important contributors to the neuronal dysfunction in the surrounding brain. Decrease of NAA in the vicinity to intracranial lesions may reflect neuronal alteration responsible for associated epilepsy.

Prognostic impact of renal dysfunction does not differ according to the clinical profiles of patients: insight from the acute decompensated heart failure syndromes (ATTEND registry.

Directory of Open Access Journals (Sweden)

Taku Inohara

Full Text Available BACKGROUND: Renal dysfunction associated with acute decompensated heart failure (ADHF is associated with impaired outcomes. Its mechanism is attributed to renal arterial hypoperfusion or venous congestion, but its prognostic impact based on each of these clinical profiles requires elucidation. METHODS AND RESULTS: ADHF syndromes registry subjects were evaluated (N = 4,321. Logistic regression modeling calculated adjusted odds ratios (OR for in-hospital mortality for patients with and without renal dysfunction. Renal dysfunction risk was calculated for subgroups with hypoperfusion-dominant (eg. cold extremities, a low mean blood pressure or a low proportional pulse pressure or congestion-dominant clinical profiles (eg. peripheral edema, jugular venous distension, or elevated brain natriuretic peptide to evaluate renal dysfunction's prognostic impact in the context of the two underlying mechanisms. On admission, 2,150 (49.8% patients aged 73.3 ± 13.6 years had renal dysfunction. Compared with patients without renal dysfunction, those with renal dysfunction were older and had dominant ischemic etiology jugular venous distension, more frequent cold extremities, and higher brain natriuretic peptide levels. Renal dysfunction was associated with in-hospital mortality (OR 2.36; 95% confidence interval 1.75-3.18, p0.05. CONCLUSIONS: Baseline renal dysfunction was significantly associated with in-hospital mortality in ADHF patients. The prognostic impact of renal dysfunction was the same, regardless of its underlying etiologic mechanism.

Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction

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Deng Xiaolu

2011-04-01

Full Text Available Abstract Background Tumor necrosis factor-α (TNF-α, a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC barrier dysfunction. Methods Bend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL. RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER. p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability. Results We observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER. Conclusions Taken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF

Attention and driving in traumatic brain injury : A question of coping with time-pressure

NARCIS (Netherlands)

Brouwer, WH; Withaar, FK; Tant, MLM; van Zomeren, AH

Background: Diffuse and focal traumatic brain injury (TBI) can result in perceptual, cognitive, and motor dysfunction possibly leading to activity limitations in driving. Characteristic dysfunctions for severe diffuse TBI are confronted with function requirements derived from the hierarchical task

Dysfunction of Rapid Neural Adaptation in Dyslexia.

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Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

2016-12-21

Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

Inside the Diabetic Brain

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Chomova M.

2014-12-01

Full Text Available CNS complications resulting from diabetes mellitus (DM are a problem gaining more acceptance and attention in the recent years. Both types 1 and 2 DM represent an significant risk factor for decreased cognitive functions, memory and learning deficits as well as development of Alzheimer’s disease. Chronic hyperglycemia through protein glycation and increased oxidative stress contributes to brain dysfunction, however increasing evidences suggest that the pathology of DM in the brain involves a progressive and coordinated disruption of insulin signaling, with profound consequences for brain function and plasticity. Since many of the CNS changes observed in diabetic patients and animal models of DM are reminiscent of the changes seen in aging, the theory of advanced brain aging in DM has been proposed. This review summarizes the findings of the literature regarding the effects of DM on the brain in the terms of diabetes-related metabolic derangements and intracellular signaling.

Functional imaging of neurocognitive dysfunction in attention deficit hyperactivity disorder

International Nuclear Information System (INIS)

Wolf, I.; Tost, H.; Ruf, M.; Ende, G.

2005-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder of early childhood onset. Defining symptoms are chronic impairments of attention, impulse control and motor hyperactivity that frequently persist until adulthood. Miscellaneous causes of the disorder have been discussed. Accumulating evidence from imaging- and molecular genetic studies strengthened the theory of ADHS being a predominantly inherited disorder of neurobiological origin. In the last 15 years, non-invasive brain imaging methods were successfully implemented in pediatric research. Functional magnetic resonance imaging studies gave major insight into the neurobiological correlates of executive malfunction, inhibitory deficits and psychomotoric soft signs. These findings are in good accordance with brain morphometric data indicating a significant volumetric decrease of major components of striato-thalamo-cortical feedback loops, primarily influencing prefrontal executive functioning (e.g. basal ganglia). Empirical evidence points to a broad array of associated behavioral disturbances like deficient visuomotor abilities and oculomotor dysfunctions. This paper reviews the current empirical evidence derived from prior imaging studies. Special emphasis is given to the relevance of oculomotor dysfunctions in clinical and research settings, as well as their assessment in the MR environment. (orig.) [de

Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus.

Science.gov (United States)

Del Bigio, Marc R; Slobodian, Ili; Schellenberg, Angela E; Buist, Richard J; Kemp-Buors, Tanya L

2011-08-11

Hydrocephalus is associated with enlargement of cerebral ventricles. We hypothesized that magnetic resonance (MR) imaging parameters known to be influenced by tissue water content would change in parallel with ventricle size in young rats and that changes in blood-brain barrier (BBB) permeability would be detected. Hydrocephalus was induced by injection of kaolin into the cisterna magna of 4-week-old rats, which were studied 1 or 3 weeks later. MR was used to measure longitudinal and transverse relaxation times (T1 and T2) and apparent diffusion coefficients in several regions. Brain tissue water content was measured by the wet-dry weight method, and tissue density was measured in Percoll gradient columns. BBB permeability was measured by quantitative imaging of changes on T1-weighted images following injection of gadolinium diethylenetriamine penta-acetate (Gd-DTPA) tracer and microscopically by detection of fluorescent dextran conjugates. In nonhydrocephalic rats, water content decreased progressively from age 3 to 7 weeks. T1 and T2 and apparent diffusion coefficients did not exhibit parallel changes and there was no evidence of BBB permeability to tracers. The cerebral ventricles enlarged progressively in the weeks following kaolin injection. In hydrocephalic rats, the dorsal cortex was more dense and the white matter less so, indicating that the increased water content was largely confined to white matter. Hydrocephalus was associated with transient elevation of T1 in gray and white matter and persistent elevation of T2 in white matter. Changes in the apparent diffusion coefficients were significant only in white matter. Ventricle size correlated significantly with dorsal water content, T1, T2, and apparent diffusion coefficients. MR imaging showed evidence of Gd-DTPA leakage in periventricular tissue foci but not diffusely. These correlated with microscopic leak of larger dextran tracers. MR characteristics cannot be used as direct surrogates for water

Magnetic resonance imaging indicators of blood-brain barrier and brain water changes in young rats with kaolin-induced hydrocephalus

Directory of Open Access Journals (Sweden)

Del Bigio Marc R

2011-08-01

Full Text Available Abstract Background Hydrocephalus is associated with enlargement of cerebral ventricles. We hypothesized that magnetic resonance (MR imaging parameters known to be influenced by tissue water content would change in parallel with ventricle size in young rats and that changes in blood-brain barrier (BBB permeability would be detected. Methods Hydrocephalus was induced by injection of kaolin into the cisterna magna of 4-week-old rats, which were studied 1 or 3 weeks later. MR was used to measure longitudinal and transverse relaxation times (T1 and T2 and apparent diffusion coefficients in several regions. Brain tissue water content was measured by the wet-dry weight method, and tissue density was measured in Percoll gradient columns. BBB permeability was measured by quantitative imaging of changes on T1-weighted images following injection of gadolinium diethylenetriamine penta-acetate (Gd-DTPA tracer and microscopically by detection of fluorescent dextran conjugates. Results In nonhydrocephalic rats, water content decreased progressively from age 3 to 7 weeks. T1 and T2 and apparent diffusion coefficients did not exhibit parallel changes and there was no evidence of BBB permeability to tracers. The cerebral ventricles enlarged progressively in the weeks following kaolin injection. In hydrocephalic rats, the dorsal cortex was more dense and the white matter less so, indicating that the increased water content was largely confined to white matter. Hydrocephalus was associated with transient elevation of T1 in gray and white matter and persistent elevation of T2 in white matter. Changes in the apparent diffusion coefficients were significant only in white matter. Ventricle size correlated significantly with dorsal water content, T1, T2, and apparent diffusion coefficients. MR imaging showed evidence of Gd-DTPA leakage in periventricular tissue foci but not diffusely. These correlated with microscopic leak of larger dextran tracers. Conclusions MR

Respiratory mechanics in brain injury: A review

OpenAIRE

Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

2016-01-01

Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case ...

Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

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Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

2014-02-01

Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

MRI T2 relaxometry of brain regions and cognitive dysfunction following electroconvulsive therapy

OpenAIRE

Kunigiri, Girish; Jayakumar, P. N.; Janakiramaiah, N.; Gangadhar, B. N.

2007-01-01

Background: Although electroconvulsive therapy (ECT) causes no structural brain damage, recent studies reported altered brain perfusion acutely following ECT. This is in keeping with brain edema which was noted in animal experiments following electroconvulsive shock. Aim: This study examined alteration in magnetic resonance imaging (MRI) T2 relaxation time, a measure of brain edema, and its relation to therapeutic efficacy, orientation and memory impairment with ECT. Materials and Methods: Fi...

Electroencephalographic power and coherence analyses suggest altered brain function in abstinent male heroin-dependent patients

NARCIS (Netherlands)

Franken, Ingmar H. A.; Stam, Cornelis J.; Hendriks, Vincent M.; van den Brink, Wim

2004-01-01

Previous studies have shown that drug abuse is associated with altered brain function. However, studies of heroin abuse-related brain dysfunctions are scarce. Electroencephalographic ( EEG) power and coherence analyses are two important tools for examining the effects of drugs on brain function. In

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

Science.gov (United States)

Garcia, Camila Araújo Bernardino; Catalão, Carlos Henrique Rocha; Machado, Hélio Rubens; Júnior, Ivair Matias; Romeiro, Thais Helena; Peixoto-Santos, José Eduardo; Santos, Marcelo Volpon; da Silva Lopes, Luiza

2017-03-01

We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus. Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies. The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p  0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group. We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

Science.gov (United States)

Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

2017-03-01

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Methods of assessing the functional status of patients with left ventricular systolic dysfunction in interventional studies: can brain natriuretic peptide measurement be used as surrogate for the traditional methods?

DEFF Research Database (Denmark)

Abdulla, Jawdat; Køber, Lars; Torp-Pedersen, Christian

2004-01-01

AIM: To review whether brain natriuretic peptides (BNP) can be used as a surrogate for the traditional methods of assessing functional status in interventional studies of patients with left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: The traditional methods for assessing...... functional status including New York Heart Association (NYHA) class, exercise intolerance and quality of life were reviewed in relation to BNP measurements in patients with LVSD. A meta-analysis of four studies evaluating BNP levels versus exercise peak oxygen uptake or 6-minute walking distance showed...

Brain volume and cognitive function in patients with revascularized coronary artery disease

NARCIS (Netherlands)

Ottens, Thomas H; Hendrikse, Jeroen; Nathoe, Hendrik M; Biessels, Geert Jan; van Dijk, Diederik

2017-01-01

BACKGROUND: The pathogenesis of cognitive dysfunction in patients with CAD remains unclear. CAD is associated with brain atrophy and specific lesions. Detailed knowledge about the association of brain volume measured with MRI, and cognitive function in patients with CAD is lacking. We therefore

The glia doctrine: addressing the role of glial cells in healthy brain ageing.

Science.gov (United States)

Nagelhus, Erlend A; Amiry-Moghaddam, Mahmood; Bergersen, Linda H; Bjaalie, Jan G; Eriksson, Jens; Gundersen, Vidar; Leergaard, Trygve B; Morth, J Preben; Storm-Mathisen, Jon; Torp, Reidun; Walhovd, Kristine B; Tønjum, Tone

2013-10-01

Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Developmental dyslexia: dysfunction of a left hemisphere reading network

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Fabio eRichlan

2012-05-01

Full Text Available This mini-review summarizes and integrates findings from recent meta-analyses and original neuroimaging studies on functional brain abnormalities in dyslexic readers. Surprisingly, there is little empirical support for the standard neuroanatomical model of developmental dyslexia, which localizes the primary phonological decoding deficit in left temporo-parietal regions. Rather, recent evidence points to a dysfunction of a left hemisphere reading network, which includes occipito-temporal, inferior frontal, and inferior parietal regions.

Decomposing the Hounsfield unit: probabilistic segmentation of brain tissue in computed tomography.

Science.gov (United States)

Kemmling, A; Wersching, H; Berger, K; Knecht, S; Groden, C; Nölte, I

2012-03-01

The aim of this study was to present and evaluate a standardized technique for brain segmentation of cranial computed tomography (CT) using probabilistic partial volume tissue maps based on a database of high resolution T1 magnetic resonance images (MRI). Probabilistic tissue maps of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) were derived from 600 normal brain MRIs (3.0 Tesla, T1-3D-turbo-field-echo) of 2 large community-based population studies (BiDirect and SEARCH Health studies). After partial tissue segmentation (FAST 4.0), MR images were linearly registered to MNI-152 standard space (FLIRT 5.5) with non-linear refinement (FNIRT 1.0) to obtain non-binary probabilistic volume images for each tissue class which were subsequently used for CT segmentation. From 150 normal cerebral CT scans a customized reference image in standard space was constructed with iterative non-linear registration to MNI-152 space. The inverse warp of tissue-specific probability maps to CT space (MNI-152 to individual CT) was used to decompose a CT image into tissue specific components (GM, WM, CSF). Potential benefits and utility of this novel approach with regard to unsupervised quantification of CT images and possible visual enhancement are addressed. Illustrative examples of tissue segmentation in different pathological cases including perfusion CT are presented. Automated tissue segmentation of cranial CT images using highly refined tissue probability maps derived from high resolution MR images is feasible. Potential applications include automated quantification of WM in leukoaraiosis, CSF in hydrocephalic patients, GM in neurodegeneration and ischemia and perfusion maps with separate assessment of GM and WM.

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies.

Science.gov (United States)

Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2017-02-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age-matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 expression around blood vessels. MMI-induced glymphatic dysfunction with delayed cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases Aquaporin-4 and induces glymphatic dysfunction which may play an important role in MMI-induced axonal/WM damage and cognitive deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigating the ''social brain'' through Williams syndrome

International Nuclear Information System (INIS)

Nagamine, Masanori; Mimura, Masaru; Reiss, A.L.; Hoeft, F.

2010-01-01

Recent advances in social cognitive neuroscience have led to the concept of the ''social brain''. The social brain includes neural processes specialized for processing social information necessary for the recognition of self and others, and interpersonal relationships. Because of its unique behavioral phenotypic features which includes 'hypersociability', Williams syndrome has gained popularity among social cognitive neuroscientists. Individuals with Williams syndrome share the same genetic risk factor for cognitive-behavioral dysfunction utilizing brain imaging to elucidate endophenotype provides us with an unprecendented opportunity to study gene, brain and behavior relationships especially those related to social cognition. In this review, we provide an overview of neuroimaging studies on social cognition in Williams syndrome and discuss the neural basis of the social brain. (author)

Vascular remodeling versus amyloid beta-induced oxidative stress in the cerebrovascular dysfunctions associated with Alzheimer's disease.

Science.gov (United States)

Tong, Xin-Kang; Nicolakakis, Nektaria; Kocharyan, Ara; Hamel, Edith

2005-11-30

The roles of oxidative stress and structural alterations in the cerebrovascular dysfunctions associated with Alzheimer's disease (AD) were investigated in transgenic mice overexpressing amyloid precusor protein (APP+) or transforming growth factor-beta1 (TGF+). Age-related impairments and their in vitro reversibility were evaluated, and underlying pathogenic mechanisms were assessed and compared with those seen in AD brains. Vasoconstrictions to 5-HT and endothelin-1 were preserved, except in the oldest (18-21 months of age) TGF+ mice. Despite unaltered relaxations to sodium nitroprusside, acetylcholine (ACh) and calcitonin gene-related peptide-mediated dilatations were impaired, and there was an age-related deficit in the basal availability of nitric oxide (NO) that progressed more gradually in TGF+ mice. The expression and progression of these deficits were unrelated to the onset or extent of thioflavin-S-positive vessels. Manganese superoxide dismutase (SOD2) was upregulated in pial vessels and around brain microvessels of APP+ mice, pointing to a role of superoxide in the dysfunctions elicited by amyloidosis. In contrast, vascular wall remodeling associated with decreased levels of endothelial NO synthase and cyclooxygenase-2 and increased contents of vascular endothelial growth factor and collagen-I and -IV characterized TGF+ mice. Exogenous SOD or catalase normalized ACh dilatations and NO availability in vessels from aged APP+ mice but had no effect in those of TGF+ mice. Increased perivascular oxidative stress was not evidenced in AD brains, but vascular wall alterations compared well with those seen in TGF+ mice. We conclude that brain vessel remodeling and associated alterations in levels of vasoactive signaling molecules are key contributors to AD cerebrovascular dysfunctions.

Evening dietary tryptophan improves post-sleep behavioral and brain measures of memory function in healthy subjects

NARCIS (Netherlands)

Markus, C.R.; Jonkman, L.M.; Lammers, J.H.C.M.; Deutz, N.E.P.

2006-01-01

Brain serotonin function has been implicated in the control of sleep and sleep related memory dysfunctions are attributed to deficient brain serotonin activity. Depletion of the serotonin precursor tryptophan reduces brain serotonin function and is found to cause sleep abnormalities and cognitive

Cingulate, Frontal and Parietal Cortical Dysfunction in Attention-Deficit/Hyperactivity Disorder

Science.gov (United States)

Bush, George

2011-01-01

Functional and structural neuroimaging have identified abnormalities of the brain that are likely to contribute to the neuropathophysiology of attention-deficit/hyperactivity disorder (ADHD). In particular, hypofunction of the brain regions comprising the cingulo-frontal-parietal (CFP) cognitive-attention network have been consistently observed across studies. These are major components of neural systems that are relevant to ADHD, including cognitive/attention networks, motor systems and reward/feedback-based processing systems. Moreover, these areas interact with other brain circuits that have been implicated in ADHD, such as the “default mode” resting state network. ADHD imaging data related to CFP network dysfunction will be selectively highlighted here to help facilitate its integration with the other information presented in this special issue. Together, these reviews will help shed light on the neurobiology of ADHD. PMID:21489409

Chediak-Higashi syndrome: brain MRI and MR spectroscopy manifestations

International Nuclear Information System (INIS)

Lolli, Valentina; Soto Ares, Gustavo; Pruvo, Jean-Pierre; Abou Chahla, Wadih; Jissendi-Tchofo, Patrice

2015-01-01

Chediak-Higashi syndrome is a rare inherited metabolic disorder characterized by partial oculocutaneous albinism, immunodeficiency, and neurological dysfunction. We present the brain magnetic resonance imaging (MRI) and MR spectroscopy (MRS) findings obtained during the accelerated phase of the disorder in an 8-year-old. The brain MRI manifestations at recurrences 15 months and 24 months later are reported as well. (orig.)

Chediak-Higashi syndrome: brain MRI and MR spectroscopy manifestations

Energy Technology Data Exchange (ETDEWEB)

Lolli, Valentina; Soto Ares, Gustavo; Pruvo, Jean-Pierre [Roger Salengro Hospital, CHRU, Neuroradiology Department, Lille (France); Abou Chahla, Wadih [Jeanne de Flandre Hospital, Pediatric Hematology and Oncology Department, Lille (France); Jissendi-Tchofo, Patrice [University Hospital Saint-Pierre, Radiology Department - Pediatric Neuroradiology Section, Brussels (Belgium)

2015-08-15

Chediak-Higashi syndrome is a rare inherited metabolic disorder characterized by partial oculocutaneous albinism, immunodeficiency, and neurological dysfunction. We present the brain magnetic resonance imaging (MRI) and MR spectroscopy (MRS) findings obtained during the accelerated phase of the disorder in an 8-year-old. The brain MRI manifestations at recurrences 15 months and 24 months later are reported as well. (orig.)

Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury

DEFF Research Database (Denmark)

Östberg, Anna; Virta, Jere; Rinne, Juha O

2018-01-01

subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication. DESIGN:: Cholinergic function was assessed with [methyl-C] N-methylpiperidyl-4-acetate-PET (C-MP4A-PET), which reflects the activity...... was notably lower throughout the cortex in both respondents and nonrespondents, without significant differences between them. CONCLUSION:: Our study suggests that frontal cholinergic dysfunction is associated with the clinical response to cholinergic stimulation in patients with traumatic brain injury....

Law, Responsibility, and the Brain

Science.gov (United States)

Mobbs, Dean; Lau, Hakwan C.; Jones, Owen D.; Frith, Chris D.

In perhaps the first attempt to link the brain to mental illness, Hippocrates elegantly wrote that it is the brain that makes us mad or delirious. Epitomizing one of the fundamental assumptions of contemporary neuroscience, Hippocrates' words resonate far beyond the classic philosophical puzzle of mind and body and posit that our behavior, no matter how monstrous, lies at the mercy of our brain's integrity. While clinicopathological observations have long pointed to several putative neurobiological systems as important in antisocial and violent criminal behavior, recent advances in brain-imaging have the potential to provide unparalleled insight. Consequently, brain-imaging studies have reinvigorated the neurophilosophical and legal debate of whether we are free agents in control of our own actions or mere prisoners of a biologically determined brain. In this chapter, we review studies pointing to brain dysfunction in criminally violent individuals and address a range of philosophical and practical issues concerning the use of brainimaging in court. We finally lay out several guidelines for its use in the legal system.

Status epilepticus in immature rats is associated with oxidative stress and mitochondrial dysfunction

Directory of Open Access Journals (Sweden)

Jaroslava eFolbergrová

2016-05-01

Full Text Available Epilepsy is a neurologic disorder, particularly frequent in infants and children where it can lead to serious consequences later in life. Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of many neurological disorders including epilepsy in adults. However, their role in immature epileptic brain is unclear since there have been two contrary opinions: oxidative stress is age-dependent and does not occur in immature brain during status epilepticus and, on the other hand, evidence of oxidative stress in immature brain during a specific model of status epilepticus. To solve this dilemma, we have decided to investigate oxidative stress following status epilepticus induced in immature 12-day-old rats by three substances with a different mechanism of action, namely 4-aminopyridine, LiCl-pilocarpine or kainic acid. FluoroJade-B staining revealed mild brain damage especially in hippocampus and thalamus in each of the tested models. Decrease of glucose and glycogen with parallel rises of lactate clearly indicate high rate of glycolysis, which was apparently not sufficient in 4-AP and Li-Pilo status, as evident from the decreases of PCr levels. Hydroethidium method revealed significantly higher levels of superoxide anion (by ~60 % in the hippocampus, cerebral cortex and thalamus of immature rats during status. Status epilepticus lead to mitochondrial dysfunction with a specific pronounced decrease of complex I activity that persisted for a long period of survival. Complex II and IV activities remained in the control range. Antioxidant treatment with SOD mimetic MnTMPYP or peroxynitrite scavenger FeTPPS significantly attenuated oxidative stress and inhibition of complex I activity. These findings bring evidence that oxidative stress and mitochondrial dysfunction are age and model independent, and may thus be considered a general phenomenon. They can have a clinical relevance for a novel approach to the treatment of epilepsy

Dogs with cognitive dysfunction as a spontaneous model for early Alzheimer's Disease

DEFF Research Database (Denmark)

Schütt, Trine; Helboe, Lone; Pedersen, Lars Østergaard

2016-01-01

Aged companion dogs with canine cognitive dysfunction (CCD) spontaneously develop varying degrees of progressive cognitive decline and particular neuropathological features correspondent to the changes associated with Alzheimer's disease (AD) in humans. The aim of the present study...... was to characterize certain aspects of neuropathology and inflammatory markers related to aging and CCD in dogs in comparison with human AD. Fifteen brains from aged dogs with normal cognitive function, mild cognitive impairment, or CCD were investigated and compared with two control brains from young dogs and brain...... sections from human AD subjects. The neuropathological investigations included evaluation of amyloid-β (Aβ) plaque deposition (N-terminally truncated and pyroglutamyl-modified Aβ included), tau pathology, and inflammatory markers in prefrontal cortex. Cortical Aβ deposition was found to be only...

Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats

NARCIS (Netherlands)

Hovens, Iris B.; van Leeuwen, Barbara L.; Nyakas, Csaba; Heineman, Erik; van der Zee, Eddy A.; Schoemaker, Regien G.

Research indicates that neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD) in older patients. However, studies have mainly focused on hippocampal neuroinflammation and hippocampal-dependent learning and memory, which does not cover the whole spectrum of POCD. We

Integrating Functional Brain Neuroimaging and Developmental Cognitive Neuroscience in Child Psychiatry Research

Science.gov (United States)

Pavuluri, Mani N.; Sweeney, John A.

2008-01-01

The use of cognitive neuroscience and functional brain neuroimaging to understand brain dysfunction in pediatric psychiatric disorders is discussed. Results show that bipolar youths demonstrate impairment in affective and cognitive neural systems and in these two circuits' interface. Implications for the diagnosis and treatment of psychiatric…

Disruption of Brain-Heart Coupling in Sepsis

NARCIS (Netherlands)

Admiraal, Marjolein M.; Gilmore, Emily J.; Van Putten, Michel J.A.M.; Zaveri, Hitten P.; Hirsch, Lawrence J.; Gaspard, Nicolas

2017-01-01

Purpose: To investigate heart rate and EEG variability and their coupling in patients with sepsis and determine their relationship to sepsis severity and severity of sepsis-Associated brain dysfunction. Methods: Fifty-Two patients with sepsis were prospectively identified, categorized as comatose (N

Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

Science.gov (United States)

Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

2014-06-01

Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions. Published by Oxford University Press on behalf of the Guarantors of Brain 2014. This work is written by US Government employees and is in the public domain in the US.

Traumatic Brain Injury: Nuclear Medicine Neuroimaging

NARCIS (Netherlands)

Sánchez-Catasús, Carlos A; Vállez Garcia, David; Le Riverend Morales, Eloísa; Galvizu Sánchez, Reinaldo; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; de Vries, Erik FJ; van Waarde, Aren; Leenders, Klaus L

2014-01-01

This chapter provides an up-to-date review of nuclear medicine neuroimaging in traumatic brain injury (TBI). 18F-FDG PET will remain a valuable tool in researching complex mechanisms associated with early metabolic dysfunction in TBI. Although evidence-based imaging studies are needed, 18F-FDG PET

Maternal thyroid dysfunction and risk of seizure in the child

DEFF Research Database (Denmark)

Andersen, Stine Linding; Laurberg, Peter; Wu, Chunsen

2013-01-01

Thyroid hormones are essential for brain development, and maternal thyroid disease may affect child neurocognitive development. Some types of seizures may also depend upon early exposure of the developing central nervous system, and we hypothesized that maternal thyroid dysfunction could increase...... the risk of seizure in the child. In a Danish population-based study we included 1,699,693 liveborn singletons, and from the Danish National Hospital Register we obtained information on maternal diagnosis of hyper- or hypothyroidism and neonatal seizure, febrile seizure, and epilepsy in the child. Maternal...... diagnosis of thyroid dysfunction before or after birth of the child was registered in two percent of the singleton births. In adjusted analyses, maternal hyperthyroidism and hypothyroidism first time diagnosed after birth of the child were associated with a significant increased risk of epilepsy...

Executive dysfunctions in pedophilic and nonpedophilic child molesters.

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Schiffer, Boris; Vonlaufen, Corinne

2011-07-01

There is some evidence that child molesters show neuropsychological abnormalities which might reflect specific structural and/or functional brain alterations, but there are also inconsistencies in the existing findings which need to be clarified. Most of the different outcomes can either be explained by the fact that different types of child molesters were examined or by not having accounted for basically confounding factors such as age, education/intelligence, or criminality. The present study therefore sought to determine whether pedophilic and nonpedophilic child molesters, compared to relevant control groups, show different profiles of executive dysfunction when accounting for potentially confounding factors. The performance of 30 child molesters (15 pedophilic and 15 nonpedophilic) and 33 age- and education-matched controls (16 nonsexual offenders and 17 healthy controls) was assessed regarding several neuropsychological functions. Scores on different neurocognitive tests and semistructured diagnostical interviews. Results indicate that pedophilic child molesters exhibited less performance deficits in cognitive functioning than nonpedophilic child molesters. Compared to healthy controls and nonsexual offenders, the pedophilic child molesters only showed executive dysfunction concerning response inhibition, whereas the nonpedophilic child molesters revealed more severe dysfunction, especially on tasks associated with cognitive flexibility and verbal memory. These results enhance our knowledge about executive dysfunction associated with criminality and/or pedophilia, as they suggest different profiles of impairment between groups. In summary, data suggest that nonpedophilic child molesters showed more severe cognitive deficits than pedophilic child molesters. However, as response inhibition is associated with prefrontal (i.e., orbitofrontal) functioning, the deficits observed in both child molester groups indicate dysfunction in the orbitofrontal cortex. This

Hypopituitarism in pediatric survivors of inflicted traumatic brain injury.

Science.gov (United States)

Auble, Bethany A; Bollepalli, Sureka; Makoroff, Kathi; Weis, Tammy; Khoury, Jane; Colliers, Tracy; Rose, Susan R

2014-02-15

Endocrine dysfunction is common after accidental traumatic brain injury (TBI). Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI) is not known. The aim of this study was to examine endocrinopathy in children after moderate-to-severe iTBI. Children with previous iTBI (n=14) were evaluated for growth/endocrine dysfunction, including anthropometric measurements and hormonal evaluation (nocturnal growth hormone [GH], thyrotropin surge, morning and low-dose adrenocorticotropin stimulated cortisol, insulin-like growth factor 1, IGF-binding protein 3, free thyroxine, prolactin [PRL], and serum/urine osmolality). Analysis used Fisher's exact test and Wilcoxon's rank-sum test, as appropriate. Eighty-six percent of subjects had endocrine dysfunction with at least one abnormality, whereas 50% had two or more abnormalities, significantly increased compared to an estimated 2.5% with endocrine abnormality in the general population (p<0.001). Elevated prolactin was common (64%), followed by abnormal thyroid function (33%), short stature (29%), and low GH peak (17%). High prolactin was common in subjects with other endocrine abnormalities. Two were treated with thyroid hormone and 2 may require GH therapy. In conclusion, children with a history of iTBI show high risk for endocrine dysfunction, including elevated PRL and growth abnormalities. This effect of iTBI has not been well described in the literature. Larger, multi-center, prospective studies would provide more data to determine the extent of endocrine dysfunction in iTBI. We recommend that any child with a history of iTBI be followed closely for growth velocity and pubertal changes. If growth velocity is slow, PRL level and a full endocrine evaluation should be performed.

Thiamin deficiency on fetal brain development with and without prenatal alcohol exposure.

Science.gov (United States)

Kloss, Olena; Eskin, N A Michael; Suh, Miyoung

2018-04-01

Adequate thiamin levels are crucial for optimal health through maintenance of homeostasis and viability of metabolic enzymes, which require thiamine as a co-factor. Thiamin deficiency occurs during pregnancy when the dietary intake is inadequate or excessive alcohol is consumed. Thiamin deficiency leads to brain dysfunction because thiamin is involved in the synthesis of myelin and neurotransmitters (e.g., acetylcholine, γ-aminobutyric acid, glutamate), and its deficiency increases oxidative stress by decreasing the production of reducing agents. Thiamin deficiency also leads to neural membrane dysfunction, because thiamin is a structural component of mitochondrial and synaptosomal membranes. Similarly, in-utero exposure to alcohol leads to fetal brain dysfunction, resulting in negative effects such as fetal alcohol spectrum disorder (FASD). Thiamin deficiency and prenatal exposure to alcohol could act synergistically to produce negative effects on fetal development; however, this area of research is currently under-studied. This minireview summarizes the evidence for the potential role of thiamin deficiency in fetal brain development, with or without prenatal exposure to alcohol. Such evidence may influence the development of new nutritional strategies for preventing or mitigating the symptoms of FASD.

The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction.

Science.gov (United States)

Hargrave, Sara L; Jones, Sabrina; Davidson, Terry L

2016-06-01

Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to a previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline.

Neocortical Transplants in the Mammalian Brain Lack a Blood-Brain Barrier to Macromolecules

Science.gov (United States)

Rosenstein, Jeffrey M.

1987-02-01

In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function.

Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin?

Science.gov (United States)

Giatti, Silvia; Diviccaro, Silvia; Panzica, Giancarlo; Melcangi, Roberto Cosimo

2018-04-19

Sexual dysfunction is a clinical condition due to different causes including the iatrogenic origin. For instance, it is well known that sexual dysfunction may occur in patients treated with antidepressants like selective serotonin reuptake inhibitors (SSRI). A similar side effect has been also reported during treatment with finasteride, an inhibitor of the enzyme 5alpha-reductase, for androgenetic alopecia. Interestingly, sexual dysfunction persists in both cases after drug discontinuation. These conditions have been named post-SSRI sexual dysfunction (PSSD) and post-finasteride syndrome (PFS). In particular, feeling of a lack of connection between the brain and penis, loss of libido and sex drive, difficulty in achieving an erection and genital paresthesia have been reported by patients of both conditions. It is interesting to note that the incidence of these diseases is probably so far underestimated and their etiopathogenesis is not sufficiently explored. To this aim, the present review will report the state of art of these two different pathologies and discuss, on the basis of the role exerted by three different neuromodulators such as dopamine, serotonin and neuroactive steroids, whether the persistent sexual dysfunction observed could be determined by common mechanisms.

Brain Imaging of Human Sexual Response: Recent Developments and Future Directions

OpenAIRE

Ruesink, Gerben B; Georgiadis, Janniko R

2017-01-01

Purpose of Review: The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Recent Findings: Stable patterns of brain activation have been established for different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From ...

[Brain imaging in autism spectrum disorders. A review].

Science.gov (United States)

Dziobek, I; Köhne, S

2011-05-01

In the past two decades, an increasing number of functional and structural brain imaging studies has provided insights into the neurobiological basis of autism spectrum disorders (ASD). This article summarizes pertinent functional brain imaging studies addressing the neuronal underpinnings of ASD symptomatology (impairments in social interaction and communication, repetitive and restrictive behavior) and associated neuropsychological deficits (theory of mind, executive functions, central coherence), complemented by relevant structural imaging findings. The results of these studies show that although cognitive functions in ASD are generally mediated by the same brain regions as in typically developed individuals, the degree and especially the patterns of brain activation often differ. Therefore, a hypothesis of aberrant network connectivity has increasingly been favored over one of focal brain dysfunction.

Neonatal hydrocephalus is a result of a block in folate handling and metabolism involving 10-formyltetrahydrofolate dehydrogenase.

Science.gov (United States)

Naz, Naila; Jimenez, Alicia Requena; Sanjuan-Vilaplana, Anna; Gurney, Megan; Miyan, Jaleel

2016-08-01

Folate is vital in a range of biological processes and folate deficiency is associated with neurodevelopmental disorders such as neural tube defects and hydrocephalus (HC). 10-formyl-tetrahydrofolate-dehydrogenase (FDH) is a key regulator for folate availability and metabolic interconversion for the supply of 1-carbon groups. In previous studies, we found a deficiency of FDH in CSF associated with the developmental deficit in congenital and neonatal HC. In this study, we therefore aimed to investigate the role of FDH in folate transport and metabolism during the brain development of the congenital hydrocephalic Texas (H-Tx) rat and normal (Sprague-Dawley) rats. We show that at embryonic (E) stage E18 and E20, FDH-positive cells and/or vesicles derived from the cortex can bind methyl-folate similarly to folate receptor alpha, the main folate transporter. Hydrocephalic rats expressed diminished nuclear FDH in both liver and brain at all postnatal (P) ages tested (P5, P15, and P20) together with a parallel increase in hepatic nuclear methyl-folate at P5 and cerebral methylfolate at P15 and P20. A similar relationship was found between FDH and 5-methyl cytosine, the main marker for DNA methylation. The data indicated that FDH binds and transports methylfolate in the brain and that decreased liver and brain nuclear expression of FDH is linked with decreased DNA methylation which could be a key factor in the developmental deficits associated with congenital and neonatal HC. Folate deficiency is associated with neurodevelopmental disorders such as neural tube defects and hydrocephalus. 10-formyl-tetrahydrofolate-dehydrogenase (FDH) is a key regulator for folate availability and metabolic interconversion. We show that FDH binds and transports methylfolate in the brain. Moreover, we found that a deficiency of FDH in the nucleus of brain and liver is linked with decreased DNA methylation which could be a key factor in the developmental deficits associated with congenital and

The resting state fMRI study of patients with Parkinson's disease associated with cognitive dysfunction

International Nuclear Information System (INIS)

Feng Jieying; Huang Biao

2013-01-01

Parkinson's disease (PD) is the most common neurodegenerative cause of Parkinsonism, but the high morbidity of PD accompanied cognitive dysfunction hasn't drawn enough attention by the clinicians. With the rapid development of the resting state functional MRI (fMRI) technique, the cause of PD patients with cognitive dysfunction may be associated with the damage of functional connectivity of the motor networks and the cognitive networks. The relationship between neuropathologic mechanism of PD patients with cognitive dysfunction and impaired cognitive circuits will be disclosed by building the changes of brain topological structure in patients. The resting state fMRI study can provide the rationale for prevention, diagnosis and treatment of PD. (authors)

Neurogenesis in the aging brain.

Science.gov (United States)

Apple, Deana M; Solano-Fonseca, Rene; Kokovay, Erzsebet

2017-10-01

Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair. In this review, we describe NSCs and their niches during tissue homeostasis and how they undergo age-associated remodeling and dysfunction. We also discuss some of the functional ramifications in the brain from NSC aging. Finally, we discuss some recent insights from interventions in NSC aging that could eventually translate into therapies for healthy brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence of cognitive dysfunction after soccer playing with ball heading using a novel tablet-based approach.

Directory of Open Access Journals (Sweden)

Marsha R Zhang

Full Text Available Does frequent head-to-ball contact cause cognitive dysfunctions and brain injury to soccer players? An iPad-based experiment was designed to examine the impact of ball-heading among high school female soccer players. We examined both direct, stimulus-driven, or reflexive point responses (Pro-Point as well as indirect, goal-driven, or voluntary point responses (Anti-Point, thought to require cognitive functions in the frontal lobe. The results show that soccer players were significantly slower than controls in the Anti-Point task but displayed no difference in Pro-Point latencies, indicating a disruption specific to voluntary responses. These findings suggest that even subconcussive blows in soccer can result in cognitive function changes that are consistent with mild traumatic brain injury of the frontal lobes. There is great clinical and practical potential of a tablet-based application for quick detection and monitoring of cognitive dysfunction.

Evidence of Cognitive Dysfunction after Soccer Playing with Ball Heading Using a Novel Tablet-Based Approach

Science.gov (United States)

Lin, Angela H.; Patel, Saumil S.; Sereno, Anne B.

2013-01-01

Does frequent head-to-ball contact cause cognitive dysfunctions and brain injury to soccer players? An iPad-based experiment was designed to examine the impact of ball-heading among high school female soccer players. We examined both direct, stimulus-driven, or reflexive point responses (Pro-Point) as well as indirect, goal-driven, or voluntary point responses (Anti-Point), thought to require cognitive functions in the frontal lobe. The results show that soccer players were significantly slower than controls in the Anti-Point task but displayed no difference in Pro-Point latencies, indicating a disruption specific to voluntary responses. These findings suggest that even subconcussive blows in soccer can result in cognitive function changes that are consistent with mild traumatic brain injury of the frontal lobes. There is great clinical and practical potential of a tablet-based application for quick detection and monitoring of cognitive dysfunction. PMID:23460843

Manganese accumulation in the brain: MR imaging

Energy Technology Data Exchange (ETDEWEB)

Uchino, A.; Nomiyama, K.; Takase, Y.; Nakazono, T.; Nojiri, J.; Kudo, S. [Saga Medical School, Department of Radiology, Saga (Japan); Noguchi, T. [Kyushu University, Department of Clinical Radiology, Graduate School of Medicine, Fukuoka (Japan)

2007-09-15

Manganese (Mn) accumulation in the brain is detected as symmetrical high signal intensity in the globus pallidi on T1-weighted MR images without an abnormal signal on T2-weighted images. In this review, we present several cases of Mn accumulation in the brain due to acquired or congenital diseases of the abdomen including hepatic cirrhosis with a portosystemic shunt, congenital biliary atresia, primary biliary cirrhosis, congenital intrahepatic portosystemic shunt without liver dysfunction, Rendu-Osler-Weber syndrome with a diffuse intrahepatic portosystemic shunt, and patent ductus venosus. Other causes of Mn accumulation in the brain are Mn overload from total parenteral nutrition and welding-related Mn intoxication. (orig.)

Metabolomic Analysis in Brain Research: Opportunities & Challenges

Directory of Open Access Journals (Sweden)

Catherine G Vasilopoulou

2016-05-01

Full Text Available Metabolism being a fundamental part of molecular physiology, elucidating the structure and regulation of metabolic pathways is crucial for obtaining a comprehensive perspective of cellular function and understanding the underlying mechanisms of its dysfunction(s. Therefore, quantifying an accurate metabolic network activity map under various physiological conditions is among the major objectives of systems biology in the context of many biological applications. Especially for CNS, metabolic network activity analysis can substantially enhance our knowledge about the complex structure of the mammalian brain and the mechanisms of neurological disorders, leading to the design of effective therapeutic treatments. Metabolomics has emerged as the high-throughput quantitative analysis of the concentration profile of small molecular weight metabolites, which act as reactants and products in metabolic reactions and as regulatory molecules of proteins participating in many biological processes. Thus, the metabolic profile provides a metabolic activity fingerprint, through the simultaneous analysis of tens to hundreds of molecules of pathophysiological and pharmacological interest. The application of metabolomics is at its standardization phase in general, and the challenges for paving a standardized procedure are even more pronounced in brain studies. In this review, we support the value of metabolomics in brain research. Moreover, we demonstrate the challenges of designing and setting up a reliable brain metabolomic study, which, among other parameters, has to take into consideration the sex differentiation and the complexity of brain physiology manifested in its regional variation. We finally propose ways to overcome these challenges and design a study that produces reproducible and consistent results.

Cardiac lipid accumulation associated with diastolic dysfunction in obese mice

DEFF Research Database (Denmark)

Christoffersen, Christina; Bollano, Entela; Lindegaard, Marie L S

2003-01-01

Obesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport....../ob mice and 2.5 +/- 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased...... across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and beta-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 +/- 0.4 vs. 2.3 +/- 0.4 microg/mg; P hearts. Histological examinations...

Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury.

Science.gov (United States)

Kim, Jae Young; Lee, Yong Woo; Kim, Jae Hwan; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

2015-07-01

Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

Alterations in blood-brain barrier function following acute hypertension: comparison of the blood-to-brain transfer of horseradish peroxidase with that of alpha-aminisobutyric acid

International Nuclear Information System (INIS)

Ellison, M.D.B.

1985-01-01

The blood-brain barrier (BBB) selectively restricts the blood-to-brain passage of many solutes owing to unique properties of cerebrovascular endothelial cell membranes. To date, experimental study of the BBB has been accomplished primarily through the use of two different methodological approaches. Morphological studies have mostly employed large molecular weight (MW) tracers to detect morphological alterations underlying increased permeability. Physiological studies, employing smaller, more physiologic tracers have successfully described, quantitatively, certain functional aspects of blood-to-brain transfer. The current work attempts to merge these two approaches and to consider barrier function/dysfunction from both a morphological and a functional perspective. Specifically, the study compares in rats, following acute hypertension, the cerebrovascular passage of 14 C-alpha-aminoisobutyric acid (AIB) and that of horseradish peroxidase (HRP). The blood-to-brain passage of AIB and HRP were compared following acute hypertension, with regard to both the distributions of the tracer extravasation patterns and the magnitude of tracer extravasation. The results of this study suggest that traditional morphological barrier studies alone do not reveal all aspects of altered barrier status and that multiple mechanisms underlying increased BBB permeability may operate simultaneously during BBB dysfunction

Brain imaging for oxidative stress and mitochondrial dysfunction in neurodegenerative diseases

International Nuclear Information System (INIS)

Okazawa, H.; Tsujikawa, T.; Kiyono, Y.; Ikawa, M.; Yoneda, M.

2014-01-01

Oxidative stress, one of the most probable molecular mechanisms for neuronal impairment, is reported to occur in the affected brain regions of various neurodegenerative diseases. Recently, many studies showed evidence of a link between oxidative stress or mitochondrial damage and neuronal degeneration. Basic in vitro experiments and postmortem studies demonstrated that biomarkers for oxidative damage can be observed in the pathogenic regions of the brain and the affected neurons. Model animal studies also showed oxidative damage associated with neuronal degeneration. The molecular imaging method with positron emission tomography (PET) is expected to delineate oxidatively stressed microenvironments to elucidate pathophysiological changes of the in vivo brain; however, only a few studies have successfully demonstrated enhanced stress in patients. Radioisotope copper labeled diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) may be the most promising candidate for this oxidative stress imaging. The tracer is usually known as a hypoxic tissue imaging PET probe, but the accumulation mechanism is based on the electron rich environment induced by mitochondrial impairment and/or microsomal over-reduction, and thus it is considered to represent the oxidative stress state correlated with the degree of disease severity. In this review, Cu-ATSM PET is introduced in detail from the basics to practical methods in clinical studies, as well as recent clinical studies on cerebrovascular diseases and neurodegenerative diseases. Several other PET probes are also introduced from the point of view of neuronal oxidative stress imaging. These molecular imaging methods should be promising tools to reveal oxidative injuries in various brain diseases

Pathogenesis of irradiation-induced cognitive dysfunction

International Nuclear Information System (INIS)

Abayomi, O.K.

1996-01-01

Neurocognitive dysfunction is a common sequela of cranial irradiation that is especially severe in young children. The underlying mechanisms of this disorder have not been described. The present review describes the role of the hippocampus and the anatomically related cortex in memory function and its marked susceptibility to ischemic and hypoxic injury. Based on studies of animal models of human amnesia and histopathological findings in the irradiated brain, the neurocognitive sequela of cranial irradiation can be seen to be mediated through vascular injury, resulting in ischemia and hypoxia in the hippocampal region. Recognition of the site and mechanisms of this injury may lead to the development of techniques to minimize the risks. (orig.)

Pathogenesis of irradiation-induced cognitive dysfunction

Energy Technology Data Exchange (ETDEWEB)

Abayomi, O.K. [Howard Univ. Hospital, Washington, DC (United States). Dept. of Radiation Oncology

1996-12-31

Neurocognitive dysfunction is a common sequela of cranial irradiation that is especially severe in young children. The underlying mechanisms of this disorder have not been described. The present review describes the role of the hippocampus and the anatomically related cortex in memory function and its marked susceptibility to ischemic and hypoxic injury. Based on studies of animal models of human amnesia and histopathological findings in the irradiated brain, the neurocognitive sequela of cranial irradiation can be seen to be mediated through vascular injury, resulting in ischemia and hypoxia in the hippocampal region. Recognition of the site and mechanisms of this injury may lead to the development of techniques to minimize the risks. (orig.).

Pseudotumor Cerebri and Glymphatic Dysfunction

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Marcio Luciano de Souza Bezerra

2018-01-01

Full Text Available In contrast to virtually all organ systems of the body, the central nervous system was until recently believed to be devoid of a lymphatic system. The demonstration of a complex system of paravascular channels formed by the endfeet of astroglial cells ultimately draining into the venous sinuses has radically changed this idea. The system is subsidized by the recirculation of cerebrospinal fluid (CSF through the brain parenchyma along paravascular spaces (PVSs and by exchanges with the interstitial fluid (IF. Aquaporin-4 channels are the chief transporters of water through these compartments. This article hypothesizes that glymphatic dysfunction is a major pathogenetic mechanism underpinning idiopathic intracranial hypertension (IIH. The rationale for the hypothesis springs from MRI studies, which have shown many signs related to IIH without evidence of overproduction of CSF. We propose that diffuse retention of IF is a direct consequence of an imbalance of glymphatic flow. This imbalance, in turn, may result from an augmented flow from the arterial PVS into the IF, by impaired outflow of the IF into the paravenous spaces, or both. Our hypothesis is supported by the facts that (i visual loss, one of the main complications of IIH, is secondary to the impaired drainage of the optic nerve, a nerve richly surrounded by water channels and with a long extracranial course in its meningeal sheath; (ii there is a high association between IIH and obesity, a condition related to paravascular inflammation and lymphatic disturbance, and (iii glymphatic dysfunction has been related to the deposition of β-amyloid in Alzheimer’s disease. We conclude that the concept of glymphatic dysfunction provides a new perspective for understanding the pathophysiology of IIH; it may likewise entice the development of novel therapeutic approaches aiming at enhancing the flow between the CSF, the glymphatic system, and the dural sinuses.

Pseudotumor Cerebri and Glymphatic Dysfunction.

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Bezerra, Marcio Luciano de Souza; Ferreira, Ana Carolina Andorinho de Freitas; de Oliveira-Souza, Ricardo

2017-01-01

In contrast to virtually all organ systems of the body, the central nervous system was until recently believed to be devoid of a lymphatic system. The demonstration of a complex system of paravascular channels formed by the endfeet of astroglial cells ultimately draining into the venous sinuses has radically changed this idea. The system is subsidized by the recirculation of cerebrospinal fluid (CSF) through the brain parenchyma along paravascular spaces (PVSs) and by exchanges with the interstitial fluid (IF). Aquaporin-4 channels are the chief transporters of water through these compartments. This article hypothesizes that glymphatic dysfunction is a major pathogenetic mechanism underpinning idiopathic intracranial hypertension (IIH). The rationale for the hypothesis springs from MRI studies, which have shown many signs related to IIH without evidence of overproduction of CSF. We propose that diffuse retention of IF is a direct consequence of an imbalance of glymphatic flow. This imbalance, in turn, may result from an augmented flow from the arterial PVS into the IF, by impaired outflow of the IF into the paravenous spaces, or both. Our hypothesis is supported by the facts that (i) visual loss, one of the main complications of IIH, is secondary to the impaired drainage of the optic nerve, a nerve richly surrounded by water channels and with a long extracranial course in its meningeal sheath; (ii) there is a high association between IIH and obesity, a condition related to paravascular inflammation and lymphatic disturbance, and (iii) glymphatic dysfunction has been related to the deposition of β-amyloid in Alzheimer's disease. We conclude that the concept of glymphatic dysfunction provides a new perspective for understanding the pathophysiology of IIH; it may likewise entice the development of novel therapeutic approaches aiming at enhancing the flow between the CSF, the glymphatic system, and the dural sinuses.

Memory deficits in abstinent MDMA (ecstasy) users: neuropsychological evidence of frontal dysfunction.

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Quednow, Boris B; Jessen, Frank; Kuhn, Kai-Uwe; Maier, Wolfgang; Daum, Irene; Wagner, Michael

2006-05-01

Chronic administration of the common club drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is associated with long-term depletion of serotonin (5-HT) and loss of 5-HT axons in the brains of rodents and non-human primates, and evidence suggests that recreational MDMA consumption may also affect the human serotonergic system. Moreover, it was consistently shown that abstinent MDMA users have memory deficits. Recently, it was supposed that these deficits are an expression of a temporal or rather hippocampal dysfunction caused by the serotonergic neurotoxicity of MDMA. The aim of this study is to examine the memory deficits of MDMA users neuropsychologically in order to evaluate the role of different brain regions. Nineteen male abstinent MDMA users, 19 male abstinent cannabis users and 19 male drug-naive control subjects were examined with a German version of the Rey Auditory Verbal Learning Test (RAVLT). MDMA users showed widespread and marked verbal memory deficits, compared to drug-naive controls as well as compared to cannabis users, whereas cannabis users did not differ from control subjects in their memory performance. MDMA users revealed impairments in learning, consolidation, recall and recognition. In addition, they also showed a worse recall consistency and strong retroactive interference whereby both measures were previously associated with frontal lobe function. There was a significant correlation between memory performance and the amount of MDMA taken. These results suggest that the memory deficits of MDMA users are not only the result of a temporal or hippocampal dysfunction, but also of a dysfunction of regions within the frontal cortex.

Symptomatic arrhythmias due to syringomyelia-induced severe autonomic dysfunction.

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Riedlbauchová, Lucie; Nedělka, Tomáš; Schlenker, Jakub

2014-10-01

Syringomyelia is characterized by cavity formation in the spinal cord, most often at C2-Th9 level. Clinical manifestation reflects extent and localization of the spinal cord injury. 20-year old woman was admitted for recurrent rest-related presyncopes with sudden manifestation. Paroxysms of sinus bradycardia with SA and AV blocks were repeatedly documented during symptoms. There was normal echocardiographic finding, (para) infectious etiology was not proved. Character of the ECG findings raised suspicion on neurogenic cause. Autonomic nervous system testing demonstrated abnormalities reflecting predominant sympathetic dysfunction. Suspicion on incipient myelopathy was subsequently confirmed by MRI, which discovered syringomyelia at Th5 level as the only pathology. A 52-year old man with hypotrophic quadruparesis resulting from perinatal brain injury was sent for 2-years lasting symptoms (sudden palpitation, sweating, muscle tightness, shaking) with progressive worsening. Symptoms occurred in association with sudden increase of sinus rhythm rate and blood pressure that were provoked by minimal physical activity. Presence of significant autonomic dysregulation with baroreflex hyperreactivity in orthostatic test and symptomatic postural orthostatic tachycardia with verticalization-associated hypertension were proved. MRI revealed syringomyelia at C7 and Th7 level affecting sympathetic centers at these levels. Sympathetic fibers dysfunction at C-Th spinal level may cause significant autonomic dysfunction with arrhythmic manifestation.

[Forensic application of brainstem auditory evoked potential in patients with brain concussion].

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Zheng, Xing-Bin; Li, Sheng-Yan; Huang, Si-Xing; Ma, Ke-Xin

2008-12-01

To investigate changes of brainstem auditory evoked potential (BAEP) in patients with brain concussion. Nineteen patients with brain concussion were studied with BAEP examination. The data was compared to the healthy persons reported in literatures. The abnormal rate of BAEP for patients with brain concussion was 89.5%. There was a statistically significant difference between the abnormal rate of patients and that of healthy persons (Pconcussion was 73.7%, indicating dysfunction of the brainstem in those patients. BAEP might be helpful in forensic diagnosis of brain concussion.

Focusing on neuronal cell-type specific mechanisms for brain circuit organization, function and dysfunction

Institute of Scientific and Technical Information of China (English)

Lu Li

2017-01-01

Mammalian brain circuits consist of dynamically interconnected neurons with characteristic morphology, physiology, connectivity and genetics which are often called neuronal cell types. Neuronal cell types have been considered as building blocks of brain circuits, but knowledge of how neuron types or subtypes connect to and interact with each other to perform neural computation is still lacking. Such mechanistic insights are critical not only to our understanding of normal brain functions, such as perception, motion and cognition, but also to brain disorders including Alzheimer's disease, Schizophrenia and epilepsy, to name a few. Thus it is necessary to carry out systematic and standardized studies on neuronal cell-type specific mechanisms for brain circuit organization and function, which will provide good opportunities to bridge basic and clinical research. Here based on recent technology advancements, we discuss the strategy to target and manipulate specific populations of neuronsin vivo to provide unique insights on how neuron types or subtypes behave, interact, and generate emergent properties in a fully connected brain network. Our approach is highlighted by combining transgenic animal models, targeted electrophysiology and imaging with robotics, thus complete and standardized mapping ofin vivo properties of genetically defined neuron populations can be achieved in transgenic mouse models, which will facilitate the development of novel therapeutic strategies for brain disorders.

White matter atrophy and cognitive dysfunctions in neuromyelitis optica.

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Frederic Blanc

Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain and VBM for focal brain volume (GM and WM, NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54% had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in

Modeling HIV-1 Induced Neuroinflammation in Mice: Role of Platelets in Mediating Blood-Brain Barrier Dysfunction.

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Letitia D Jones

Full Text Available The number of HIV-1 positive individuals developing some form of HIV-associated neurocognitive disorder (HAND is increasing. In these individuals, the integrity of the blood-brain barrier (BBB is compromised due to an increase in exposure to pro-inflammatory mediators, viral proteins, and virus released from infected cells. It has been shown that soluble CD40L (sCD40L is released upon platelet activation and is an important mediator of the pathogenesis of HAND but the underlying mechanisms are unclear, emphasizing the need of an effective animal model. Here, we have utilized a novel animal model in which wild-type (WT mice were infected with EcoHIV; a derivative of HIV-1 that contains a substitution of envelope protein gp120 with that of gp80 derived from murine leukemia virus-1 (MuLV-1. As early as two-weeks post-infection, EcoHIV led to increased permeability of the BBB associated with decreased expression of tight junction protein claudin-5, in CD40L and platelet activation-dependent manner. Treatment with an antiplatelet drug, eptifibatide, in EcoHIV-infected mice normalized BBB function, sCD40L release and platelet activity, thus implicating platelet activation and platelet-derived CD40L in virally induced BBB dysfunction. Our results also validate and underscore the importance of EcoHIV infection mouse model as a tool to explore therapeutic targets for HAND.

Energy metabolism and inflammation in brain aging and Alzheimer's disease.

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Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-11-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Epilepsy and Mitochondrial Dysfunction

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Russell P. Saneto DO, PhD

2017-10-01

Full Text Available Epilepsy is a common manifestation of mitochondrial disease. In a large cohort of children and adolescents with mitochondrial disease (n = 180, over 48% of patients developed seizures. The majority (68% of patients were younger than 3 years and medically intractable (90%. The electroencephalographic pattern of multiregional epileptiform discharges over the left and right hemisphere with background slowing occurred in 62%. The epilepsy syndrome, infantile spasms, was seen in 17%. Polymerase γ mutations were the most common genetic etiology of seizures, representing Alpers-Huttenlocher syndrome (14%. The severity of disease in those patients with epilepsy was significant, as 13% of patients experienced early death. Simply the loss of energy production cannot explain the development of seizures or all patients with mitochondrial dysfunction would have epilepsy. Until the various aspects of mitochondrial physiology that are involved in proper brain development are understood, epilepsy and its treatment will remain unsatisfactory.

Roles of inflammation and apoptosis in experimental brain death-induced right ventricular failure.

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Belhaj, Asmae; Dewachter, Laurence; Rorive, Sandrine; Remmelink, Myriam; Weynand, Birgit; Melot, Christian; Galanti, Laurence; Hupkens, Emeline; Sprockeels, Thomas; Dewachter, Céline; Creteur, Jacques; McEntee, Kathleen; Naeije, Robert; Rondelet, Benoît

2016-12-01

Right ventricular (RV) dysfunction remains the leading cause of early death after cardiac transplantation. Methylprednisolone is used to improve graft quality; however, evidence for that remains empirical. We sought to determine whether methylprednisolone, acting on inflammation and apoptosis, might prevent brain death-induced RV dysfunction. After randomization to placebo (n = 11) or to methylprednisolone (n = 8; 15 mg/kg), 19 pigs were assigned to a brain-death procedure. The animals underwent hemodynamic evaluation at 1 and 5 hours after Cushing reflex (i.e., hypertension and bradycardia). The animals euthanized, and myocardial tissue was sampled. This was repeated in a control group (n = 8). At 5 hours after the Cushing reflex, brain death resulted in increased pulmonary artery pressure (27 ± 2 vs 18 ± 1 mm Hg) and in a 30% decreased ratio of end-systolic to pulmonary arterial elastances (Ees/Ea). Cardiac output and right atrial pressure did not change. This was prevented by methylprednisolone. Brain death-induced RV dysfunction was associated with increased RV expression of heme oxygenase-1, interleukin (IL)-6, IL-10, IL-1β, tumor necrosis factor (TNF)-α, IL-1 receptor-like (ST)-2, signal transducer and activator of transcription-3, intercellular adhesion molecules-1 and -2, vascular cell adhesion molecule-1, and neutrophil infiltration, whereas IL-33 expression decreased. RV apoptosis was confirmed by terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling staining. Methylprednisolone pre-treatment prevented RV-arterial uncoupling and decreased RV expression of TNF-α, IL-1 receptor-like-2, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and neutrophil infiltration. RV Ees/Ea was inversely correlated to RV TNF-α and IL-6 expression. Brain death-induced RV dysfunction is associated with RV activation of inflammation and apoptosis and is partly limited by methylprednisolone. Copyright © 2016

Dysfunctional whole brain networks in mild cognitive impairment patients: an fMRI study

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Liu, Zhenyu; Bai, Lijun; Dai, Ruwei; Zhong, Chongguang; Xue, Ting; You, Youbo; Tian, Jie

2012-03-01

Mild cognitive impairment (MCI) was recognized as the prodromal stage of Alzheimer's disease (AD). Recent researches have shown that cognitive and memory decline in AD patients is coupled with losses of small-world attributes. However, few studies pay attention to the characteristics of the whole brain networks in MCI patients. In the present study, we investigated the topological properties of the whole brain networks utilizing graph theoretical approaches in 16 MCI patients, compared with 18 age-matched healthy subjects as a control. Both MCI patients and normal controls showed small-world architectures, with large clustering coefficients and short characteristic path lengths. We detected significantly longer characteristic path length in MCI patients compared with normal controls at the low sparsity. The longer characteristic path lengths in MCI indicated disrupted information processing among distant brain regions. Compared with normal controls, MCI patients showed decreased nodal centrality in the brain areas of the angular gyrus, heschl gyrus, hippocampus and superior parietal gyrus, while increased nodal centrality in the calcarine, inferior occipital gyrus and superior frontal gyrus. These changes in nodal centrality suggested a widespread rewiring in MCI patients, which may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline. Our findings may be helpful for further understanding the pathological mechanisms of MCI.

The clinical use of brain SPECT imaging in neuropsychiatry

International Nuclear Information System (INIS)

Amen, Daniel G; Wu, Joseph C; Carmichael, Blake

2003-01-01

This article reviews the literature on brain SPECT imaging in brain trauma, dementia, and temporal lobe epilepsy. Brain SPECT allows clinicians the ability to view cerebral areas of healthy, low, and excessive perfusion. This information can be correlated with what is known about the function or dysfunction of each area. SPECT has a number of advantages over other imaging techniques, including wider availability, lower cost, and high quality resolution with multi-headed cameras. There are a number of issues that compromise the effective use of SPECT, including low quality of some imaging cameras, and variability of image rendering and readings (Au)

A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.

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Kiehl, Kent A

2006-06-15

Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed 'the paralimbic system'. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy.

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice.

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Adamski, Mateusz G; Sternak, Magdalena; Mohaissen, Tasnim; Kaczor, Dawid; Wierońska, Joanna M; Malinowska, Monika; Czaban, Iwona; Byk, Katarzyna; Lyngsø, Kristina S; Przyborowski, Kamil; Hansen, Pernille B L; Wilczyński, Grzegorz; Chlopicki, Stefan

2018-03-26

Although advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved. Tgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte-specific overexpression of G-αq*44 protein were studied before the end-stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6- to 10-month-old but not in 3-month-old Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised blood-brain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased E-selectin immunoreactivity, which was accompanied by increased amyloid-β 1-42 accumulation in piriform cortex and increased cortical oxidative stress (8-OHdG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo NO-dependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3- to 10-month-old Tgαq*44 mice, but it was not associated with increased platelet-dependent thrombogenicity. We report for the first time that vascular cognitive impairment is already present in the early stage of HF development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation. © 2018 The Authors. Published on behalf of the American Heart

Depression as a Glial-Based Synaptic Dysfunction

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Daniel eRial

2016-01-01

Full Text Available Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processing occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the ‘quad-partite’ synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increase microglia ‘activation’ in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, BDNF affect glia functioning, whereas antidepressant treatments (SSRIs, electroshock, deep brain stimulation recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication - such as the purinergic neuromodulation system operated by ATP and adenosine - emerge as promising candidates to re-normalize synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage depression.

Health Status and Performance of United States Air Force Airmen Following Mild Traumatic Brain Injury

Science.gov (United States)

2010-09-01

adrenal insufficiency, hypopituitarism, hypothyroidism , growth- hormone deficiency and posterior pituitary dysfunction [53, 54, 56-60]. Growth...central hypothyroidism which can result in fatigue, apathy, decreased strength and cognitive dysfunction, symptoms commonly observed in PTSD [54...injury: Detecting high risk patients. In: Leon-Carrion J vK ZG, editor. Brain Injury Treatment , Theories, and Practices. London and New York: Taylor

Thinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.

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Hovens, Iris B; Schoemaker, Regien G; van der Zee, Eddy A; Heineman, Erik; Izaks, Gerbrand J; van Leeuwen, Barbara L

2012-10-01

Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account. Copyright © 2012 Elsevier Inc. All rights reserved.

Thyroid hormones states and brain development interactions.

Science.gov (United States)

Ahmed, Osama M; El-Gareib, A W; El-Bakry, A M; Abd El-Tawab, S M; Ahmed, R G

2008-04-01

The action of thyroid hormones (THs) in the brain is strictly regulated, since these hormones play a crucial role in the development and physiological functioning of the central nervous system (CNS). Disorders of the thyroid gland are among the most common endocrine maladies. Therefore, the objective of this study was to identify in broad terms the interactions between thyroid hormone states or actions and brain development. THs regulate the neuronal cytoarchitecture, neuronal growth and synaptogenesis, and their receptors are widely distributed in the CNS. Any deficiency or increase of them (hypo- or hyperthyroidism) during these periods may result in an irreversible impairment, morphological and cytoarchitecture abnormalities, disorganization, maldevelopment and physical retardation. This includes abnormal neuronal proliferation, migration, decreased dendritic densities and dendritic arborizations. This drastic effect may be responsible for the loss of neurons vital functions and may lead, in turn, to the biochemical dysfunctions. This could explain the physiological and behavioral changes observed in the animals or human during thyroid dysfunction. It can be hypothesized that the sensitive to the thyroid hormones is not only remarked in the neonatal period but also prior to birth, and THs change during the development may lead to the brain damage if not corrected shortly after the birth. Thus, the hypothesis that neurodevelopmental abnormalities might be related to the thyroid hormones is plausible. Taken together, the alterations of neurotransmitters and disturbance in the GABA, adenosine and pro/antioxidant systems in CNS due to the thyroid dysfunction may retard the neurogenesis and CNS growth and the reverse is true. In general, THs disorder during early life may lead to distortions rather than synchronized shifts in the relative development of several central transmitter systems that leads to a multitude of irreversible morphological and biochemical

High-Definition and Non-Invasive Brain Modulation of Pain and Motor Dysfunction in Chronic TMD

Science.gov (United States)

Donnell, Adam; Nascimento, Thiago; Lawrence, Mara; Gupta, Vikas; Zieba, Tina; Truong, Dennis Q.; Bikson, Marom; Datta, Abhi; Bellile, Emily; DaSilva, Alexandre F.

2015-01-01

Background Temporomandibular disorders (TMD) have a relatively high prevalence and in many patients pain and masticatory dysfunction persist despite a range of treatments. Non-invasive brain neuromodulatory methods, namely transcranial direct current stimulation (tDCS), can provide relatively long-lasting pain relief in chronic pain patients. Objective To define the neuromodulatory effect of five daily 2×2 motor cortex high-definition tDCS (HD-tDCS) sessions on clinical pain and motor measures in chronic TMD patients. It is predicted that M1 HD-tDCS will selectively modulate clinical measures, by showing greater analgesic after-effects compared to placebo, and active treatment will increase pain free jaw movement more than placebo. Methods Twenty-four females with chronic myofascial TMD pain underwent five daily, 20-minute sessions of active or sham 2 milliamps (mA) HD-tDCS. Measurable outcomes included pain-free mouth opening, visual analog scale (VAS), sectional sensory-discriminative pain measures tracked by a mobile application, short form of the McGill Pain Questionnaire, and the Positive and Negative Affect Schedule. Follow-up occurred at one-week and four-weeks post treatment. Results There were significant improvements for clinical pain and motor measurements in the active HD-tDCS group compared to the placebo group for: responders with pain relief above 50% in the VAS at four-week follow-up (p=0.04); pain-free mouth opening at one-week follow-up (ppain area, intensity and their sum measures contralateral to putative M1 stimulation during the treatment week (ppain and motor measures during stimulation, and up to four weeks post-treatment in chronic myofascial TMD pain patients. PMID:26226938

Acute behavioural dysfunctions following exposure to γ-rays

International Nuclear Information System (INIS)

Kumar, Mayank; Haridas, Seenu; Manda, Kailash

2014-01-01

Exposure to ionizing radiations (IR) has been reported to have many ill effects. These are manifested immediately after exposure and may persist or develop long after the incident. The severity and manifestation is dependent on the absorbed dose and type of the IR. These have been reported extensively in human subjects; especially among the victims of the accidental exposure and radiotherapy patients. Additionally, there have been a plethora of studies in animal models which support these findings, and are being used to test radio-mitigative or radio-protective strategies. The vulnerability of neuronal tissue to IR is well known, however the acute dose-dependent behavioural consequences have yet to be understood. Thus, our laboratory has been trying to decipher the dose-dependent behavioural dysfunctions which have occurred 24-72 hours post IR exposure and possible radio-protective strategies. We are utilizing mouse models of studying the behavioural processes, in a test battery conceptualized to study the affective and cognitive skills as well as motor skills of the animals. Additionally, we have observed cellular damage to different areas of the brain and subsequent correlations to behavioural dysfunctions. This has being carried out by using single cell gel electrophoresis (SCGE) and Diffusion Tensor Imaging (DTI). The findings show that after exposure to sub-lethal γ-rays, there are significant changes that occur in all the behavioural parameters. The most sensitive area has been found to be the Hippocampus as visualized by DTI and the SCGE. Consequently, short term and long term memory functions have been shown to be disrupted within 24-72 hours of exposure. Acute dysfunctions of affective functions have also been demonstrated to materialise within 24 hours post exposure. Unexpectedly, the behavioural dysfunctions were seen to be dose independent. Thus, this study provides a foundation to help decipher the acute behavioural manifestations of IR exposure

Brain Connectivity Studies in Schizophrenia: Unravelling the Effects of Antipsychotics

DEFF Research Database (Denmark)

Nejad, A.B.; Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte Yding

2012-01-01

Impaired brain connectivity is a hallmark of schizophrenia brain dysfunction. However, the effect of drug treatment and challenges on the dysconnectivity of functional networks in schizophrenia is an understudied area. In this review, we provide an overview of functional magnetic resonance imaging...... studies examining dysconnectivity in schizophrenia and discuss the few studies which have also attempted to probe connectivity changes with antipsychotic drug treatment. We conclude with a discussion of possible avenues for further investigation....

Regional brain morphometry predicts memory rehabilitation outcome after traumatic brain injury

Directory of Open Access Journals (Sweden)

Gary E Strangman

2010-10-01

Full Text Available Cognitive deficits following traumatic brain injury (TBI commonly include difficulties with memory, attention, and executive dysfunction. These deficits are amenable to cognitive rehabilitation, but optimally selecting rehabilitation programs for individual patients remains a challenge. Recent methods for quantifying regional brain morphometry allow for automated quantification of tissue volumes in numerous distinct brain structures. We hypothesized that such quantitative structural information could help identify individuals more or less likely to benefit from memory rehabilitation. Fifty individuals with TBI of all severities who reported having memory difficulties first underwent structural MRI scanning. They then participated in a 12 session memory rehabilitation program emphasizing internal memory strategies (I-MEMS. Primary outcome measures (HVLT, RBMT were collected at the time of the MRI scan, immediately following therapy, and again at one month post-therapy. Regional brain volumes were used to predict outcome, adjusting for standard predictors (e.g., injury severity, age, education, pretest scores. We identified several brain regions that provided significant predictions of rehabilitation outcome, including the volume of the hippocampus, the lateral prefrontal cortex, the thalamus, and several subregions of the cingulate cortex. The prediction range of regional brain volumes were in some cases nearly equal in magnitude to prediction ranges provided by pretest scores on the outcome variable. We conclude that specific cerebral networks including these regions may contribute to learning during I-MEMS rehabilitation, and suggest that morphometric measures may provide substantial predictive value for rehabilitation outcome in other cognitive interventions as well.

Neural Basis of Brain Dysfunction Produced by Early Sleep Problems

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Jun Kohyama

2016-01-01

Full Text Available There is a wealth of evidence that disrupted sleep and circadian rhythms, which are common in modern society even during the early stages of life, have unfavorable effects on brain function. Altered brain function can cause problem behaviors later in life, such as truancy from or dropping out of school, quitting employment, and committing suicide. In this review, we discuss findings from several large cohort studies together with recent results of a cohort study using the marshmallow test, which was first introduced in the 1960s. This test assessed the ability of four-year-olds to delay gratification and showed how this ability correlated with success later in life. The role of the serotonergic system in sleep and how this role changes with age are also discussed. The serotonergic system is involved in reward processing and interactions with the dorsal striatum, ventral striatum, and the prefrontal cortex are thought to comprise the neural basis for behavioral patterns that are affected by the quantity, quality, and timing of sleep early in life.

Neural Basis of Brain Dysfunction Produced by Early Sleep Problems.

Science.gov (United States)

Kohyama, Jun

2016-01-29

There is a wealth of evidence that disrupted sleep and circadian rhythms, which are common in modern society even during the early stages of life, have unfavorable effects on brain function. Altered brain function can cause problem behaviors later in life, such as truancy from or dropping out of school, quitting employment, and committing suicide. In this review, we discuss findings from several large cohort studies together with recent results of a cohort study using the marshmallow test, which was first introduced in the 1960s. This test assessed the ability of four-year-olds to delay gratification and showed how this ability correlated with success later in life. The role of the serotonergic system in sleep and how this role changes with age are also discussed. The serotonergic system is involved in reward processing and interactions with the dorsal striatum, ventral striatum, and the prefrontal cortex are thought to comprise the neural basis for behavioral patterns that are affected by the quantity, quality, and timing of sleep early in life.

Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

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Hemanth Kumar, Boyina; Arun Reddy, Ravula; Mahesh Kumar, Jerald; Dinesh Kumar, B; Diwan, Prakash V

2017-01-01

This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

Diabetes : Brain changes in T1DM—a microvascular complication?

NARCIS (Netherlands)

Biessels, Geert Jan

2015-01-01

A recent study indicates that type 1 diabetes mellitus is associated with vascular brain lesions that affect cognition and might represent a target for preventive measures. This commentary discusses methods to ascertain vascular contributions to cerebral dysfunction in diabetes mellitus and

Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery

NARCIS (Netherlands)

Kok, W F; Koerts, Janneke; Tucha, O; Scheeren, T W L; Absalom, A R

Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage-specific biomarkers, including brain fatty acid-binding protein, neuron-specific enolase and S100 calcium-binding protein β, as well as plasma-free

Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

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Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-01-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

Traumatic Brain Injury: At the Crossroads of Neuropathology and Common Metabolic Endocrinopathies

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Melanie Li

2018-03-01

Full Text Available Building on the seminal work by Geoffrey Harris in the 1970s, the neuroendocrinology field, having undergone spectacular growth, has endeavored to understand the mechanisms of hormonal connectivity between the brain and the rest of the body. Given the fundamental role of the brain in the orchestration of endocrine processes through interactions among neurohormones, it is thus not surprising that the structural and/or functional alterations following traumatic brain injury (TBI can lead to endocrine changes affecting the whole organism. Taking into account that systemic hormones also act on the brain, modifying its structure and biochemistry, and can acutely and chronically affect several neurophysiological endpoints, the question is to what extent preexisting endocrine dysfunction may set the stage for an adverse outcome after TBI. In this review, we provide an overview of some aspects of three common metabolic endocrinopathies, e.g., diabetes mellitus, obesity, and thyroid dysfunction, and how these could be triggered by TBI. In addition, we discuss how the complex endocrine networks are woven into the responses to sudden changes after TBI, as well as some of the potential mechanisms that, separately or synergistically, can influence outcomes after TBI.

Aflatoxin B1-contaminated diet disrupts the blood-brain barrier and affects fish behavior: Involvement of neurotransmitters in brain synaptosomes.

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Baldissera, Matheus D; Souza, Carine F; Zeppenfeld, Carla Cristina; Descovi, Sharine N; Moreira, Karen Luise S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; da Silva, Aleksandro S; Baldisserotto, Bernardo

2018-04-04

It is known that the cytotoxic effects of aflatoxin B 1 (AFB 1 ) in endothelial cells of the blood-brain barrier (BBB) are associated with behavioral dysfunction. However, the effects of a diet contaminated with AFB 1 on the behavior of silver catfish remain unknown. Thus, the aim of this study was to evaluate whether an AFB 1 -contaminated diet (1177 ppb kg feed -1 ) impaired silver catfish behavior, as well as whether disruption of the BBB and alteration of neurotransmitters in brain synaptosomes are involved. Fish fed a diet contaminated with AFB 1 presented a behavioral impairment linked with hyperlocomotion on days 14 and 21 compared with the control group (basal diet). Neurotransmitter levels were also affected on days 14 and 21. The permeability of the BBB to Evans blue dye increased in the intoxicated animals compared with the control group, which suggests that the BBB was disrupted. Moreover, acetylcholinesterase (AChE) activity in brain synaptosomes was increased in fish fed a diet contaminated with AFB 1 , while activity of the sodium-potassium pump (Na + , K + -ATPase) was decreased. Based on this evidence, the present study shows that silver catfish fed a diet containing AFB 1 exhibit behavioral impairments related to hyperlocomotion. This diet caused a disruption of the BBB and brain lesions, which may contribute to the behavioral changes. Also, the alterations in the activities of AChE and Na + , K + -ATPase in brain synaptosomes may directly contribute to this behavior, since they may promote synapse dysfunction. In addition, the hyperlocomotion may be considered an important macroscopic marker indicating possible AFB 1 intoxication. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessment of Autophagy in Neurons and Brain Tissue

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Benito-Cuesta, Irene; Diez, Héctor; Ordoñez, Lara; Wandosell, Francisco

2017-01-01

Autophagy is a complex process that controls the transport of cytoplasmic components into lysosomes for degradation. This highly conserved proteolytic system involves dynamic and complex processes, using similar molecular elements and machinery from yeast to humans. Moreover, autophagic dysfunction may contribute to a broad spectrum of mammalian diseases. Indeed, in adult tissues, where the capacity for regeneration or cell division is low or absent (e.g., in the mammalian brain), the accumulation of proteins/peptides that would otherwise be recycled or destroyed may have pathological implications. Indeed, such changes are hallmarks of pathologies, like Alzheimer’s, Prion or Parkinson’s disease, known as proteinopathies. However, it is still unclear whether such dysfunction is a cause or an effect in these conditions. One advantage when analysing autophagy in the mammalian brain is that almost all the markers described in different cell lineages and systems appear to be present in the brain, and even in neurons. By contrast, the mixture of cell types present in the brain and the differentiation stage of such neurons, when compared with neurons in culture, make translating basic research to the clinic less straightforward. Thus, the purpose of this review is to describe and discuss the methods available to monitor autophagy in neurons and in the mammalian brain, a process that is not yet fully understood, focusing primarily on mammalian macroautophagy. We will describe some general features of neuronal autophagy that point to our focus on neuropathologies in which macroautophagy may be altered. Indeed, we centre this review around the hypothesis that enhanced autophagy may be able to provide therapeutic benefits in some brain pathologies, like Alzheimer’s disease, considering this pathology as one of the most prevalent proteinopathies. PMID:28832529

[Focal cerebral ischemia in rats with estrogen deficiency and endothelial dysfunction].

Science.gov (United States)

Litvinov, A A; Volotova, E V; Kurkin, D V; Logvinova, E O; Darmanyan, A P; Tyurenkov, I N

2017-01-01

To assess an effect of ovariectomy (OE) on the cerebral blood flow, endothelium-dependent vasodilation, neurological, cognitive and locomotor deficit as markers of brain damage after focal ischemia in rats. The study was conducted in 48 female Wistar rats. Ovariectomy was performed with ovaries and uterine body extirpation, cerebral ischemia was performed by middle cerebral artery occlusion (MCAO) in rats. To assess brain damage, Combs and Garcia scores, 'open field' test (OFT), 'extrapolatory escape test' (EET), 'passive avoidance test' (PAT), 'beam-walking test' were used. Cerebral blood flow was measured using ultrasonic flowmetry. After 7 days of MCAO, the cerebral blood flow in ovarioectomized animals was reduced by 20% compared to sham-ovariectomized animals. Ovariectomized animals with MCAO showed a three-fold endothelium-dependent vasodilation reduction (the reaction of cerebral vessels to the introduction of acetylcholine and N-L-arginine), indicating the presence of severe endothelial dysfunction. In ovarioectomized animals, the cerebral blood flow was reduced by 34% compared to sham-operated animals. MCAO and OE taken together resulted in more than 2-fold increase in neurological, motor disturbances, 3-fold decrease in motor activity of the animals in the OP test. Focal ischemia in ovarioectomized animals with endothelial dysfunction led to memory decrease by 1/5 fold in PAT and by 2-fold in EET.

Radiation-induced cognitive dysfunction: an experimental model in the old rat

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Lamproglou, Ioannis; Chen, QI Ming; Boisserie, Gilbert; Mazeron, Jean-Jacques; Poisson, Michel; Baillet, Francois; Le Poncin, Monique; Delattre, Jean-Yves

1995-01-01

Purpose: To develop a model of radiation-induced behavioral dysfunction. Methods and Materials: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Results: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p {<=} 0.001) and two-way avoidance (18% vs. 40%, p {<=} 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p {<=} 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Conclusion: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

Radiation-induced cognitive dysfunction: an experimental model in the old rat

International Nuclear Information System (INIS)

Lamproglou, Ioannis; Chen, QI Ming; Boisserie, Gilbert; Mazeron, Jean-Jacques; Poisson, Michel; Baillet, Francois; Le Poncin, Monique; Delattre, Jean-Yves

1995-01-01

Purpose: To develop a model of radiation-induced behavioral dysfunction. Methods and Materials: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Results: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Conclusion: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes

Radiation-induced cognitive dysfunction: An experimental model in the old rat

International Nuclear Information System (INIS)

Lamproglou, I.; Chen, Q.M.; Poisson, M.

1995-01-01

To develop a model of radiation-induced behavioral dysfunction. A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes. 15 refs., 3 figs., 1 tab

Effects of neuroinflammation on the regenerative capacity of brain stem cells

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Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

2011-01-01

In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system ...

Effects of metformin on learning and memory behaviors and brain mitochondrial functions in high fat diet induced insulin resistant rats.

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Pintana, Hiranya; Apaijai, Nattayaporn; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2012-10-05

Metformin is a first line drug for the treatment of type 2 diabetes mellitus (T2DM). Our previous study reported that high-fat diet (HFD) consumption caused not only peripheral and neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment. However, the effects of metformin on learning behavior and brain mitochondrial functions in HFD-induced insulin resistant rats have never been investigated. Thirty-two male Wistar rats were divided into two groups to receive either a normal diet (ND) or a high-fat diet (HFD) for 12weeks. Then, rats in each group were divided into two treatment groups to receive either vehicle or metformin (15mg/kg BW twice daily) for 21days. All rats were tested for cognitive behaviors using the Morris water maze (MWM) test, and blood samples were collected for the determination of glucose, insulin, and malondialdehyde. At the end of the study, animals were euthanized and the brain was removed for studying brain mitochondrial function and brain oxidative stress. We found that in the HFD group, metformin significantly attenuated the insulin resistant condition by improving metabolic parameters, decreasing peripheral and brain oxidative stress levels, and improving learning behavior, compared to the vehicle-treated group. Furthermore, metformin completely prevented brain mitochondrial dysfunction caused by long-term HFD consumption. Our findings suggest that metformin effectively improves peripheral insulin sensitivity, prevents brain mitochondrial dysfunction, and completely restores learning behavior, which were all impaired by long-term HFD consumption. Copyright © 2012 Elsevier Inc. All rights reserved.

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

NARCIS (Netherlands)

Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

2017-01-01

BACKGROUND: Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients

The Risk of Neurological Dysfunctions after Deep Hypothermic Circulatory Arrest with Retrograde Cerebral Perfusion.

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Gatti, Giuseppe; Benussi, Bernardo; Currò, Placido; Forti, Gabriella; Rauber, Elisabetta; Minati, Alessandro; Gabrielli, Marco; Tognolli, Umberto; Sinagra, Gianfranco; Pappalardo, Aniello

2017-12-01

Retrograde cerebral perfusion (RCP) is a brain protection technique that is adopted generally for anticipated short periods of deep hypothermic circulatory arrest (DHCA). However, the real impact of this technique on cerebral protection during DHCA remains a controversial issue. For 344 (59.5%) of 578 consecutive patients (mean age, 66.9 ± 10.9 years) who underwent cardiovascular surgery under DHCA at the present authors' institution (1999-2015), RCP was the sole technique of cerebral protection that was adopted in addition to deep hypothermia. Surgery of the thoracic aorta was performed in 95.9% of these RCP patients; in 92 cases there was an aortic arch involvement. Outcomes were reviewed retrospectively. The focus was on postoperative neurological dysfunctions. There were 33 (9.6%) in-hospital deaths. Thirty-one (9%) patients had permanent neurological dysfunctions and 66 (19.1%) transitory neurological dysfunctions alone. Age older than 74 years (odds ratio [OR], 1.88, P = .023), surgery for acute aortic dissection (OR, 2.57; P = .0009), and DHCA time longer than 25 minutes (OR, 2.44; P = .0021) were predictors of neurological dysfunctions. The 10-year nonparametric estimate of freedom from all-cause death was 61.8% (95% confidence interval, 57.8%-65.8%). Permanent postoperative neurological dysfunctions were risk factors for cardiac or cerebrovascular death (hazard ratio, 2.6; P = .039) even after an adjusted survival analysis (P RCP, in addition to deep hypothermia, combines with a low risk of neurological dysfunctions provided that DHCA length is 25 minutes or less. Permanent postoperative neurological dysfunctions are predictors of poor late survival. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors.

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Elizabeth Harford-Wright

Full Text Available The neuropeptide substance P (SP has been implicated in the disruption of the blood-brain barrier (BBB and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg, dexamethasone (8 mg/kg or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05. Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants

Ammonia causes decreased brain monoamines in fathead minnows (Pimephales promelas)

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Ronan, Patrick J.; Gaikowski, Mark P.; Hamilton, Steven J.; Buhl, Kevin J.; Summers, Cliff H.

2007-01-01

Hyperammonemia, arising from variety of disorders, leads to severe neurological dysfunction. The mechanisms of ammonia toxicity in brain are not completely understood. This study investigated the effects of ammonia on monoaminergic systems in brains of fathead minnows (Pimephales promelas). Fish serve as a good model system to investigate hyperammonemic effects on brain function since no liver manipulations are necessary to increase endogenous ammonia concentrations. Using high performance liquid chromatography with electrochemical detection, monoamines and some associated metabolites were measured from whole brain homogenate. Adult males were exposed for 48 h to six different concentrations of ammonia (0.01–2.36 mg/l unionized) which bracketed the 96-h LC50 for this species. Ammonia concentration-dependent decreases were found for the catecholamines (norepinephrine and dopamine) and the indoleamine serotonin (5-HT). After an initial increase in the 5-HT precursor 5-hydroxytryptophan it too decreased with increasing ammonia concentrations. There were also significant increases in the 5-HIAA/5-HT and DOPAC/DA ratios, often used as measures of turnover. There were no changes in epinephrine (Epi) or monoamine catabolites (DOPAC, 5-HIAA) at any ammonia concentrations tested. Results suggest that ammonia causes decreased synthesis while also causing increased release and degradation. Increased release may underlie behavioral reactions to ammonia exposure in fish. This study adds weight to a growing body of evidence demonstrating that ammonia leads to dysfunctional monoaminergic systems in brain which may underlie neurological symptoms associated with human disorders such as hepatic encephalopathy.

Lysosomal storage diseases and the blood-brain barrier.

Science.gov (United States)

Begley, David J; Pontikis, Charles C; Scarpa, Maurizio

2008-01-01

The blood-brain barrier becomes a crucial issue in neuronopathic lysosomal storage diseases for three reasons. Firstly, the function of the blood-brain barrier may be compromised in many of the lysosomal storage diseases and this barrier dysfunction may contribute to the neuropathology seen in the diseases and accelerate cell death. Secondly, the substrate reduction therapies, which successfully reduce peripheral lysosomal storage, because of the blood-brain barrier may not have as free an access to brain cells as they do to peripheral cells. And thirdly, enzyme replacement therapy appears to have little access to the central nervous system as the mannose and mannose-6-phosphate receptors involved in their cellular uptake and transport to the lysosome do not appear to be expressed at the adult blood-brain barrier. This review will discuss in detail these issues and their context in the development of new therapeutic strategies.

Diastolic dysfunction characterizes cirrhotic cardiomyopathy

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Piyush O. Somani

2014-11-01

Conclusions: Present study shows that although diastolic dysfunction is a frequent event in cirrhosis, it is usually of mild degree and does not correlate with severity of liver dysfunction. There are no significant differences in echocardiographic parameters between alcoholic and non-alcoholic cirrhosis. HRS is not correlated to diastolic dysfunction in cirrhotic patients. There is no difference in survival at one year between patients with or without diastolic dysfunction. Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS.

Brain mitochondrial metabolic dysfunction and glutamate level reduction in the pilocarpine model of temporal lobe epilepsy in mice

Science.gov (United States)

Smeland, Olav B; Hadera, Mussie G; McDonald, Tanya S; Sonnewald, Ursula; Borges, Karin

2013-01-01

Although certain metabolic characteristics such as interictal glucose hypometabolism are well established for temporal lobe epilepsy (TLE), its pathogenesis still remains unclear. Here, we performed a comprehensive study of brain metabolism in a mouse model of TLE, induced by pilocarpine–status epilepticus (SE). To investigate glucose metabolism, we injected mice 3.5–4 weeks after SE with [1,2-13C]glucose before microwave fixation of the head. Using 1H and 13C nuclear magnetic resonance spectroscopy, gas chromatography—mass spectrometry and high-pressure liquid chromatography, we quantified metabolites and 13C labeling in extracts of cortex and hippocampal formation (HF). Hippocampal levels of glutamate, glutathione and alanine were decreased in pilocarpine–SE mice compared with controls. Moreover, the contents of N-acetyl aspartate, succinate and reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H were decreased in HF indicating impairment of mitochondrial function. In addition, the reduction in 13C enrichment of hippocampal citrate and malate suggests decreased tricarboxylic acid (TCA) cycle turnover in this region. In cortex, we found reduced 13C labeling of glutamate, glutamine and aspartate via the pyruvate carboxylation and pyruvate dehydrogenation pathways, suggesting slower turnover of these amino acids and/or the TCA cycle. In conclusion, mitochondrial metabolic dysfunction and altered amino-acid metabolism is found in both cortex and HF in this epilepsy model. PMID:23611869

Burden of Sexual Dysfunction.

Science.gov (United States)

Balon, Richard

2017-01-02

Similar to the burden of other diseases, the burden of sexual dysfunction has not been systematically studied. However, there is growing evidence of various burdens (e.g., economic, symptomatic, humanistic) among patients suffering from sexual dysfunctions. The burden of sexual dysfunction has been studied a bit more often in men, namely the burden of erectile dysfunction (ED), premature ejaculation (PE) and testosterone deficiency syndrome (TDS). Erectile dysfunction is frequently associated with chronic conditions such as cardiovascular disease, diabetes, and depression. These conditions could go undiagnosed, and ED could be a marker of those diseases. The only available report from the United Kingdom estimated the total economic burden of ED at £53 million annually in terms of direct costs and lost productivity. The burden of PE includes significant psychological distress: anxiety, depression, lack of sexual confidence, poor self-esteem, impaired quality of life, and interpersonal difficulties. Some suggest that increase in female sexual dysfunction is associated with partner's PE, in addition to significant interpersonal difficulties. The burden of TDS includes depression, sexual dysfunction, mild cognitive impairment, and osteoporosis. One UK estimate of the economic burden of female sexual dysfunctions demonstrated that the average cost per patient was higher than the per annum cost of ED. There are no data on burden of paraphilic disorders. The burden of sexual dysfunctions is underappreciated and not well studied, yet it is significant for both the patients and the society.

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

Science.gov (United States)

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

2003-03-01

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

Pathogenesis of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea: A Hypothesis with Emphasis on the Nucleus Tractus Solitarius

Directory of Open Access Journals (Sweden)

Mak Adam Daulatzai

2012-01-01

Full Text Available OSA is characterized by the quintessential triad of intermittent apnea, hypoxia, and hypoxemia due to pharyngeal collapse. This paper highlights the upstream mechanisms that may trigger cognitive decline in OSA. Three interrelated steps underpin cognitive dysfunction in OSA patients. First, several risk factors upregulate peripheral inflammation; these crucial factors promote neuroinflammation, cerebrovascular endothelial dysfunction, and oxidative stress in OSA. Secondly, the neuroinflammation exerts negative impact globally on the CNS, and thirdly, important foci in the neocortex and brainstem are rendered inflamed and dysfunctional. A strong link is known to exist between neuroinflammation and neurodegeneration. A unique perspective delineated here underscores the importance of dysfunctional brainstem nuclei in etiopathogenesis of cognitive decline in OSA patients. Nucleus tractus solitarius (NTS is the central integration hub for afferents from upper airway (somatosensory/gustatory, respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor and other systems. The NTS has an essential role in sympathetic and parasympathetic systems also; it projects to most key brain regions and modulates numerous physiological functions. Inflamed and dysfunctional NTS and other key brainstem nuclei may play a pivotal role in triggering memory and cognitive dysfunction in OSA. Attenuation of upstream factors and amelioration of the NTS dysfunction remain important challenges.

TorsinA dysfunction causes persistent neuronal nuclear pore defects.

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Pappas, Samuel S; Liang, Chun-Chi; Kim, Sumin; Rivera, CheyAnne O; Dauer, William T

2018-02-01

A critical challenge to deciphering the pathophysiology of neurodevelopmental disease is identifying which of the myriad abnormalities that emerge during CNS maturation persist to contribute to long-term brain dysfunction. Childhood-onset dystonia caused by a loss-of-function mutation in the AAA+ protein torsinA exemplifies this challenge. Neurons lacking torsinA develop transient nuclear envelope (NE) malformations during CNS maturation, but no NE defects are described in mature torsinA null neurons. We find that during postnatal CNS maturation torsinA null neurons develop mislocalized and dysfunctional nuclear pore complexes (NPC) that lack NUP358, normally added late in NPC biogenesis. SUN1, a torsinA-related molecule implicated in interphase NPC biogenesis, also exhibits localization abnormalities. Whereas SUN1 and associated nuclear membrane abnormalities resolve in juvenile mice, NPC defects persist into adulthood. These findings support a role for torsinA function in NPC biogenesis during neuronal maturation and implicate altered NPC function in dystonia pathophysiology. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

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Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

2010-05-01

Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

Status epilepticus, blood-brain barrier disruption, inflammation, and epileptogenesis

NARCIS (Netherlands)

Gorter, Jan A.; van Vliet, Erwin A.; Aronica, Eleonora

2015-01-01

Over the last 15 years, attention has been focused on dysfunction of the cerebral vasculature and inflammation as important players in epileptogenic processes, with a specific emphasis on failure of the blood-brain barrier (BBB; Fig. 1) (Seiffert et al., 2004; Marchi et al., 2007; Oby and Janigro,

Regional cerebral blood flow in psychiatry: The resting and activated brains of schizophrenic patients

International Nuclear Information System (INIS)

Gur, R.E.

1984-01-01

The investigation of regional brain functioning in schizophrenia has been based on behavioral techniques. Although results are sometimes inconsistent, the behavioral observations suggest left hemispheric dysfunction and left hemispheric overreaction. Recent developments in neuroimaging technology make possible major refinements in assessing regional brain function. Both anatomical and physiological information now be used to study regional brain development in psychiatric disorders. This chapter describes the application of one method - the xenon-133 technique for measuring regional cerebral blood flow (rCBF) - in studying the resting and activated brains of schizoprenic patients

Bipolar Disorder and Immune Dysfunction: Epidemiological Findings, Proposed Pathophysiology and Clinical Implications

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Joshua D. Rosenblat

2017-10-01

Full Text Available Bipolar disorder (BD is strongly associated with immune dysfunction. Replicated epidemiological studies have demonstrated that BD has high rates of inflammatory medical comorbidities, including autoimmune disorders, chronic infections, cardiovascular disease and metabolic disorders. Cytokine studies have demonstrated that BD is associated with chronic low-grade inflammation with further increases in pro-inflammatory cytokine levels during mood episodes. Several mechanisms have been identified to explain the bidirectional relationship between BD and immune dysfunction. Key mechanisms include cytokine-induced monoamine changes, increased oxidative stress, pathological microglial over-activation, hypothalamic-pituitary-adrenal (HPA axis over-activation, alterations of the microbiome-gut-brain axis and sleep-related immune changes. The inflammatory-mood pathway presents several potential novel targets in the treatment of BD. Several proof-of-concept clinical trials have shown a positive effect of anti-inflammatory agents in the treatment of BD; however, further research is needed to determine the clinical utility of these treatments. Immune dysfunction is likely to only play a role in a subset of BD patients and as such, future clinical trials should also strive to identify which specific group(s of BD patients may benefit from anti-inflammatory treatments.

The emerging role of norepinephrine in cognitive dysfunctions of Parkinson’s disease

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Elena eVazey

2012-07-01

Full Text Available Parkinson’s disease (PD is the second most common neurodegenerative disorder, affecting 1% of the population over age 60. In those patients cognitive dysfunction is a persistent issue that impairs quality of life and productivity. Neuropathological studies demonstrate significant damage in brain regions outside the nigral dopamine (DA system, including early degeneration of locus coeruleus norepinephrine (LC-NE neurons, yet discussion of PD and treatment focus has remained dopaminergic-based. Motor symptoms benefit from DA replacement for many years, but other symptoms including several cognitive deficits continue unabated. Recent interest in non-DA substrates of PD highlights early involvement of LC-NE neurons and provides evidence for a prodromal phase, with cognitive disturbance, even in sporadic PD. We outline insights from basic research in LC-NE function to clinical and pathological evidence highlighting a role for NE in PD cognitive dysfunction. We propose that loss of LC-NE regulation, particularly in higher cortical regions, critically underlies certain cognitive dysfunctions in early PD. As a major unmet need for patients, research and use of NE drugs in PD may provide significant benefits for cognitive processing.

Clinical utility of partial flip angle T2-weighted spin-echo imaging of the brain

International Nuclear Information System (INIS)

Chang, K.H.; Yi, J.G.; Han, M.H.; Han, M.C.; Kim, C.W.; Cho, M.H.; Cho, Z.H.

1990-01-01

To assess the clinical usefulness of partial flip angle (PFA) spin-echo (SE) brain imaging, a total of eighty patients were examined with both conventional double echo T2-weighted SE (2500/30, 80/90deg/one excitation) and PFA double echo SE (1200/30, 70/45deg/two excitations) on 2.0T system. Two comparative studies were performed: (1) In 65 patients PFA SE technique was compared with conventional SE without flow compensating gradients, and (2) in 15 patients the former was compared with the latter with flow compensating gradients. Imaging time was nearly identical in each sequence. In both studies we found that PFA T2-weighted SE images were almost identical to those obtained with the conventional SE technique in the contrast characteristics and the detection rate of the abnormalities (100%, 85/85 lesions), and more importantly, PFA SE revealed few flow artifacts in the brain stem, temporal lobes and basal ganglia which were frequently seen on conventional SE without flow compensating gradients. Additionally, PFA SE images demonstrated no suppression of CSF flow void in the aqueduct which was commonly seen on conventional SE with flow compensating gradients. In overall image quality, the PFA SE images, particularly the second echo images, were almost comparable with those of conventional SE with flow compensating gradients. A flip angle of 45deg seems to be close to Ernst angle, the angle at which maximum signal occurs, for a given TR of 1200 msec for CSF and most of the abnormalities containing higher water content. In conclusion, PFA SE sequence (i.e. 1200/30, 70/45deg/2) appears to be useful as a primary or an adjunctive technique in certain clinical circumstances, particularly in imaging of hydrocephalic patients for assessing aqueductal patency. (orig.)

Reward system dysfunction in autism spectrum disorders

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Schulte-Rüther, Martin; Nehrkorn, Barbara; Müller, Kristin; Fink, Gereon R.; Kamp-Becker, Inge; Herpertz-Dahlmann, Beate; Schultz, Robert T.; Konrad, Kerstin

2013-01-01

Although it has been suggested that social deficits of autism spectrum disorders (ASDs) are related to reward circuitry dysfunction, very little is known about the neural reward mechanisms in ASD. In the current functional magnetic resonance imaging study, we investigated brain activations in response to both social and monetary reward in a group of children with ASD, relative to matched controls. Participants with ASD showed the expected hypoactivation in the mesocorticolimbic circuitry in response to both reward types. In particular, diminished activation in the nucleus accumbens was observed when money, but not when social reward, was at stake, whereas the amygdala and anterior cingulate cortex were hypoactivated within the ASD group in response to both rewards. These data indicate that the reward circuitry is compromised in ASD in social as well as in non-social, i.e. monetary conditions, which likely contributes to atypical motivated behaviour. Taken together, with incentives used in this study sample, there is evidence for a general reward dysfunction in ASD. However, more ecologically valid social reward paradigms are needed to fully understand, whether there is any domain specificity to the reward deficit that appears evident in ASD, which would be most consistent with the ASD social phenotype. PMID:22419119

Visual processing of multiple elements in the dyslexic brain: evidence for a superior parietal dysfunction

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Muriel Anne Lobier

2014-07-01

Full Text Available The visual attention (VA span deficit hypothesis of developmental dyslexia posits that impaired multiple element processing can be responsible for poor reading outcomes. In VA span impaired dyslexic children, poor performance on letter report tasks is associated with reduced parietal activations for multiple letter processing. While this hints towards a non-specific, attention-based dysfunction, it is still unclear whether reduced parietal activity generalizes to other types of stimuli. Furthermore, putative links between reduced parietal activity and reduced ventral occipito-temporal (vOT in dyslexia have yet to be explored. Using fMRI, we measured brain activity in 12 VA span impaired dyslexic adults and 12 adult skilled readers while they carried out a categorization task on single or multiple alphanumeric or non-alphanumeric characters. While healthy readers activated parietal areas more strongly for multiple than single element processing (right-sided for alphanumeric and bilateral for non-alphanumeric, similar stronger multiple element right parietal activations were absent for dyslexic participants. Contrasts between skilled and dyslexic readers revealed significantly reduced right superior parietal lobule (SPL activity for dyslexic readers regardless of stimuli type. Using a priori anatomically defined ROI, we showed that neural activity was reduced for dyslexic participants in both SPL and vOT bilaterally. Finally, we used multiple regressions to test whether SPL activity could predict vOT activity in each group. In the left hemisphere, SPL activity modulated vOT activity for both normal and dyslexic readers. In contrast, in the right hemisphere, SPL activity modulated vOT activity only for dyslexic readers. These results bring critical support to the visual attention interpretation of the VA Span deficit. In addition, they offer a new insight on how deficits in automatic vOT based word recognition could arise in developmental dyslexia.

A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

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Farjam, Reza [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Pramanik, Priyanka; Aryal, Madhava P. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Srinivasan, Ashok [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Chapman, Christopher H. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Tsien, Christina I. [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue, E-mail: yuecao@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States)

2015-11-15

Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K{sup trans}, and the fraction of blood plasma volume, V{sub p}. The temporal changes in the means of hippocampal transfer constant K{sup trans} and V{sub p} after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K{sup trans} Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

International Nuclear Information System (INIS)

Farjam, Reza; Pramanik, Priyanka; Aryal, Madhava P.; Srinivasan, Ashok; Chapman, Christopher H.; Tsien, Christina I.; Lawrence, Theodore S.; Cao, Yue

2015-01-01

Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K"t"r"a"n"s, and the fraction of blood plasma volume, V_p. The temporal changes in the means of hippocampal transfer constant K"t"r"a"n"s and V_p after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K"t"r"a"n"s Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

Attention and driving in traumatic brain injury: a question of coping with time-pressure.

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Brouwer, Wiebo H; Withaar, Frederiec K; Tant, Mark L M; van Zomeren, Adriaan H

2002-02-01

Diffuse and focal traumatic brain injury (TBI) can result in perceptual, cognitive, and motor dysfunction possibly leading to activity limitations in driving. Characteristic dysfunctions for severe diffuse TBI are confronted with function requirements derived from the hierarchical task analysis of driving skill. Specifically, we focus on slow information processing, divided attention, and the development of procedural knowledge. Also the effects of a combination of diffuse and focal dysfunctions, specifically homonymous hemianopia and the dysexecutive syndrome, are discussed. Finally, we turn to problems and challenges with regard to assessment and rehabilitation methods in the areas of driving and fitness to drive.

The Brewed Rice Vinegar Kurozu Increases HSPA1A Expression and Ameliorates Cognitive Dysfunction in Aged P8 Mice.

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Hiroaki Kanouchi

Full Text Available Kurozu is a traditional Japanese rice vinegar. During fermentation and aging of the Kurozu liquid in an earthenware jar over 1 year, a solid residue called Kurozu Moromi is produced. In the present study, we evaluated whether concentrated Kurozu or Kurozu Moromi could ameliorate cognitive dysfunction in the senescence-accelerated P8 mouse. Senescence-accelerated P8 mice were fed 0.25% (w/w concentrated Kurozu or 0.5% (w/w Kurozu Moromi for 4 or 25 weeks. Kurozu suppressed cognitive dysfunction and amyloid accumulation in the brain, while Kurozu Moromi showed a tendency to ameliorate cognitive dysfunction, but the effect was not significant. We hypothesize that concentrated Kurozu has an antioxidant effect; however, the level of lipid peroxidation in the brain did not differ in senescence-accelerated P8 mice. DNA microarray analysis indicated that concentrated Kurozu increased HSPA1A mRNA expression, a protein that prevents protein misfolding and aggregation. The increase in HSPA1A expression by Kurozu was confirmed using quantitative real-time PCR and immunoblotting methods. The suppression of amyloid accumulation by concentrated Kurozu may be associated with HSPA1A induction. However, concentrated Kurozu could not increase HSPA1A expression in mouse primary neurons, suggesting it may not directly affect neurons.

Oxidative Stress, Synaptic Dysfunction, and Alzheimer's Disease.

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Tönnies, Eric; Trushina, Eugenia

2017-01-01

Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding of the disease mechanism hinders the development of efficacious therapeutic approaches. The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss. Oxidative stress has been recognized as a contributing factor in aging and in the progression of multiple neurodegenerative diseases including AD. Increased production of reactive oxygen species (ROS) associated with age- and disease-dependent loss of mitochondrial function, altered metal homeostasis, and reduced antioxidant defense directly affect synaptic activity and neurotransmission in neurons leading to cognitive dysfunction. In addition, molecular targets affected by ROS include nuclear and mitochondrial DNA, lipids, proteins, calcium homeostasis, mitochondrial dynamics and function, cellular architecture, receptor trafficking and endocytosis, and energy homeostasis. Abnormal cellular metabolism in turn could affect the production and accumulation of amyloid-β (Aβ) and hyperphosphorylated Tau protein, which independently could exacerbate mitochondrial dysfunction and ROS production, thereby contributing to a vicious cycle. While mounting evidence implicates ROS in the AD etiology, clinical trials with antioxidant therapies have not produced consistent results. In this review, we will discuss the role of oxidative stress in synaptic dysfunction in AD, innovative therapeutic strategies evolved based on a better understanding of the complexity of molecular mechanisms of AD, and the dual role ROS play in health and disease.

Contemporary Patterns of Multiple Organ Dysfunction in Trauma.

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Shepherd, Joanna M; Cole, Elaine; Brohi, Karim

2017-04-01

Multiple organ dysfunction syndrome (MODS) is associated with poor outcomes for trauma patients. Different forms of MODS may exist and have different consequences. The ability to distinguish them clinically may have implications for prognosis and treatment. We wished to study whether prolonged MODS (PRMODS) could be observed as a distinct clinical entity to early resolving MODS (ERMODS) in critically injured patients. Adult major trauma patients recruited to a prospective observational study at a single major trauma center were eligible for inclusion. MODS was defined as Sequential Organ Failure Assessment (SOFA) score >5; and PRMODS as lasting >7 days. Time to recovery (TTR) was calculated as the number of days before the SOFA fell below the MODS threshold (≤5). Five hundred ninety-five patients were enrolled of whom 285 developed ERMODS (48%) and 184 (31%) PRMODS. Organ dysfunction was more severe and protracted in PRMODS, especially in patients without brain injury (mean SOFA 11 vs. 6, Day 2, P < 0.001; TTR 17 vs. 3 days, P < 0.001). PRMODS exhibited higher rates of hepatic and renal dysfunction (84% vs. 56%; and 78% vs. 47%, P≤0.001). Patterns of recovery were distinct in hepatic, renal, and neurological systems (TTR 15 vs. 4; 20 vs. 3; and 28 vs. 7 days, P < 0.01). PRMODS was associated with higher infection and mortality rates (91% vs. 41%; and 22% vs. 7%, P < 0.001). PRMODS appears common, a distinct clinical entity, and associated with worse patient outcomes. PRMODS may represent an important endpoint for studies evaluating outcomes following trauma.

Is Internet Pornography Causing Sexual Dysfunctions? A Review with Clinical Reports

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Park, Brian Y.; Wilson, Gary; Berger, Jonathan; Christman, Matthew; Reina, Bryn; Bishop, Frank; Klam, Warren P.; Doan, Andrew P.

2016-01-01

Traditional factors that once explained men’s sexual difficulties appear insufficient to account for the sharp rise in erectile dysfunction, delayed ejaculation, decreased sexual satisfaction, and diminished libido during partnered sex in men under 40. This review (1) considers data from multiple domains, e.g., clinical, biological (addiction/urology), psychological (sexual conditioning), sociological; and (2) presents a series of clinical reports, all with the aim of proposing a possible direction for future research of this phenomenon. Alterations to the brain's motivational system are explored as a possible etiology underlying pornography-related sexual dysfunctions. This review also considers evidence that Internet pornography’s unique properties (limitless novelty, potential for easy escalation to more extreme material, video format, etc.) may be potent enough to condition sexual arousal to aspects of Internet pornography use that do not readily transition to real-life partners, such that sex with desired partners may not register as meeting expectations and arousal declines. Clinical reports suggest that terminating Internet pornography use is sometimes sufficient to reverse negative effects, underscoring the need for extensive investigation using methodologies that have subjects remove the variable of Internet pornography use. In the interim, a simple diagnostic protocol for assessing patients with porn-induced sexual dysfunction is put forth. PMID:27527226

Primary brain lymphoma in a patient after renal transplantation

International Nuclear Information System (INIS)

Arteaga, Carlos; Duarte, Monica; Bayona, Hernan

2009-01-01

The incidence of primary central nervous system lymphoma (PCNSL) has increased during the past 40 years. This has been associated with immunodeficiency, mainly in patients infected with the human immunodeficiency virus (HIV) and in transplant patients. Tumor genesis is related with the Epstein-Barr virus (EBV). The most frequent PCNSL immuno phenotype is B-cell lymphoma. Clinical manifestations depend on tumor localization, and are usually behavior dysfunctions and intracranial hypertension syndrome. Differential diagnosis must take into consideration infectious processes, stroke, primary brain tumors, and metastases. The diagnosis of PCNSL requires brain MRI and brain biopsy. It is important to assess HIV infection when diagnosing PCNSL. This review reports a case of primary brain lymphoma in a patient who underwent renal transplantation due to polycystic kidney disease 8 years before.

Brain abnormalities in murderers indicated by positron emission tomography.

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Raine, A; Buchsbaum, M; LaCasse, L

1997-09-15

Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.

MEG-based detection and localization of perilesional dysfunction in chronic stroke

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Ron K.O. Chu

2015-01-01

Full Text Available Post-stroke impairment is associated not only with structural lesions, but also with dysfunction in surviving perilesional tissue. Previous studies using equivalent current dipole source localization of MEG/EEG signals have demonstrated a preponderance of slow-wave activity localized to perilesional areas. Recent studies have also demonstrated the utility of nonlinear analyses such as multiscale entropy (MSE for quantifying neuronal dysfunction in a wide range of pathologies. The current study utilized beamformer-based reconstruction of signals in source space to compare spectral and nonlinear measures of electrical activity in perilesional and healthy cortices. Data were collected from chronic stroke patients and healthy controls, both young and elderly. We assessed relative power in the delta (1–4 Hz, theta (4–7 Hz, alpha (8–12 Hz and beta (15–30 Hz frequency bands, and also measured the nonlinear complexity of electrical activity using MSE. Perilesional tissue exhibited a general slowing of the power spectrum (increased delta/theta, decreased beta as well as a reduction in MSE. All measures tested were similarly sensitive to changes in the posterior perilesional regions, but anterior perilesional dysfunction was detected better by MSE and beta power. The findings also suggest that MSE is specifically sensitive to electrophysiological dysfunction in perilesional tissue, while spectral measures were additionally affected by an increase in rolandic beta power with advanced age. Furthermore, perilesional electrophysiological abnormalities in the left hemisphere were correlated with the degree of language task-induced activation in the right hemisphere. Finally, we demonstrate that single subject spectral and nonlinear analyses can identify dysfunctional perilesional regions within individual patients that may be ideal targets for interventions with noninvasive brain stimulation.

Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

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Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

2017-07-04

This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

Sacroiliac joint dysfunction.

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Ilaslan, Hakan; Arslan, Ahmet; Koç, Omer Nadir; Dalkiliç, Turker; Naderi, Sait

2010-07-01

Sacroiliac joint dysfunction is a disorder presenting with low back and groin pain. It should be taken into consideration during the preoperative differential diagnosis of lumbar disc herniation, lumbar spinal stenosis and facet syndrome. Four cases with sacroiliac dysfunction are presented. The clinical and radiological signs supported the evidence of sacroiliac dysfunction, and exact diagnosis was made after positive response to sacroiliac joint block. A percutaneous sacroiliac fixation provided pain relief in all cases. The mean VAS scores reduced from 8.2 to 2.2. It is concluded that sacroiliac joint dysfunction diagnosis requires a careful physical examination of the sacroiliac joints in all cases with low back and groin pain. The diagnosis is made based on positive response to the sacroiliac block. Sacroiliac fixation was found to be effective in carefully selected cases.

Stress-induced cognitive dysfunction: hormone-neurotransmitter interactions in the prefrontal cortex

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Rebecca M Shansky

2013-04-01

Full Text Available The mechanisms and neural circuits that drive emotion and cognition are inextricably linked. Activation of the hypothalamic-pituitary-adrenal (HPA axis as a result of stress or other causes of arousal initiates a flood of hormone and neurotransmitter release throughout the brain, affecting the way we think, decide, and behave. This review will focus on factors that influence the function of the prefrontal cortex (PFC, a brain region that governs higher-level cognitive processes and executive function. The PFC becomes markedly impaired by stress, producing measurable deficits in working memory. These deficits arise from the interaction of multiple neuromodulators, including glucocorticoids, catecholamines, and gonadal hormones; here we will discuss the non- human primate and rodent literature that has furthered our understanding of the circuitry, receptors, and signaling cascades responsible for stress-induced prefrontal dysfunction.

Blood-brain barrier dysfunction and amyloid precursor protein accumulation in microvascular compartment following ischemia-reperfusion brain injury with 1-year survival.

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Pluta, R

2003-01-01

This study examined the late microvascular consequences of brain ischemia due to cardiac arrest in rats. In reacted vibratome sections scattered foci of extravasated horseradish peroxidase were noted throughout the brain and did not appear to be restricted to any specific area of brain. Ultrastructural investigation of leaky sites frequently presented platelets adhering to the endothelium of venules and capillaries. Endothelial cells demonstrated pathological changes with evidence of perivascular astrocytic swelling. At the same time, we noted C-terminal of amyloid precursor protein/beta-amyloid peptide (CAPP/betaA) deposits in cerebral blood vessels, with a halo of CAPP/betaA immunoreactivity in the surrounding parenchyma suggested diffusion of CAPP/betaA out of the vascular compartment. Changes predominated in the hippocampus, cerebral and entorhinal cortex, corpus callosum, thalamus, basal ganglia and around the lateral ventricles. These data implicate delayed abnormal endothelial function of vessels following ischemia-reperfusion brain injury as a primary event in the pathogenesis of the recurrent cerebral infarction.

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

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Petra eSántha

2016-01-01

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

Time dysperception perspective for acquired brain injury

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Federica ePiras

2014-01-01

Full Text Available Distortions of time perception are presented by a number of neuropsychiatric disorders. Here we survey timing abilities in clinical populations with acquired brain injuries in key cerebral areas recently implicated in human studies of timing. We purposely analyzed the complex relationship between cognitive and contextual factors involved in time estimation, as to characterize the correlation between timed and other cognitive behaviors in each group. We assume that interval timing is a solid construct to study cognitive dysfunctions following brain injury, as timing performance is a sensitive metric of information processing, while temporal cognition has the potential of influencing a wide range of cognitive processes. Moreover, temporal performance is a sensitive assay of damage to the underlying neural substrate after a brain insult. Further research in neurological and psychiatric patients will definitively answer the question of whether time distortions are manifestations of cognitive and behavioral symptoms of brain damage and definitively clarify their mechanisms.

PiB fails to map amyloid deposits in cerebral cortex of aged dogs with canine cognitive dysfunction

DEFF Research Database (Denmark)

Fast, Rikke; Rodell, Anders; Gjedde, Albert

2013-01-01

to the understanding of AD. However, the sensitivity of the biomarker Pittsburgh Compound B (PiB) to the presence of Aβ in humans and in other mammalian species is in doubt. To test the sensitivity and assess the distribution of Aβ in dog brain, we mapped the brains of dogs with signs of CCD (n = 16) and a control......]PiB in the cerebellum, compared to the cerebral cortex. Retention in the cerebellum is at variance with evidence from brains of humans with AD. To confirm the lack of sensitivity, we stained two dog brains with the immunohistochemical marker 6E10, which is sensitive to the presence of both Aβ and Aβ precursor protein......Dogs with Canine Cognitive Dysfunction (CCD) accumulate amyloid beta (Aβ) in the brain. As the cognitive decline and neuropathology of these old dogs share features with Alzheimer's disease (AD), the relation between Aβ and cognitive decline in animal models of cognitive decline is of interest...

A PET study on brain control of micturition in humans

NARCIS (Netherlands)

Blok, BFM; Willemsen, ATM; Holstege, G

Although the brain plays a crucial role in the control of micturition, little is known about the structures involved. Identification of these areas is important because their dysfunction is thought to cause urge incontinence, a major problem in the elderly. In the cat, three areas in the brainstem

Brain inflammatory cytokines and microglia morphology changes throughout hibernation phases in Syrian hamster

NARCIS (Netherlands)

Cogut, V.; Bruintjes, J. J.; Eggen, B. J. L.; van der Zee, E. A.; Henning, R. H.

Hibernators tolerate low metabolism, reduced cerebral blood flow and hypothermia during torpor without noticeable neuronal or synaptic dysfunction upon arousal. Previous studies found extensive changes in brain during torpor, including synaptic rearrangements, documented both morphologically and

Risperidone treatment increases CB1 receptor binding in rat brain

DEFF Research Database (Denmark)

Secher, Anna; Husum, Henriette; Holst, Birgitte

2010-01-01

, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. METHODS: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

Analysis of the Role of Neurospecific Proteins in the Diagnosis of Cognitive Dysfunction in Patients with Type 1 Diabetes Mellitus

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Yulia Gennad'evna Samoylova

2014-04-01

Full Text Available Background. Impairment of the central nervous system manifested as cognitive dysfunction caused by metabolic or structural changes is a severe progressive vascular complication of type 1 diabetes mellitus (T1DM. Significant difficulties in the diagnosis of cognitive dysfunction are associated with subjective diagnostic techniques. Objective. To identify the role of neurospecific markers in the diagnosis of cognitive dysfunction in patients with T1DM. Materials and Methods. A total of 58 patients with T1DM aged 16?30 years were included in this study. The control group included 29 healthy young adults matched by gender and age. The survey included clinical and laboratory examinations, psychological testing and magnetic resonance imaging (MRI of the brain. The Montreal Cognitive Assessment (MoCA was used to screen for cognitive impairment. The levels of neurospecific proteins (S100, glial fibrillary acidic protein and myelin basic protein were determined to identify early markers of cognitive impairment. MRI of the brain was performed using a Siemens Magnetom 1.0 T system to assess structural changes in the central nervous system. Results. The study revealed increased levels of all neurospecific proteins, which correlated with parameters of hyperglycaemia and cognitive deficit (MoCA scores of

The NCAN gene: schizophrenia susceptibility and cognitive dysfunction

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Wang P

2016-11-01

Full Text Available Peirong Wang,1 Jun Cai,2 Jianliang Ni,1 Jiangtao Zhang,1 Wei Tang,3 Chen Zhang2 1Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 2Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 3Wenzhou Kangning Hospital, Wenzhou, Zhejiang, People’s Republic of China Background: Cognitive dysfunction has been recognized as a cardinal feature of schizophrenia. Elucidating the neurobiological substrates of cognitive dysfunction in schizophrenia would help identify the underlying mechanism of this disorder. The rs1064395 single nucleotide polymorphism, within the gene encoding neurocan (NCAN, is reported to be associated with schizophrenia in European populations and may influence brain structure in patients with schizophrenia.Methods: In this study, we aimed to explore whether NCAN rs1064395 confers some risk for schizophrenia and cognitive dysfunction in Han Chinese. We recruited 681 patients with schizophrenia and 699 healthy subjects. Two hundred and fifty-four patients were evaluated according to Repeatable Battery for the Assessment of Neuropsychological Status (RBANS.Results: There were no significant differences in genotype or allele distributions of the rs1064395 polymorphism between the schizophrenia and control groups. Patients showed significantly poorer performance than controls on immediate memory, visuospatial skill, language, attention, delayed memory, and total RBANS score. Patients with the A/A or A/G genotype of rs1064395 had lower scores of immediate memory, visuospatial skill, attention, and total RBANS score than those with the G/G genotype. We performed an expression quantitative trait loci analysis and observed a significant association between rs1064395 and NCAN expression in the frontal (P=0.0022, P=0.022 after Bonferroni correction and cerebellar cortex (P=0.0032, P=0.032 after Bonferroni correction.Conclusion: Our findings indicate

Contribution Of Brain Tissue Oxidative Damage In Hypothyroidism-associated Learning and Memory Impairments

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Yousef Baghcheghi

2017-01-01

Full Text Available The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments.

[Nicorandil improves cognitive dysfunction in mice with streptozotocin-induced diabetes].

Science.gov (United States)

Yan, Wen-Hui; Zhang, Chun-Xi; Xing, Tong; Gong, Xue; Yang, Yu-Xuan; Li, Yi-Nuo; Liu, Xuan; Ayijiang, Jiamaliding; Yu, Ye; Zhang, Meng; Chen, Li-Na

2018-04-20

To observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin (STZ)-induced diabetes. C57BL/6J mouse models of type 1 diabetes mellitus (T1DM) were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline (model group) for 4 consecutive weeks, with normal C57BL/6J mice serving as control. Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week. At the end of the experiment, the mice were sacrificed to observe the ultrastructural changes in the hippocampus and pancreas under transmission electron microscopy; the contents of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the hippocampus and SOD activity and MDA level in the brain tissue were determined. Compared with the control group, the model group showed significantly increased fasting blood glucose (P<0.001), significantly prolonged escape latency (P<0.05) and increased swimming distance (P<0.01) with ultrastructural damage of pancreatic β cells and in the hippocampus; GIP and GLP-1 contents in the hippocampus (P<0.01) and SOD activity in the brain were significantly decreased (P<0.05) and MDA content was significantly increased in the model group (P<0.05). Compared with the model group, nicorandil treatment did not cause significant changes in fasting blood glucose, but significantly reduced the swimming distance (P<0.05); nicorandil did not improve the ultrastructural changes in pancreatic β cells but obviously improved the ultrastructures of hippocampal neurons and synapses. Nicorandil also significantly increased the contents of GIP and GLP-1 in the hippocampus (P<0.05), enhanced SOD activity (P<0.05) and decreased MDA level (P<0.01) in the brain tissue. Nicorandil improves cognitive dysfunction in mice with STZ-induced diabetes by

Pharmacologic modeling of primary mitochondrial respiratory chain dysfunction in zebrafish.

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Byrnes, James; Ganetzky, Rebecca; Lightfoot, Richard; Tzeng, Michael; Nakamaru-Ogiso, Eiko; Seiler, Christoph; Falk, Marni J

2017-07-18

Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects as well as effects on mitochondrial biochemistry and physiology. Here, we characterize four pharmacologic inhibitor models of mitochondrial RC dysfunction in early larval zebrafish, including rotenone (complex I inhibitor), azide (complex IV inhibitor), oligomycin (complex V inhibitor), and chloramphenicol (mitochondrial translation inhibitor that leads to multiple RC complex dysfunction). A range of concentrations and exposure times of each RC inhibitor were systematically evaluated on early larval development, animal survival, integrated behaviors (touch and startle responses), organ physiology (brain death, neurologic tone, heart rate), and fluorescence-based analyses of mitochondrial physiology in zebrafish skeletal muscle. Pharmacologic RC inhibitor effects were validated by spectrophotometric analysis of Complex I, II and IV enzyme activities, or relative quantitation of ATP levels in larvae. Outcomes were prioritized that utilize in vivo animal imaging and quantitative behavioral assessments, as may optimally inform the translational potential of pre-clinical drug screens for future clinical study in human mitochondrial disease subjects. The RC complex inhibitors each delayed early embryo development, with short-term exposures of these three agents or chloramphenicol from 5 to 7 days

Assessment of functional status in children with brain tumors

International Nuclear Information System (INIS)

Sugita, Yasuo; Kobayashi, Seiichi; Uegaki, Masami; Katayama, Masahiko; Miyagi, Jun; Iryo, Osamu; Shigemori, Minoru; Kuramoto, Shinken; Ootsubo, Masaaki

1987-01-01

Thirty children treated for brain tumors between 1978 - 1985 at Kurume university hospital were evaluated for alternation in intellectual, emotional, and social function. They were 15 males and 15 females, aged 3 to 16 years, on the averaged 1.7 years after treatment. Twenty-eight children had no neurological deficits and 2 children had slight neurological deficits. It was possible for twenty-eight children to be evaluated for intelligence quotient by Wechsler Intelligence Scale for Children-revised and Tanaka-Binet. The median score and standard deviation of intelligence quotient (IQ) test in children with brain tumors were as follows; verbal IQ: 84 ± 16, performance IQ: 77 ± 20, full scale IQ: 80 ± 20. There children with brain tumors obtained significant low IQ scores than children (t-test, P < 0.01). Twenty-one (72 %) children showed subnormal IQ scores (IQ < 90) and 7 children showed normal IQ scores (IQ ≥ 90). Concerning social and emotional function, twelve children (45.7 %) showed abnormal behaviour. The median scores and standard deviation of IQ scores in cranial irradiated patients were as follows; verbal IQ: 79 ± 13, performance IQ: 71 ± 15, full scale IQ: 71 ± 14. Especially, ten of twelve cranial irradiated patients showed subnormal IQ scores. Also, cranial irradiated patients obtained significant low IQ scores than non-cranial irradiated patients (t-test, P < 0.05). Serial evaluation of three cranial irradiated patients revealed further deterioration without recurrence of tumor and hydrocephalus. The results are discussed to: (1) the effects and mechanism of cranial irradiation on cognitive development: (2) the relationship between cognitive dysfunction and irradiation methods. The effects and mechanism of cranial irradiation on cognitive dysfunction is considered to be not only injury of cortex but also injury of fiber tracts. Also, cognitive dysfunction is apt to be related to age of irradiated patients. (J.P.N.)

Assessment of functional status in children with brain tumors

Energy Technology Data Exchange (ETDEWEB)

Sugita, Yasuo; Kobayashi, Seiichi; Uegaki, Masami; Katayama, Masahiko; Miyagi, Jun; Iryo, Osamu; Shigemori, Minoru; Kuramoto, Shinken; Ootsubo, Masaaki

1987-06-01

Thirty children treated for brain tumors between 1978 - 1985 at Kurume university hospital were evaluated for alternation in intellectual, emotional, and social function. They were 15 males and 15 females, aged 3 to 16 years, on the averaged 1.7 years after treatment. Twenty-eight children had no neurological deficits and 2 children had slight neurological deficits. It was possible for twenty-eight children to be evaluated for intelligence quotient by Wechsler Intelligence Scale for Children-revised and Tanaka-Binet. The median score and standard deviation of intelligence quotient (IQ) test in children with brain tumors were as follows; verbal IQ: 84 +- 16, performance IQ: 77 +- 20, full scale IQ: 80 +- 20. There children with brain tumors obtained significant low IQ scores than children (t-test, P < 0.01). Twenty-one (72 %) children showed subnormal IQ scores (IQ < 90) and 7 children showed normal IQ scores (IQ greater than or equal to 90). Concerning social and emotional function, twelve children (45.7 %) showed abnormal behaviour. The median scores and standard deviation of IQ scores in cranial irradiated patients were as follows; verbal IQ: 79 +- 13, performance IQ: 71 +- 15, full scale IQ: 71 +- 14. Especially, ten of twelve cranial irradiated patients showed subnormal IQ scores. Also, cranial irradiated patients obtained significant low IQ scores than non-cranial irradiated patients (t-test, P < 0.05). Serial evaluation of three cranial irradiated patients revealed further deterioration without recurrence of tumor and hydrocephalus. The results are discussed to: (1) the effects and mechanism of cranial irradiation on cognitive development: (2) the relationship between cognitive dysfunction and irradiation methods. The effects and mechanism of cranial irradiation on cognitive dysfunction is considered to be not only injury of cortex but also injury of fiber tracts. Also, cognitive dysfunction is apt to be related to age of irradiated patients. (J.P.N.).

Dysfunctions of decision-making and cognitive control as transdiagnostic mechanisms of mental disorders: advances, gaps, and needs in current research.

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Goschke, Thomas

2014-01-01

Disadvantageous decision-making and impaired volitional control over actions, thoughts, and emotions are characteristics of a wide range of mental disorders such as addiction, eating disorders, depression, and anxiety disorders and may reflect transdiagnostic core mechanisms and possibly vulnerability factors. Elucidating the underlying neurocognitive mechanisms is a precondition for moving from symptom-based to mechanism-based disorder classifications and ultimately mechanism-targeted interventions. However, despite substantial advances in basic research on decision-making and cognitive control, there are still profound gaps in our current understanding of dysfunctions of these processes in mental disorders. Central unresolved questions are: (i) to which degree such dysfunctions reflect transdiagnostic mechanisms or disorder-specific patterns of impairment; (ii) how phenotypical features of mental disorders relate to dysfunctional control parameter settings and aberrant interactions between large-scale brain systems involved in habit and reward-based learning, performance monitoring, emotion regulation, and cognitive control; (iii) whether cognitive control impairments are consequences or antecedent vulnerability factors of mental disorders; (iv) whether they reflect generalized competence impairments or context-specific performance failures; (v) whether not only impaired but also chronic over-control contributes to mental disorders. In the light of these gaps, needs for future research are: (i) an increased focus on basic cognitive-affective mechanisms underlying decision and control dysfunctions across disorders; (ii) longitudinal-prospective studies systematically incorporating theory-driven behavioural tasks and neuroimaging protocols to assess decision-making and control dysfunctions and aberrant interactions between underlying large-scale brain systems; (iii) use of latent-variable models of cognitive control rather than single tasks; (iv) increased focus on

Keeping brains young with making music.

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Rogenmoser, Lars; Kernbach, Julius; Schlaug, Gottfried; Gaser, Christian

2018-01-01

Music-making is a widespread leisure and professional activity that has garnered interest over the years due to its effect on brain and cognitive development and its potential as a rehabilitative and restorative therapy of brain dysfunctions. We investigated whether music-making has a potential age-protecting effect on the brain. For this, we studied anatomical magnetic resonance images obtained from three matched groups of subjects who differed in their lifetime dose of music-making activities (i.e., professional musicians, amateur musicians, and non-musicians). For each subject, we calculated a so-called BrainAGE score which corresponds to the discrepancy (in years) between chronological age and the "age of the brain", with negative values reflecting an age-decelerating brain and positive values an age-accelerating brain, respectively. The index of "brain age" was estimated using a machine-learning algorithm that was trained in a large independent sample to identify anatomical correlates of brain-aging. Compared to non-musicians, musicians overall had lower BrainAGE scores, with amateur musicians having the lowest scores suggesting that music-making has an age-decelerating effect on the brain. Unlike the amateur musicians, the professional musicians showed a positive correlation between their BrainAGE scores and years of music-making, possibly indicating that engaging more intensely in just one otherwise enriching activity might not be as beneficial than if the activity is one of several that an amateur musician engages in. Intense music-making activities at a professional level could also lead to stress-related interferences and a less enriched environment than that of amateur musicians, possibly somewhat diminishing the otherwise positive effect of music-making.

Lipidomic and Transcriptomic Basis of Lysosomal Dysfunction in Progranulin Deficiency

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Bret M. Evers

2017-09-01

Full Text Available Defective lysosomal function defines many neurodegenerative diseases, such as neuronal ceroid lipofuscinoses (NCL and Niemann-Pick type C (NPC, and is implicated in Alzheimer’s disease (AD and frontotemporal lobar degeneration (FTLD-TDP with progranulin (PGRN deficiency. Here, we show that PGRN is involved in lysosomal homeostasis and lipid metabolism. PGRN deficiency alters lysosome abundance and morphology in mouse neurons. Using an unbiased lipidomic approach, we found that brain lipid composition in humans and mice with PGRN deficiency shows disease-specific differences that distinguish them from normal and other pathologic groups. PGRN loss leads to an accumulation of polyunsaturated triacylglycerides, as well as a reduction of diacylglycerides and phosphatidylserines in fibroblast and enriched lysosome lipidomes. Transcriptomic analysis of PGRN-deficient mouse brains revealed distinct expression patterns of lysosomal, immune-related, and lipid metabolic genes. These findings have implications for the pathogenesis of FTLD-TDP due to PGRN deficiency and suggest lysosomal dysfunction as an underlying mechanism.

Cerebral Activity Changes in Different Traditional Chinese Medicine Patterns of Psychogenic Erectile Dysfunction Patients

OpenAIRE

Liu, Qi; Zhang, Peihai; Pan, Junjie; Li, Zhengjie; Liu, Jixin; Li, Guangsen; Qin, Wei; You, Yaodong; Yu, Xujun; Sun, Jinbo; Dong, Minghao; Gong, Qiyong; Guo, Jun; Chang, Degui

2015-01-01

Background. Pattern differentiation is the foundation of traditional Chinese medicine (TCM) treatment for erectile dysfunction (ED). This study aims to investigate the differences in cerebral activity in ED patients with different TCM patterns. Methods. 27 psychogenic ED patients and 27 healthy subjects (HS) were enrolled in this study. Each participant underwent an fMRI scan in resting state. The fractional amplitude of low-frequency fluctuation (fALFF) was used to detect the brain activity ...

Sociosexual and communication deficits after traumatic injury to the developing murine brain.

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Bridgette D Semple

Full Text Available Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. Age-dependent vulnerability of the developing brain to social deficits was addressed by comparing behavioral and neuroanatomical outcomes in mice injured at either a pediatric age (p21 or during adolescence (p35. Sociosexual behaviors including social investigation and mounting were evaluated in a resident-intruder paradigm at adulthood. These outcomes were complemented by assays of urine scent marking and ultrasonic vocalizations as indices of social communication. We provide evidence of sociosexual deficits after brain injury at p21, which manifest as reduced mounting behavior and scent marking towards an unfamiliar female at adulthood. In contrast, with the exception of the loss of social recognition in a three-chamber social approach task, mice that received TBI at adolescence were remarkably resilient to social deficits at adulthood. Increased emission of ultrasonic vocalizations (USVs as well as preferential emission of high frequency USVs after injury was dependent upon both the stimulus and prior social experience. Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21

Selective neuronal vulnerability to oxidative stress in the brain

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Xinkun Wang

2010-03-01

Full Text Available Oxidative stress (OS, caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS, plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer’s disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.

Brain changes in diabetes mellitus patients with gastrointestinal symptoms

DEFF Research Database (Denmark)

Drewes, Anne M; Søfteland, Eirik; Dimcevski, Georg

2016-01-01

to stimulation of GI organs. Imaging studies on patients with diabetes and GI symptoms mainly showed microstructural changes, especially in brain areas involved in visceral sensory processing. As the electrophysiological and imaging changes were associated with GI and autonomic symptoms they may represent...... neuropathy of the central nervous system (CNS) may play a major role. This systematic review provides an overview of the neurodegenerative changes that occur as a consequence of diabetes with a focus on the CNS changes and gastrointestinal (GI) dysfunction. Animal models where diabetes was induced...... experimentally support that the disease induces changes in CNS. Recent investigations with electroencephalography and functional brain imaging in patients with diabetes confirm these structural and functional brain changes. Encephalographic studies demonstrated that altered insular processing of sensory stimuli...

Insulin resistance in brain and possible therapeutic approaches.

Science.gov (United States)

Cetinkalp, Sevki; Simsir, Ilgin Y; Ertek, Sibel

2014-01-01

Although the brain has long been considered an insulin-independent organ, recent research has shown that insulin has significant effects on the brain, where it plays a role in maintaining glucose and energy homeostasis. To avoid peripheral insulin resistance, the brain may act via hypoinsulinemic responses, maintaining glucose metabolism and insulin sensitivity within its own confines; however, brain insulin resistance may develop due to environmental factors. Insulin has two important functions in the brain: controlling food intake and regulating cognitive functions, particularly memory. Notably, defects in insulin signaling in the brain may contribute to neurodegenerative disorders. Insulin resistance may damage the cognitive system and lead to dementia states. Furthermore, inflammatory processes in the hypothalamus, where insulin receptors are expressed at high density, impair local signaling systems and cause glucose and energy metabolism disorders. Excessive caloric intake and high-fat diets initiate insulin and leptin resistance by inducing mitochondrial dysfunction and endoplasmic reticulum stress in the hypothalamus. This may lead to obesity and diabetes mellitus (DM). Exercise can enhance brain and hypothalamic insulin sensitivity, but it is the option least preferred and/or continuously practiced by the general population. Pharmacological treatments that increase brain and hypothalamic insulin sensitivity may provide new insights into the prevention of dementia disorders, obesity, and type 2 DM in the future.

Potential Moderators of Physical Activity on Brain Health

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Regina L. Leckie

2012-01-01

Full Text Available Age-related cognitive decline is linked to numerous molecular, structural, and functional changes in the brain. However, physical activity is a promising method of reducing unfavorable age-related changes. Physical activity exerts its effects on the brain through many molecular pathways, some of which are regulated by genetic variants in humans. In this paper, we highlight genes including apolipoprotein E (APOE, brain derived neurotrophic factor (BDNF, and catechol-O-methyltransferase (COMT along with dietary omega-3 fatty acid, docosahexaenoic acid (DHA, as potential moderators of the effect of physical activity on brain health. There are a growing number of studies indicating that physical activity might mitigate the genetic risks for disease and brain dysfunction and that the combination of greater amounts of DHA intake with physical activity might promote better brain function than either treatment alone. Understanding whether genes or other lifestyles moderate the effects of physical activity on neurocognitive health is necessary for delineating the pathways by which brain health can be enhanced and for grasping the individual variation in the effectiveness of physical activity interventions on the brain and cognition. There is a need for future research to continue to assess the factors that moderate the effects of physical activity on neurocognitive function.

Effect of different modes of therapy on vestibular and balance dysfunction in Parkinson’s disease

OpenAIRE

El-Kholy, Wafaa Abdel-Hay; Taha, Hesham Mohamed; Hamada, Soha Mohamed; Sayed, Mona Abdel-Fattah

2015-01-01

Background: Patients with Parkinson’s disease (PD) have difficulties in performing various motor tasks such as walking, writing and speaking, together with significant balance dysfunction. Despite gains made in the field of pharmacotherapy and deep brain stimulation, dopaminergic medications may produce a limited improvement in postural stability. Sustained improvement in motor skills can be achieved through physiotherapy. Aim of the work: To measure the effect of different modes of therap...

Fluorescein isothiocyanate (FITC)-Dextran Extravasation as a Measure of Blood-Brain Barrier Permeability

Science.gov (United States)

Natarajan, Reka; Northrop, Nicole

2017-01-01

The blood-brain barrier (BBB) is formed in part by vascular endothelial cells that constitute the capillaries and microvessels of the brain. The function of this barrier is to maintain homeostasis within the brain microenvironment and buffer the brain from changes in the periphery. A dysfunction of the BBB would permit circulating molecules and pathogens typically restricted to the periphery to enter the brain and interfere with normal brain function. As increased permeability of the BBB is associated with several neuropathologies, it is important to have a reliable and sensitive method that determines BBB permeability and the degree of BBB disruption. A detailed protocol is presented for assessing the integrity of the BBB by transcardial perfusion of a 10,000 Da FITC labeled dextran molecule and its visualization to determine the degree of extravasation from brain microvessels. PMID:28398646

[Social dysfunction in schizotypy].

Science.gov (United States)

de Wachter, O; De La Asuncion, J; Sabbe, B; Morrens, M

2016-01-01

Schizotypy is a personality organisation that is closely related to schizotypal personality disorder and schizophrenia and is characterised by deficits in social functioning. Although the dimensions of social dysfunction have not yet been fully explored certain aspects of social dysfunction are promising predictive markers for schizophrenia. To describe schizotypy and its influence on social functioning. We reviewed the literature systematically using the online databases PubMed and PsycINFO. The disorder known as schizotypy lies at the basis of schizotypal personality disorder. Both disorders are characterised by an increased risk for schizophrenia. The social dysfunctioning seen in schizotypy corresponds to the social dysfunction seen in schizophrenia. Impairments in social cognition are causal factors of this social dysfunction. Both the negative and the positive dimension of schizotypy influence social cognition. More focused, objective and interactive research to the various aspects of social functioning in schizotypy is needed in order to discover potential premorbid markers for schizophrenia.

Dysfunctional GABAergic inhibition in the prefrontal cortex leading to "psychotic" hyperactivation

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Tanaka Shoji

2008-04-01

Full Text Available Abstract Background The GABAergic system in the brain seems to be dysfunctional in various psychiatric disorders. Many studies have suggested so far that, in schizophrenia patients, GABAergic inhibition is selectively but consistently reduced in the prefrontal cortex (PFC. Results This study used a computational model of the PFC to investigate the dynamics of the PFC circuit with and without chandelier cells and other GABAergic interneurons. The inhibition by GABAergic interneurons other than chandelier cells effectively regulated the PFC activity with rather low or modest levels of dopaminergic neurotransmission. This activity of the PFC is associated with normal cognitive functions and has an inverted-U shaped profile of dopaminergic modulation. In contrast, the chandelier cell-type inhibition affected only the PFC circuit dynamics in hyperdopaminergic conditions. Reduction of chandelier cell-type inhibition resulted in bistable dynamics of the PFC circuit, in which the upper stable state is associated with a hyperactive mode. When both types of inhibition were reduced, this hyperactive mode and the conventional inverted-U mode merged. Conclusion The results of our simulation suggest that, in schizophrenia, a reduction of GABAergic inhibition increases vulnerability to psychosis by (i producing the hyperactive mode of the PFC with hyperdopaminergic neurotransmission by dysfunctional chandelier cells and (ii increasing the probability of the transition to the hyperactive mode from the conventional inverted-U mode by dysfunctional GABAergic interneurons.

Social connectedness, mental health and the adolescent brain.

Science.gov (United States)

Lamblin, M; Murawski, C; Whittle, S; Fornito, A

2017-09-01

Social relationships promote health and wellbeing. Brain regions regulating social behavior continue to develop throughout adolescence, as teens learn to navigate their social environment with increasing sophistication. Adolescence is also a time of increased risk for the development of psychiatric disorders, many of which are characteristically associated with social dysfunction. In this review, we consider the links between adolescent brain development and the broader social environment. We examine evidence that individual differences in social ability, partly determined by genetic influences on brain structure and function, impact the quality and quantity of social ties during adolescence and that, conversely, the structure of one's social network exerts complex yet profound influences on individual behavior and mental health. In this way, the brain and social environment sculpt each other throughout the teenage years to influence one's social standing amongst peers. Reciprocal interactions between brain maturation and the social environment at this critical developmental stage may augment risk or promote resilience for mental illness and other health outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

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Lukoshe, Akvile; White, Tonya; Schmidt, Marcus N; van der Lugt, Aad; Hokken-Koelega, Anita C

2013-01-01

Background Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical foc...

The Influence of Adipose Tissue on Brain Development, Cognition, and Risk of Neurodegenerative Disorders.

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Letra, Liliana; Santana, Isabel

2017-01-01

The brain is a highly metabolic organ and thus especially vulnerable to changes in peripheral metabolism, including those induced by obesity-associated adipose tissue dysfunction. In this context, it is likely that the development and maturation of neurocognitive circuits may also be affected and modulated by metabolic environmental factors, beginning in utero. It is currently recognized that maternal obesity, either pre-gestational or gestational, negatively influences fetal brain development and elevates the risk of cognitive impairment and neuropsychiatric disorders in the offspring. During infancy and adolescence, obesity remains a limiting factor for healthy neurodevelopment, especially affecting executive functions but also attention, visuospatial ability, and motor skills. In middle age, obesity seems to induce an accelerated brain aging and thus may increase the risk of age-related neurodegenerative diseases such as Alzheimer's disease. In this chapter we review and discuss experimental and clinical evidence focusing on the influence of adipose tissue dysfunction on neurodevelopment and cognition across lifespan, as well as some possible mechanistic links, namely the role of the most well studied adipokines.

Clinical Significance of Brain SPECT in Zipeprol Abusers

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Cho, Dai Ok; Kim, Jae Phil; Kim, Deog Yoon; Yang, Hyung In; Koh, Eun Mi; Kim, Kwang Won; Choi, Young Kil [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

1993-03-15

Drug abuse is widespread in worldwide and has been associated with neurologic complication. Zipeprol is one of drugs which been abused for psychological satisfaction in some adolescents. This agent is non-opioid antitussive agent, which is not legally considered as being capable of creating dependence or abuse liability at therapeutic serum levels. But it has been reported that acute or chronic overdose create neurologic complication such as convulsion as well as dependence. Recently we experienced six zipeprol abusers who admitted due to convulsion and variable neurologic symptoms. The aim of our study was to determine the role of Tc-99m- HMPAO brain SPECT in those patients. EEG and brain CT showed no abnormal finding, but brain SPECT showed focal or multiple perfusion abnormalities in frontal, parietal, occipital cortex, basal ganglia, thalamus and especially at temporal cortex. These results suggest that brain SPECT may be a useful diagnostic tool to evaluate the cerebral dysfunction induced by zipeprol abuse.

Clinical Significance of Brain SPECT in Zipeprol Abusers

International Nuclear Information System (INIS)

Cho, Dai Ok; Kim, Jae Phil; Kim, Deog Yoon; Yang, Hyung In; Koh, Eun Mi; Kim, Kwang Won; Choi, Young Kil

1993-01-01

Drug abuse is widespread in worldwide and has been associated with neurologic complication. Zipeprol is one of drugs which been abused for psychological satisfaction in some adolescents. This agent is non-opioid antitussive agent, which is not legally considered as being capable of creating dependence or abuse liability at therapeutic serum levels. But it has been reported that acute or chronic overdose create neurologic complication such as convulsion as well as dependence. Recently we experienced six zipeprol abusers who admitted due to convulsion and variable neurologic symptoms. The aim of our study was to determine the role of Tc-99m- HMPAO brain SPECT in those patients. EEG and brain CT showed no abnormal finding, but brain SPECT showed focal or multiple perfusion abnormalities in frontal, parietal, occipital cortex, basal ganglia, thalamus and especially at temporal cortex. These results suggest that brain SPECT may be a useful diagnostic tool to evaluate the cerebral dysfunction induced by zipeprol abuse.

Proximate Mediators of Microvascular Dysfunction at the Blood-Brain Barrier: Neuroinflammatory Pathways to Neurodegeneration

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Barry W. Festoff

2017-01-01

Full Text Available Current projections are that by 2050 the numbers of people aged 65 and older with Alzheimer’s disease (AD in the US may increase threefold while dementia is projected to double every 20 years reaching ~115 million by 2050. AD is clinically characterized by progressive dementia and neuropathologically by neuronal and synapse loss, accumulation of amyloid plaques, and neurofibrillary tangles (NFTs in specific brain regions. The preclinical or presymptomatic stage of AD-related brain changes may begin over 20 years before symptoms occur, making development of noninvasive biomarkers essential. Distinct from neuroimaging and cerebrospinal fluid biomarkers, plasma or serum biomarkers can be analyzed to assess (i the presence/absence of AD, (ii the risk of developing AD, (iii the progression of AD, or (iv AD response to treatment. No unifying theory fully explains the neurodegenerative brain lesions but neuroinflammation (a lethal stressor for healthy neurons is universally present. Current consensus is that the earlier the diagnosis, the better the chance to develop treatments that influence disease progression. In this article we provide a detailed review and analysis of the role of the blood-brain barrier (BBB and damage-associated molecular patterns (DAMPs as well as coagulation molecules in the onset and progression of these neurodegenerative disorders.

Brain structure and the relationship with neurocognitive functioning in schizophrenia and bipolar disorder : MRI studies

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Hartberg, Cecilie Bhandari

2011-01-01

Brain structural abnormalities as well as neurocognitive dysfunction, are found in schizophrenia and in bipolar disorder. Based on the fact that both brain structure and neurocognitive functioning are significantly heritable and affected in both schizophrenia and bipolar disorder, relationships between them are expected. However, previous studies report inconsistent findings. Also, schizophrenia and bipolar disorder are classified as separate disease entities, but demonstrate overlap with reg...

Basic visual dysfunction allows classification of patients with schizophrenia with exceptional accuracy.

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González-Hernández, J A; Pita-Alcorta, C; Padrón, A; Finalé, A; Galán, L; Martínez, E; Díaz-Comas, L; Samper-González, J A; Lencer, R; Marot, M

2014-10-01

Basic visual dysfunctions are commonly reported in schizophrenia; however their value as diagnostic tools remains uncertain. This study reports a novel electrophysiological approach using checkerboard visual evoked potentials (VEP). Sources of spectral resolution VEP-components C1, P1 and N1 were estimated by LORETA, and the band-effects (BSE) on these estimated sources were explored in each subject. BSEs were Z-transformed for each component and relationships with clinical variables were assessed. Clinical effects were evaluated by ROC-curves and predictive values. Forty-eight patients with schizophrenia (SZ) and 55 healthy controls participated in the study. For each of the 48 patients, the three VEP components were localized to both dorsal and ventral brain areas and also deviated from a normal distribution. P1 and N1 deviations were independent of treatment, illness chronicity or gender. Results from LORETA also suggest that deficits in thalamus, posterior cingulum, precuneus, superior parietal and medial occipitotemporal areas were associated with symptom severity. While positive symptoms were more strongly related to sensory processing deficits (P1), negative symptoms were more strongly related to perceptual processing dysfunction (N1). Clinical validation revealed positive and negative predictive values for correctly classifying SZ of 100% and 77%, respectively. Classification in an additional independent sample of 30 SZ corroborated these results. In summary, this novel approach revealed basic visual dysfunctions in all patients with schizophrenia, suggesting these visual dysfunctions represent a promising candidate as a biomarker for schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Targeting synaptic dysfunction in Alzheimer's disease by administering a specific nutrient combination.

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van Wijk, Nick; Broersen, Laus M; de Wilde, Martijn C; Hageman, Robert J J; Groenendijk, Martine; Sijben, John W C; Kamphuis, Patrick J G H

2014-01-01

Synapse loss and synaptic dysfunction are pathological processes already involved in the early stages of Alzheimer's disease (AD). Synapses consist principally of neuronal membranes, and the neuronal and synaptic losses observed in AD have been linked to the degeneration and altered composition and structure of these membranes. Consequently, synapse loss and membrane-related pathology provide viable targets for intervention in AD. The specific nutrient combination Fortasyn Connect (FC) is designed to ameliorate synapse loss and synaptic dysfunction in AD by addressing distinct nutritional needs believed to be present in these patients. This nutrient combination comprises uridine, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium, and is present in Souvenaid, a medical food intended for use in early AD. It has been hypothesized that FC counteracts synaptic loss and reduces membrane-related pathology in AD by providing nutritional precursors and cofactors that act together to support neuronal membrane formation and function. Preclinical studies formed the basis of this hypothesis which is being validated in a broad clinical study program investigating the potential of this nutrient combination in AD. Memory dysfunction is one key early manifestation in AD and is associated with synapse loss. The clinical studies to date show that the FC-containing medical food improves memory function and preserves functional brain network organization in mild AD compared with controls, supporting the hypothesis that this intervention counteracts synaptic dysfunction. This review provides a comprehensive overview of basic scientific studies that led to the creation of FC and of its effects in various preclinical models.

Organizational Dysfunctions: Sources and Areas

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Jacek Pasieczny

2016-12-01

Full Text Available Objective:The purpose of this article is to identify and describe various types and sources of organizational dysfunctions. Research Design & Methods: The findings are based on literature review and an ongoing empirical research project conducted in private sector organisations. The empirical study can be situated within interpretative approach. In this qualitative project open interviews and observations were used to collect data. Findings: The study indicates that various types and sources of organizational dysfunctions can be identified in organizations operating in Poland. The sources of dysfunctions may be found both within the organization and its environment. Regardless of its specific features, most of the dysfunctions may be interpreted as an undesirable goal displacement. Very often areas of these dysfunctions are strongly interconnected and create a system that hinders organizational performance. Yet, it is difficult to study these phenomena as respondents are unwilling, for various reasons, to disclose the problems faced by their organizations. Implications & Recommendations: The results imply that the issue of organisational dysfunctions requires open, long-lasting and comparative studies. Recommendations for further studies are formulated in the last section of the paper. Contribution & Value Added: The paper provides insight into "the dark side of organising" by identifying sources and areas of dysfunctions. It also reveals difficulties connected with conducting research on dysfunctions in the Polish context.

Bladder Dysfunction and Vesicoureteral Reflux

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Ulla Sillén

2008-01-01

Full Text Available In this overview the influence of functional bladder disturbances and of its treatment on the resolution of vesicoureteral reflux (VUR in children is discussed. Historically both bladder dysfunction entities, the overactive bladder (OAB and the dysfunctional voiding (DV, have been described in conjunction with VUR. Treatment of the dysfunction was also considered to influence spontaneous resolution in a positive way. During the last decades, however, papers have been published which could not support these results. Regarding the OAB, a prospective study with treatment of the bladder overactivity with anticholinergics, did not influence spontaneous resolution rate in children with a dysfunction including also the voiding phase, DV and DES (dysfunctional elimination syndrome, most studies indicate a negative influence on the resolution rate of VUR in children, both before and after the age for bladder control, both with and without treatment. However, a couple of uncontrolled studies indicate that there is a high short-term resolution rate after treatment with flow biofeedback. It should be emphasized that the voiding phase dysfunctions (DV and DES are more severe than the genuine filling phase dysfunction (OAB, with an increased frequency of UTI and renal damage in the former groups. To be able to answer the question if treatment of bladder dysfunction influence the resolution rate of VUR in children, randomized controlled studies must be performed.

Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis.

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Symmonds, Mkael; Moran, Catherine H; Leite, M Isabel; Buckley, Camilla; Irani, Sarosh R; Stephan, Klaas Enno; Friston, Karl J; Moran, Rosalyn J

2018-04-30

Neurological and psychiatric practice frequently lack diagnostic probes that can assess mechanisms of neuronal communication non-invasively in humans. In N-methyl-d-aspartate (NMDA) receptor antibody encephalitis, functional molecular assays are particularly important given the presence of NMDA antibodies in healthy populations, the multifarious symptomology and the lack of radiological signs. Recent advances in biophysical modelling techniques suggest that inferring cellular-level properties of neural circuits from macroscopic measures of brain activity is possible. Here, we estimated receptor function from EEG in patients with NMDA receptor antibody encephalitis (n = 29) as well as from encephalopathic and neurological patient controls (n = 36). We show that the autoimmune patients exhibit distinct fronto-parietal network changes from which ion channel estimates can be obtained using a microcircuit model. Specifically, a dynamic causal model of EEG data applied to spontaneous brain responses identifies a selective deficit in signalling at NMDA receptors in patients with NMDA receptor antibody encephalitis but not at other ionotropic receptors. Moreover, though these changes are observed across brain regions, these effects predominate at the NMDA receptors of excitatory neurons rather than at inhibitory interneurons. Given that EEG is a ubiquitously available clinical method, our findings suggest a unique re-purposing of EEG data as an assay of brain network dysfunction at the molecular level.

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

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Jones Janette JL

2009-03-01

Full Text Available Abstract Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD, the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML. We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA, increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.

A case of burn encephalopathy with reversible brain atrophy on brain computed tomography (CT)

International Nuclear Information System (INIS)

Hirose, Hisaaki; Suzuki, Koh-ichirou; Nakamura, Yoshihiro; Kido, Kun-ichi; Sato, Masaharu; Fujii, Chiho; Kohama, Akitsugu

1985-01-01

We present an interesting case of burn encephalopathy. The patient is a three-year-old girl with second to third degree and 30 % scald burn. She developed central nervous symptom on the second day with high fever and systemic convulsions and was transferred to our clinic on the third day from a local hospital. Her level of consciousness was 30 to 100 (3-3-9 formula) and she developed extra-pyramidal involuntary movement; these neurological signs persisted untill 66th day when she spoke for the first time since admission. Her EEG showed diffuse brain dysfunction and CT showed marked brain atrophy. She began to improve after around 50 days systematically as well as neurologically and was discharged after four months. EEG, CT findings and neurological signs were normal 1.5 years later. We could not find a case of reversible brain atrophy in the reports on burn encephalopathy or other neurological disorders except for the cases of long-term steroid administration on autoimmune diseases or ACTH therapy on infantile spasm. In our case, the reversible brain atrophy might be caused by the rise of endogenous steroid under burn stress, or transient malfunction of cerebro-spinal fluid absorption, or some other causes. (author)

Dysfunctions in public psychiatric bureaucracies.

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Marcos, L R

1988-03-01

The author describes common dysfunctions in public psychiatric organizations according to the model of bureaucracy articulated by Max Weber. Dysfunctions are divided into the categories of goal displacement, outside interference, unclear authority structure and hierarchy, and informal relations in the work place. The author emphasizes the bureaucratic nature of public psychiatry and the need for mental health professionals to understand the dysfunctions of the organizations in which they work, including the impact of these dysfunctions on the provision of quality care.

Coupled Imaging with [18F]FBB and [18F]FDG in AD Subjects Show a Selective Association Between Amyloid Burden and Cortical Dysfunction in the Brain.

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Chiaravalloti, Agostino; Castellano, Anna Elisa; Ricci, Maria; Barbagallo, Gaetano; Sannino, Pasqualina; Ursini, Francesco; Karalis, Georgios; Schillaci, Orazio

2018-02-05

The present study was aimed to investigate the relationships between dysfunction of cortical glucose metabolism as detectable by means of 2-deoxy-2-[ 18 F]fluoro -D-glucose ([ 18 F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) and amyloid burden as detectable by means of 4-{(E)-2-[4-(2-{2-[2-[ 18 F]fluoroethoxy]ethoxy}ethoxy)phenyl]vinyl}-N-methylaniline (florbetaben; [ 18 F]FBB) in a group of patients affected by Alzheimer's disease (AD). We examined 38 patients newly diagnosed with AD according to the NINCDS-ADRDA criteria. All the subjects underwent a PET/CT scan using both [ 18 F]FDG and [ 18 F]FBB with an average interval of 1 month. We used statistical parametric mapping (SPM8) implemented in Matlab R2012b and WFU pickatlas for the definition of a region of interest (ROI) mask including the whole cortex. These data were then normalized on the counts of the cerebellum and then used for a regression analysis on [ 18 F]FDG scans in SPM. Furthermore, 58 control subjects were used as control group for [ 18 F]FDG PET/CT scans. SPM analysis in AD patients showed a significant negative correlation between [ 18 F] FBB and [ 18 F] FDG uptake in temporal and parietal lobes bilaterally. Of note, these areas in AD patients displayed a marked glucose hypometabolism compared to control group. Combined imaging with [ 18 F]FBB and [ 18 FFDG shows that amyloid burden in the brain is related to cortical dysfunction of temporal and parietal lobes in AD.

Brain Sciences – An Open Access Journal

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Germán Barrionuevo

2010-07-01

Full Text Available During the first ten years that followed “The Decade of the Brain”, the quest of neuroscience for understanding brain function in health and disease has greatly expanded to include molecular, developmental, cognitive and evolutionary aspects of the nervous system. This increased multidisciplinary effort has been complemented by the spectacular development of highly sophisticated experimental methods. Neuroscientists can now perform studies ranging from molecular and imaging analysis of single pre- and postsynaptic neuronal processes to imaging of neural activity in the whole brain during perceptual and motor behavioral tasks. At the same time, theoretical advances in neuroscience have been aided by the rapid development of mathematical and computational simulations of biologically and functionally realistic single cells and complex neural networks across multiple spatiotemporal scales. Therefore, neuroscientists are more than ever in a position to deliver answers to basic, medical and biotechnological questions related to brain function and dysfunction. [...

Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications.

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Hamed, Sherifa A

2017-04-01

Diabetes mellitus is a risk for brain injury. Brain injury is associated with acute and chronic hyperglycaemia, insulin resistance, hyperinsulinemia, diabetic ketoacidosis (DKA) and hypoglycaemic events in diabetic patients. Hyperglycemia is a cause of cognitive deterioration, low intelligent quotient, neurodegeneration, brain aging, brain atrophy and dementia. Areas covered: The current review highlights the experimental, clinical, neuroimaging and neuropathological evidence of brain injury induced by diabetes and its associated metabolic derangements. It also highlights the mechanisms of diabetes-induced brain injury. It seems that the pathogenesis of hyperglycemia-induced brain injury is complex and includes combination of vascular disease, oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, reduction of neurotrophic factors, acetylcholinesterase (AChE) activation, neurotransmitters' changes, impairment of brain repair processes, impairment of brain glymphatic system, accumulation of amyloid β and tau phosphorylation and neurodegeneration. The potentials for prevention and treatment are also discussed. Expert commentary: We summarize the risks and the possible mechanisms of DM-induced brain injury and recommend strategies for neuroprotection and neurorestoration. Recently, a number of drugs and substances [in addition to insulin and its mimics] have shown promising potentials against diabetes-induced brain injury. These include: antioxidants, neuroinflammation inhibitors, anti-apoptotics, neurotrophic factors, AChE inhibitors, mitochondrial function modifiers and cell based therapies.

Connexins and pannexins: New insights into microglial functions and dysfunctions

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Rosario Gajardo-Gómez

2016-09-01

Full Text Available In a physiological context, microglia adopt a resting phenotype that is associated with the production of anti-inflammatory and neurotrophic factors. In response to a wide variety of insults, they shift to the activated phenotype that is necessary for the proper restoration of brain homeostasis. When the intensity of the threat is relatively high, microglial activation can worsen the damage progression instead of providing protection, with potentially significant consequences for neuronal survival. Coordinated interactions among microglia and with other brain cells, including astrocytes and neurons, is critical for the development of timely and optimal inflammatory responses in the brain parenchyma. Tissue synchronization is in part mediated by connexins and pannexins, which are protein families that form different plasma membrane channels to communicate with neighboring cells. At one end, the gap junction channels (which are exclusively formed by connexins in vertebrates connect the cytoplasm of contacting cells to coordinate electrical and metabolic coupling. At the other end, hemichannels and pannexons (which are formed by connexins and pannexins, respectively communicate via intra- and extracellular compartments and serve as diffusion pathways for the exchange of ions and small molecules. In this review, we discuss the evidence available concerning the functional expression and regulation of connexin- and pannexin-based channels in microglia and their contribution to microglial function and dysfunction. We focus on the possible implications of these channels in microglia-to-microglia, microglia-to-astrocyte and neuron-to-microglia interactions in the inflamed brain.

Neural Correlates of Antidepressant-Related Sexual Dysfunction: A Placebo-Controlled fMRI Study on Healthy Males Under Subchronic Paroxetine and Bupropion

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Abler, Birgit; Seeringer, Angela; Hartmann, Antonie; Grön, Georg; Metzger, Coraline; Walter, Martin; Stingl, Julia

2011-01-01

Sexual dysfunction is a common side effect of selective serotonin reuptake inhibitors (SSRIs) like paroxetine in the treatment of depression, imposing a considerable risk on medication adherence and hence therapeutic success. Bupropion, a norepinephrine and dopamine reuptake inhibitor, is recommended as an alternative treatment without adverse effects concerning sexual arousal and libido. We investigated the neural bases of paroxetine-related subjective sexual dysfunction when compared with bupropion and placebo. We scanned 18 healthy, heterosexual males in a randomized, double-blind, within-subject design while watching video clips of erotic and nonerotic content under steady-state conditions after taking 20 mg of paroxetine, 150 mg of bupropion, and placebo for 7 days each. Under paroxetine, ratings of subjective sexual dysfunction increased compared with placebo or bupropion. Activation along the anterior cingulate cortex (ACC), including subgenual, pregenual, and midcingulate cortices, in the ventral striatum and midbrain was decreased when compared with placebo. In contrast, bupropion let subjective ratings and ACC activations unchanged and increased activity of brain regions including posterior midcingulate cortex, mediodorsal thalamus, and extended amygdala relative to placebo and paroxetine. Brain regions that have been related to the processing of motivational (ventral striatum), emotional, and autonomic components of erotic stimulation (anterior cingulate) in previous studies showed reduced responsiveness under paroxetine in our study. Drug effects on these regions may be part of the mechanism underlying SSRI-related sexual dysfunction. Increased activation under bupropion may point to an opposite effect that may relate to the lack of impaired sexual functioning. PMID:21544071

Frontostriatal Dysfunction During Decision Making in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder.

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Norman, Luke J; Carlisi, Christina O; Christakou, Anastasia; Murphy, Clodagh M; Chantiluke, Kaylita; Giampietro, Vincent; Simmons, Andrew; Brammer, Michael; Mataix-Cols, David; Rubia, Katya

2018-03-24

The aim of the current paper is to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with attention-deficit/hyperactivity disorder (ADHD) and adolescents with obsessive-compulsive disorder (OCD) during decision making under ambiguity. Sixteen boys with ADHD, 20 boys with OCD, and 20 matched control subjects (12-18 years of age) completed a functional magnetic resonance imaging version of the Iowa Gambling Task. Brain activation was compared between groups using three-way analysis of covariance. Hierarchical Bayesian analysis was used to compare computational modeling parameters between groups. Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision making relative to control subjects, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in the ventromedial orbitofrontal cortex. During outcome evaluation, shared underactivation to losses in patients relative to control subjects was found in the medial prefrontal cortex and shared underactivation to wins was found in the left putamen/caudate. ADHD boys showed disorder-specific dysfunction in the right putamen/caudate, which was activated more to losses in patients with ADHD but more to wins in control subjects. The findings suggest shared deficits in using learned reward expectancies to guide decision making, as well as shared dysfunction in medio-fronto-striato-limbic brain regions. However, findings of unique dysfunction in the ventromedial orbitofrontal cortex in OCD and in the right putamen in ADHD indicate additional, disorder-specific abnormalities and extend similar findings from inhibitory control tasks in the disorders to the domain of decision making under ambiguity. Copyright © 2018 Society of Biological Psychiatry. Published by

Brain perivascular macrophages: characterization and functional roles in health and disease.

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Faraco, Giuseppe; Park, Laibaik; Anrather, Josef; Iadecola, Costantino

2017-11-01

Perivascular macrophages (PVM) are a distinct population of resident brain macrophages characterized by a close association with the cerebral vasculature. PVM migrate from the yolk sac into the brain early in development and, like microglia, are likely to be a self-renewing cell population that, in the normal state, is not replenished by circulating monocytes. Increasing evidence implicates PVM in several disease processes, ranging from brain infections and immune activation to regulation of the hypothalamic-adrenal axis and neurovascular-neurocognitive dysfunction in the setting of hypertension, Alzheimer disease pathology, or obesity. These effects involve crosstalk between PVM and cerebral endothelial cells, interaction with circulating immune cells, and/or production of reactive oxygen species. Overall, the available evidence supports the idea that PVM are a key component of the brain-resident immune system with broad implications for the pathogenesis of major brain diseases. A better understanding of the biology and pathobiology of PVM may lead to new insights and therapeutic strategies for a wide variety of brain diseases.

Functional Magnetic Resonance Study of Non-conventional Morphological Brains: malnourished rats

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Martin R.

2015-08-01

Full Text Available Malnutrition during brain development can cause serious problems that can be irreversible. Dysfunctional patterns of brain activity can be detected with functional MRI. We used BOLD functional Magnetic Resonance Imaging (fMRI to investigate region differences of brain activity between control and malnourished rats. The food-competition method was applied to a rat model to induce malnutrition during lactation. A 7T magnet was used to detect changes of the BOLD signal associated with changes in brain activity caused by the trigeminal nerve stimulation in malnourished and control rats. Major neuronal activation was observed in malnourished rats in several brain regions, including cerebellum, somatosensory cortex, hippocampus, and hypothalamus. Statistical analysis of the BOLD signals from various brain areas revealed significant differences in somatosensory cortex between the control and experimental groups, as well as a significant difference between the cerebellum and other structures in the experimental group. This study, particularly in malnourished rats, demonstrates increased BOLD activation in the cerebellum.

Noninvasive brain stimulation of the parietal lobe for improving neurologic, neuropsychologic, and neuropsychiatric deficits.

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Bolognini, Nadia; Miniussi, Carlo

2018-01-01

Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (tES) are noninvasive brain stimulation (NIBS) tools that are now widely used in neuroscientific research in humans. The fact that both TMS and tES are able to modulate brain plasticity and, in turn, affect behavior is opening up new horizons in the treatment of brain circuit and plasticity disorders. In the present chapter, we will first provide the reader with a brief background on the basic principles of NIBS, describing the electromagnetic and physical foundations of TMS and tES, as well as the current knowledge of the neurophysiologic basis of their effects on brain activity and plasticity. In the main part, we will outline studies aimed at improving persistent symptoms and deficits in patients suffering from neurologic and neuropsychiatric disorders featured by dysfunction of the parietal lobe. The emerging view is that NIBS of parietal areas holds the promise to overcome various sensory, motor, and cognitive disorders that are often refractory to standard medical or behavioral therapies. The chapter closes with an outlook on further developments in this realm, discussing novel therapeutic approaches that could lead to more effective rehabilitation procedures, better suited for the specific parietal lobe dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder.

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Konrad, Kerstin; Eickhoff, Simon B

2010-06-01

In recent years, a change in perspective in etiological models of attention deficit hyperactivity disorder (ADHD) has occurred in concordance with emerging concepts in other neuropsychiatric disorders such as schizophrenia and autism. These models shift the focus of the assumed pathology from regional brain abnormalities to dysfunction in distributed network organization. In the current contribution, we report findings from functional connectivity studies during resting and task states, as well as from studies on structural connectivity using diffusion tensor imaging, in subjects with ADHD. Although major methodological limitations in analyzing connectivity measures derived from noninvasive in vivo neuroimaging still exist, there is convergent evidence for white matter pathology and disrupted anatomical connectivity in ADHD. In addition, dysfunctional connectivity during rest and during cognitive tasks has been demonstrated. However, the causality between disturbed white matter architecture and cortical dysfunction remains to be evaluated. Both genetic and environmental factors might contribute to disruptions in interactions between different brain regions. Stimulant medication not only modulates regionally specific activation strength but also normalizes dysfunctional connectivity, pointing to a predominant network dysfunction in ADHD. By combining a longitudinal approach with a systems perspective in ADHD in the future, it might be possible to identify at which stage during development disruptions in neural networks emerge and to delineate possible new endophenotypes of ADHD. (c) 2010 Wiley-Liss, Inc.

Endo-lysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease?

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Whyte, Lauren S; Lau, Adeline A; Hemsley, Kim M; Hopwood, John J; Sargeant, Timothy J

2017-03-01

Alzheimer's disease (AD) is the most common cause of dementia, and its prevalence will increase significantly in the coming decades. Although important progress has been made, fundamental pathogenic mechanisms as well as most hereditary contributions to the sporadic form of the disease remain unknown. In this review, we examine the now substantial links between AD pathogenesis and lysosomal biology. The lysosome hydrolyses and processes cargo delivered by multiple pathways, including endocytosis and autophagy. The endo-lysosomal and autophagic networks are central to clearance of cellular macromolecules, which is important given there is a deficit in clearance of amyloid-β in AD. Numerous studies show prominent lysosomal dysfunction in AD, including perturbed trafficking of lysosomal enzymes and accumulation of the same substrates that accumulate in lysosomal storage disorders. Examination of the brain in lysosomal storage disorders shows the accumulation of amyloid precursor protein metabolites, which further links lysosomal dysfunction with AD. This and other evidence leads us to hypothesise that genetic variation in lysosomal genes modifies the disease course of sporadic AD. © 2016 International Society for Neurochemistry.

Impairments of learning and memory in the rats after brain irradiation

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Takai, Nobuhiko [National Inst. of Radiological Sciences, Chiba (Japan)

2002-06-01

Clinical trials of hadrontherapy have been carried out world wide at several facilities including National Institute of Radiological Sciences (NIRS). Cerebral dysfunction is one of the major concerns associated with radiotherapy of brain tumors. However, little is known about the neurochemical basis of brain dysfunction induced by proton irradiation. We investigated and reported here the early consequences of brain damages caused by proton beam. The animals that had memorized the location of the standard position were locally irradiated to brain with either 70 MeV protons or 290 MeV carbon ions. At 24 hr after irradiation, impairment of the long-term memory was not observed in the irradiated rats compared to control. Irradiated animals, however, required substantially longer time finding out the standard position than control rats when the standard platform displaced to a position different from memorized position. This follows that a single doses of 30 Gy, either protons or carbon ions, impairs the working memory of animals. Function of muscarinic acetylcholine receptors was analyzed by an in vivo binding assay using radioligand quinuclidinyl benzilate (QNB). Irradiated rats were intravenously injected with 5.5 MBq of {sup 3}H-QNB 24 hr after the irradiation, and decapitated 60 min after tracer injection. The autoradiographic studies showed an transitional increase of {sup 3}H-QNB in vivo binding in the early phase after proton irradiation, even though no change in in-vitro {sup 3}H-QNB binding was see in brain autoradiograms of irradiated rats. The cerebral blood flow and the histrogical features of brain were also changed at 3 months post-irradiation. These results indicate that the memory impairment caused by radiation is closely related to the early change of acetylcholine receptor in vivo. (author)

Impairments of learning and memory in the rats after brain irradiation

International Nuclear Information System (INIS)

Takai, Nobuhiko

2002-01-01

Clinical trials of hadrontherapy have been carried out world wide at several facilities including National Institute of Radiological Sciences (NIRS). Cerebral dysfunction is one of the major concerns associated with radiotherapy of brain tumors. However, little is known about the neurochemical basis of brain dysfunction induced by proton irradiation. We investigated and reported here the early consequences of brain damages caused by proton beam. The animals that had memorized the location of the standard position were locally irradiated to brain with either 70 MeV protons or 290 MeV carbon ions. At 24 hr after irradiation, impairment of the long-term memory was not observed in the irradiated rats compared to control. Irradiated animals, however, required substantially longer time finding out the standard position than control rats when the standard platform displaced to a position different from memorized position. This follows that a single doses of 30 Gy, either protons or carbon ions, impairs the working memory of animals. Function of muscarinic acetylcholine receptors was analyzed by an in vivo binding assay using radioligand quinuclidinyl benzilate (QNB). Irradiated rats were intravenously injected with 5.5 MBq of 3 H-QNB 24 hr after the irradiation, and decapitated 60 min after tracer injection. The autoradiographic studies showed an transitional increase of 3 H-QNB in vivo binding in the early phase after proton irradiation, even though no change in in-vitro 3 H-QNB binding was see in brain autoradiograms of irradiated rats. The cerebral blood flow and the histrogical features of brain were also changed at 3 months post-irradiation. These results indicate that the memory impairment caused by radiation is closely related to the early change of acetylcholine receptor in vivo. (author)

Effect of virtual reality on cognitive dysfunction in patients with brain tumor.

Science.gov (United States)

Yang, Seoyon; Chun, Min Ho; Son, Yu Ri

2014-12-01

To investigate whether virtual reality (VR) training will help the recovery of cognitive function in brain tumor patients. Thirty-eight brain tumor patients (19 men and 19 women) with cognitive impairment recruited for this study were assigned to either VR group (n=19, IREX system) or control group (n=19). Both VR training (30 minutes a day for 3 times a week) and computer-based cognitive rehabilitation program (30 minutes a day for 2 times) for 4 weeks were given to the VR group. The control group was given only the computer-based cognitive rehabilitation program (30 minutes a day for 5 days a week) for 4 weeks. Computerized neuropsychological tests (CNTs), Korean version of Mini-Mental Status Examination (K-MMSE), and Korean version of Modified Barthel Index (K-MBI) were used to evaluate cognitive function and functional status. The VR group showed improvements in the K-MMSE, visual and auditory continuous performance tests (CPTs), forward and backward digit span tests (DSTs), forward and backward visual span test (VSTs), visual and verbal learning tests, Trail Making Test type A (TMT-A), and K-MBI. The VR group showed significantly (p<0.05) better improvements than the control group in visual and auditory CPTs, backward DST and VST, and TMT-A after treatment. VR training can have beneficial effects on cognitive improvement when it is combined with computer-assisted cognitive rehabilitation. Further randomized controlled studies with large samples according to brain tumor type and location are needed to investigate how VR training improves cognitive impairment.

miR-98 and let-7g* protect the blood-brain barrier under neuroinflammatory conditions.

Science.gov (United States)

Rom, Slava; Dykstra, Holly; Zuluaga-Ramirez, Viviana; Reichenbach, Nancy L; Persidsky, Yuri

2015-12-01

Pathologic conditions in the central nervous system, regardless of the underlying injury mechanism, show a certain level of blood-brain barrier (BBB) impairment. Endothelial dysfunction is the earliest event in the initiation of vascular damage caused by inflammation due to stroke, atherosclerosis, trauma, or brain infections. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators. The relationship between neuroinflammation and miRNA expression in brain endothelium remains unexplored. Previously, we showed the BBB-protective and anti-inflammatory effects of glycogen synthase kinase (GSK) 3β inhibition in brain endothelium in in vitro and in vivo models of neuroinflammation. Using microarray screening, we identified miRNAs induced in primary human brain microvascular endothelial cells after exposure to the pro-inflammatory cytokine, tumor necrosis factor-α, with/out GSK3β inhibition. Among the highly modified miRNAs, let-7 and miR-98 were predicted to target the inflammatory molecules, CCL2 and CCL5. Overexpression of let-7 and miR-98 in vitro and in vivo resulted in reduced leukocyte adhesion to and migration across endothelium, diminished expression of pro-inflammatory cytokines, and increased BBB tightness, attenuating barrier 'leakiness' in neuroinflammation conditions. For the first time, we showed that miRNAs could be used as a therapeutic tool to prevent the BBB dysfunction in neuroinflammation.

17β-Estradiol prevents cell death and mitochondrial dysfunction by estrogen receptor-dependent mechanism in astrocytes following oxygen-glucose deprivation/reperfusion

Science.gov (United States)

Guo, Jiabin; Duckles, Sue P.; Weiss, John H.; Li, Xuejun; Krause, Diana N.

2012-01-01

17β-estradiol (E2) has been shown to protect against ischemic brain injury, yet its targets and the mechanisms are unclear. E2 may exert multiple regulatory actions on astrocytes that may greatly contribute to its ability to protect the brain. Mitochondria are recognized to play central roles in the development of injury during ischemia. Increasing evidence indicates that mitochondrial mechanisms are critically involved in E2-mediated protection. In this study, the effect of E2 and the role of mitochondria were evaluated in primary cultures of astrocytes subjected to an ischemia-like condition of oxygen-glucose deprivation (OGD)/reperfusion. We showed that E2 treatment significantly protects against OGD/reperfusion-induced cell death as determined by cell viability, apoptosis and lactate dehydrogenase leakage. The protective effects of E2 on astrocytic survival were blocked by an estrogen receptor (ER) antagonist (ICI 182,780), and were mimicked by an estrogen receptor (ER) agonist selective for ERα (PPT), but not by an ER agonist selective for ERβ (DPN). OGD/reperfusion provoked mitochondria dysfunction as manifested by an increase of cellular reactive oxygen species production, loss of mitochondrial membrane potential and depletion of ATP. E2 pretreatment significantly inhibited OGD/reperfusion-induced mitochondrial dysfunction, and this effect was also blocked by ICI 182,780. Therefore, we concluded that E2 provides direct protection to astrocytes from ischemic injury by an ER-dependent mechanism, highlighting an important role for ERα. Estrogen protects against mitochondria dysfunction at the early phase of ischemic injury. However, overall implications for protection against brain ischemia and its complex sequelae await further exploration. PMID:22554613

Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome

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Li Zhou

2016-01-01

Full Text Available Obstructive sleep apnea syndrome (OSAS is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients’ career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction. OS in brain could trigger neuron injury especially in the hippocampus and cerebral cortex regions. Those two regions are fairly susceptible to hypoxia and oxidative stress production which could consequently result in cognitive dysfunction. Apart from continuous positive airway pressure (CPAP, antioxidant may be a promising therapeutic method to improve partially reversible neurocognitive function. Understanding the role that OS played in the cognitive deficits is crucial for future research and therapeutic strategy development. In this paper, recent important literature concerning the relationship between oxidative stress and cognitive impairment in OSAS will be summarized and the results can provide a rewarding overview for future breakthrough in this field.

Glucose deficit triggers tau pathology and synaptic dysfunction in a tauopathy mouse model.

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Lauretti, E; Li, J-G; Di Meco, A; Praticò, D

2017-01-31

Clinical investigations have highlighted a biological link between reduced brain glucose metabolism and Alzheimer's disease (AD). Previous studies showed that glucose deprivation may influence amyloid beta formation in vivo but no data are available on the effect that this condition might have on tau protein metabolism. In the current paper, we investigated the effect of glucose deficit on tau phosphorylation, memory and learning, and synaptic function in a transgenic mouse model of tauopathy, the h-tau mice. Compared with controls, h-tau mice with brain glucose deficit showed significant memory impairments, reduction of synaptic long-term potentiation, increased tau phosphorylation, which was mediated by the activation of P38 MAPK Kinase pathway. We believe our studies demonstrate for the first time that reduced glucose availability in the central nervous system directly triggers behavioral deficits by promoting the development of tau neuropathology and synaptic dysfunction. Since restoring brain glucose levels and metabolism could afford the opportunity to positively influence the entire AD phenotype, this approach should be considered as a novel and viable therapy for preventing and/or halting the disease progression.

Muscle dysfunction in cancer patients

DEFF Research Database (Denmark)

Christensen, Jesper Frank; Jones, L W; Andersen, J L

2014-01-01

dysfunction in cancer patients lies in the correlation to vital clinical end points such as cancer-specific and all-cause mortality, therapy complications and quality of life (QoL). Such associations strongly emphasize the need for effective therapeutic countermeasures to be developed and implemented...... implications of muscle dysfunction in cancer patients. The efficacy of exercise training to prevent and/or mitigate cancer-related muscle dysfunction is also discussed. DESIGN: We identified 194 studies examining muscular outcomes in cancer patients by searching PubMed and EMBASE databases. RESULTS: Muscle...... dysfunction is evident across all stages of the cancer trajectory. The causes of cancer-related muscle dysfunction are complex, but may involve a wide range of tumor-, therapy- and/or lifestyle-related factors, depending on the clinical setting of the individual patient. The main importance of muscle...

Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder

OpenAIRE

Pu, Weidan; Luo, Qiang; Jiang, Yali; Gao, Yidian; Ming, Qingsen; Yao, Shuqiao

2017-01-01

Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holist...

Occlusion and brain function: mastication as a prevention of cognitive dysfunction.

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Ono, Y; Yamamoto, T; Kubo, K-ya; Onozuka, M

2010-08-01

Research in animals and humans has shown that mastication maintains cognitive function in the hippocampus, a brain area important for learning and memory. Reduced mastication, an epidemiological risk factor for the development of dementia in humans, attenuates spatial memory and causes hippocampal neurons to deteriorate morphologically and functionally, especially in aged animals. Active mastication rescues the stress-attenuated hippocampal memory process in animals and attenuates the perception of stress in humans by suppressing endocrinological and autonomic stress responses. Active mastication further improves the performance of sustained cognitive tasks by increasing the activation of the hippocampus and the prefrontal cortex, the brain regions that are essential for cognitive processing. Abnormal mastication caused by experimental occlusal disharmony in animals produces chronic stress, which in turn suppresses spatial learning ability. The negative correlation between mastication and corticosteroids has raised the hypothesis that the suppression of the hypothalamic-pituitary-adrenal (HPA) axis by masticatory stimulation contributes, in part, to preserving cognitive functions associated with mastication. In the present review, we examine research pertaining to the mastication-induced amelioration of deficits in cognitive function, its possible relationship with the HPA axis, and the neuronal mechanisms that may be involved in this process in the hippocampus.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

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Sato Wataru

2012-08-01

Full Text Available Abstract Background Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD. However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI. Result Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG, fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG. Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex–MTG–IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. Conclusions These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Short-term fructose ingestion affects the brain independently from establishment of metabolic syndrome.

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Jiménez-Maldonado, Alberto; Ying, Zhe; Byun, Hyae Ran; Gomez-Pinilla, Fernando

2018-01-01

Chronic fructose ingestion is linked to the global epidemic of metabolic syndrome (MetS), and poses a serious threat to brain function. We asked whether a short period (one week) of fructose ingestion potentially insufficient to establish peripheral metabolic disorder could impact brain function. We report that the fructose treatment had no effect on liver/body weight ratio, weight gain, glucose tolerance and insulin sensitivity, was sufficient to reduce several aspects of hippocampal plasticity. Fructose consumption reduced the levels of the neuronal nuclear protein NeuN, Myelin Basic Protein, and the axonal growth-associated protein 43, concomitant with a decline in hippocampal weight. A reduction in peroxisome proliferator-activated receptor gamma coactivator-1 alpha and Cytochrome c oxidase subunit II by fructose treatment is indicative of mitochondrial dysfunction. Furthermore, the GLUT5 fructose transporter was increased in the hippocampus after fructose ingestion suggesting that fructose may facilitate its own transport to brain. Fructose elevated levels of ketohexokinase in the liver but did not affect SIRT1 levels, suggesting that fructose is metabolized in the liver, without severely affecting liver function commensurable to an absence of metabolic syndrome condition. These results advocate that a short period of fructose can influence brain plasticity without a major peripheral metabolic dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution.

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Calderón-Garcidueñas, Lilian; Reed, William; Maronpot, Robert R; Henríquez-Roldán, Carlos; Delgado-Chavez, Ricardo; Calderón-Garcidueñas, Ana; Dragustinovis, Irma; Franco-Lira, Maricela; Aragón-Flores, Mariana; Solt, Anna C; Altenburg, Michael; Torres-Jardón, Ricardo; Swenberg, James A

2004-01-01

Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of beta-amyloid (Abeta42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor-kappaB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Abeta42 compared to residents in low air pollution cities. Increased COX2 expression and Abeta42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe air pollution is associated with brain inflammation and Abeta42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

[Immune dysfunction and cognitive deficit in stress and physiological aging (Part I): Pathogenesis and risk factors].

Science.gov (United States)

Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

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Khushbu Jain

2015-01-01

Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

How does brain insulin resistance develop in Alzheimer's disease?

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De Felice, Fernanda G; Lourenco, Mychael V; Ferreira, Sergio T

2014-02-01

Compelling preclinical and clinical evidence supports a pathophysiological connection between Alzheimer's disease (AD) and diabetes. Altered metabolism, inflammation, and insulin resistance are key pathological features of both diseases. For many years, it was generally considered that the brain was insensitive to insulin, but it is now accepted that this hormone has central neuromodulatory functions, including roles in learning and memory, that are impaired in AD. However, until recently, the molecular mechanisms accounting for brain insulin resistance in AD have remained elusive. Here, we review recent evidence that sheds light on how brain insulin dysfunction is initiated at a molecular level and why abnormal insulin signaling culminates in synaptic failure and memory decline. We also discuss the cellular basis underlying the beneficial effects of stimulation of brain insulin signaling on cognition. Discoveries summarized here provide pathophysiological background for identification of novel molecular targets and for development of alternative therapeutic approaches in AD. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Neuroprotective Effect of Matricaria chamomilla Extract on Motor Dysfunction Induced by Transient Global Cerebral Ischemia and Reperfusion in Rat

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Azam Moshfegh

2017-09-01

Full Text Available Background Stroke can cause paralysis, muscle weakness, and loss of balance that may affect walking and routine activities. Objectives The aim of this study was to evaluate the effect of ethyl alcohol extract of Matricaria chamomilla on cerebral ischemia-induced motor dysfunctions in rats. Methods In this experimental study, forty two male Wistar rats were divided into 6 groups consisting of control group, sham group, ischemia/reperfusion group and three treatment groups [treated with 50, 100, and 200 mg/kg doses of M. chamomilla extract and undergoing ischemia/reperfusion(I/R]. Motor coordination and balance were evaluated using Rotarod test. Total antioxidant capacity, malondialdehyde (MDA, and nitric oxide (NO levels of serum and brain were also determined. Results The extract of M. chamomilla significantly improved I/R-induced motor dysfunction. Induction of I/R led to increase serum MDA, while the extract of M, chamomlla significantly reduced it. Administration all doses of M. chamomilla extract to the ischemic rats did not reduce the hippocampus MDA levels (P > 0.05. The extract of M. chamomilla at dose of 200 mg/kg slightly decreased cortex MDA (P > 0.01. It had no significant effects on the total antioxidant capacity of the brain (hippocampus and cortex and serum. Injection of Matricaria chamomilla extract also did not change serum NO level. Conclusions Our findings suggested that the Matricaria chamomilla extract could improve motor dysfunction.

Exploring neural dysfunction in 'clinical high risk' for psychosis: a quantitative review of fMRI studies.

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Dutt, Anirban; Tseng, Huai-Hsuan; Fonville, Leon; Drakesmith, Mark; Su, Liang; Evans, John; Zammit, Stanley; Jones, Derek; Lewis, Glyn; David, Anthony S

2015-02-01

Individuals at clinical high risk (CHR) of developing psychosis present with widespread functional abnormalities in the brain. Cognitive deficits, including working memory (WM) problems, as commonly elicited by n-back tasks, are observed in CHR individuals. However, functional MRI (fMRI) studies, comprising a heterogeneous cluster of general and social cognition paradigms, have not necessarily demonstrated consistent and conclusive results in this population. Hence, a comprehensive review of fMRI studies, spanning almost one decade, was carried out to observe for general trends with respect to brain regions and cognitive systems most likely to be dysfunctional in CHR individuals. 32 studies were included for this review, out of which 22 met the criteria for quantitative analysis using activation likelihood estimation (ALE). Task related contrast activations were firstly analysed by comparing CHR and healthy control participants in the total pooled sample, followed by a comparison of general cognitive function studies (excluding social cognition paradigms), and finally by only looking at n-back working memory task based studies. Findings from the ALE implicated four key dysfunctional and distinct neural regions in the CHR group, namely the right inferior parietal lobule (rIPL), the left medial frontal gyrus (lmFG), the left superior temporal gyrus (lSTG) and the right fronto-polar cortex (rFPC) of the superior frontal gyrus (SFG). Narrowing down to relatively few significant dysfunctional neural regions is a step forward in reducing the apparent ambiguity of overall findings, which would help to target specific neural regions and pathways of interest for future research in CHR populations. Copyright © 2014. Published by Elsevier Ltd.

Aberrant brain regional homogeneity and functional connectivity in middle-aged T2DM patients: a resting-state functional MRI study

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Daihong Liu

2016-09-01

Full Text Available Type 2 diabetes mellitus (T2DM has been associated with cognitive impairment. However, its neurological mechanism remains elusive. Combining regional homogeneity (ReHo and functional connectivity (FC analyses, the present study aimed to investigate brain functional alterations in middle-aged T2DM patients, which could provide complementary information for the neural substrates underlying T2DM-associated brain dysfunction. Twenty-five T2DM patients and 25 healthy controls were involved in neuropsychological testing and structural and resting-state functional magnetic resonance imaging data acquisition. ReHo analysis was conducted to determine the peak coordinates of brain regions with abnormal local brain activity synchronization. Then, the identified brain regions were considered as seeds, and FC between these brain regions and global voxels was computed. Finally, the potential correlations between the imaging indices and neuropsychological data were also explored. Compared with healthy controls, T2DM patients exhibited higher ReHo values in the anterior cingulate gyrus and lower ReHo in right fusiform gyrus, right precentral gyrus and right medial orbit of the superior frontal gyrus. Considering these areas as seed regions, T2DM patients displayed aberrant FC, mainly in the frontal and parietal lobes. The pattern of FC alterations in T2DM patients was characterized by decreased connectivity and positive to negative or negative to positive converted connectivity. Digital Span Test forward scores revealed significant correlations with the ReHo values of the right precentral gyrus (ρ = 0.527, p = 0.014 and FC between the right fusiform gyrus and middle temporal gyrus (ρ = -0.437, p = 0.048. Our findings suggest that T2DM patients suffer from cognitive dysfunction related to spatially local and remote brain activity synchronization impairment. The patterns of ReHo and FC alterations shed light on the mechanisms underlying T2DM-associated brain

Lack of evidence for dysfunction of the blood-brain barrier in Alzheimer's disease: an immunohistochemical study

NARCIS (Netherlands)

Rozemuller, J. M.; Eikelenboom, P.; Kamphorst, W.; Stam, F. C.

1988-01-01

With immunohistoperoxidase techniques the presence of plasma (serum) proteins was investigated in senile plaques, congophilic angiopathy, neurons and glial cells in brains of patients with Alzheimer's dementia. Other investigators have found plasma proteins in brain parenchyma and suggested that

A characteristic ventricular shape in myelomeningocele-associated hydrocephalus? A CT stereology study

International Nuclear Information System (INIS)

Roost, D. van; Solymosi, L.; Funke, K.

1995-01-01

We measured the volume of the supratentorial ventricles in 39 consecutive children with myelomeningocele (MMC) and associated hydrocephalus, using a stereological method based on the Cavalieri theorem of systematic sampling. We distinguished the following groups: newborns before and after cerebrospinal fluid shunting (14), a somewhat larger group of newborns with an untreated MMC-associated hydrocephalus (25) and a group of shunted children at a mean age of 1.5 years (28). We paid special attention to the shape of the lateral ventricles, looking separately at the anterior and posterior halves. The measurements were compared with a healthy control group (10) and with children with hydrocephalus unrelated to MMC (15). The average volume ratio of the posterior to the anterior half of the lateral ventricles was 1.05 ± 0.39 in non-hydrocephalic children, 1.11 ± 0.55 in untreated hydrocephalic children without MMC, and 2.15 ± 0.65 in MMC-associated hydrocephalus prior to shunting. These ratios did not change significantly after shunting. This confirms our impression that MMC-associated hydrocephalus shows a characteristic shape, with a disproportionate enlargement of the posterior part of the lateral ventricles, in clear contrast to the normal-width frontal horns. This shape is reminiscent of the fetal ventricular shape. It reveals disturbance of brain development in children with MMC, which goes beyond the classic description of the Chiari malformation. (orig.)

Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

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Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman

2014-03-01

The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

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Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas

17β-Estradiol prevents cell death and mitochondrial dysfunction by an estrogen receptor-dependent mechanism in astrocytes after oxygen-glucose deprivation/reperfusion.

Science.gov (United States)

Guo, Jiabin; Duckles, Sue P; Weiss, John H; Li, Xuejun; Krause, Diana N

17β-Estradiol (E2) has been shown to protect against ischemic brain injury, yet its targets and the mechanisms are unclear. E2 may exert multiple regulatory actions on astrocytes that may greatly contribute to its ability to protect the brain. Mitochondria are recognized as playing central roles in the development of injury during ischemia. Increasing evidence indicates that mitochondrial mechanisms are critically involved in E2-mediated protection. In this study, the effects of E2 and the role of mitochondria were evaluated in primary cultures of astrocytes subjected to an ischemia-like condition of oxygen-glucose deprivation (OGD)/reperfusion. We showed that E2 treatment significantly protects against OGD/reperfusion-induced cell death as determined by cell viability, apoptosis, and lactate dehydrogenase leakage. The protective effects of E2 on astrocytic survival were blocked by an estrogen receptor (ER) antagonist (ICI-182,780) and were mimicked by an ER agonist selective for ERα (PPT), but not by an ER agonist selective for ERβ (DPN). OGD/reperfusion provoked mitochondrial dysfunction as manifested by an increase in cellular reactive oxygen species production, loss of mitochondrial membrane potential, and depletion of ATP. E2 pretreatment significantly inhibited OGD/reperfusion-induced mitochondrial dysfunction, and this effect was also blocked by ICI-182,780. Therefore, we conclude that E2 provides direct protection to astrocytes from ischemic injury by an ER-dependent mechanism, highlighting an important role for ERα. Estrogen protects against mitochondrial dysfunction at the early phase of ischemic injury. However, overall implications for protection against brain ischemia and its complex sequelae await further exploration. Copyright © 2012 Elsevier Inc. All rights reserved.

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

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Nakagawa, Yutaka; Chiba, Kenji

2016-09-01

Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Chronic pelvic floor dysfunction.

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Hartmann, Dee; Sarton, Julie

2014-10-01

The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management. Copyright © 2014 Elsevier Ltd. All rights reserved.

Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain's control circuit

OpenAIRE

Volkow, Nora D.; Wang, Gene-Jack; Fowler, Joanna S.; Tomasi, Dardo; Telang, Frank; Baler, Ruben

2010-01-01

Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is larg...

Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

Science.gov (United States)

Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Mahmoud, Motamed Elsayed; Yokoyama, Naoaki; Nagamune, Kisaburo; Nishikawa, Yoshifumi

2016-10-01

Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Cardiac diastolic dysfunction is associated with cerebral white matter lesions in elderly patients with risk factors for atherosclerosis

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Masugata, Hisashi; Senda, Shoichi; Goda, Fuminori [Kagawa Univ., Faculty of Medicine, Miki, Kagawa (Japan)

2008-10-15

Cerebral white matter lesions on magnetic resonance imaging (MRI) are considered to be the result of brain ischemic injury and a risk factor for clinical stroke. The purpose of this study was to elucidate the relationship between the cardiac diastolic function and cerebral white matter lesions in elderly patients with risk factors for atherosclerosis. The study subjects were 55 patients (75{+-}7 years) with risk factors for atherosclerosis including hypertension, diabetes mellitus, and dyslipidemia. Patients with symptomatic cerebrovascular events were excluded from the study. Cerebral white matter lesions, which were defined as exhibiting high intensity regions on brain MRI, were evaluated with the degrees of periventricular hyperintensity (PVH) according to the Japanese Brain Dock Guidelines of 2003. Peak early diastolic mitral annular velocity (E' velocity) was measured by tissue Doppler echocardiography, and was used as a parameter of cardiac diastolic function. The mean value of E' velocity was decreased due to the cardiac diastolic dysfunction (5.2{+-}1.4 cm/s). In addition, the E' velocity was inversely correlated with the degree of PVH ({rho}=-0.701, p<0.001). Stepwise regression analysis showed that the decrease in the E' velocity ({beta} coefficient=-0.42, p<0.001) and the presence of hypertension ({beta} coefficient=0.31, p=0.001) were independent determinants of the degree of PVH. Thus, cardiac diastolic dysfunction is correlated to the severity of cerebral white matter lesions, suggesting the cardio-cerebral connection in elderly patients with risk factors for atherosclerosis. (author)

Immune dysfunction in cirrhosis

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Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

2014-01-01

Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

History of the Treatment of Female Sexual Dysfunction(s).

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Kleinplatz, Peggy J

2018-01-22

This article reviews the history of the treatment of women's sexual problems from the Victorian era to the twenty-first century. The contextual nature of determining what constitutes female sexual psychopathology is highlighted. Conceptions of normal sexuality are subject to cultural vagaries, making it difficult to identify female sexual dysfunctions. A survey of the inclusion, removal, and collapsing of women's sexual diagnoses in the Diagnostic and Statistical Manual of Mental Disorders from 1952 to 2013 illuminates the biases in the various editions. Masters and Johnson's models of sexual response and dysfunction paved the way for the diagnosis and treatment of women's sexual dysfunctions. Their sex therapy paradigm is described. Conceptions of and treatments for anorgasmia, arousal difficulties, vaginismus, dyspareunia, and low desire are reviewed. The medicalization of human sexuality and the splintering of sex therapy are discussed, along with current trends and new directions in sexual health care for women. Expected final online publication date for the Annual Review of Clinical Psychology Volume 14 is May 7, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

A review of mild traumatic brain injury diagnostics: current perspectives, limitations, and emerging technology.

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Cook, Glen A; Hawley, Jason S

2014-10-01

Mild traumatic brain injury (mTBI) or concussion is a common battlefield and in-garrison injury caused by transmission of mechanical forces to the head. The energy transferred in such events can cause structural and/or functional changes in the brain that manifest as focal neurological, cognitive, or behavioral dysfunction. Current diagnostic criteria for mTBI are highly limited, variable, and based on subjective self-report. The subjective nature of the symptoms, both in quantity and quality, together with their large overlap in other physical and behavioral maladies, limit the clinician's ability to accurately diagnose, treat, and make prognostic decisions after such injuries. These diagnostic challenges are magnified in an operational environment as well. The Department of Defense has invested significant resources into improving the diagnostic tools and accuracy for mTBI. This focus has been to supplement the clinician's examination with technology that is better able to objectify brain dysfunction after mTBI. Through this review, we discuss the current state of three promising technologies--soluble protein biomarkers, advanced neuroimaging, and quantitative electroencephalography--that are of particular interest within military medicine. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Multimodal brain monitoring in fulminant hepatic failure

Science.gov (United States)

Paschoal Jr, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

2016-01-01

Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting. PMID:27574545

Temporal lobe dysfunction in childhood autism: a PET study

International Nuclear Information System (INIS)

Boddaert, N.; Poline, J.B.; Brunelle, F.; Zilbovicius, M.; Boddaert, N.; Brunelle, F.; Chabane, N.; Barthelemy, C.; Zilbovicius, M.; Bourgeois, M.; Samson, Y.

2002-01-01

Childhood autism is a severe developmental disorder that impairs the acquisition of some of the most important skills in human life. Progress in understanding the neural basis of childhood autism requires clear and reliable data indicating specific neuro-anatomical or neuro-physiological abnormalities. The purpose of the present study was to research localized brain dysfunction in autistic children using functional brain imaging. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) in 21 primary autistic children and 10 age-matched non autistic children. A statistical parametric analysis of rCBF images revealed significant bilateral temporal hypoperfusion in the associative auditory cortex (superior temporal gyrus) and in the multimodal cortex (superior temporal sulcus) in the autistic group (p<0.001). In addition, temporal hypoperfusion was detected individually in 77% of autistic children. These findings provide robust evidence of well localized functional abnormalities in autistic children located in the superior temporal lobe. Such localized abnormalities were not detected with the low resolution PET camera (14-22). This study suggests that high resolution PET camera combined with statistical parametric mapping is useful to understand developmental disorders. (authors)

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

Science.gov (United States)

Greco, Tiffany; Hovda, David A; Prins, Mayumi L

2015-02-01

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

Loneliness and Sexual Dysfunctions.

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Mijuskovic, Ben

1987-01-01

Argues that sexual dysfunctions result from early childhood experiences which were originally nonsexual in nature. Contends that psychological difficulties centered around problems of loneliness tend to generate certain sexual dysfunctions. Extends and explores suggestion that genesis of sexual conflicts is in nonsexual infant separation anxiety…

Characteristics of patients with erectile dysfunction in a family physician-led erectile dysfunction clinic: Retrospective case series

OpenAIRE

Lap Kin Chiang; Cheuk-Wai Kam; Kin-Chung Michael Yau; Lorna Ng

2017-01-01

Objectives: 1. To examine the characteristics of patients with erectile dysfunction in a family physician led erectile dysfunction clinic; 2. To review association of chronic disease spectrum and erectile dysfunction; 3. To review initial treatment pattern and outcome. Design: Retrospective case series review. Subjects: All consecutive patients seen in a regional hospital family physician led erectile dysfunction clinic from April 2014 to March 2015. Main outcome measures: 1. The severity of ...

Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma

International Nuclear Information System (INIS)

Shen, Qingyu; Lin, Focai; Rong, Xiaoming; Yang, Wuyang; Li, Yi; Cai, Zhaoxi; Xu, Pengfei; Xu, Yongteng; Tang, Yamei

2016-01-01

Purpose: Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may be complicated with radiation-induced brain necrosis (RN), resulting in deteriorated cognitive function. However, the underlying mechanism of this phenomenon remains unclear. This study attempts to elucidate the association between cerebral microbleeds (CMBs) and radiation necrosis and cognitive dysfunction in NPC patients treated with radiation therapy. Methods and Materials: This cross-sectional study included 106 NPC patients who were exposed to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients without discernable intracranial pathology were included as the control group. CMBs were confirmed using susceptibility-weighted magnetic resonance imaging. Cognitive function was accessed using Montreal Cognitive Assessment. Patients with a total score below 26 were defined as cognitively dysfunction. Results: Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non-RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control group had CMBs. In patients with a history of radiation therapy, CMBs most commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%). Patients with RN had more temporal CMBs than those in the non-RN group (37.7 ± 51.9 vs 3.8 ± 12.6, respectively; P<.001). The number of temporal lobe CMBs was predictive for larger volume of brain necrosis (P<.001) in multivariate linear regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001). After adjusting for age, sex, education, period after radiation therapy, CMBs in other lobes, and RN volume, the number of temporal CMBs remained an independent risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04; P=.003). Conclusions: CMBs is a common radiological manifestation in NPC patients with RN

Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma

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Shen, Qingyu [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Department of Neurology, Zengcheng People' s Hospital, Guangzhou (China); Lin, Focai; Rong, Xiaoming [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Yang, Wuyang [Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Li, Yi; Cai, Zhaoxi; Xu, Pengfei; Xu, Yongteng [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Tang, Yamei, E-mail: yameitang@hotmail.com [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou (China); Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province (China)

2016-04-01

Purpose: Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may be complicated with radiation-induced brain necrosis (RN), resulting in deteriorated cognitive function. However, the underlying mechanism of this phenomenon remains unclear. This study attempts to elucidate the association between cerebral microbleeds (CMBs) and radiation necrosis and cognitive dysfunction in NPC patients treated with radiation therapy. Methods and Materials: This cross-sectional study included 106 NPC patients who were exposed to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients without discernable intracranial pathology were included as the control group. CMBs were confirmed using susceptibility-weighted magnetic resonance imaging. Cognitive function was accessed using Montreal Cognitive Assessment. Patients with a total score below 26 were defined as cognitively dysfunction. Results: Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non-RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control group had CMBs. In patients with a history of radiation therapy, CMBs most commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%). Patients with RN had more temporal CMBs than those in the non-RN group (37.7 ± 51.9 vs 3.8 ± 12.6, respectively; P<.001). The number of temporal lobe CMBs was predictive for larger volume of brain necrosis (P<.001) in multivariate linear regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001). After adjusting for age, sex, education, period after radiation therapy, CMBs in other lobes, and RN volume, the number of temporal CMBs remained an independent risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04; P=.003). Conclusions: CMBs is a common radiological manifestation in NPC patients with RN

Radiation-induced neurobehavioral dysfunctions

International Nuclear Information System (INIS)

Manda, Kailash

2013-01-01

There is a lacuna between sparsely reported immediate effects and the well documented delayed effects on cognitive functions seen after ionizing radiation exposure. We reported the radiation-dose dependent incongruity in the early cognitive changes and its correlation with the structural aberration as reported by imaging study. The delayed effect of radiation was investigated to understand the role of hippocampal neurogenesis in the functional recovery of cognition. C57BL/6 mice were exposed to different doses of γ-radiation and 24 hrs after exposure, the stress and anxiety levels were examined in the Open Field Exploratory Paradigms (OFT). 48hrs after irradiation, the hippocampal dependent recognition memory was observed by the Novel Object Recognition Test (NORT) and the cognitive function related to memory processing and recall was tested using the Elevated Plus Maze (EPM). Visualization of damage to the brain was done by diffusion tensor imaging at 48 hours post-irradiation. Results indicate a complex dose independent effect on the cognitive functions immediately after exposure to gamma rays. Radiation exposure caused short term memory dysfunctions at lower doses which were seen to be abrogated at higher doses, but the long term memory processing was disrupted at higher doses. The Hippocampus emerged as one of the sensitive regions to be affected by whole body exposure to gamma rays, which led to profound immediate alterations in cognitive functions. Furthermore, the results indicate a cognitive recovery process, which might be dependent on the extent of damage to the hippocampal region. While evaluating the delayed effect of radiation on the hippocampal neurogenesis, we observed that higher doses groups showed comparatively more adaptive regenerative neurogenic potential which they could not sustain at later stages. Our studies reported an important hitherto uncovered phenomenon of neurobehavioral dysfunctions in relation to radiation dose. Nevertheless, a

Tryptophan as an evolutionarily conserved signal to brain serotonin : Molecular evidence and psychiatric implications

NARCIS (Netherlands)

Russo, Sascha; Kema, Ido P.; Bosker, Fokko; Haavik, Jan; Korf, Jakob

2009-01-01

The role of serotonin (5-HT) in psychopathology has been investigated for decades. Among others, symptoms of depression, panic, aggression and suicidality have been associated with serotonergic dysfunction. Here we summarize the evidence that low brain 5-HT signals a metabolic imbalance that is

Thyroid dysfunction and pregnancy outcomes

Directory of Open Access Journals (Sweden)

Sima Nazarpour

2015-07-01

Full Text Available Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective, case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly

Electrophysiological correlates of word recognition memory process in patients with ischemic left ventricular dysfunction.

Science.gov (United States)

Giovannelli, Fabio; Simoni, David; Gavazzi, Gioele; Giganti, Fiorenza; Olivotto, Iacopo; Cincotta, Massimo; Pratesi, Alessandra; Baldasseroni, Samuele; Viggiano, Maria Pia

2016-09-01

The relationship between left ventricular ejection fraction (LVEF) and cognitive performance in patients with coronary artery disease without overt heart failure is still under debate. In this study we combine behavioral measures and event-related potentials (ERPs) to verify whether electrophysiological correlates of recognition memory (old/new effect) are modulated differently as a function of LVEF. Twenty-three male patients (12 without [LVEF>55%] and 11 with [LVEF25 were enrolled. ERPs were recorded while participants performed an old/new visual word recognition task. A late positive ERP component between 350 and 550ms was differentially modulated in the two groups: a clear old/new effect (enhanced mean amplitude for old respect to new items) was observed in patients without LVEF dysfunction; whereas patients with overt LVEF dysfunction did not show such effect. In contrast, no significant differences emerged for behavioral performance and neuropsychological evaluations. These data suggest that ERPs may reveal functional brain abnormalities that are not observed at behavioral level. Detecting sub-clinical measures of cognitive decline may contribute to set appropriate treatments and to monitor asymptomatic or mildly symptomatic patients with LVEF dysfunction. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders

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Mami eNoda

2015-06-01

Full Text Available It is widely accepted that there is a close relationship between the endocrine system and the central nervous system (CNS. Among hormones closely related to the nervous system, thyroid hormones (THs are critical for the development and function of the CNS; not only for neuronal cells but also for glial development and differentiation. Any impairment of TH supply to the developing CNS causes severe and irreversible changes in the overall architecture and function of human brain, leading to various neurological dysfunctions. In adult brain, impairment of THs, such as hypothyroidism and hyperthyroidism, can cause psychiatric disorders such as schizophrenia, bipolar disorder, anxiety and depression. Though hypothyroidism impairs synaptic transmission and plasticity, its effect on glial cells and cellular mechanisms are unknown. This mini-review article summarizes how THs are transported to the brain, metabolized in astrocytes and affect microglia and oligodendrocytes, showing an example of glioendocrine system. It may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hypo- and hyper-thyroidism may cause mental disorders.

Analysis of the apoptosis of brain and liver cells induced by ionizing radiation

International Nuclear Information System (INIS)

Konoplya, E.F.; Litvinchuk, A.V.; Zajtseva, O.A.; Stashkevich, D.G.

2010-01-01

The PCR-analysis of the expression of two oncogenes (bax/bcl-2) in the liver and brain tissues of the animals after being exposed to gamma-rays at doses of 1,0 and 4,0 Gy at remote terms after the action of (30, 60, 90 days) was made. The proofs of start-up of the genetic program of apoptosis of brain and liver cells were obtained. This can be a reason for functional dysfunction of a particular organ and the whole organism. (authors)

Brain disease, connectivity, plasticity and cognitive therapy: A neurological view of mental disorders.

Science.gov (United States)

Lubrini, G; Martín-Montes, A; Díez-Ascaso, O; Díez-Tejedor, E

2018-04-01

Our conception of the mind-brain relationship has evolved from the traditional idea of dualism to current evidence that mental functions result from brain activity. This paradigm shift, combined with recent advances in neuroimaging, has led to a novel definition of brain functioning in terms of structural and functional connectivity. The purpose of this literature review is to describe the relationship between connectivity, brain lesions, cerebral plasticity, and functional recovery. Assuming that brain function results from the organisation of the entire brain in networks, brain dysfunction would be a consequence of altered brain network connectivity. According to this approach, cognitive and behavioural impairment following brain damage result from disrupted functional organisation of brain networks. However, the dynamic and versatile nature of these circuits makes recovering brain function possible. Cerebral plasticity allows for functional reorganisation leading to recovery, whether spontaneous or resulting from cognitive therapy, after brain disease. Current knowledge of brain connectivity and cerebral plasticity provides new insights into normal brain functioning, the mechanisms of brain damage, and functional recovery, which in turn serve as the foundations of cognitive therapy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Epilepsy and brain tumors

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ENGLOT, DARIO J.; CHANG, EDWARD F.; VECHT, CHARLES J.

2016-01-01

Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70–80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60–75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20–50% of patients with meningioma and 20–35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60–90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

Autism as an adaptive common variant pathway for human brain development

Directory of Open Access Journals (Sweden)

Mark H. Johnson

2017-06-01

Full Text Available While research on focal perinatal lesions has provided evidence for recovery of function, much less is known about processes of brain adaptation resulting from mild but widespread disturbances to neural processing over the early years (such as alterations in synaptic efficiency. Rather than being viewed as a direct behavioral consequence of life-long neural dysfunction, I propose that autism is best viewed as the end result of engaging adaptive processes during a sensitive period. From this perspective, autism is not appropriately described as a disorder of neurodevelopment, but rather as an adaptive common variant pathway of human functional brain development.

[A 53-year-old man with herpes encephalitis showing acceleration of improvement in higher brain function after general anesthesia with sevoflurane: a case report].

Science.gov (United States)

Togashi, Naohiko; Kaida, Kenichi; Hongo, Yu; Ogawa, Go; Ishikawa, Yukinobu; Takeda, Katsuhiko; Kamakura, Keiko

2014-01-01

We experienced a right-handed 53-year-old man who presented with disturbance of consciousness and fever. Herpes simplex encephalitis (HSE) was diagnosed based on the detection of herpes simplex virus DNA in the cerebrospinal fluid. The administration of acyclovir for 42 days improved his consciousness level. Drowsiness, fever and seizures reappeared 20 days after stopping acyclovir treatment (day 67) and he responded well to vidarabine and methylprednisolone pulse therapy. An assessment of aphasia on day 98 revealed transcortical sensory aphasia. Brain MRI showed lesion in the left temporal lobe, bilateral insular cortexes and bilateral frontal lobe. His higher brain dysfunction continued. On day 156, he underwent hip replacement arthroplasty under general anesthesia sevoflurane. His higher brain dysfunction rapidly improved thereafter. We concluded that the accelerated improvement in our patient's higher brain function was related to the protective effect of sevoflurane. Some reports also show the protective effects of sevoflurane in experimental allergic encephalomyelitis by inhibition of T cell activation. These protective and anti-inflammatory effects may explain the accelerated improvement in higher brain function after general anesthesia.

Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment

NARCIS (Netherlands)

Tosun, Duygu; Schuff, Norbert; Mathis, Chester A.; Jagust, William; Weiner, Michael W.; Saradha, A.; Abdi, Herve; Abdulkadir, Ahmed; Abeliovich, Asa; Abellan van Kan, Gabor; Abner, Erin; Acharya, Deepa; Agrusti, Antonella; Agyemang, Alex; Ahdidan, Jamila; Ahmed, Shiek; Ahn, Jae Eun; Aisen, Paul; Aksu, Yaman; Al-Akhras, Mousa; Alarcon, Marcelo; Alberca, Roman; Alexander, Gene; Alexander, Daniel; Alin, Aylin; Almeida, Fabio; Amlien, Inge; Anand, Shyam; Anderson, Dallas; Andrew, Marilee; Angersbach, Steve; Anjum, Ayesha; Aoyama, Eiji; Arfanakis, Konstantinos; Armor, Tom; Arnold, Steven; Arunagiri, Vidhya; Asatryan, Albert; Ashe-McNalley, Cody; Ashiga, Hirokazu; Assareh, Arezoo; Le Page, Aurelie; Avants, Brian; Avinash, Gopal; Aviv, Richard; Awasthi, Sukrati; Ayan-Oshodi, Mosun; Babic, Tomislav; Baek, Young; Bagci, Ulas; Bai, Shuyang; Baird, Geoffrey; Baker, John; Banks, Sarah; Bard, Jonathan; Barnes, Josephine; Bartlett, Jonathan; Bartzokis, George; Barua, Neil; Bauer, Corinna; Bayley, Peter; Beck, Irene; Becker, James; Becker, J. Alex; Beckett, Laurel; Bednar, Martin; Beg, Mirza Faisal; Bek, Stephan; Belaroussi, Boubakeur; Belmokhtar, Nabil; Bernard, Charlotte; Bertram, Lars; Bhaskar, Uday; Biffi, Alessandro; Bigler, Erin; Bilgic, Basar; Bishop, Courtney; Bittner, Daniel; Black, Ronald; Bogorodzki, Piotr; Bokde, Arun; Bonner-Jackson, Aaron; Boppana, Madhu; Bourgeat, Pierrick; Bowes, Mike; Bowman, DuBois; Bowman, Gene; Braskie, Meredith; Braunewell, Karl; Breitner, Joihn; Bresell, Anders; Brewer, James; Brickman, Adam; Britschgi, Markus; Broadbent, Steve; Brogren, Jacob; Brooks, David; Browndyke, Jeffrey; Brunton, Simon; Buchert, Ralph; Buchsbaum, Monte; Buckley, Chris; Buerger, Katharina; Burger, Cyrill; Burnham, Samantha; Burns, Jeffrey; Burton, David; Butman, John; Cabeza, Rafael; Cairns, Nigel; Callhoff, Johanna; Calvini, Piero; Cantillon, Marc; Capella, Heraldo; Carbotti, Angela; Cardona-Sanclemente, Luis Eduardo; Carle, Adam; Carmasin, Jeremy; Carranza-Ath, Fredy; Casabianca, Jodi; Casanova, Ramon; Cash, David; Cedarbaum, Jesse; Cella, Massimo; Celsis, Pierre; Chanu, Pascal; Chao, Linda; Charil, Arnaud; Chemali, Zeina; Chen, Rong; Chen, Jake; Chen, Gennan; Chen, Wei; Chen, Kewei; Chen, Shuzhong; Chen, Minhua; Cheng, Wei-Chen; Cherkas, Yauheniya; Chertkow, Howard; Cheung, Charlton; Cheung, Vinci; Chiang, Gloria; Chiba, Koji; Chin, Simon; Chisholm, Jane; Cho, Youngsang; Choe, John; Choubey, Suresh; Chowbina, Sudhir; Christensen, Anette Luther; Clark, David; Clark, Chris; Clarkson, Matt; Clayton, David; Clunie, David; Coen, Michael; Coimbra, Alexandre; Compton, David; Coppola, Giovanni; Coulin, Samuel; Cover, Keith S.; Crane, Paul; Crans, Gerald; Croop, Robert; Crowther, Daniel; Crum, William; Cui, Yue; Curry, Charles; Curtis, Steven; Cutter, Gary; Daiello, Lori; Dake, Michael; Dale, Anders; Daliri, Mohammad Reza; Damato, Vito Domenico; Darby, Eveleen; Darkner, Sune; Davatzikos, Christos; Dave, Jay; David, Renaud; DavidPrakash, Bhaskaran; Davidson, Julie; de Bruijne, Marleen; de Meyer, Geert; de Nunzio, Giorgio; Decarli, Charles; Dechairo, Bryan; DeDuck, Kristina; Dehghan, Hossein; Dejkam, Arsalan; Delfino, Manuel; Della Rosa, Pasquale Anthony; Dellavedova, Luca; Delpassand, Ebrahim; Delrieu, Julien; DeOrchis, Vincent; Depy Carron, Delphine; deToledo-Morrell, Leyla; Devanand, Davangere; Devanarayan, Viswanath; DeVous, Michael; Diaz-Arrastia, Ramon; Bradford, Dickerson; Ding, Xiaobo; Dinov, Ivo; Dobson, Howard; Dodge, Hiroko; Donohue, Michael; Dore, Vincent; Dorflinger, Ernest; Dowling, Maritza; Duan, Xujun; Dubal, Dena; Duchesne, Simon; Duff, Kevin; Dukart, Jrgen; Durazzo, Timothy; Dykstra, Kevin; Earl, Nancy; Edula, Goutham; Ekin, Ahmet; Elcoroaristizabal, Xabier; Emahazion, Tesfai; Engelman, Corinne; Epstein, Noam; Erten-Lyons, Deniz; Eskildsen, Simon; Falcone, Guido; Fan, Lingzhong; Fan, Yong; Farahibozorg, Seyedehrezvan; Farb, Norman; Farnum, Michael; Farrer, Lindsay; Farzan, Ali; Faux, Noel; Feldman, Betsy; Feldman, Howard; Feldman, Susan; Fennema-Notestine, Christine; Fernandes, Michel; Fernandez, Elsa; Ferrarini, Luca; Ferreira, Manuel Joao; Ferrer, Eugene; Figurski, Michal; Filipovych, Roman; Fillit, Howard; Finch, Stephen; Finlay, Daniel; Fiot, Jean-Baptiste; Flenniken, Derek; Fletcher, P. Thomas; Fletcher, Evan; Flynn Longmire, Crystal; Focke, Niels; Forman, Mark; Forsythe, Alan; Fox, Steven; Fox-Bosetti, Sabrina; Francis, Alexander L.; Franco-Villalobos, Conrado; Franko, Edit; Freeman, Stefanie; Friedrich, Christoph M.; Friesenhahn, Michel; Frings, Lars; Frisoni, Giovanni; Fritzsche, Klaus; Fujimoto, Yoko; Fujiwara, Ken; Fullerton, Terence; Furney, Simon; Gallins, Paul; Galvin, Ben; Gamst, Anthony; Gan, Ke; Garcia, Maria Teresa; Garg, Gaurav; Gaser, Christian; Gastineau, Edward; Gauthier, Serge; Gavett, Brandon; Gavidia, Giovana; Gazdzinski, Stefan; Ge, Qi; Ge, Tian; Gemme, Gianluca; Geraci, Joseph; Ghassabi, Zeinab; Gieschke, Ronald; Gil, Juan E.; Gill, Ryan; Gitelman, Darren; Gleason, Carey; Glymour, M. 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Ilyas; Kaneko, Tomoki; Kaneta, Tomohiro; Kang, Ju Hee; Karageorgiou, Elissaios; Karantzoulis, Stella; Karlawish, Jason; Katz, Elyse; Kaushik, Sandeep S.; Kauwe, John; Kawakami, Hirofumi; Kazimipoor, Borhan; Kelleher, Thomas; Kennedy, Richard; Kerchner, Geoffrey; Kerrouche, Nacer; Khalil, Iya; Khalil, Andre; Killeen, Neil; Killiany, Ron; Kim, Jong Hun; Kim, Heeyoung; Kim, Ana; Kim, Yeonhee; Kim, Hyoungkyu; Kim, Seongkyun; Kim, Hyewon; Kimberg, Daniel; Kimura, Tokunori; King, Richard; Kirby, Justin; Kirsch, Wolff; Klimas, Michael; Kline, Richard; Kling, Mitchel; Klopfenstein, Erin; Koikkalainen, Juha; Kokomoor, Anders; Kolasny, Anthony; Koppel, Jeremy; Korolev, Igor; Kotran, Nickolas; Kouassi, Alex; Kowalczyk, Adam; Kozma, Lynn; Krams, Michael; Kratzer, Martina; Kuceyeski, Amy; Kuhn, Felix Pierre; Kumar, Sreedhar; Kuo, Hsun Ting; Kuo, Julie; Kurosawa, Ken; Kwon, Oh Hun; Labrish, Catherine; Laforet, Genevieve; Lai, Song; Lakatos, Anita; Lam, On Ki; Lampron, Antoine; Landau, Susan; Landen, Jaren; Lane, Richard; Langbaum, Jessica; Langford, Dianne; Lanius, Vivian; Laxamana, Joel; Le, Trung; Leahy, Richard; Lee, Jong-Min; Lee, Vita; Lee, Joseph H.; Lee, Grace; Lee, Dongsoo; Lee, Noah; Lefkimmiatis, Stamatis; Lemaitre, Herve; Lenfant, Pierre; Lenz, Robert; Leoutsakos, Jeannie-Marie; Lester, Gayle; Levey, Allan; Li, Shi-jiang; Li, Shanshan; Li, Wenjun; Li, Chin-Shang; Li, Xiaodong; Li, Rui; Li, Ming; Li, Lexin; Li, Jinhe; Li, Yi; Li, Quanzheng; Li, Gang; Liang, Kuchang; Liang, Peipeng; Liang, Lichen; Liao, Yuan-Lin; Lin, Ling-chih; Lin, Lan; Lin, Mingkuan; Lin, Ai-Ling; Liu, Songling; Liu, Yuan; Liu, Tianming; Liu, Meijie; Liu, Xiuwen; Liu, Li; Liu, Honggang; Liu, Pu; Liu, Tao; Liu, Sophia; Liu, Dazhong; Lo, Raymond; Lobanov, Victor; Loewenstein, David; Logovinsky, Veronika; Long, Xiaojing; Long, Ziyi; Looi, Jeffrey; Lu, Po-Haong; Lukic, Ana; Lull, Juan J.; Luo, Xiongjian; Lynch, John; Ma, Lei; Mackin, Scott; Mada, Marius; Magda, Sebastian; Maglio, Silvio; Maikusa, Norihide; Mak, Henry Ka-Fung; Malave, Vicente; Maldjian, Joseph; Mandal, Pravat; Mangin, Jean-Francois; Manjon, Jose; Mantri, Ninad; Manzour, Amir; Marambaud, Philippe; Marchewka, Artur; Marek, Kenneth; Markind, Samuel; Marshall, Gad; Martinez Torteya, Antonio; Mather, Mara; Mathis, Chester; Matoug, Sofia; Matsuo, Yoshiyuki; Mattei, Peter; Matthews, Dawn; McArdle, John; McCarroll, Steven; McEvoy, Linda; McGeown, William; McGonigle, John; McIntyre, John; McLaren, Donald; McQuail, Joseph; Meadowcroft, Mark; Meda, Shashwath; Mehta, Nirav; Melie-Garcia, Lester; Melrose, Rebecca; Mendonca, Brian; Menendez, Manuel; Meredith, Jere; Merrill, David; Mesulam, Marek-Marsel; Metti, Andrea; Meyer, Carsten; Mez, Jesse; Mickael, Guedj; Miftahof, Roustem; Mikhno, Arthur; Miller, David; Millikin, Colleen; Min, Ye; Mirza, Mubeena; Mistridis, Panagiota; Mitchell, Meghan; Mitsis, Effie; Mohan, Ananth; Moore, Dana; Moradi Birgani, Parmida; Moratal, David; Morimoto, Bruce; Mormino, Elizabeth; Mortamet, Benedicte; Moscato, Pablo; Mueller, Kathyrne; Mueller, Susanne; Mueller, Notger; Mukherjee, Shubhabrata; Mulder, Emma; Murayama, Shigeo; Murphy, Michael; Murray, Brian; Musiek, Erik; Myers, Amanda; Najafi, Shahla; Nazarparvar, Babak; Nazeri, Arash; Nettiksimmons, Jasmine; Neu, Scott; Ng, Yen-Bee; Nguyen, Nghi; Nguyen Xuan, Tuong; Nichols, Thomas; Nicodemus, Kristin; Niecko, Timothy; Nielsen, Casper; Notomi, Keiji; Nutakki, Gopi Chand; O'Bryant, Sid; O'Neil, Alison; Obisesan, Thomas; Oh, Dong Hoon; Oh, Joonmi; Okonkwo, Ozioma; Olde Rikkert, Marcel; Olmos, Salvador; Ortner, Marion; Ostrowitzki, Susanne; Oswald, Annahita; Ott, Brian; Ourselin, Sebastien; Ouyang, Gaoxiang; Paiva, Renata; Pan, Zhifang; Pande, Yogesh; Pardo, Jose; Pardoe, Heath; Park, Hyunjin; Park, Lovingly; Park, Moon Ho; Park, Sang hyun; Park, Kee Hyung; Park, Sujin; Parsey, Ramin; Parveen, Riswana; Paskavitz, James; Patel, Yogen; Patil, Manasi; Pawlak, Mikolaj; Payoux, Pierre; Pearson, Jim; Peavy, Guerry; Pell, Gaby; Peng, Yahong; Pennec, Xavier; Pepin, Jean louis; Perea, Rodrigo; Perneczky, Robert; Petitti, Diana; Petrella, Jeffrey; Peyrat, Jean-Marc; Pezoa, Jorge; Pham, Chi-Tuan; Phillips, Justin; Phillips, Nicole; Pierson, Ronald; Piovezan, Mauro; Podhorski, Adam; Pollari, Mika; Pontecorvo, Michael; Poppenk, Jordan; Posner, Holly; Potkin, Steven; Potter, Guy; Potter, Elizabeth; Poulin, Stephane; Prasad, Gautam; Prenger, Kurt; Prince, Jerry; Priya, Anandh; Puchakayala, Shashidhar Reddy; Qiu, Ruolun; Qiu, Anqi; Qiu, Wendy; Qualls, Constance Dean; Rabie, Huwaida; Rajeesh, Rajeesh; Rallabandi, V. 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2011-01-01

Amyloid-β accumulation in the brain is thought to be one of the earliest events in Alzheimer's disease, possibly leading to synaptic dysfunction, neurodegeneration and cognitive/functional decline. The earliest detectable changes seen with neuroimaging appear to be amyloid-β accumulation detected by

Network dynamics with BrainX(3): a large-scale simulation of the human brain network with real-time interaction.

Science.gov (United States)

Arsiwalla, Xerxes D; Zucca, Riccardo; Betella, Alberto; Martinez, Enrique; Dalmazzo, David; Omedas, Pedro; Deco, Gustavo; Verschure, Paul F M J

2015-01-01

BrainX(3) is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX(3) in real-time by perturbing brain regions with transient stimulations to observe reverberating network activity, simulate lesion dynamics or implement network analysis functions from a library of graph theoretic measures. BrainX(3) can thus be used as a novel immersive platform for exploration and analysis of dynamical activity patterns in brain networks, both at rest or in a task-related state, for discovery of signaling pathways associated to brain function and/or dysfunction and as a tool for virtual neurosurgery. Our results demonstrate these functionalities and shed insight on the dynamics of the resting-state attractor. Specifically, we found that a noisy network seems to favor a low firing attractor state. We also found that the dynamics of a noisy network is less resilient to lesions. Our simulations on TMS perturbations show that even though TMS inhibits most of the network, it also sparsely excites a few regions. This is presumably due to anti-correlations in the dynamics and suggests that even a lesioned network can show sparsely distributed increased activity compared to healthy resting-state, over specific brain areas.

Network dynamics with BrainX3: a large-scale simulation of the human brain network with real-time interaction

Science.gov (United States)

Arsiwalla, Xerxes D.; Zucca, Riccardo; Betella, Alberto; Martinez, Enrique; Dalmazzo, David; Omedas, Pedro; Deco, Gustavo; Verschure, Paul F. M. J.

2015-01-01

BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimulations to observe reverberating network activity, simulate lesion dynamics or implement network analysis functions from a library of graph theoretic measures. BrainX3 can thus be used as a novel immersive platform for exploration and analysis of dynamical activity patterns in brain networks, both at rest or in a task-related state, for discovery of signaling pathways associated to brain function and/or dysfunction and as a tool for virtual neurosurgery. Our results demonstrate these functionalities and shed insight on the dynamics of the resting-state attractor. Specifically, we found that a noisy network seems to favor a low firing attractor state. We also found that the dynamics of a noisy network is less resilient to lesions. Our simulations on TMS perturbations show that even though TMS inhibits most of the network, it also sparsely excites a few regions. This is presumably due to anti-correlations in the dynamics and suggests that even a lesioned network can show sparsely distributed increased activity compared to healthy resting-state, over specific brain areas. PMID:25759649

Network Dynamics with BrainX3: A Large-Scale Simulation of the Human Brain Network with Real-Time Interaction

Directory of Open Access Journals (Sweden)

Xerxes D. Arsiwalla

2015-02-01

Full Text Available BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimulations to observe reverberating network activity, simulate lesion dynamics or implement network analysis functions from a library of graph theoretic measures. BrainX3 can thus be used as a novel immersive platform for real-time exploration and analysis of dynamical activity patterns in brain networks, both at rest or in a task-related state, for discovery of signaling pathways associated to brain function and/or dysfunction and as a tool for virtual neurosurgery. Our results demonstrate these functionalities and shed insight on the dynamics of the resting-state attractor. Specifically, we found that a noisy network seems to favor a low firing attractor state. We also found that the dynamics of a noisy network is less resilient to lesions. Our simulations on TMS perturbations show that even though TMS inhibits most of the network, it also sparsely excites a few regions. This is presumably, due to anti-correlations in the dynamics and suggests that even a lesioned network can show sparsely distributed increased activity compared to healthy resting-state, over specific brain areas.

[Hypopituitarism following traumatic brain injury: diagnostic and therapeutic issues].

Science.gov (United States)

Lecoq, A-L; Chanson, P

2015-10-01

Traumatic Brain Injury (TBI) is a well-known public health problem worldwide and is a leading cause of death and disability, particularly in young adults. Besides neurological and psychiatric issues, pituitary dysfunction can also occur after TBI, in the acute or chronic phase. The exact prevalence of post-traumatic hypopituitarism is difficult to assess due to the wide heterogeneity of published studies and bias in interpretation of hormonal test results in this specific population. Predictive factors for hypopituitarism have been proposed and are helpful for the screening. The pathophysiology of pituitary dysfunction after TBI is not well understood but the vascular hypothesis is privileged. Activation of pituitary stem/progenitor cells is probably involved in the recovery of pituitary functions. Those cells also play a role in the induction of pituitary tumors, highlighting their crucial place in pituitary conditions. This review updates the current data related to anterior pituitary dysfunction after TBI and discusses the bias and difficulties encountered in its diagnosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Menopause-related brain activation patterns during visual sexual arousal in menopausal women: An fMRI pilot study using time-course analysis.

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Kim, Gwang-Won; Jeong, Gwang-Woo

2017-02-20

The aging process and menopausal transition are important factors in sexual dysfunction of menopausal women. No neuroimaging study has assessed the age- and menopause-related changes on brain activation areas associated with sexual arousal in menopausal women. The purpose of this study was to evaluate the time course of regional brain activity associated with sexual arousal evoked by visual stimulation in premenopausal and menopausal women, and further to assess the effect of menopause on the brain areas associated with sexual arousal in menopausal women using functional magnetic resonance imaging (fMRI). Thirty volunteers consisting of 15 premenopausal and 15 menopausal women underwent the fMRI. For the activation condition, volunteers viewed sexually arousing visual stimulation. The brain areas with significantly higher activation in premenopausal women compared with menopausal women included the thalamus, amygdala, and anterior cingulate cortex (ACC) using analysis of covariance adjusting for age (psexual arousal. These findings might help elucidate the neural mechanisms associated with sexual dysfunction in menopausal women. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

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Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

Female Sexual Dysfunction-Medical and Psychological Treatments, Committee 14.

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Kingsberg, Sheryl A; Althof, Stanley; Simon, James A; Bradford, Andrea; Bitzer, Johannes; Carvalho, Joana; Flynn, Kathryn E; Nappi, Rossella E; Reese, Jennifer B; Rezaee, Roya L; Schover, Leslie; Shifrin, Jan L

2017-12-01

Since the millennium we have witnessed significant strides in the science and treatment of female sexual dysfunction (FSD). This forward progress has included (i) the development of new theoretical models to describe healthy and dysfunctional sexual responses in women; (ii) alternative classification strategies of female sexual disorders; (iii) major advances in brain, hormonal, psychological, and interpersonal research focusing on etiologic factors and treatment approaches; (iv) strong and effective public advocacy for FSD; and (v) greater educational awareness of the impact of FSD on the woman and her partner. To review the literature and describe the best practices for assessing and treating women with hypoactive sexual desire disorder, female sexual arousal disorder, and female orgasmic disorders. The committee undertook a comprehensive review of the literature and discussion among themselves to determine the best assessment and treatment methods. Using a biopsychosocial lens, the committee presents recommendations (with levels of evidence) for assessment and treatment of hypoactive sexual desire disorder, female sexual arousal disorder, and female orgasmic disorders. The numerous significant strides in FSD that have occurred since the previous International Consultation of Sexual Medicine publications are reviewed in this article. Although evidence supports an integrated biopsychosocial approach to assessment and treatment of these disorders, the biological and psychological factors are artificially separated for review purposes. We recognize that best outcomes are achieved when all relevant factors are identified and addressed by the clinician and patient working together in concert (the sum is greater than the whole of its parts). Kingsberg SA, Althof S, Simon JA, et al. Female Sexual Dysfunction-Medical and Psychological Treatments, Committee 14. J Sex Med 2017;14:1463-1491. Copyright © 2017 International Society for Sexual Medicine. Published by

Cognitive dysfunction after cardiovascular surgery

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Funder, K S; Steinmetz, J; Rasmussen, L S

2009-01-01

This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive neuropsychol......This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive...... neuropsychological test battery must be used to detect POCD and a well-matched control group is very useful for the analysis and interpretation of the test RESULTS: Cardiovascular surgery is associated with a high incidence of POCD. Cardiopulmonary bypass was thought to explain this difference, but randomized...

Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of white matter-rich regions without altering flow in brain-irrigating arteries: Relationship to blood-brain barrier breakdown?

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Dhaya, Ibtihel; Griton, Marion; Raffard, Gérard; Amri, Mohamed; Hiba, Bassem; Konsman, Jan Pieter

2018-01-15

To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection. In parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity in white matter. These findings indicate that systemic inflammation can result in increased perfusion, blood-brain barrier breakdown and altered water diffusion in white matter. Copyright © 2017 Elsevier B.V. All rights reserved.

White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus.

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Cannerfelt, B; Nystedt, J; Jönsen, A; Lätt, J; van Westen, D; Lilja, A; Bengtsson, A; Nilsson, P; Mårtensson, J; Sundgren, P C

2018-06-01

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

One-year high fat diet affects muscle-but not brain mitochondria

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