WorldWideScience

Sample records for neurodegenerative brain tissue

  1. Chronic neurodegenerative consequences of traumatic brain injury.

    Science.gov (United States)

    Chauhan, Neelima B

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  3. Epidemiology of mild traumatic brain injury and neurodegenerative disease

    OpenAIRE

    Gardner, Raquel C.; Yaffe, Kristine

    2015-01-01

    Every year an estimated 42 million people worldwide suffer a mild traumatic brain injury (MTBI) or concussion. More severe traumatic brain injury (TBI) is a well-established risk factor for a variety of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Recently, large epidemiological studies have additionally identified MTBI as a risk factor for dementia. The role of MTBI in risk of PD or ALS is less well established. Repet...

  4. Resting state brain networks and their implications in neurodegenerative disease

    Science.gov (United States)

    Sohn, William S.; Yoo, Kwangsun; Kim, Jinho; Jeong, Yong

    2012-10-01

    Neurons are the basic units of the brain, and form network by connecting via synapses. So far, there have been limited ways to measure the brain networks. Recently, various imaging modalities are widely used for this purpose. In this paper, brain network mapping using resting state fMRI will be introduced with several applications including neurodegenerative disease such as Alzheimer's disease, frontotemporal lobar degeneration and Parkinson's disease. The resting functional connectivity using intrinsic functional connectivity in mouse is useful since we can take advantage of perturbation or stimulation of certain nodes of the network. The study of brain connectivity will open a new era in understanding of brain and diseases thus will be an essential foundation for future research.

  5. Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis.

    Science.gov (United States)

    Westfall, Susan; Lomis, Nikita; Kahouli, Imen; Dia, Si Yuan; Singh, Surya Pratap; Prakash, Satya

    2017-10-01

    The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastrointestinal tract communicates with the central nervous system through the gut-brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecular communication network that link systemic imbalances with the development of neurodegeneration including insulin regulation, fat metabolism, oxidative markers and immune signaling. Age is a common factor in the development of neurodegenerative disease and probiotics prevent many harmful effects of aging such as decreased neurotransmitter levels, chronic inflammation, oxidative stress and apoptosis-all factors that are proven aggravators of neurodegenerative disease. Indeed patients with Parkinson's and Alzheimer's diseases have a high rate of gastrointestinal comorbidities and it has be proposed by some the management of the gut microbiota may prevent or alleviate the symptoms of these chronic diseases.

  6. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

    Science.gov (United States)

    Quigley, Eamonn M M

    2017-10-17

    The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

  7. Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Federica Ciregia

    2017-08-01

    Full Text Available Extracellular vesicles (EVs can be classified into apoptotic bodies, microvesicles (MVs, and exosomes, based on their origin or size. Exosomes are the smallest and best characterized vesicles which derived from the endosomal system. These vesicles are released from many different cell types including neuronal cells and their functions in the nervous system are investigated. They have been proposed as novel means for intercellular communication, which takes part not only to the normal neuronal physiology but also to the transmission of pathogenic proteins. Indeed, exosomes are fundamental to assemble and transport proteins during development, but they can also transfer neurotoxic misfolded proteins in pathogenesis. The present review will focus on their roles in neurological diseases, specifically brain tumors, such as glioblastoma (GBM, neuroblastoma (NB, medulloblastoma (MB, and metastatic brain tumors and chronic neurodegenerative diseases, such as Alzheimer, Parkinson, multiple sclerosis (MS, amyotrophic lateral sclerosis (ALS, Huntington, and Prion diseseases highlighting their involvement in spreading neurotoxicity, in therapeutics, and in pathogenesis.

  8. Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases

    Science.gov (United States)

    Ciregia, Federica; Urbani, Andrea; Palmisano, Giuseppe

    2017-01-01

    Extracellular vesicles (EVs) can be classified into apoptotic bodies, microvesicles (MVs), and exosomes, based on their origin or size. Exosomes are the smallest and best characterized vesicles which derived from the endosomal system. These vesicles are released from many different cell types including neuronal cells and their functions in the nervous system are investigated. They have been proposed as novel means for intercellular communication, which takes part not only to the normal neuronal physiology but also to the transmission of pathogenic proteins. Indeed, exosomes are fundamental to assemble and transport proteins during development, but they can also transfer neurotoxic misfolded proteins in pathogenesis. The present review will focus on their roles in neurological diseases, specifically brain tumors, such as glioblastoma (GBM), neuroblastoma (NB), medulloblastoma (MB), and metastatic brain tumors and chronic neurodegenerative diseases, such as Alzheimer, Parkinson, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington, and Prion diseseases highlighting their involvement in spreading neurotoxicity, in therapeutics, and in pathogenesis. PMID:28912682

  9. The bovine brain: an in vitro translational model in developmental neuroscience and neurodegenerative research.

    Directory of Open Access Journals (Sweden)

    Antonella ePeruffo

    2014-07-01

    Full Text Available Animal models provide convenient and clinically relevant tools in the research on neurodegenerative diseases. Studies on developmental disorders extensively rely on the use of laboratory rodents. The present mini-review proposes an alternative translational model, based on the use of fetal bovine brain tissue. The bovine (Bos taurus possesses a large and highly gyrencephalic brain and the long gestation period (41 weeks is comparable to the human pregnancy (38-40 weeks. Primary cultures obtained from fetal bovine brain constitute a validated in vitro model that allows examinations of neurons and/or glial cells under controlled and reproducible conditions. Physiological processes can be also studied on cultured bovine neural cells incubated with specific substrates or by electrically coupled electrolyte-oxide-semiconductor capacitors that permit direct recording from neuronal cells. Bovine neural cells and specific in vitro cell culture could be an alternative in comparative neuroscience and in neurodegenerative research, useful for studying development of normal and altered circuitry in a long gestation mammalian species. Use of bovine tissues would promote a substantial reduction in the use of laboratory animals.

  10. Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program.

    Science.gov (United States)

    Beach, Thomas G; Adler, Charles H; Sue, Lucia I; Serrano, Geidy; Shill, Holly A; Walker, Douglas G; Lue, LihFen; Roher, Alex E; Dugger, Brittany N; Maarouf, Chera; Birdsill, Alex C; Intorcia, Anthony; Saxon-Labelle, Megan; Pullen, Joel; Scroggins, Alexander; Filon, Jessica; Scott, Sarah; Hoffman, Brittany; Garcia, Angelica; Caviness, John N; Hentz, Joseph G; Driver-Dunckley, Erika; Jacobson, Sandra A; Davis, Kathryn J; Belden, Christine M; Long, Kathy E; Malek-Ahmadi, Michael; Powell, Jessica J; Gale, Lisa D; Nicholson, Lisa R; Caselli, Richard J; Woodruff, Bryan K; Rapscak, Steven Z; Ahern, Geoffrey L; Shi, Jiong; Burke, Anna D; Reiman, Eric M; Sabbagh, Marwan N

    2015-08-01

    The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0-hour median post-mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200

  11. Banking brain tissue for research

    NARCIS (Netherlands)

    Klioueva, Natasja; Bovenberg, Jasper; Huitinga, I.

    2017-01-01

    Well-characterized human brain tissue is crucial for scientific breakthroughs in research of the human brain and brain diseases. However, the collection, characterization, management, and accessibility of brain human tissue are rather complex. Well-characterized human brain tissue is often provided

  12. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    Science.gov (United States)

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  13. Assessment of brain reference genes for RT-qPCR studies in neurodegenerative diseases

    DEFF Research Database (Denmark)

    Rydbirk, Rasmus; Folke, Jonas; Winge, Kristian

    2016-01-01

    . This is especially important in relation to neurodegenerative diseases where disease-related structural changes may affect the most commonly used RGs. We analysed 15 candidate RGs in 98 brain samples from two brain regions from Alzheimer's disease (AD), Parkinson's disease (PD), Multiple System Atrophy...

  14. Assessment of the degree of asymmetry of pathological features in neurodegenerative diseases. What is the significance for brain banks?

    Science.gov (United States)

    King, Andrew; Bodi, Istvan; Nolan, Matthew; Troakes, Claire; Al-Sarraj, Safa

    2015-10-01

    Brain banks allow researchers access to tissue from well-characterised neurodegenerative disease cases. Fixed tissue employed for diagnosis is often not appropriate for research and frozen tissue is therefore made available. Many brain banks use a protocol where half the brain is fixed and half frozen. Recently a study has shown that there can be asymmetry in protein deposition between the hemispheres especially with tau and TDP-43. We aimed to test this hypothesis by prospectively taking bilateral cortical blocks from 30 brains on arrival, and immunostaining to assess the degree of asymmetry. In 6 out 14 cases of AD (Alzheimer's Disease) (Modified Braak Stage V-VI), there was some asymmetrical staining for tau. In 2 cases, there was moderate discrepancy for tau staining between left and right calcarine cortices. However, careful analysis in both these cases revealed discrepancies in tau staining in adjacent regions even on the same side. The α-synuclein staining showed asymmetry in one case only, the Aβ showed only mild asymmetry in 3 cases of AD. The TDP-43 pathology appeared symmetrical in the 2 cases of frontotemporal lobar degeneration with motor neurone disease, but there was asymmetry noted when seen in conjunction with AD. In conclusion, there is the potential for asymmetrical pathology in neurodegenerative diseases and caution should be maintained when freezing half and fixing half of the brain in neurodegenerative diseases. Nevertheless, marked variability in staining can also be identified in adjacent cortical areas so there is no guarantee that an alternative strategy would be superior.

  15. Alteration of brain insulin and leptin signaling promotes energy homeostasis impairment and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Taouis Mohammed

    2011-09-01

    Full Text Available The central nervous system (CNS controls vital functions, by efficiently coordinating peripheral and central cascades of signals and networks in a coordinated manner. Historically, the brain was considered to be an insulin-insensitive tissue. But, new findings demonstrating that insulin is present in different regions of themammalian brain, in particular the hypothalamus and the hippocampus. Insulin acts through specific receptors and dialogues with numerous peptides, neurotransmitters and adipokines such as leptin. The cross-talk between leptin and insulin signaling pathways at the hypothalamic level is clearly involved in the control of energy homeostasis. Both hormones are anorexigenic through their action on hypothalamic arcuate nucleus by inducing the expression of anorexigenic neuropetides such as POMC (pro-opiomelanocortin, the precursor of aMSH and reducing the expression of orexigenic neuropeptide such as NPY (Neuropeptide Y. Central defect of insulin and leptin signaling predispose to obesity (leptin-resistant state and type-2 diabetes (insulin resistant state. Obesity and type-2 diabetes are associated to deep alterations in energy homeostasis control but also to other alterations of CNS functions as the predisposition to neurodegenerative diseases such as Alzheimer’s disease (AD. AD is a neurodegenerative disorder characterized by distinct hallmarks within the brain. Postmortem observation of AD brains showed the presence of parenchymal plaques due to the accumulation of the amyloid beta (AB peptide and neurofibrillary tangles. These accumulations result from the hyperphosphorylation of tau (a mictrotubule-interacting protein. Both insulin and leptin have been described to modulate tau phosphorylation and therefore in leptin and insulin resistant states may contribute to AD. The concentrations of leptin and insulin cerebrospinal fluid are decreased type2 diabetes and obese patients. In addition, the concentration of insulin in the

  16. Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Alana M. Horowitz

    2017-08-01

    Full Text Available Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

  17. Transplantation of human fetal tissue for neurodegenerative diseases: validation of a new protocol for microbiological analysis and bacterial decontamination.

    Science.gov (United States)

    Piroth, Tobias; Pauly, Marie-Christin; Schneider, Christian; Wittmer, Annette; Möllers, Sven; Döbrössy, Máté; Winkler, Christian; Nikkhah, Guido

    2014-01-01

    Restorative cell therapy concepts in neurodegenerative diseases are aimed at replacing lost neurons. Despite advances in research on pluripotent stem cells, fetal tissue from routine elective abortions is still regarded as the only safe cell source. Progenitor cells isolated from distinct first-trimester fetal CNS regions have already been used in clinical trials and will be used again in a new multicenter trial funded by the European Union (TRANSEURO). Bacterial contamination of human fetal tissue poses a potential risk of causing infections in the brain of the recipient. Thus, effective methods of microbial decontamination and validation of these methods are required prior to approval of a neurorestorative cell therapy trial. We have developed a protocol consisting of subsequent washing steps at different stages of tissue processing. Efficacy of microbial decontamination was assessed on rat embryonic tissue incubated with high concentrations of defined microbe solutions including representative bacterial and fungal species. Experimental microbial contamination was reduced by several log ranks. Subsequently, we have analyzed the spectrum of microbial contamination and the effect of subsequent washing steps on aborted human fetal tissue; 47.7% of the samples taken during human fetal tissue processing were positive for a microbial contamination, but after washing, no sample exhibited bacterial growth. Our data suggest that human fetal tissue for neural repair can carry microbes of various species, highlighting the need for decontamination procedures. The decontamination protocol described in this report has been shown to be effective as no microbes could be detected at the end of the procedure.

  18. Assessing Neurodegenerative Phenotypes in Drosophila Dopaminergic Neurons by Climbing Assays and Whole Brain Immunostaining

    OpenAIRE

    Barone, Maria Cecilia; Bohmann, Dirk

    2013-01-01

    Drosophila melanogaster is a valuable model organism to study aging and pathological degenerative processes in the nervous system. The advantages of the fly as an experimental system include its genetic tractability, short life span and the possibility to observe and quantitatively analyze complex behaviors. The expression of disease-linked genes in specific neuronal populations of the Drosophila brain, can be used to model human neurodegenerative diseases such as Parkinson's and Alzheimer's 5.

  19. Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Jean E. Vance

    2012-11-01

    Full Text Available Dysregulation of cholesterol homeostasis in the brain is increasingly being linked to chronic neurodegenerative disorders, including Alzheimer’s disease (AD, Huntington’s disease (HD, Parkinson’s disease (PD, Niemann-Pick type C (NPC disease and Smith-Lemli Opitz syndrome (SLOS. However, the molecular mechanisms underlying the correlation between altered cholesterol metabolism and the neurological deficits are, for the most part, not clear. NPC disease and SLOS are caused by mutations in genes involved in the biosynthesis or intracellular trafficking of cholesterol, respectively. However, the types of neurological impairments, and the areas of the brain that are most affected, differ between these diseases. Some, but not all, studies indicate that high levels of plasma cholesterol correlate with increased risk of developing AD. Moreover, inheritance of the E4 isoform of apolipoprotein E (APOE, a cholesterol-carrying protein, markedly increases the risk of developing AD. Whether or not treatment of AD with statins is beneficial remains controversial, and any benefit of statin treatment might be due to anti-inflammatory properties of the drug. Cholesterol balance is also altered in HD and PD, although no causal link between dysregulated cholesterol homeostasis and neurodegeneration has been established. Some important considerations for treatment of neurodegenerative diseases are the impermeability of the blood-brain barrier to many therapeutic agents and difficulties in reversing brain damage that has already occurred. This article focuses on how cholesterol balance in the brain is altered in several neurodegenerative diseases, and discusses some commonalities and differences among the diseases.

  20. Network functional connectivity and whole-brain functional connectomics to investigate cognitive decline in neurodegenerative conditions.

    Science.gov (United States)

    Dipasquale, O; Cercignani, Mara

    Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain's intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC. In this paper we provide an overview of these two techniques and some examples of their clinical applications in the most common neurodegenerative disorders associated with cognitive decline, including mild cognitive impairment, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies and behavioral variant frontotemporal dementia.

  1. Intensive training of phonological skills in progressive aphasia: a model of brain plasticity in neurodegenerative disease.

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    Louis, M; Espesser, R; Rey, V; Daffaure, V; Di Cristo, A; Habib, M

    2001-01-01

    Three patients with a typical syndrome of nonfluent primary progressive aphasia (Mesulam's syndrome) were trained daily with a remediation protocol including auditory exercises specifically designed to involve several aspects of phonological processing, a domain known to be specifically affected in the condition. The speech content of the exercises was based on the temporal theory of phonological processes according to which increasing the duration of formant transition should facilitate phoneme discrimination and phoneomic awareness. Significantly improved performance on the trained tasks was demonstrated in the three patients. Improvement further generalized to other tasks such as nonword repetition and reading. We conclude that such results (1) argue for using intensive focused therapy of language impairment in neurodegenerative disorders, (2) may constitute a good model of brain plasticity in neurodegenerative disorders in general, and (3) support theories of phonological processing emphasizing temporal features of the auditory signal.

  2. Edible and Medicinal Mushrooms: Emerging Brain Food for the Mitigation of Neurodegenerative Diseases.

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    Phan, Chia-Wei; David, Pamela; Sabaratnam, Vikineswary

    2017-01-01

    There is an exponential increase in dementia in old age at a global level because of increasing life expectancy. The prevalence of neurodegenerative diseases such as dementia and Alzheimer's disease (AD) will continue to rise steadily, and is expected to reach 42 million cases worldwide in 2020. Despite the advancement of medication, the management of these diseases remains largely ineffective. Therefore, it is vital to explore novel nature-based nutraceuticals to mitigate AD and other age-related neurodegenerative disorders. Mushrooms and their extracts appear to hold many health benefits, including immune-modulating effects. A number of edible mushrooms have been shown to contain rare and exotic compounds that exhibit positive effects on brain cells both in vitro and in vivo. In this review, we summarize the scientific information on edible and culinary mushrooms with regard to their antidementia/AD active compounds and/or pharmacological test results. The bioactive components in these mushrooms and the underlying mechanism of their activities are discussed. In short, these mushrooms may be regarded as functional foods for the mitigation of neurodegenerative diseases.

  3. Brain Atrophy of Secondary REM-Sleep Behavior Disorder in Neurodegenerative Disease.

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    Kim, Hee-Jin; Im, Hyung Kyun; Kim, Juhan; Han, Jee-Young; de Leon, Mony; Deshpande, Anup; Moon, Won-Jin

    2016-04-05

    Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy. We investigated that dementia with RBD might show distinctive cortical atrophic patterns. A total of 31 patients with idiopathic Parkinson's disease (IPD), 23 with clinically probable Alzheimer's disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for detection of regional brain atrophy among groups of subjects. Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes. The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α-synucleinopathy.

  4. The 2,6-disubstituted naphthalene derivative FDDNP labeling reliably predicts Congo red birefringence of protein deposits in brain sections of selected human neurodegenerative diseases.

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    Smid, Lojze M; Vovko, Tomaz D; Popovic, Mara; Petric, Andrej; Kepe, Vladimir; Barrio, Jorge R; Vidmar, Gaj; Bresjanac, Mara

    2006-04-01

    Deposition of conformationally altered proteins prominently characterizes pathogenesis and pathomorphology of a number of neurodegenerative disorders. 2-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl} ethylidene) malononitrile ([F-18]FDDNP), a hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent imaging probe has been used with positron emission tomography to visualize brain pathology in the living brain of Alzheimer disease (AD) patients. Its non-radiofluorinated analog FDDNP was shown to label senile plaques and neurofibrillary tangles (NFTs) in brain tissue sections. This work aimed at evaluating FDDNP labeling of various protein deposits in fixed, paraffin-embedded brain tissue sections of selected neurodegenerative disorders: AD, cerebral amyloid angiopathy (CAA), transmissible spongiform encephalopathies, progressive supranuclear palsy (PSP), Pick disease (PiD), Parkinson disease, dementia with Lewy bodies, multiple system atrophy (MSA). Cerebral hypertensive vascular hyalinosis (HVH) was used as negative control. Significant agreement between amyloid histochemical properties and FDDNP labeling of the deposits was established. FDDNP labeling showed high positive predictive value for birefringence in senile plaques and NFTs in AD, prion plaques and amyloid deposits in CAA. No FDDNP labeled structures were observed in HVH, PSP, PiD or MSA tissue sections. Our findings may be of significant value for the detection of neuropathological aggregates with [F-18]FDDNP in some of these disorders in the living brain of human subjects.

  5. Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases.

    Science.gov (United States)

    Mendelsohn, Andrew R; Larrick, James W

    2013-12-01

    Decline of cognition and increasing risk of neurodegenerative diseases are major problems associated with aging in humans. Of particular importance is how the brain removes potentially toxic biomolecules that accumulate with normal neuronal function. Recently, a biomolecule clearance system using convective flow between the cerebrospinal fluid (CSF) and interstitial fluid (ISF) to remove toxic metabolites in the brain was described. Xie and colleagues now report that in mice the clearance activity of this so-called "glymphatic system" is strongly stimulated by sleep and is associated with an increase in interstitial volume, possibly by shrinkage of astroglial cells. Moreover, anesthesia and attenuation of adrenergic signaling can activate the glymphatic system to clear potentially toxic proteins known to contribute to the pathology of Alzheimer disease (AD) such as beta-amyloid (Abeta). Clearance during sleep is as much as two-fold faster than during waking hours. These results support a new hypothesis to answer the age-old question of why sleep is necessary. Glymphatic dysfunction may pay a hitherto unsuspected role in the pathogenesis of neurodegenerative diseases as well as maintenance of cognition. Furthermore, clinical studies suggest that quality and duration of sleep may be predictive of the onset of AD, and that quality sleep may significantly reduce the risk of AD for apolipoprotein E (ApoE) ɛ4 carriers, who have significantly greater chances of developing AD. Further characterization of the glymphatic system in humans may lead to new therapies and methods of prevention of neurodegenerative diseases. A public health initiative to ensure adequate sleep among middle-aged and older people may prove useful in preventing AD, especially in apolipoprotein E (ApoE) ɛ4 carriers.

  6. Role of Sex Hormones on Brain Mitochondrial Function, with Special Reference to Aging and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Pauline Gaignard

    2017-12-01

    Full Text Available The mitochondria have a fundamental role in both cellular energy supply and oxidative stress regulation and are target of the effects of sex steroids, particularly the neuroprotective ones. Aging is associated with a decline in the levels of different steroid hormones, and this decrease may underline some neural dysfunctions. Besides, modifications in mitochondrial functions associated with aging processes are also well documented. In this review, we will discuss studies that describe the modifications of brain mitochondrial function and of steroid levels associated with physiological aging and with neurodegenerative diseases. A special emphasis will be placed on describing and discussing our recent findings concerning the concomitant study of mitochondrial function (oxidative phosphorylation, oxidative stress and brain steroid levels in both young (3-month-old and aged (20-month-old male and female mice.

  7. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Tansey Malú G

    2008-10-01

    Full Text Available Abstract The role of tumor necrosis factor (TNF as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1 is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF or transmembrane TNF (tmTNF, with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD, Parkinson's (PD, amyotrophic lateral sclerosis (ALS, and multiple sclerosis (MS. The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS.

  8. Is there evidence for neurodegenerative change following traumatic brain injury in children and youth? A scoping review.

    Directory of Open Access Journals (Sweden)

    Michelle eKeightley

    2014-03-01

    Full Text Available While generalized cerebral atrophy and neurodegenerative change following traumatic brain injury (TBI is well recognized in adults, it remains comparatively understudied in the pediatric population, suggesting that research should address the potential for neurodegenerative change in children and youth following TBI. This focused review examines original research findings documenting evidence for neurodegenerative change following TBI of all severities in children and youth. Our relevant inclusion and exclusion criteria identified a total of 16 articles for review. Taken together, the studies reviewed suggest there is evidence for long-term neurodegenerative change following TBI in children and youth. In particular both cross-sectional and longitudinal studies revealed volume loss in selected brain regions including the hippocampus, amygdala, globus pallidus, thalamus, periventricular white matter, cerebellum and brain stem as well as overall decreased whole brain volume and increased CSF and ventricular space. Diffusion Tensor Imaging (DTI studies also report evidence for decreased cellular integrity, particularly in the corpus callosum. Sensitivity of the hippocampus and deep limbic structures in pediatric populations are similar to findings in the adult literature and we consider the data supporting these changes as well as the need to investigate the possibility of neurodegenerative onset in childhood associated with mTBI.

  9. Brain transplants. A new approach to the therapy of neurodegenerative disease.

    Science.gov (United States)

    Tulipan, N

    1988-05-01

    There is now a wealth of experimental evidence to suggest that transplantation to the brain may ameliorate a variety of neurologic and endocrine disorders. Many unanswered questions remain. Chief among these questions are the duration of any salutary effects and the potential long-term risks to the host CNS. Answers to these questions will only come with carefully controlled long-term clinical studies. Given the high incidence and devastating nature of many of these diseases, such studies will have enormous scientific and social impact. Regardless of the outcome, there is the potential for a greater understanding of the pathologic mechanisms underlying neurodegenerative diseases and, thus, the possibility that definitive therapies will be found as a result.

  10. Fetal programming of the human brain: is there a link with insurgence of neurodegenerative disorders in adulthood?

    Science.gov (United States)

    Faa, G; Marcialis, M A; Ravarino, A; Piras, M; Pintus, M C; Fanos, V

    2014-01-01

    In recent years, evidence is growing on the role played by gestational factors in shaping brain development and on the influence of intrauterine experiences on later development of neurodegenerative diseases including Parkinson's (PD) and Alzheimer's disease (AD). The nine months of intrauterine development and the first three years of postnatal life are appearing to be extremely critical for making connections among neurons and among neuronal and glial cells that will shape a lifetime of experience. Here, the multiple epigenetic factors acting during gestation - including maternal diet, malnutrition, stress, hypertension, maternal diabetes, fetal hypoxia, prematurity, low birth weight, prenatal infection, intrauterine growth restriction, drugs administered to the mother or to the baby - are reported, and their ability to modulate brain development, resulting in interindividual variability in the total neuronal and glial burden at birth is discussed. Data from recent literature suggest that prevention of neurodegeneration should be identified as the one method to halt the diffusion of neurodegenerative diseases. The "two hits" hypothesis, first introduced for PD and successfully applied to AD and other neurodegenerative human pathologies, should focus our attention on a peculiar period of our life: the intrauterine and perinatal periods. The first hit to our nervous system occurs early in life, determining a PD or AD imprinting to our brain that will condition our resistance or, alternatively, our susceptibility to develop a neurodegenerative disease later in life. In conclusion, how early life events contribute to late-life development of adult neurodegenerative diseases, including PD and AD, is emerging as a new fascinating research focus. This assumption implies that research on prevention of neurodegenerative diseases should center on events taking place early in life, during gestation and in the perinatal periods, thus presenting a new challenge to

  11. Specific Transfection of Inflamed Brain by Macrophages: A New Therapeutic Strategy for Neurodegenerative Diseases

    Science.gov (United States)

    Haney, Matthew J.; Zhao, Yuling; Harrison, Emily B.; Mahajan, Vivek; Ahmed, Shaheen; He, Zhijian; Suresh, Poornima; Hingtgen, Shawn D.; Klyachko, Natalia L.; Mosley, R. Lee; Gendelman, Howard E.; Kabanov, Alexander V.; Batrakova, Elena V.

    2013-01-01

    The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA) encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD). This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders. PMID:23620794

  12. Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases.

    Directory of Open Access Journals (Sweden)

    Matthew J Haney

    Full Text Available The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD. This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders.

  13. Measurement of Steroid Concentrations in Brain Tissue: Methodological Considerations

    Science.gov (United States)

    Taves, Matthew D.; Ma, Chunqi; Heimovics, Sarah A.; Saldanha, Colin J.; Soma, Kiran K.

    2011-01-01

    It is well recognized that steroids are synthesized de novo in the brain (neurosteroids). In addition, steroids circulating in the blood enter the brain. Steroids play numerous roles in the brain, such as influencing neural development, adult neuroplasticity, behavior, neuroinflammation, and neurodegenerative diseases such as Alzheimer’s disease. In order to understand the regulation and functions of steroids in the brain, it is important to directly measure steroid concentrations in brain tissue. In this brief review, we discuss methods for the detection and quantification of steroids in the brain. We concisely present the major advantages and disadvantages of different technical approaches at various experimental stages: euthanasia, tissue collection, steroid extraction, steroid separation, and steroid measurement. We discuss, among other topics, the potential effects of anesthesia and saline perfusion prior to tissue collection; microdissection via Palkovits punch; solid phase extraction; chromatographic separation of steroids; and immunoassays and mass spectrometry for steroid quantification, particularly the use of mass spectrometry for “steroid profiling.” Finally, we discuss the interpretation of local steroid concentrations, such as comparing steroid levels in brain tissue with those in the circulation (plasma vs. whole blood samples; total vs. free steroid levels). We also present reference values for a variety of steroids in different brain regions of adult rats. This brief review highlights some of the major methodological considerations at multiple experimental stages and provides a broad framework for designing studies that examine local steroid levels in the brain as well as other steroidogenic tissues, such as thymus, breast, and prostate. PMID:22654806

  14. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Adriana Covarrubias-Pinto

    2015-11-01

    Full Text Available Ascorbic acid is a key antioxidant of the Central Nervous System (CNS. Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders.

  15. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders.

    Science.gov (United States)

    Covarrubias-Pinto, Adriana; Acuña, Aníbal Ignacio; Beltrán, Felipe Andrés; Torres-Díaz, Leandro; Castro, Maite Aintzane

    2015-11-27

    Ascorbic acid is a key antioxidant of the Central Nervous System (CNS). Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS) generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders.

  16. Chronic traumatic encephalopathy: a neurodegenerative consequence of repetitive traumatic brain injury.

    Science.gov (United States)

    Kiernan, Patrick T; Montenigro, Philip H; Solomon, Todd M; McKee, Ann C

    2015-02-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that develops as a result of repetitive mild traumatic brain injury. Chronic traumatic encephalopathy is characterized by a unique pattern of accumulation of hyperphosphorylated tau in neurons and astrocytes. The tau abnormalities begin focally and perivascularly at the depths of the cerebral sulci, spread to the superficial layers of the adjacent cortex, and eventually become widespread throughout the medial temporal lobes, diencephalon, and brainstem. Abnormalities in 43 kDa TAR DNA-binding protein are also found in most cases of CTE. To date, CTE can only be diagnosed by postmortem neuropathological examination, although there are many ongoing research studies examining imaging techniques and biomarkers that might prove to have diagnostic utility. Currently, the incidence and prevalence of CTE are unknown, although great strides are being made to better understand the clinical symptoms and signs of CTE. Further research is critically needed to better identify the genetic and environmental risk factors for CTE as well as potential rehabilitation and therapeutic strategies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders

    Science.gov (United States)

    Covarrubias-Pinto, Adriana; Acuña, Aníbal Ignacio; Beltrán, Felipe Andrés; Torres-Díaz, Leandro; Castro, Maite Aintzane

    2015-01-01

    Ascorbic acid is a key antioxidant of the Central Nervous System (CNS). Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS) generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders. PMID:26633354

  18. Brain tissue banking for stem cells for our future.

    Science.gov (United States)

    Palmero, Emily; Palmero, Sheryl; Murrell, Wayne

    2016-12-19

    In our lab we study neurogenesis and the development of brain tumors. We work towards treatment strategies for glioblastoma and towards using autologous neural stem cells for tissue regeneration strategies for brain damage and neurodegenerative disorders. It has been our policy to try to establish living cell cultures from all human biopsy material that we obtain. We hypothesized that small pieces of brain tissue could be cryopreserved and that live neural stem cells could be recovered at a later time. DMSO has been shown to possess a remarkable ability to diffuse through cell membranes and pass into cell interiors. Its chemical properties prevent the formation of damaging ice crystals thus allowing cell storage at or below -180 C. We report here a protocol for successful freezing of small pieces of tissue derived from human brain and human brain tumours. Virtually all specimens could be successfully revived. Assays of phenotype and behaviour show that the cell cultures derived were equivalent to those cultures previously derived from fresh tissue.

  19. [Neuropathological diagnosis of neurodegenerative and dementia diseases].

    Science.gov (United States)

    Kretzschmar, H A; Neumann, M

    2000-09-01

    Neurodegenerative and dementing disorders such as Parkinson disease and Alzheimer disease are among the most common diseases of advanced age. Despite progress in the clinical diagnosis of neurodegenerative disorders, definite diagnosis for most of these disorders is still possible only by neuropathological examination of the brain. The neuropathological diagnosis and classification of neurodegenerative disorders has made clear advances in recent years, particularly due to the results of genetic and biochemical studies, resulting in the development of new disease-specific antibodies. Internationally recognized consensus criteria for most neurodegenerative disorders allow a definite and standardized diagnosis to be made. To obtain further knowledge about the etiopathogenesis, particularly with regard to new therapeutic strategies, studies with clinically and neuropathologically well-documented cases are needed. The project "Brain-Net" has therefore been established with the aim of setting up a German Brain and Tissue Bank for Diseases of the Central Nervous System. The project is funded by the Federal Ministry of Education and Research.

  20. DNA damage in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Coppedè, Fabio, E-mail: fabio.coppede@med.unipi.it; Migliore, Lucia, E-mail: lucia.migliore@med.unipi.it

    2015-06-15

    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  1. BRAIM: A computer-aided diagnosis system for neurodegenerative diseases and brain lesion monitoring from volumetric analyses.

    Science.gov (United States)

    Morales, Sandra; Bernabeu-Sanz, Angela; López-Mir, Fernando; González, Pablo; Luna, Luis; Naranjo, Valery

    2017-07-01

    This paper presents BRAIM, a computer-aided diagnosis (CAD) system to help clinicians in diagnosing and treatment monitoring of brain diseases from magnetic resonance image processing. BRAIM can be used for early diagnosis of neurodegenerative diseases such as Parkinson, Alzheimer or Multiple Sclerosis and also for brain lesion diagnosis and monitoring. The developed CAD system includes different user-friendly tools for segmenting and determining whole brain and brain structure volumes in an easy and accurate way. Specifically, three types of measurements can be performed: (1) total volume of white, gray matter and cerebrospinal fluid; (2) brain structure volumes (volume of putamen, thalamus, hippocampus and caudate nucleus); and (3) brain lesion volumes. As a proof of concept, some study cases were analyzed with the presented system achieving promising results. In addition to be used to quantify treatment effectiveness in patients with brain lesions, it was demonstrated that BRAIM is able to classify a subject according to the brain volume measurements using as reference a healthy control database created for this purpose. The CAD system presented in this paper simplifies the daily work of clinicians and provides them with objective and quantitative volume data for prospective and retrospective analyses. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Are there roles for brain cell senescence in aging and neurodegenerative disorders?

    Science.gov (United States)

    Tan, Florence C C; Hutchison, Emmette R; Eitan, Erez; Mattson, Mark P

    2014-12-01

    The term cellular senescence was introduced more than five decades ago to describe the state of growth arrest observed in aging cells. Since this initial discovery, the phenotypes associated with cellular senescence have expanded beyond growth arrest to include alterations in cellular metabolism, secreted cytokines, epigenetic regulation and protein expression. Recently, senescence has been shown to play an important role in vivo not only in relation to aging, but also during embryonic development. Thus, cellular senescence serves different purposes and comprises a wide range of distinct phenotypes across multiple cell types. Whether all cell types, including post-mitotic neurons, are capable of entering into a senescent state remains unclear. In this review we examine recent data that suggest that cellular senescence plays a role in brain aging and, notably, may not be limited to glia but also neurons. We suggest that there is a high level of similarity between some of the pathological changes that occur in the brain in Alzheimer's and Parkinson's diseases and those phenotypes observed in cellular senescence, leading us to propose that neurons and glia can exhibit hallmarks of senescence previously documented in peripheral tissues.

  3. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Amin Mottahedin

    2017-07-01

    Full Text Available The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function. In this article, we will review the role of glia cells in synaptic physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following perinatal inflammatory challenges and potential implications for neurodevelopmental and neurodegenerative disorders.

  4. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders.

    Science.gov (United States)

    Romanucci, Mariarita; Della Salda, Leonardo

    2015-01-01

    Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.

  5. Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases.

    Science.gov (United States)

    Youssef, S A; Capucchio, M T; Rofina, J E; Chambers, J K; Uchida, K; Nakayama, H; Head, E

    2016-03-01

    According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases. © The Author(s) 2016.

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

    Science.gov (United States)

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

    2015-05-01

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

  7. Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should it be classified together as traumatic encephalopathy?

    Science.gov (United States)

    Washington, Patricia M.; Villapol, Sonia; Burns, Mark P.

    2015-01-01

    Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer’s disease (AD), while mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position—examining epidemiological and case-control human studies, neuropathological evidence, and preclinical studies. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson’s disease. Further, human post-mortem studies on either single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a ‘polypathology’. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI are viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. PMID:26091850

  8. Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

    Science.gov (United States)

    Washington, Patricia M; Villapol, Sonia; Burns, Mark P

    2016-01-01

    Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disease (AD), while repeat mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position-examining epidemiological and case control human studies, neuropathological evidence, and preclinical data. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson's disease. Further, human post-mortem studies on both single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a 'polypathology'. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI is viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Proteomic analysis of the human brain in Huntington's Disease indicates pathogenesis by molecular processes linked to other neurodegenerative diseases and to type-2 diabetes.

    Science.gov (United States)

    Schönberger, Sarah J; Jezdic, Dina; Faull, Richard L M; Cooper, Garth J S

    2013-01-01

    Huntington's disease (HD) is a neurodegenerative disorder in which the aetiological defect is inherited or spontaneous mutation in the HTT gene, which alters the structure of the corresponding huntingtin protein and initiates a pathogenetic cascade that ultimately leads to or causes dementia. Here our main objective was to elucidate further the pathogenic processes that underlie neurodegeneration in HD. By using two-dimensional gel electrophoresis we performed a proteomic case-control study of two brain regions in post-mortem human tissue from seven well-characterized HD patients and eight matched controls. In the middle frontal gyrus we identified twenty-two differentially-expressed proteins whereas by contrast in visual cortex only seven were altered. Twenty of these proteins have not to our knowledge been associated with the pathogenesis of HD before although all functional families implicated have previously been linked to other neurodegenerative diseases. Most of the proteins identified play roles in cell stress responses, apoptosis, metabolic regulation linked to type-2 diabetes, the ubiquitin-proteasome system, or protein trafficking/endocytosis. We propose that HTT mutations lead to or cause functional impairment of these pathways and that simultaneous restoration of their functions by targeted pharmacotherapy could ameliorate the signs and symptoms of HD. These studies provide a unique illustration of the interlinked disease processes that underpin/contribute to the pathogenesis of neurodegeneration in a genetically-mediated disorder of protein structure, and provide a signpost towards the design of new therapeutic interventions.

  10. The Identification of Aluminum in Human Brain Tissue Using Lumogallion and Fluorescence Microscopy.

    Science.gov (United States)

    Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

    2016-10-18

    Aluminum in human brain tissue is implicated in the etiologies of neurodegenerative diseases including Alzheimer's disease. While methods for the accurate and precise measurement of aluminum in human brain tissue are widely acknowledged, the same cannot be said for the visualization of aluminum. Herein we have used transversely-heated graphite furnace atomic absorption spectrometry to measure aluminum in the brain of a donor with Alzheimer's disease, and we have developed and validated fluorescence microscopy and the fluor lumogallion to show the presence of aluminum in the same tissue. Aluminum is observed as characteristic orange fluorescence that is neither reproduced by other metals nor explained by autofluorescence. This new and relatively simple method to visualize aluminum in human brain tissue should enable more rigorous testing of the aluminum hypothesis of Alzheimer's disease (and other neurological conditions) in the future.

  11. Trace element determinations in brain tissues from normal and clinically demented individuals

    Energy Technology Data Exchange (ETDEWEB)

    Saiki, Mitiko; Genezini, Frederico A., E-mail: mitiko@ipen.br, E-mail: fredzini@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro do Reator de Pesquisas; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson, E-mail: renataleite@usp.br, E-mail: lea@grinberg.com.br, E-mail: reloah@usp.br, E-mail: farfel@usp.br, E-mail: csuemoto@gmail.com, E-mail: cpasqua@usp.br, E-mail: wijac@usp.br [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Fac. de Medicina

    2013-07-01

    Studies on trace element levels in human brains under normal and pathological conditions have indicated a possible correlation between some trace element concentrations and neurodegenerative diseases. In this study, analysis of brain tissues was carried out to investigate if there are any differences in elemental concentrations between brain tissues from a normal population above 50 years of age presenting Clinical Dementia Rating (CDR) equal to zero (CDR=0) and that cognitively affected population ( CDR=3). The tissues were dissected, ground, freeze-dried and then analyzed by instrumental neutron activation analysis. Samples and elemental standards were irradiated in a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. The induced gamma ray activities were measured using a hyperpure Ge detector coupled to a gamma ray spectrometer. The one-way ANOVA test (p< 0.05) was used to compare the results. All the elements determined in the hippocampus brain region presented differences between the groups presenting CDR=0 and CDR=3. In the case of frontal region only the elements Na, Rb and Zn showed differences between these two groups. These findings proved the correlation between elemental levels present in brain tissues neurodegenerative diseases. Biological standard reference materials SRM 1566b Oyster Tissue and SRM 1577b Bovine Liver analyzed for quality control indicated good accuracy and precision of the results. (author)

  12. Temperature Effects on Brain Tissue in Compression

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.04.005

    2013-01-01

    Extensive research has been carried out for at least 50 years to understand the mechanical properties of brain tissue in order to understand the mechanisms of traumatic brain injury (TBI). The observed large variability in experimental results may be due to the inhomogeneous nature of brain tissue and to the broad range of test conditions. However, test temperature is also considered as one of the factors influencing the properties of brain tissue. In this research, the mechanical properties of porcine brain have been investigated at 22C (room temperature) and at 37C (body temperature) while maintaining a constant preservation temperature of approximately 4-5C. Unconfined compression tests were performed at dynamic strain rates of 30 and 50/s using a custom made test apparatus. There was no significant difference (p = 0.8559 - 0.9290) between the average engineering stresses of the brain tissue at the two different temperature conditions. The results of this study should help to understand the behavior of bra...

  13. Low-dose, continuous enzyme replacement therapy ameliorates brain pathology in the neurodegenerative lysosomal disorder mucopolysaccharidosis type IIIA.

    Science.gov (United States)

    King, Barbara; Hassiotis, Sofia; Rozaklis, Tina; Beard, Helen; Trim, Paul J; Snel, Marten F; Hopwood, John J; Hemsley, Kim M

    2016-05-01

    Repeated replacement of sulphamidase via cerebrospinal fluid injection is an effective treatment for pathological changes in the brain in mice and dogs with the lysosomal storage disorder, mucopolysaccharidosis type IIIA (MPS IIIA). Investigational trials of this approach are underway in children with this condition, however, infusions require attendance at a specialist medical facility. We sought to comprehensively evaluate the effectiveness of sustained-release (osmotic pump-delivered) enzyme replacement therapy in murine MPS IIIA as this method, if applied to humans, would require only subcutaneous administration of enzyme once the pump was installed. Six-week-old MPS IIIA and unaffected mice were implanted with subcutaneous mini-osmotic pumps connected to an infusion cannula directed at the right lateral ventricle. Either recombinant human sulphamidase or vehicle were infused over the course of 7 weeks, with pumps replaced part-way through the experimental period. We observed near-normalisation of primarily stored substrate (heparan sulphate) in both hemispheres of the MPS IIIA brain and cervical spinal cord, as determined using tandem mass spectrometry. Immunohistochemistry indicated a reduction in secondarily stored GM 3 ganglioside and neuroinflammatory markers. A bias towards the infusion side was seen in some, but not all outcomes. The recombinant enzyme appears stable under pump-like conditions for at least 1 month. Given that infusion pumps are in clinical use in other nervous system disorders, e.g. for treatment of spasticity or brain tumours, this treatment method warrants consideration for testing in large animal models of MPS IIIA and other lysosomal storage disorders that affect the brain. Clinical trials of repeated injection of replacement enzyme into CSF are underway in patients with the inherited neurodegenerative disorder mucopolysaccharidosis type IIIA. In this pre-clinical study, we examined an alternative approach - slow, continual infusion

  14. On the Central Role of Brain Connectivity in Neurodegenerative Disease Progression

    Directory of Open Access Journals (Sweden)

    Yasser eIturria Medina

    2015-05-01

    Full Text Available Increased brain connectivity, in all its variants, is often considered an evolutionary advantage by mediating complex sensorimotor function and higher cognitive faculties. Interaction among components at all spatial scales, including genes, proteins, neurons, local neuronal circuits and macroscopic brain regions, are indispensable for such vital functions. However, a growing body of evidence suggests that, from the microscopic to the macroscopic levels, such connections might also be a conduit for in intra-brain disease spreading. For instance, cell-to-cell misfolded proteins transmission and neuronal toxicity are prominent connectivity-mediated factors in aging and neurodegeneration. This article offers an overview of connectivity dysfunctions associated with neurodegeneration, with a specific focus on how these may be central to both normal aging and the neuropathologic degenerative progression.

  15. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders

    NARCIS (Netherlands)

    Kos, Claire; van Tol, Marie-Jose; Marsman, Jan-Bernard C.; Knegtering, Henderikus; Aleman, Andre

    2016-01-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar

  16. Identification, tissue distribution and evaluation of brain ...

    Indian Academy of Sciences (India)

    Prakash

    mechanisms regulating feeding in order to improve its performance in captivity. The objectives of this study were to clone NPY cDNA, evaluate the mRNA levels in different tissues of flounder, and also evaluate brain NPY expression to associate food intake with NPY expression levels. A 597 bp NPY cDNA was cloned from ...

  17. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...

  18. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders.

    Science.gov (United States)

    Kos, Claire; van Tol, Marie-José; Marsman, Jan-Bernard C; Knegtering, Henderikus; Aleman, André

    2016-10-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. Copyright © 2016. Published by Elsevier Ltd.

  19. Cyanotoxins at low doses induce apoptosis and inflammatory effects in murine brain cells: Potential implications for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Larissa Takser

    2016-01-01

    Full Text Available Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study investigated whether mammalian brain and immune cells can be a target of certain cyanotoxins, at doses approximating those in the guideline levels for drinking water, either alone or in mixtures. We examined the effects on cellular viability, apoptosis and inflammation signalling of several toxins on murine macrophage-like RAW264.7, microglial BV-2 and neuroblastoma N2a cell lines. We tested cylindrospermopsin (CYN, microcystin-LR (MC-LR, and anatoxin-a (ATX-a, individually as well as their mixture. In addition, we studied the neurotoxins β-N-methylamino-l-alanine (BMAA and its isomer 2,4-diaminobutyric acid (DAB, as well as the mixture of both. Cellular viability was determined by the MTT assay. Apoptosis induction was assessed by measuring the activation of caspases 3/7. Cell death and inflammation are the hallmarks of neurodegenerative diseases. Thus, our final step was to quantify the expression of a major proinflammatory cytokine TNF-α by ELISA. Our results show that CYN, MC-LR and ATX-a, but not BMAA and DAB, at low doses, especially when present in a mixture at threefold less concentrations than individual compounds are 3–15 times more potent at inducing apoptosis and inflammation. Our results suggest that common cyanotoxins at low doses have a potential to induce inflammation and apoptosis in immune and brain cells. Further research of the neuroinflammatory effects of these compounds in vivo is needed to improve safety limit levels for cyanotoxins in drinking water and food.

  20. Non-invasive Brain Stimulation in the Treatment of Post-stroke and Neurodegenerative Aphasia: Parallels, Differences, and Lessons Learned

    Science.gov (United States)

    Norise, Catherine; Hamilton, Roy H.

    2017-01-01

    Numerous studies over the span of more than a decade have shown that non-invasive brain stimulation (NIBS) techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can facilitate language recovery for patients who have suffered from aphasia due to stroke. While stroke is the most common etiology of aphasia, neurodegenerative causes of language impairment—collectively termed primary progressive aphasia (PPA)—are increasingly being recognized as important clinical phenotypes in dementia. Very limited data now suggest that (NIBS) may have some benefit in treating PPAs. However, before applying the same approaches to patients with PPA as have previously been pursued in patients with post-stroke aphasia, it will be important for investigators to consider key similarities and differences between these aphasia etiologies that is likely to inform successful approaches to stimulation. While both post-stroke aphasia and the PPAs have clear overlaps in their clinical phenomenology, the mechanisms of injury and theorized neuroplastic changes associated with the two etiologies are notably different. Importantly, theories of plasticity in post-stroke aphasia are largely predicated on the notion that regions of the brain that had previously been uninvolved in language processing may take on new compensatory roles. PPAs, however, are characterized by slow distributed degeneration of cellular units within the language system; compensatory recruitment of brain regions to subserve language is not currently understood to be an important aspect of the condition. This review will survey differences in the mechanisms of language representation between the two etiologies of aphasia and evaluate properties that may define and limit the success of different neuromodulation approaches for these two disorders. PMID:28167904

  1. Functional Brain Imaging Synthesis Based on Image Decomposition and Kernel Modeling: Application to Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Francisco J. Martinez-Murcia

    2017-11-01

    Full Text Available The rise of neuroimaging in research and clinical practice, together with the development of new machine learning techniques has strongly encouraged the Computer Aided Diagnosis (CAD of different diseases and disorders. However, these algorithms are often tested in proprietary datasets to which the access is limited and, therefore, a direct comparison between CAD procedures is not possible. Furthermore, the sample size is often small for developing accurate machine learning methods. Multi-center initiatives are currently a very useful, although limited, tool in the recruitment of large populations and standardization of CAD evaluation. Conversely, we propose a brain image synthesis procedure intended to generate a new image set that share characteristics with an original one. Our system focuses on nuclear imaging modalities such as PET or SPECT brain images. We analyze the dataset by applying PCA to the original dataset, and then model the distribution of samples in the projected eigenbrain space using a Probability Density Function (PDF estimator. Once the model has been built, we can generate new coordinates on the eigenbrain space belonging to the same class, which can be then projected back to the image space. The system has been evaluated on different functional neuroimaging datasets assessing the: resemblance of the synthetic images with the original ones, the differences between them, their generalization ability and the independence of the synthetic dataset with respect to the original. The synthetic images maintain the differences between groups found at the original dataset, with no significant differences when comparing them to real-world samples. Furthermore, they featured a similar performance and generalization capability to that of the original dataset. These results prove that these images are suitable for standardizing the evaluation of CAD pipelines, and providing data augmentation in machine learning systems -e.g. in deep

  2. Metabolomics studies in brain tissue: A review.

    Science.gov (United States)

    Gonzalez-Riano, Carolina; Garcia, Antonia; Barbas, Coral

    2016-10-25

    Brain is still an organ with a composition to be discovered but beyond that, mental disorders and especially all diseases that curse with dementia are devastating for the patient, the family and the society. Metabolomics can offer an alternative tool for unveiling new insights in the discovery of new treatments and biomarkers of mental disorders. Until now, most of metabolomic studies have been based on biofluids: serum/plasma or urine, because brain tissue accessibility is limited to animal models or post mortem studies, but even so it is crucial for understanding the pathological processes. Metabolomics studies of brain tissue imply several challenges due to sample extraction, along with brain heterogeneity, sample storage, and sample treatment for a wide coverage of metabolites with a wide range of concentrations of many lipophilic and some polar compounds. In this review, the current analytical practices for target and non-targeted metabolomics are described and discussed with emphasis on critical aspects: sample treatment (quenching, homogenization, filtration, centrifugation and extraction), analytical methods, as well as findings considering the used strategies. Besides that, the altered analytes in the different brain regions have been associated with their corresponding pathways to obtain a global overview of their dysregulation, trying to establish the link between altered biological pathways and pathophysiological conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Mechanical characterization of human brain tissue.

    Science.gov (United States)

    Budday, S; Sommer, G; Birkl, C; Langkammer, C; Haybaeck, J; Kohnert, J; Bauer, M; Paulsen, F; Steinmann, P; Kuhl, E; Holzapfel, G A

    2017-01-15

    Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed

  4. Influence of liver pathology on markers of postmortem brain tissue quality.

    Science.gov (United States)

    Sheedy, Donna; Say, Meichien; Stevens, Julia; Harper, Clive G; Kril, Jillian J

    2012-01-01

    Postmortem brain tissue provides an important resource to investigate various brain disorders, including those resulting from the effects of alcohol abuse. Unlike the traditionally recognized confounders to tissue quality (e.g., coma, hypoxia), our understanding of the effects of liver disease is incomplete. The aim of this study was to determine the effects of liver pathology, and in particular cirrhosis resulting in hepatic encephalopathy (HE), on 2 postmortem brain tissue quality markers, brain pH and RNA integrity. We measured tissue quality markers in a cohort of alcohol abuse and control cases collected by the NSW Tissue Resource Centre. Cerebellar tissue was used to evaluate both brain pH and RNA quality (as indicated by the RNA integrity number: RIN). A histological assessment was performed on each case to exclude coexisting pathologies (e.g., cerebrovascular disease, hypoxic encephalopathy, neurodegenerative disease) and to assess the presence or absence of HE. Autopsy reports were reviewed for liver pathology and toxicology. Analysis revealed that cases of alcohol abuse had a lower mean (±SD) brain pH, 6.46 (±0.3) as compared with the control mean 6.64 (±0.2). The mean RIN for the alcohol abuse group was 6.97 (±1.3) and controls 7.66 (±0.5). The severity of liver pathology affected both brain pH (p brain pH (p = 0.0019). The results show that the presence of cirrhosis and, more so, HE reduces the pH and RIN of postmortem brain tissue. Copyright © 2011 by the Research Society on Alcoholism.

  5. Cytochrome c release from rat brain mitochondria is proportional to the mitochondrial functional deficit: implications for apoptosis and neurodegenerative disease.

    Science.gov (United States)

    Clayton, Rebecca; Clark, John B; Sharpe, Martyn

    2005-02-01

    Apoptosis may be initiated in neurons via mitochondrial release of the respiratory protein, cytochrome c. The mechanism of cytochrome c release has been studied extensively, but little is known about its dynamics. It has been claimed that release is all-or-none, however, this is not consistent with accumulating evidence of cytosolic mechanisms for 'buffering' cytochrome c. This study has attempted to model an underlying disease pathology, rather than inducing apoptosis directly. The model adopted was diminished activity of the mitochondrial respiratory chain complex I, a recognized feature of Parkinson's disease. Titration of rat brain mitochondrial respiratory function, with the specific complex I inhibitor rotenone, caused proportional release of cytochrome c from isolated synaptic and non-synaptic mitochondria. The mechanism of release was mediated, at least in part, by the mitochondrial outer membrane component Bak and voltage-dependent anion channel rather than non-specific membrane rupture. Furthermore, preliminary data were obtained demonstrating that in primary cortical neurons, titration with rotenone induced cytochrome c release that was subthreshold for the induction of apoptosis. Implications for the therapy of neurodegenerative diseases are discussed.

  6. Effect of vitro preservation on mechanical properties of brain tissue

    Science.gov (United States)

    Zhang, Wei; Liu, Yi-fan; Liu, Li-fu; Niu, Ying; Ma, Jian-li; Wu, Cheng-wei

    2017-05-01

    To develop the protective devices for preventing traumatic brain injuries, it requires the accurate characterization of the mechanical properties of brain tissue. For this, it necessary to elucidate the effect of vitro preservation on the mechanical performance of brain tissue as usually the measurements are carried out in vitro. In this paper, the thermal behavior of brain tissue preserved for various period of time was first investigated and the mechanical properties were also measured. Both reveals the deterioration with prolonged preservation duration. The observations of brain tissue slices indicates the brain tissue experiences karyorrhexis and karyorrhexis in sequence, which accounts for the deterioration phenomena.

  7. First-in-class thyrotropin-releasing hormone (TRH)-based compound binds to a pharmacologically distinct TRH receptor subtype in human brain and is effective in neurodegenerative models.

    Science.gov (United States)

    Kelly, Julie A; Boyle, Noreen T; Cole, Natalie; Slator, Gillian R; Colivicchi, M Alessandra; Stefanini, Chiara; Gobbo, Oliviero L; Scalabrino, Gaia A; Ryan, Sinead M; Elamin, Marwa; Walsh, Cathal; Vajda, Alice; Goggin, Margaret M; Campbell, Matthew; Mash, Deborah C; O'Mara, Shane M; Brayden, David J; Callanan, John J; Tipton, Keith F; Della Corte, Laura; Hunter, Jackie; O'Boyle, Kathy M; Williams, Carvell H; Hardiman, Orla

    2015-02-01

    JAK4D, a first-in-class thyrotropin-releasing hormone (TRH)-based compound, is a prospective therapeutic candidate offering a multifaceted approach to treating neurodegeneration and other CNS conditions. The purpose of these studies was to determine the ability of JAK4D to bind to TRH receptors in human brain and to evaluate its neuropharmacological effects in neurodegenerative animal models. Additionally, JAK4D brain permeation was examined in mouse, and initial toxicology was assessed in vivo and in vitro. We report that JAK4D bound selectively with nanomolar affinity to native TRH receptors in human hippocampal tissue and showed for the first time that these receptors are pharmacologically distinct from TRH receptors in human pituitary, thus revealing a new TRH receptor subtype which represents a promising neurotherapeutic target in human brain. Systemic administration of JAK4D elicited statistically significant and clinically-relevant neuroprotective effects in three established neurodegenerative animal models: JAK4D reduced cognitive deficits when administered post-insult in a kainate (KA)-induced rat model of neurodegeneration; it protected against free radical release and neuronal damage evoked by intrastriatal microdialysis of KA in rat; and it reduced motor decline, weight loss, and lumbar spinal cord neuronal loss in G93A-SOD1 transgenic Amyotrophic Lateral Sclerosis mice. Ability to cross the blood-brain barrier and a clean initial toxicology profile were also shown. In light of these findings, JAK4D is an important tool for investigating the hitherto-unidentified central TRH receptor subtype reported herein and an attractive therapeutic candidate for neurodegenerative disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Large cerebral perfusion defects observed in brain perfusion SPECT may herald psychiatric or neurodegenerative diseases of transient global amnesia patients

    Energy Technology Data Exchange (ETDEWEB)

    So, Young; Kim, Hahn Young; Roh, Hong Gee; Han, Seol Heui [Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Transient global amnesia (TGA) is a memory disorder characterized by an episode of antegrade amnesia and bewilderment which persists for several hours. We analyzed brain perfusion SPECT findings and clinical outcome of patients who suffered from TGA. From September 2005 to August 2007, 12 patients underwent Tc-99m ECD brain perfusion SPECT for neuroimaging of TGA. All patients also underwent MRI and MRA including DWI (MRI). Among them, 10 patients who could be chased more than 6 months were included in this study. Their average age was 60.74.0 yrs (M: F = 2: 8) and the average duration of amnesia was 4.42.2 hrs (1 hr {approx} 7 hrs). Duration from episode of amnesia to SPECT was 4.32.4 days (1{approx}9 days). Precipitating factors could be identified in 6 patients: emotional stress 3, hair dyeing 1, taking a nap 1 and angioplasty 1. SPECT and MRI was visually assessed, No cerebral perfusion defect was observed on SPECT in 3 patients and their clinical outcome was all good. Among 7 patients who had cerebral perfusion defects on SPECT, 3 patients had good clinical outcome, while others did not: one had hypercholesterolemia, another had depression, and 2 patients with cerebral perfusion defects at both temporoparetal cortex was later diagnosed as early Alzheimer's disease (AD) and mild cognitive impairment (MCI). MRI was negative in 6 patients and 3 of them had excellent clinical outcome while other 3 were diagnosed as hypercholesterolemia, early AD and MCI. Among 4 patients with positive MRI, 3 showed good clinical outcome and their MRI showed lesions at medial temporal cortex and/or vertebral artery. One patient with microcalcification at left putamen was diagnosed to have depression. Large cerebral perfusion defects on SPECT may herald psychiatric or neurodegenerative diseases of transient global amnesia patients which usually shows negative MRI.

  9. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease.

    Science.gov (United States)

    Levesque, Shannon; Surace, Michael J; McDonald, Jacob; Block, Michelle L

    2011-08-24

    Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months. DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m³ significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m³ and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m³) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m³ exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.

  10. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    McDonald Jacob

    2011-08-01

    Full Text Available Abstract Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3 by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3 in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may

  11. Adaptive online learning based tissue segmentation of MR brain images

    NARCIS (Netherlands)

    Damkat, C.

    2007-01-01

    The aging population in the European Union and the US has increased the importance of research in neurodegenerative diseases. Imaging plays an essential role in this endeavor by providing insight to the intricate cellular and inter-cellular processes in living tissues that will otherwise be

  12. Viscoelastic parameter identification of human brain tissue.

    Science.gov (United States)

    Budday, S; Sommer, G; Holzapfel, G A; Steinmann, P; Kuhl, E

    2017-10-01

    Understanding the constitutive behavior of the human brain is critical to interpret the physical environment during neurodevelopment, neurosurgery, and neurodegeneration. A wide variety of constitutive models has been proposed to characterize the brain at different temporal and spatial scales. Yet, their model parameters are typically calibrated with a single loading mode and fail to predict the behavior under arbitrary loading conditions. Here we used a finite viscoelastic Ogden model with six material parameters-an elastic stiffness, two viscoelastic stiffnesses, a nonlinearity parameter, and two viscous time constants-to model the characteristic nonlinearity, conditioning, hysteresis and tension-compression asymmetry of the human brain. We calibrated the model under shear, shear relaxation, compression, compression relaxation, and tension for four different regions of the human brain, the cortex, basal ganglia, corona radiata, and corpus callosum. Strikingly, unconditioned gray matter with 0.36kPa and white matter with 0.35kPa were equally stiff, whereas conditioned gray matter with 0.52kPa was three times stiffer than white matter with 0.18kPa. While both unconditioned viscous time constants were larger in gray than in white matter, both conditioned constants were smaller. These rheological differences suggest a different porosity between both tissues and explain-at least in part-the ongoing controversy between reported stiffness differences in gray and white matter. Our unconditioned and conditioned parameter sets are readily available for finite element simulations with commercial software packages that feature Ogden type models at finite deformations. As such, our results have direct implications on improving the accuracy of human brain simulations in health and disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

    Energy Technology Data Exchange (ETDEWEB)

    Diniz, P.R.B.; Brum, D.G. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Dept. de Neurociencias e Ciencias do Comportamento; Santos, A. C. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Dept. de Clinica Medica; Murta-Junior, L.O.; Araujo, D.B. de, E-mail: murta@usp.b [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras. Dept. de Fisica e Matematica

    2010-01-15

    The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously. (author)

  14. Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

    Directory of Open Access Journals (Sweden)

    P.R.B. Diniz

    2010-01-01

    Full Text Available The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously.

  15. Gene expression Analysis of Neurons and Astrocytes Isolated by Laser Capture Microdissection from Frozen Human Brain Tissues.

    Directory of Open Access Journals (Sweden)

    Lidia Tagliafierro

    2016-08-01

    Full Text Available Different cell types and multiple cellular connections characterize the human brain. Gene expression analysis using a specific population of cells is more accurate than conducting analysis of the whole tissue homogenate, particularly in the context of neurodegenerative diseases, where a specific subset of cells is affected by the different pathology. Due to the difficulty to obtain homogenous cell populations, gene expression in specific cell-types (neurons, astrocytes, etc. has been understudied. To leverage the use of archive resources of frozen human brains in studies of neurodegenerative diseases, we developed and calibrated a method to quantify cell-type specific – neuronal, astrocytes – expression profiles of genes implicated in neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases. Archive human frozen brain tissues were used to prepare slides for rapid immunostaining using cell-specific antibodies. The immunoreactive-cells were isolated by Laser Capture Microdissection (LCM. The enrichment for a particular cell-type of interest was validated in post-analysis stage by the expression of cell-specific markers. We optimized the technique to preserve the RNA integrity, so that the RNA was suitable for downstream expression analyses. Following RNA extraction, the expression levels were determined digitally using nCounter Single Cell Gene Expression assay (NanoString Technologies®. The results demonstrated that using our optimized technique we successfully isolated single neurons and astrocytes from human frozen brain tissues and obtained RNA of a good quality that was suitable for mRNA expression analysis. We present here new advancements compared to previous reported methods, which improve the method’s feasibility and its applicability for a variety of downstream molecular analyses. Our new developed method can be implemented in genetic and functional genomic research of neurodegenerative diseases and has the

  16. Robotic multimodality stereotactic brain tissue identification: work in progress

    Science.gov (United States)

    Andrews, R.; Mah, R.; Galvagni, A.; Guerrero, M.; Papasin, R.; Wallace, M.; Winters, J.

    1997-01-01

    Real-time identification of tissue would improve procedures such as stereotactic brain biopsy (SBX), functional and implantation neurosurgery, and brain tumor excision. To standard SBX equipment has been added: (1) computer-controlled stepper motors to drive the biopsy needle/probe precisely; (2) multiple microprobes to track tissue density, detect blood vessels and changes in blood flow, and distinguish the various tissues being penetrated; (3) neural net learning programs to allow real-time comparisons of current data with a normative data bank; (4) three-dimensional graphic displays to follow the probe as it traverses brain tissue. The probe can differentiate substances such as pig brain, differing consistencies of the 'brain-like' foodstuff tofu, and gels made to simulate brain, as well as detect blood vessels imbedded in these substances. Multimodality probes should improve the safety, efficacy, and diagnostic accuracy of SBX and other neurosurgical procedures.

  17. [Late-onset Neurodegenerative Diseases Following Traumatic Brain Injury: Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease Secondary to TBI (AD-TBI)].

    Science.gov (United States)

    Takahata, Keisuke; Tabuchi, Hajime; Mimura, Masaru

    2016-07-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease, which is associated with mild repetitive traumatic brain injury (TBI). This long-term and progressive symptom due to TBI was initially called punch-drunk syndrome or dementia pugilistica, since it was believed to be associated with boxing. However, serial neuropathological studies of mild repetitive TBI in the last decade have revealed that CTE occurs not only in boxers but also in a wider population including American football players, wrestlers, and military personnel. CTE has gained large public interest owing to dramatic cases involving retired professional athletes wherein serious behavioral problems and tragic incidents were reported. Unlike mild repetitive TBI, a single episode of severe TBI can cause another type of late-onset neuropsychiatric disease including Alzheimer's disease (AD). Several epidemiological studies have shown that a single episode of severe TBI is one of the major risk factors of AD. Pathologically, both AD and CTE are characterized by abnormal accumulations of hyperphosphorylated tau proteins. However, recent neuropathological studies revealed that CTE demonstrates a unique pattern of tau pathology in neurons and astrocytes, and accumulation of other misfolded proteins such as TDP-43. Currently, no reliable biomarkers of late-onset neurodegenerative diseases following TBI are available, and a definitive diagnosis can be made only via postmortem neuropathological examination. Development in neuroimaging techniques such as tau and amyloid positron emission tomography imaging might not only enable early diagnosis of CTE, but also contribute to the interventions for prevention of late-onset neurodegenerative diseases following TBI. Further studies are necessary to elucidate the mechanisms of neurodegeneration in the living brain of patients with TBI.

  18. Mannitol Improves Brain Tissue Oxygenation in a Model of Diffuse Traumatic Brain Injury.

    Science.gov (United States)

    Schilte, Clotilde; Bouzat, Pierre; Millet, Anne; Boucheix, Perrine; Pernet-Gallay, Karin; Lemasson, Benjamin; Barbier, Emmanuel L; Payen, Jean-François

    2015-10-01

    Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. Experimental study. Neurosciences and physiology laboratories. Adult male Wistar rats. Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue

  19. Cost-effective elimination of lipofuscin fluorescence from formalin-fixed brain tissue by white phosphor light emitting diode array.

    Science.gov (United States)

    Sun, Yulong; Chakrabartty, Avi

    2016-12-01

    Autofluorescence of aldehyde-fixed tissues greatly hinders fluorescence microscopy. In particular, lipofuscin, an autofluorescent component of aged brain tissue, complicates fluorescence imaging of tissue in neurodegenerative diseases. Background and lipofuscin fluorescence can be reduced by greater than 90% through photobleaching using white phosphor light emitting diode arrays prior to treatment with fluorescent probes. We compared the effect of photobleaching versus established chemical quenchers on the quality of fluorescent staining in formalin-fixed brain tissue of frontotemporal dementia with tau-positive inclusions. Unlike chemical quenchers, which reduced fluorescent probe signals as well as background, photobleaching treatment had no effect on probe fluorescence intensity while it effectively reduced background and lipofuscin fluorescence. The advantages and versatility of photobleaching over established methods are discussed.

  20. Sleep in Neurodegenerative Diseases.

    Science.gov (United States)

    Iranzo, Alex

    2016-03-01

    Disorders of sleep are an integral part of neurodegenerative diseases and include insomnia, sleep-wake cycle disruption, excessive daytime sleepiness that may be manifested as persistent somnolence or sudden onset of sleep episodes, obstructive and central sleep apnea, rapid eye movement sleep behavior disorder, and restless legs syndrome. The origin of these sleep disorders is multifactorial including degeneration of the brain areas that modulate sleep, the symptoms of the disease, and the effect of medications. Treatment of sleep disorders in patients with neurodegenerative diseases should be individualized and includes behavioral therapy, sleep hygiene, bright light therapy, melatonin, hypnotics, waking-promoting agents, and continuous positive airway pressure. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. C-11-verapamil to Assess P-gp Function in Human Brain During Aging, Depression and Neurodegenerative Disease

    NARCIS (Netherlands)

    Bartels, A. L.; de Klerk, O. L.; Kortekaas, R.; de Vries, J. J.; Leenders, K. L.

    2010-01-01

    P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a wide range of substrates from the brain. This is important for maintaining loco-regional homeostasis and for protecting the brain against blood-borne toxic substances. Altered P-gp function seems

  2. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  3. Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series.

    Science.gov (United States)

    Kovacs, Gabor G; Milenkovic, Ivan; Wöhrer, Adelheid; Höftberger, Romana; Gelpi, Ellen; Haberler, Christine; Hönigschnabl, Selma; Reiner-Concin, Angelika; Heinzl, Harald; Jungwirth, Susanne; Krampla, Wolfgang; Fischer, Peter; Budka, Herbert

    2013-09-01

    Neurodegenerative diseases are characterised by neuronal loss and cerebral deposition of proteins with altered physicochemical properties. The major proteins are amyloid-β (Aβ), tau, α-synuclein, and TDP-43. Although neuropathological studies on elderly individuals have emphasised the importance of mixed pathologies, there have been few observations on the full spectrum of proteinopathies in the ageing brain. During a community-based study we performed comprehensive mapping of neurodegeneration-related proteins and vascular pathology in the brains of 233 individuals (age at death 77-87; 73 examined clinically in detail). While all brains (from individuals with and without dementia) showed some degree of neurofibrillary degeneration, Aβ deposits were observed only in 160 (68.7 %). Further pathologies included α-synucleinopathies (24.9 %), non-Alzheimer tauopathies (23.2 %; including novel forms), TDP-43 proteinopathy (13.3 %), vascular lesions (48.9 %), and others (15.1 %; inflammation, metabolic encephalopathy, and tumours). TDP-43 proteinopathy correlated with hippocampal sclerosis (p pathology (CERAD score and Braak and Braak stages, p = 0.001). The presence of one specific variable (cerebral amyloid angiopathy, Aβ parenchymal deposits, TDP-43 proteinopathy, α-synucleinopathy, vascular lesions, non-Alzheimer type tauopathy) did not increase the probability of the co-occurrence of others (p = 0.24). The number of observed pathologies correlated with AD-neuropathologic change (p pathology and α-synucleinopathy showed strong effects but lost significance when evaluated together with AD-neuropathologic change. Non-AD neurodegenerative pathologies and their combinations have been underestimated, but are frequent in reality as demonstrated here. This should be considered in diagnostic evaluation of biomarkers, and for better clinical stratification of patients.

  4. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

    2012-01-01

    Iron and copper are important co-factors for a number of enzymes in the brain, including enzymes involved in neurotransmitter synthesis and myelin formation. Both shortage and an excess of iron or copper will affect the brain. The transport of iron and copper into the brain from the circulation...... is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead......) is involved in the uptake of both iron and copper. Furthermore, copper is an essential co-factor in numerous proteins that are vital for iron homeostasis and affects the binding of iron-response proteins to iron-response elements in the mRNA of the transferrin receptor, DMT1, and ferroportin, all highly...

  5. The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner.

    Directory of Open Access Journals (Sweden)

    Glen E Kisby

    Full Text Available Methylazoxymethanol (MAM, the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O⁶-methyldeoxyguanosine lesions, O⁶-mG that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O⁶-mG DNA methyltransferase (MGMT showed elevated O⁶-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer or not (neurodegeneration. Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease.

  6. Fractality of sensations and the brain health: the theory linking neurodegenerative disorder with distortion of spatial and temporal scale-invariance and fractal complexity of the visible world

    Science.gov (United States)

    Zueva, Marina V.

    2015-01-01

    The theory that ties normal functioning and pathology of the brain and visual system with the spatial–temporal structure of the visual and other sensory stimuli is described for the first time in the present study. The deficit of fractal complexity of environmental influences can lead to the distortion of fractal complexity in the visual pathways of the brain and abnormalities of development or aging. The use of fractal light stimuli and fractal stimuli of other modalities can help to restore the functions of the brain, particularly in the elderly and in patients with neurodegenerative disorders or amblyopia. Non-linear dynamics of these physiological processes have a strong base of evidence, which is seen in the impaired fractal regulation of rhythmic activity in aged and diseased brains. From birth to old age, we live in a non-linear world, in which objects and processes with the properties of fractality and non-linearity surround us. Against this background, the evolution of man took place and all periods of life unfolded. Works of art created by man may also have fractal properties. The positive influence of music on cognitive functions is well-known. Insufficiency of sensory experience is believed to play a crucial role in the pathogenesis of amblyopia and age-dependent diseases. The brain is very plastic in its early development, and the plasticity decreases throughout life. However, several studies showed the possibility to reactivate the adult’s neuroplasticity in a variety of ways. We propose that a non-linear structure of sensory information on many spatial and temporal scales is crucial to the brain health and fractal regulation of physiological rhythms. Theoretical substantiation of the author’s theory is presented. Possible applications and the future research that can experimentally confirm or refute the theoretical concept are considered. PMID:26236232

  7. Alkali metals levels in the human brain tissue: Anatomical region differences and age-related changes.

    Science.gov (United States)

    Ramos, Patrícia; Santos, Agostinho; Pinto, Edgar; Pinto, Nair Rosas; Mendes, Ricardo; Magalhães, Teresa; Almeida, Agostinho

    2016-12-01

    The link between trace elements imbalances (both "toxic" and "essential") in the human brain and neurodegenerative disease has been subject of extensive research. More recently, some studies have highlighted the potential role of the homeostasis deregulation of alkali metals in specific brain regions as key factor in the pathogenesis of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. Using flame atomic emission spectrometry and inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of the samples, alkali metals (Na, K, Li, Rb and Cs) were determined in 14 different areas of the human brain (frontal cortex, superior and middle temporal gyri, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons, medulla and cerebellum) of adult individuals (n=42; 71±12, range: 50-101 years old) with no known history and evidence of neurodegenerative, neurological or psychiatric disorder. Potassium was found as the most abundant alkali metal, followed by Na, Rb, Cs and Li. Lithium, K and Cs distribution showed to be quite heterogeneous. On the contrary, Rb and Na appeared quite homogeneously distributed within the human brain tissue. The lowest levels of Na, K, Rb and Li were found in the brainstem (midbrain, medulla and pons) and cerebellum, while the lowest levels of Cs were found in the frontal cortex. The highest levels of K (mean±sd; range 15.5±2.5; 8.9-21.8mg/g) Rb (17.2±6.1; 3.9-32.4μg/g and Cs (83.4±48.6; 17.3-220.5ng/g) were found in putamen. The highest levels of Na and Li were found in the frontal cortex (11.6±2.4; 6.6-17.1mg/g) and caudate nucleus (7.6±4.6 2.2-21.3ng/g), respectively. Although K, Cs and Li levels appear to remain largely unchanged with age, some age-related changes were observed for Na and Rb levels in particular brain regions (namely in the hippocampus). Copyright © 2016 Elsevier GmbH. All

  8. Preventive and therapeutic potential of ascorbic acid in neurodegenerative diseases.

    Science.gov (United States)

    Moretti, Morgana; Fraga, Daiane Bittencourt; Rodrigues, Ana Lúcia S

    2017-12-01

    In this review, we summarize the involvement of ascorbic acid in neurodegenerative diseases by presenting available evidence on the behavioral and biochemical effects of this compound in animal models of neurodegeneration as well as the use of ascorbic acid as a therapeutic approach to alleviate neurodegenerative progression in clinical studies. Ascorbate, a reduced form of vitamin C, has gained interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration. In the brain, ascorbate exerts neuromodulatory functions and scavenges reactive oxygen species generated during synaptic activity and neuronal metabolism. These are important properties as redox imbalance and abnormal protein aggregation constitute central mechanisms implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Indeed, several studies have indicated an association between low serum ascorbate concentrations and neurodegeneration. Moreover, ascorbic acid is a suitable candidate for supplying either antioxidant defense or modulation of neuronal and astrocytic metabolism under neurodegenerative conditions. Ascorbic acid acts mainly by decreasing oxidative stress and reducing the formation of protein aggregates, which may contribute to the reduction of cognitive and/or motor impairments observed in neurodegenerative processes. Although several studies support a possible role of ascorbic acid administration against neurodegeneration, more researches are essential to substantiate the existing results and accelerate the knowledge in this field. © 2017 John Wiley & Sons Ltd.

  9. Measuring thrombin activity in frozen brain tissue.

    Science.gov (United States)

    Reuveni, Gilad; Golderman, Valery; Shavit-Stein, Efrat; Rosman, Yossi; Shrot, Shai; Chapman, Joab; Harnof, Sagi

    2017-12-06

    Thrombin is a coagulation factor implicated in various pathological and physiological processes in the brain, exerting beneficial and deleterious effects in a concentration-dependent manner. Measurement of thrombin activity levels in pathological animal models is needed and in some cases, because of technical considerations, only frozen samples are available. In the current study, we used a quantitative method to evaluate thrombin activity in fresh and frozen brain sections of 43 male and female adult healthy mice. We stratified data per brain section, brain hemisphere, and mouse sex. We found lower thrombin activity in frozen sections compared with fresh sections, falling within levels considered central nervous system protective in previous studies. The results suggest that fresh section thrombin activity levels in healthy mice can be extrapolated from frozen brain sections. In addition, we found varying thrombin activity across the brain sections, with maximal activity in the olfactory system and hippocampus-containing sections. Thrombin activity did not vary between males and females, or between the right and the left hemispheres, in a statistically significantly manner.

  10. Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

    Science.gov (United States)

    Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

    2017-06-22

    Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Redox Imbalance and Viral Infections in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Dolores Limongi

    2016-01-01

    Full Text Available Reactive oxygen species (ROS are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson’s disease (PD, Alzheimer’s disease (AD, and amyotrophic lateral sclerosis (ALS.

  12. Facilitated assessment of tissue loss following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Anders eHånell

    2012-03-01

    Full Text Available All experimental models of traumatic brain injury (TBI result in a progressive loss of brain tissue. The extent of tissue loss reflects the injury severity and can be measured to evaluate the potential neuroprotective effect of experimental treatments. Quantitation of tissue volumes is commonly performed using evenly spaced brain sections stained using routine histochemical methods and digitally captured. The brain tissue areas are then measured and the corresponding volumes are calculated using the distance between the sections. Measurements of areas are usually performed using a general purpose image analysis software and the results are then transferred to another program for volume calculations. To facilitate the measurement of brain tissue loss we developed novel algorithms which automatically separate the areas of brain tissue from the surrounding image background and identify the ventricles. We implemented these new algorithms by creating a new computer program (SectionToVolume which also has functions for image organization, image adjustments and volume calculations. We analyzed brain sections from mice subjected to severe focal TBI using both SectionToVolume and ImageJ, a commonly used image analysis program. The volume measurements made by the two programs were highly correlated and analysis using SectionToVolume required considerably less time. The inter-rater reliability was high. Given the extensive use of brain tissue loss measurements in TBI research, SectionToVolume will likely be a useful tool for TBI research. We therefore provide both the source code and the program as attachments to this article.

  13. Brain-gut-adipose-tissue communication pathways at a glance.

    Science.gov (United States)

    Yi, Chun-Xia; Tschöp, Matthias H

    2012-09-01

    One of the 'side effects' of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain's survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure. Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders.

  14. Brain tissue characterisation by infrared imaging in a rat glioma model.

    Science.gov (United States)

    Amharref, Nadia; Beljebbar, Abdelilah; Dukic, Sylvain; Venteo, Lydie; Schneider, Laurence; Pluot, Michel; Vistelle, Richard; Manfait, Michel

    2006-07-01

    Pathological changes associated with the development of brain tumor were investigated by Fourier transform infrared microspectroscopy (FT-IRM) with high spatial resolution. Using multivariate statistical analysis and imaging, all normal brain structures were discriminated from tumor and surrounding tumor tissues. These structural changes were mainly related to qualitative and quantitative changes in lipids (tumors contain little fat) and were correlated to the degree of myelination, an important factor in several neurodegenerative disorders. Lipid concentration and composition may thus be used as spectroscopic markers to discriminate between healthy and tumor tissues. Additionally, we have identified one peculiar structure all around the tumor. This structure could be attributed to infiltrative events, such as peritumoral oedema observed during tumor development. Our results highlight the ability of FT-IRM to identify the molecular origin that gave rise to the specific changes between healthy and diseased states. Comparison between pseudo-FT-IRM maps and histological examinations (Luxol fast blue, Luxol fast blue-cresyl violet staining) showed the complementarities of both techniques for early detection of tissue abnormalities.

  15. Pesticide residues in brain tissues of dairy cattle in Lembang

    Directory of Open Access Journals (Sweden)

    Indraningsih

    2006-03-01

    Full Text Available The use of pesticides to control plant diseases may cause residual formation in crops, its byproduct and environmental. Furthermore, the use of agriculture byproduct as animal feed may cause poisoning or residual formation in animal products. The purpose of this study is to investigate of pesticide residues in brain tissues of dairy cattle in relation to animal feed as a contamination source. Samples consisted of animal feeds (19 samples of fodder and 6 samples of feed, 31 samples of sera and 25 samples of brain tissues of dairy cattle collected from Lembang, West Java. Feeds and fodders were collected from dairy farms located in Lembang. Sera were directly collected from 31 heads of Frisien Holstein (FH cattle from the same location, while brain tissues of FH cattle were collected from a local animal slaughtering house. Pesticide residues were analysed using gas chromatography (GC. Both residues of organochlorines and organophosphates were detected from brain tissues with average residue concentration OP was 22.7 ppb and OC was 5.1 ppb and a total residue was 27.8 ppb. The pesticide residues in brain tissues are new information that should be taken into consideration since the Indonesian consumed this tissues as an oval. Although pesticides residue concentration was low, pathological changes were noted microscopically from the brain tissues including extracellular vacuolisation, focal necrosis, haemorrhages, dilatation of basement membrane without cellular infiltration. Both pesticide residues were also detected in sera, where OP (9.0 ppb was higher than OC (4.9 ppb. These pesticides were also detected in animal feeds consisting fodders and feeds. Residues of OP (12.0 ppb were higher than OC (1.8 ppb in feeds, but residues of OP (16.8 ppb were lower than OC (18.7 ppb in fodders. Although, pesticide residues in sera and brain tissues were below the maximum residue limits (MRL of fat, the presence of pesticides in brain tissues should be taken

  16. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    DEFF Research Database (Denmark)

    Mottahedin, Amin; Ardalan, Maryam; Chumak, Tetyana

    2017-01-01

    The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly...... physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following...

  17. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    Science.gov (United States)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  18. Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

    NARCIS (Netherlands)

    Youssef Hassan, Sameh; Capucchio, M T; Rofina, J E; Chambers, J K; Uchida, K; Nakayama, H; Head, E

    2016-01-01

    According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with

  19. Digital tissue and what it may reveal about the brain.

    Science.gov (United States)

    Morgan, Josh L; Lichtman, Jeff W

    2017-10-30

    Imaging as a means of scientific data storage has evolved rapidly over the past century from hand drawings, to photography, to digital images. Only recently can sufficiently large datasets be acquired, stored, and processed such that tissue digitization can actually reveal more than direct observation of tissue. One field where this transformation is occurring is connectomics: the mapping of neural connections in large volumes of digitized brain tissue.

  20. Neurobehavioral changes and activation of neurodegenerative apoptosis on long-term consumption of aspartame in the rat brain

    Directory of Open Access Journals (Sweden)

    I. Ashok

    2015-12-01

    Full Text Available Though several studies on toxic effect of aspartame metabolite have been studied, there are scanty data on whether aspartame exposure administration could release formate, a methanol metabolite thereby inducing oxidative stress and neurodegeneration in brain discrete region. To mimic the human methanol metabolism, the methotrexate (MTX treated folate deficient rats were used. Aspartame was administered orally to the MTX treated animals and was studied along with controls and MTX treated controls. Oral intubations of FDA approved 40 mg/kg b.wt aspartame were given daily for 90 days. The loco–motor activity and emotionality behavior in the aspartame treated animals showed a marked increase in the immobilization, fecal bolus with a marked decrease in ambulation, rearing, grooming. The anxiety behavior in the aspartame treated animals showed a marked decrease in percentage of open arm entry, percentage of time spent in open arm and number of head dips. It is appropriate to point out, formaldehyde and formate could have led to an increased formation of free radical in the aspartame treated animals resulting in altered neurobehavioral changes owing to neuronal oxidative damage. Aspartame induced ROS may be also linked to increased neuronal apoptosis. In this study the aspartame treated animals showed an up regulation in the apoptotic gene expression along with protein expression in the respective brain region indicating the enhancement of neuronal cell death. This study intends to corroborate that chronic aspartame consumption can alter the behavior and neurodegeneration in brain discrete regions.

  1. Transgenic Rat Model of Huntington’s Disease: A Histopathological Study and Correlations with Neurodegenerative Process in the Brain of HD Patients

    Directory of Open Access Journals (Sweden)

    Yvona Mazurová

    2014-01-01

    Full Text Available Rats transgenic for Huntington’s disease (tgHD51 CAG rats, surviving up to two years, represent an animal model of HD similar to the late-onset form of human disease. This enables us to follow histopathological changes in course of neurodegenerative process (NDP within the striatum and compare them with postmortem samples of human HD brains. A basic difference between HD pathology in human and tgHD51 rats is in the rate of NDP progression that originates primarily from slow neuronal degeneration consequently resulting in lesser extent of concomitant reactive gliosis in the brain of tgHD51 rats. Although larger amount of striatal neurons displays only gradual decrease in their size, their number is significantly reduced in the oldest tgHD51 rats. Our quantitative analysis proved that the end of the first year represents the turn in the development of morphological changes related to the progression of NDP in tgHD51 rats. Our data also support the view that all types of CNS glial cells play an important, irreplaceable role in NDP. To the best of our knowledge, our findings are the first to document that tgHD51 CAG rats can be used as a valid animal model for detailed histopathological studies related to HD in human.

  2. Coronaviruses in brain tissue from patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Dessau, R B; Lisby, G; Frederiksen, J L

    2001-01-01

    Brain tissue from 25 patients with clinically definite multiple sclerosis (MS) and as controls brain tissue from 36 patients without neurological disease was tested for the presence of human coronaviral RNA. Four PCR assays with primers specific for N-protein of human coronavirus strain 229E and ...... in the proportion of positive signals from the MS patients compared to controls. Evidence for a chronic infection with the human coronaviruses strain 229E or OC43 in brain tissue from patients with MS or controls has not been found in this study.......Brain tissue from 25 patients with clinically definite multiple sclerosis (MS) and as controls brain tissue from 36 patients without neurological disease was tested for the presence of human coronaviral RNA. Four PCR assays with primers specific for N-protein of human coronavirus strain 229E...... and three PCR assays with primers specific for the nucleocapsid protein of human coronavirus strain OC43 were performed. Sporadic positive PCR assays were observed in both patients and controls in some of the PCR assays. However, these results were not reproducible and there was no difference...

  3. Evaluating the Patterns of Aging-Related Tau Astrogliopathy Unravels Novel Insights Into Brain Aging and Neurodegenerative Diseases.

    Science.gov (United States)

    Kovacs, Gabor G; Robinson, John L; Xie, Sharon X; Lee, Edward B; Grossman, Murray; Wolk, David A; Irwin, David J; Weintraub, Dan; Kim, Christopher F; Schuck, Theresa; Yousef, Ahmed; Wagner, Stephanie T; Suh, Eunran; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Trojanowski, John Q

    2017-04-01

    The term "aging-related tau astrogliopathy" (ARTAG) describes pathological accumulation of abnormally phosphorylated tau protein in astrocytes. We evaluated the correlates of ARTAG types (i.e., subpial, subependymal, white and gray matter, and perivascular) in different neuroanatomical regions. Clinical, neuropathological, and genetic (eg, APOE ε4 allele, MAPT H1/H2 haplotype) data from 628 postmortem brains from subjects were investigated; most of the patients had been longitudinally followed at the University of Pennsylvania. We found that (i) the amygdala is a hotspot for all ARTAG types; (ii) age at death, male sex, and presence of primary frontotemporal lobar degeneration (FTLD) tauopathy are significantly associated with ARTAG; (iii) age at death, greater degree of brain atrophy, ventricular enlargement, and Alzheimer disease (AD)-related variables are associated with subpial, white matter, and perivascular ARTAG types; (iv) AD-related variables are associated particularly with lobar white matter ARTAG; and (v) gray matter ARTAG in primary FTLD-tauopathies appears in areas without neuronal tau pathology. We provide a reference map of ARTAG types and propose at least 5 constellations of ARTAG. Furthermore, we propose a conceptual link between primary FTLD-tauopathy and ARTAG-related astrocytic tau pathologies. Our observations serve as a basis for etiological stratification and definition of progression patterns of ARTAG. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  4. A novel approach to quantify different iron forms in ex-vivo human brain tissue

    Science.gov (United States)

    Kumar, Pravin; Bulk, Marjolein; Webb, Andrew; van der Weerd, Louise; Oosterkamp, Tjerk H.; Huber, Martina; Bossoni, Lucia

    2016-12-01

    We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40-50 nm, which is not compatible with the ferritin protein, the core of which is typically 6-8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain.

  5. Relationship between Concentrations of Lutein and StARD3 among Pediatric and Geriatric Human Brain Tissue.

    Science.gov (United States)

    Tanprasertsuk, Jirayu; Li, Binxing; Bernstein, Paul S; Vishwanathan, Rohini; Johnson, Mary Ann; Poon, Leonard; Johnson, Elizabeth J

    2016-01-01

    Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and cognitive health have been poorly evaluated at a molecular level. The objective of this study was to evaluate the cross-sectional relationship between concentrations of brain lutein and StARD3 (identified as its binding protein in retinal tissue) among three age groups: infants (1-4 months, n = 10), older adults (55-86 years, n = 8), and centenarians (98-105 years, n = 10). Brain lutein concentrations were analyzed by high-performance liquid chromatography and StARD3 levels were analyzed by Western Blot analysis. The strong relationship in infant brains (r = 0.75, P lutein has a role in neural development. The relationship remained significant but weaker in older adults (r = 0.51, P 0.05), seven of whom had mild cognitive impairment (MCI) or dementia. These exploratory findings suggest an age-related decrease or abnormality of StARD3 activity in human brain. Given that StARD3 is also involved in cholesterol transportation, a process that is aberrant in neurodegenerative diseases, the potential protective function of lutein against these diseases remains to be explored.

  6. Aluminium in brain tissue in familial Alzheimer's disease.

    Science.gov (United States)

    Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

    2017-03-01

    The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  7. Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

    Science.gov (United States)

    Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

    2009-01-01

    This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

  8. Isolation of Borna Disease Virus from Human Brain Tissue

    Science.gov (United States)

    Nakamura, Yurie; Takahashi, Hirokazu; Shoya, Yuko; Nakaya, Takaaki; Watanabe, Makiko; Tomonaga, Keizo; Iwahashi, Kazuhiko; Ameno, Kiyoshi; Momiyama, Noriko; Taniyama, Hiroyuka; Sata, Tetsutaro; Kurata, Takeshi; de la Torre, Juan Carlos; Ikuta, Kazuyoshi

    2000-01-01

    Serological and molecular epidemiological studies indicate that Borna disease virus (BDV) can infect humans and is possibly associated with certain neuropsychiatric disorders. We examined brain tissue collected at autopsy from four schizophrenic patients and two healthy controls for the presence of BDV markers in 12 different brain regions. BDV RNA and antigen was detected in four brain regions of a BDV-seropositive schizophrenic patient (P2) with a very recent (2 years) onset of disease. BDV markers exhibited a regionally localized distribution. BDV RNA was found in newborn Mongolian gerbils intracranially inoculated with homogenates from BDV-positive brain regions of P2. Human oligodendroglia (OL) cells inoculated with brain homogenates from BDV-positive gerbils allowed propagation and isolation of BDVHuP2br, a human brain-derived BDV. Virus isolation was also possible by transfection of Vero cells with ribonucleoprotein complexes prepared from BDV-positive human and gerbil brain tissues. BDVHuP2br was genetically closely related to but distinct from previously reported human- and animal-derived BDV sequences. PMID:10775596

  9. Paleoneurology: neurodegenerative diseases are age-related diseases of specific brain regions recently developed by Homo sapiens.

    Science.gov (United States)

    Ghika, J

    2008-11-01

    Bipedal locomotion and fine motility of hand and larynx of humans introduced musculoskeletal adaptations, new pyramidal, corticostriatal, corticobulbar, nigrostriatal, and cerebellar pathways and expansions of prefrontal, cingular, parieto-temporal and occipital cortices with derived new brain capabilities. All selectively degenerate in aged homo sapiens following 16 syndromic presentations: (1) Parkinsonism: nigrostriatal control for fast automatic movements of hand, larynx, bipedal posture and gait ("simian gait and hand"). (2) Frontal (highest level) gait disorders (lower body parkinsonism, gait apraxia, retropulsion): prefrontostriatal executive control of bipedal locomotion. (3) ataxia: new synergistic coordination of bipedal gait and fine motility. (4) Dyskinesias (chorea, dystonia, tremor...): intrusions of simian basal ganglia motor subroutines. (5) motoneuron diseases: new proximo-distal and bulbar motoneurones, preserving older ones (oculomotor, abdominal...). (6) Archaic reflexes: prefrontal disinhibition of old mother/tree-climbing-oriented reflexes (sucking, grasping, Babinski/triple retraction, gegenhalten), group alarms (laughter, crying, yawning, grunting...) or grooming (tremor=scratching). (7) Dysautonomia: contextual regulation (orthostatism...). (8) REM sleep disorders of new cortical functions. (9) Corticobasal syndrome: melokinetic control of hand prehension-manipulation and language (retrocession to simian patterns). (10) Frontal/temporal lobe degeneration: medial-orbitofrontal behavioural variant: self monitoring of internal needs and social context: apathy, loss of personal hygiene, stereotypia, disinhibition, loss of concern for consequences of acts, social rules, danger and empathy; dorsolateral executive variant: inadequacy to the context of action (goal, environmental changes...); progressive non-fluent aphasia: executive and praxic processing of speech; temporal variant: abstract concepts for speech, gestures and vision (semantic

  10. Progression of thanatophagy in cadaver brain and heart tissues

    Directory of Open Access Journals (Sweden)

    Gulnaz T. Javan

    2016-03-01

    Full Text Available Autophagy is an evolutionarily conserved catabolic process for maintaining cellular homeostasis during both normal and stress conditions. Metabolic reprogramming in tissues of dead bodies is inevitable due to chronic ischemia and nutrient deprivation, which are well-known features that stimulate autophagy. Currently, it is not fully elucidated whether postmortem autophagy, also known as thanatophagy, occurs in dead bodies is a function of the time of death. In this study, we tested the hypothesis that thanatophagy would increase in proportion to time elapsed since death for tissues collected from cadavers. Brain and heart tissue from corpses at different time intervals after death were analyzed by Western blot. Densitometry analysis demonstrated that thanatophagy occurred in a manner that was dependent on the time of death. The autophagy-associated proteins, LC3 II, p62, Beclin-1 and Atg7, increased in a time-dependent manner in heart tissues. A potent inducer of autophagy, BNIP3, decreased in the heart tissues as time of death increased, whereas the protein levels increased in brain tissues. However, there was no expression of BNIP3 at extended postmortem intervals in both brain and heart samples. Collectively, the present study demonstrates for the first time that thanatophagy occurs in brain and heart tissues of cadavers in a time-dependent manner. Further, our data suggest that cerebral thanatophagy may occur in a Beclin-1- independent manner. This unprecedented study provides potential insight into thanatophagy as a novel method for the estimation of the time of death in criminal investigationsAbstract: Autophagy is an evolutionarily conserved catabolic process for maintaining cellular homeostasis during both normal and stress conditions. Metabolic reprogramming in tissues of dead bodies is inevitable due to chronic ischemia and nutrient deprivation, which are well-known features that stimulate autophagy. Currently, it is not fully

  11. Low-dose, continual enzyme delivery ameliorates some aspects of established brain disease in a mouse model of a childhood-onset neurodegenerative disorder.

    Science.gov (United States)

    King, Barbara; Setford, Meghan L; Hassiotis, Sofia; Trim, Paul J; Duplock, Stephen; Tucker, Justin N; Hattersley, Kathryn; Snel, Marten F; Hopwood, John J; Hemsley, Kim M

    2016-04-01

    To determine the capacity of continual low-dose lysosomal enzyme infusion into the cerebrospinal fluid of mucopolysaccharidosis type IIIA (MPS IIIA) mice to reverse established neurodegenerative disease. The rationale behind the study is that there is only limited animal model-derived evidence supporting treatment of symptomatic patients, principally because few studies have been designed to examine disease reversibility. Twelve-week old MPS IIIA mice were implanted with indwelling unilateral intra-ventricular cannulae. These were connected to subcutaneous mini-osmotic pumps infusing recombinant human sulphamidase. Pump replacement was carried out in some mice at 16-weeks of age, enabling treatment to continue for a further month. Control affected/unaffected mice received vehicle via the same method. Behavioural, neuropathological and biochemical parameters of disease were assessed. Improvement in some, but not all, behavioural parameters occurred. Sulphamidase infusion mediated a statistically significant reduction in primary (heparan sulphate) and secondary (gangliosides GM2, GM3) substrate accumulation in the brain, with small reductions in micro- but not astro-gliosis. There was no change in axonal spheroid number. All mice developed a humoural response, however the antibodies were non-neutralising and no adverse clinical effects were observed. Continual infusion of replacement enzyme partially ameliorates clinical, histological and biochemical aspects of MPS IIIA mice, when treatment begins at an early symptomatic stage. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. A High Rate Tension Device for Characterizing Brain Tissue

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1177/1754337112436900

    2013-01-01

    The mechanical characterization of brain tissue at high loading velocities is vital for understanding and modeling Traumatic Brain Injury (TBI). The most severe form of TBI is diffuse axonal injury (DAI) which involves damage to individual nerve cells (neurons). DAI in animals and humans occurs at strains > 10% and strain rates > 10/s. The mechanical properties of brain tissues at these strains and strain rates are of particular significance, as they can be used in finite element human head models to accurately predict brain injuries under different impact conditions. Existing conventional tensile testing machines can only achieve maximum loading velocities of 500 mm/min, whereas the Kolsky bar apparatus is more suitable for strain rates > 100/s. In this study, a custom-designed high rate tension device is developed and calibrated to estimate the mechanical properties of brain tissue in tension at strain rates < 90/s, while maintaining a uniform velocity. The range of strain can also be extended to 100% de...

  13. Discovery of Undescribed Brain Tissue Changes Around Implanted Microelectrode Arrays

    Directory of Open Access Journals (Sweden)

    Himanshi Desai

    2012-01-01

    Full Text Available Brain-implantable microelectrode arrays are devicesdesigned to record or electrically stimulate the activity ofneurons in the brain. These devices hold the potential tohelp treat epilepsy, paralysis, blindness, and deafness, andalso provide researchers with insights into a varietyof neural processes, such as memory formation.While these devices have a very promising future,researchers are discovering that their long-termfunctionality is greatly limited by the brain’s naturalimmune response to foreign objects. To improve thefunctional lifetime of these devices, one solution lies infully characterizing and understanding this tissue response.Roles for microglia and astrocytes in this biologicalresponse have been characterized. However, changesto oligodendrocytes, cells that myelinate axons, remainpoorly understood. These cells provide insulationto the axons, which is required for proper neuralfunctioning. Here we report on the changes that occurwith oligodendrocyte processes in tissue aroundmicroelectrode implants in the brain.Six rats were surgically implanted with microelectrodearrays and allowed to recover for 1, 2, or 4 weeks.Subjects were then sacrificed and the brain tissue wasprocessed using our recently developed method, Device-Capture Histology. Immunohistochemistry and confocalmicroscopy was employed to assess the responsearound the device. Results indicated a decrease inoligodendrocyte density and a loss in typical directionalorientation of oligodendrocyte processes in tissue near thedevice. These results suggest alterations in the underlyingneuronal networks around these devices, which maygreatly impact the current functional utility of thesepromising devices.

  14. Histopathological changes in the Brain Tissue of Africa Catfish ...

    African Journals Online (AJOL)

    ... post juvenile African catfish C. gariepinus as characterized by severe degeneration of dark-stained purkinje neurons, oedema, vacuolar changes with empty spaces which appeared as moth eaten area and showed proliferation of glial cells. There is need for more research work on the histopathology of brain tissue of fish ...

  15. Detection of Rabies Antigen in the Brain Tissues of Apparetly ...

    African Journals Online (AJOL)

    Rabies is a serious public health hazard and recently outbreaks of the disease have been reported in three local government areas in Cross River State. Detection of rabies antigen in the brain tissues of apparently healthy dogs indicates the presence of rabies virus and this is a significant factor in the transmission and ...

  16. A novel three-phase model of brain tissue microstructure.

    Directory of Open Access Journals (Sweden)

    Jana L Gevertz

    Full Text Available We propose a novel biologically constrained three-phase model of the brain microstructure. Designing a realistic model is tantamount to a packing problem, and for this reason, a number of techniques from the theory of random heterogeneous materials can be brought to bear on this problem. Our analysis strongly suggests that previously developed two-phase models in which cells are packed in the extracellular space are insufficient representations of the brain microstructure. These models either do not preserve realistic geometric and topological features of brain tissue or preserve these properties while overestimating the brain's effective diffusivity, an average measure of the underlying microstructure. In light of the highly connected nature of three-dimensional space, which limits the minimum diffusivity of biologically constrained two-phase models, we explore the previously proposed hypothesis that the extracellular matrix is an important factor that contributes to the diffusivity of brain tissue. Using accurate first-passage-time techniques, we support this hypothesis by showing that the incorporation of the extracellular matrix as the third phase of a biologically constrained model gives the reduction in the diffusion coefficient necessary for the three-phase model to be a valid representation of the brain microstructure.

  17. General solutions to poroviscoelastic model of hydrocephalic human brain tissue.

    Science.gov (United States)

    Mehrabian, Amin; Abousleiman, Younane

    2011-12-21

    Hydrocephalus is a well-known disorder of brain fluidic system. It is commonly associated with complexities in cerebrospinal fluid (CSF) circulation in brain. In this paper, hydrocephalus and shunting surgery which is used in its treatment are modeled. Brain tissues are considered to follow a poroviscoelastic constitutive model in order to address the effects of time dependence of mechanical properties of soft tissues and fluid flow hydraulics. Our solution draws from Biot's theory of poroelasticity, generalized to account for viscoelastic effects through the correspondence principle. Geometrically, the brain is conceived to be spherically symmetric, where the ventricles are assumed to be a hollow concentric space filled with cerebrospinal fluid. A generalized Kelvin model is considered for the rheological properties of brain tissues. The solution presented is useful in the analysis of the disorder of hydrocephalus as well as the treatment associated with it, namely, ventriclostomy surgery. The sensitivity of the solution to various factors such as aqueduct blockage level and trabeculae stiffness is thoroughly analyzed using numerical examples. Results indicate that partial aqueduct stenosis may be a cause of hydrocephalus. However, only severe occlusion of the aqueduct can cause a significant increase in the ventricle and brain's extracellular fluid pressure. Ventriculostomy shunts are commonly used as a remedy to hydrocephalus. They serve to reduce the ventricular pressure to the normal level. However, sensitivity analysis on the shunt's fluid deliverability parameter has shown that inappropriate design or selection of design shunt may cause under-drainage or over-drainage of the ventricles. Excessive drainage of CSF may increase the normal tensile stress on trabeculae. It can cause rupture of superior cerebral veins or damage to trabeculae or even brain tissues which in turn may lead to subdural hematoma, a common side-effect of the surgery. These Post

  18. Depressive symptoms in neurodegenerative diseases

    Science.gov (United States)

    Baquero, Miquel; Martín, Nuria

    2015-01-01

    Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer’s disease and related conditions like Parkinson’s disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have a particular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment. PMID:26301229

  19. Determination of Friction Coefficient in Unconfined Compression of Brain Tissue

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.05.001

    2013-01-01

    Unconfined compression tests are more convenient to perform on cylindrical samples of brain tissue than tensile tests in order to estimate mechanical properties of the brain tissue because they allow for homogeneous deformations. The reliability of these tests depends significantly on the amount of friction generated at the specimen/platen interface. Thus, there is a crucial need to find an approximate value of the friction coefficient in order to predict a possible overestimation of stresses during unconfined compression tests. In this study, a combined experimental-computational approach was adopted to estimate the dynamic friction coefficient mu of porcine brain matter against metal platens in compressive tests. Cylindrical samples of porcine brain tissue were tested up to 30% strain at variable strain rates, both under bonded and lubricated conditions in the same controlled environment. It was established that mu was equal to 0.09 +/- 0.03, 0.18 +/- 0.04, 0.18 +/- 0.04 and 0.20 +/- 0.02 at strain rates of...

  20. Imaging cellular and subcellular structure of human brain tissue using micro computed tomography

    Science.gov (United States)

    Khimchenko, Anna; Bikis, Christos; Schweighauser, Gabriel; Hench, Jürgen; Joita-Pacureanu, Alexandra-Teodora; Thalmann, Peter; Deyhle, Hans; Osmani, Bekim; Chicherova, Natalia; Hieber, Simone E.; Cloetens, Peter; Müller-Gerbl, Magdalena; Schulz, Georg; Müller, Bert

    2017-09-01

    Brain tissues have been an attractive subject for investigations in neuropathology, neuroscience, and neurobiol- ogy. Nevertheless, existing imaging methodologies have intrinsic limitations in three-dimensional (3D) label-free visualisation of extended tissue samples down to (sub)cellular level. For a long time, these morphological features were visualised by electron or light microscopies. In addition to being time-consuming, microscopic investigation includes specimen fixation, embedding, sectioning, staining, and imaging with the associated artefacts. More- over, optical microscopy remains hampered by a fundamental limit in the spatial resolution that is imposed by the diffraction of visible light wavefront. In contrast, various tomography approaches do not require a complex specimen preparation and can now reach a true (sub)cellular resolution. Even laboratory-based micro computed tomography in the absorption-contrast mode of formalin-fixed paraffin-embedded (FFPE) human cerebellum yields an image contrast comparable to conventional histological sections. Data of a superior image quality was obtained by means of synchrotron radiation-based single-distance X-ray phase-contrast tomography enabling the visualisation of non-stained Purkinje cells down to the subcellular level and automated cell counting. The question arises, whether the data quality of the hard X-ray tomography can be superior to optical microscopy. Herein, we discuss the label-free investigation of the human brain ultramorphology be means of synchrotron radiation-based hard X-ray magnified phase-contrast in-line tomography at the nano-imaging beamline ID16A (ESRF, Grenoble, France). As an example, we present images of FFPE human cerebellum block. Hard X-ray tomography can provide detailed information on human tissues in health and disease with a spatial resolution below the optical limit, improving understanding of the neuro-degenerative diseases.

  1. Magnetic resonance electric property imaging of brain tissues.

    Science.gov (United States)

    Zhang, Xiaotong; Zhu, Shanan; He, Bin

    2009-01-01

    The electric properties (EPs) of brain tissues, i.e., the electric conductivity and permittivity, can provide important information for diagnosis of various brain disorders. A high-field MRI system is accompanied by significant wave propagation effects, and the radio frequency (RF) radiation is dependent on EPs of the biological tissue. Based on the measurement of the active transverse magnetic component of the applied RF field (known as B1-mapping technique), we have developed a dual-excitation algorithm, which uses two sets of measured B1 data, to noninvasively reconstruct the biological tissue's electric properties. A series of computer simulations were conducted to evaluate the feasibility and performance of the proposed method on a 3-D head model within a birdcage coil and a transverse electromagnetic coil. Compared with other B1-mapping based reconstruction algorithms, our approach provides superior performance without the need for iterative computations. The present simulation results indicate good reconstruction of electric properties of brain tissues from noninvasive MRI B1 mapping.

  2. [Neurotropic effects of heptapeptide mystixin studied on brain tissue sections].

    Science.gov (United States)

    Mokrushin, A A

    2011-01-01

    Neurotropic effects of heptapeptide mystixin have been studied on olfactory cortex neurons in rat brain tissue sections. The application of mystixin onto brain section produced a dose-dependent inhibition of AMPA- and NMDA-receptor-dependent processes. The peptide suppressed the activity of inhibitory processes only at small doses (10, 25, and 50 mg/ml) and potentiated these processes at greater doses (100 and 250 mg/ml). These effects of mystixin are reversible: after washing, the activities of both exciting (except for NMDA-related) and inhibitory mechanisms were restored.

  3. In vivo mapping of current density distribution in brain tissues during deep brain stimulation (DBS)

    Science.gov (United States)

    Sajib, Saurav Z. K.; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2017-01-01

    New methods for in vivo mapping of brain responses during deep brain stimulation (DBS) are indispensable to secure clinical applications. Assessment of current density distribution, induced by internally injected currents, may provide an alternative method for understanding the therapeutic effects of electrical stimulation. The current flow and pathway are affected by internal conductivity, and can be imaged using magnetic resonance-based conductivity imaging methods. Magnetic resonance electrical impedance tomography (MREIT) is an imaging method that can enable highly resolved mapping of electromagnetic tissue properties such as current density and conductivity of living tissues. In the current study, we experimentally imaged current density distribution of in vivo canine brains by applying MREIT to electrical stimulation. The current density maps of three canine brains were calculated from the measured magnetic flux density data. The absolute current density values of brain tissues, including gray matter, white matter, and cerebrospinal fluid were compared to assess the active regions during DBS. The resulting current density in different tissue types may provide useful information about current pathways and volume activation for adjusting surgical planning and understanding the therapeutic effects of DBS.

  4. Regional mechanical properties of human brain tissue for computational models of traumatic brain injury.

    Science.gov (United States)

    Finan, John D; Sundaresh, Sowmya N; Elkin, Benjamin S; McKhann, Guy M; Morrison, Barclay

    2017-06-01

    To determine viscoelastic shear moduli, stress relaxation indentation tests were performed on samples of human brain tissue resected in the course of epilepsy surgery. Through the use of a 500µm diameter indenter, regional mechanical properties were measured in cortical grey and white matter and subregions of the hippocampus. All regions were highly viscoelastic. Cortical grey matter was significantly more compliant than the white matter or hippocampus which were similar in modulus. Although shear modulus was not correlated with the age of the donor, cortex from male donors was significantly stiffer than from female donors. The presented material properties will help to populate finite element models of the brain as they become more anatomically detailed. We present the first mechanical characterization of fresh, post-operative human brain tissue using an indentation loading mode. Indentation generates highly localized data, allowing structure-specific mechanical properties to be determined from small tissue samples resected during surgery. It also avoids pitfalls of cadaveric tissue and allows data to be collected before degenerative processes alter mechanical properties. To correctly predict traumatic brain injury, finite element models must calculate intracranial deformation during head impact. The functional consequences of injury depend on the anatomical structures injured. Therefore, morbidity depends on the distribution of deformation across structures. Accurate prediction of structure-specific deformation requires structure-specific mechanical properties. This data will facilitate deeper understanding of the physical mechanisms that lead to traumatic brain injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. Assessing fibrinogen extravasation into Alzheimer's disease brain using high-content screening of brain tissue microarrays.

    Science.gov (United States)

    Narayan, Pritika J; Kim, Sue-Ling; Lill, Claire; Feng, Sheryl; Faull, Richard L M; Curtis, Maurice A; Dragunow, Michael

    2015-05-30

    Tissue microarrays are commonly used to evaluate disease pathology however methods to automate and quantify pathological changes are limited. This article demonstrates the utility of the VSlide scanner (MetaSystems) for automated image acquisition from immunolabelled tissue microarray slides, and subsequent automated image analysis with MetaXpress (Molecular Devices) software to obtain objective, efficient and reproducible data from immunolabelled tissue microarray sections. Significant increases in fibrinogen immunolabelling were observed in 29 Alzheimer's disease cases compared to 28 control cases analysed from a single tissue microarray slide. Western blot analysis also demonstrated significant increases in fibrinogen immunolabelling in 6 Alzheimer's cases compared to 6 control cases. The observed changes were also validated with gold standard blinded manual H-scoring. VSlide Metafer software offers a 'tissue microarray acquisition' plugin for easy mapping of tissue cores with their original position on the tissue microarray map. High resolution VSlide images are compatible with MetaXpress image analysis software. This article details the coupling of these two technologies to accurately and reproducibly analyse immunolabelled tissue microarrays within minutes, compared to the gold standard method of manual counting using H-scores which is significantly slower and prone to inter-observer variation. Here, we couple brain tissue microarray technology with high-content screening and automated image analysis as a powerful way to address bottle necks in data generation and improve throughput, as well as sensitivity to study biological/pathological changes in brain disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Meditation and neurodegenerative diseases

    National Research Council Canada - National Science Library

    Newberg, Andrew B; Serruya, Mijail; Wintering, Nancy; Moss, Aleezé Sattar; Reibel, Diane; Monti, Daniel A

    2014-01-01

    .... Meditation techniques present an interesting potential adjuvant treatment for patients with neurodegenerative diseases and have the advantage of being inexpensive, and easy to teach and perform...

  7. Inhomogeneous Deformation of Brain Tissue During Tension Tests

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael D; 10.1016/j.commatsci.2012.05.030

    2013-01-01

    Mechanical characterization of brain tissue has been investigated extensively by various research groups over the past fifty years. These properties are particularly important for modelling Traumatic Brain Injury (TBI). In this research, we present the design and calibration of a High Rate Tension Device (HRTD) capable of performing tests up to a maximum strain rate of 90/s. We use experimental and numerical methods to investigate the effects of inhomogeneous deformation of porcine brain tissue during tension at different specimen thicknesses (4.0-14.0 mm), by performing tension tests at a strain rate of 30/s. One-term Ogden material parameters (mu = 4395.0 Pa, alpha = -2.8) were derived by performing an inverse finite element analysis to model all experimental data. A similar procedure was adopted to determine Young's modulus (E= 11200 Pa) of the linear elastic regime. Based on this analysis, brain specimens of aspect ratio (diameter/thickness) S < 1.0 are required to minimise the effects of inhomogeneous...

  8. Distribution of opiate alkaloids in brain tissue of experimental animals

    Science.gov (United States)

    Pilija, Vladimir; Mimica-Dukic, Neda; Budakov, Branislav; Cvjeticanin, Stanko

    2012-01-01

    The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of µ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography–mass spectrometry (GC–MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake. PMID:23554560

  9. Probabilistic brain tissue segmentation in neonatal magnetic resonance imaging.

    Science.gov (United States)

    Anbeek, Petronella; Vincken, Koen L; Groenendaal, Floris; Koeman, Annemieke; van Osch, Matthias J P; van der Grond, Jeroen

    2008-02-01

    A fully automated method has been developed for segmentation of four different structures in the neonatal brain: white matter (WM), central gray matter (CEGM), cortical gray matter (COGM), and cerebrospinal fluid (CSF). The segmentation algorithm is based on information from T2-weighted (T2-w) and inversion recovery (IR) scans. The method uses a K nearest neighbor (KNN) classification technique with features derived from spatial information and voxel intensities. Probabilistic segmentations of each tissue type were generated. By applying thresholds on these probability maps, binary segmentations were obtained. These final segmentations were evaluated by comparison with a gold standard. The sensitivity, specificity, and Dice similarity index (SI) were calculated for quantitative validation of the results. High sensitivity and specificity with respect to the gold standard were reached: sensitivity >0.82 and specificity >0.9 for all tissue types. Tissue volumes were calculated from the binary and probabilistic segmentations. The probabilistic segmentation volumes of all tissue types accurately estimated the gold standard volumes. The KNN approach offers valuable ways for neonatal brain segmentation. The probabilistic outcomes provide a useful tool for accurate volume measurements. The described method is based on routine diagnostic magnetic resonance imaging (MRI) and is suitable for large population studies.

  10. Microscopy and chemical imaging of Behcet brain tissue

    Science.gov (United States)

    Aranyosiova, Monika; Michalka, Miroslav; Kopani, Martin; Rychly, Boris; Jakubovsky, Jan; Velic, Dusan

    2008-12-01

    Chemical composition and distribution of molecules and elements in a human brain tissue of Behcet diseased patient are of interest. Behcet disease is a multi-system disorder of which pathogenesis and chemical causality are still uncertain. Time-of-flight secondary ion mass spectrometry is used along with scanning electron microscopy and energy dispersive X-ray analysis providing complex composition in Behcet disease and control tissues. Determined organic compounds are represented by fragments of carbohydrates, phospholipids, amino acids, and peptides. The distributions of inorganic species are well represented by heavy trace elements and by oxides in positive and negative polarities of time-of-flight secondary ion mass spectrometry, respectively. Organic and inorganic compounds are qualitatively determined in both samples, Behcet and control, providing complementary chemical images. The complementary chemical images interestingly change with the quantitative regression of organic compounds distribution, characteristic for the healthy control, towards inorganic compounds distribution, characteristic for Behcet tissue.

  11. Arsenic affects inflammatory cytokine expression in Gallus gallus brain tissues.

    Science.gov (United States)

    Sun, Xiao; He, Ying; Guo, Ying; Li, Siwen; Zhao, Hongjing; Wang, Yu; Zhang, Jingyu; Xing, Mingwei

    2017-06-05

    The heavy metal arsenic is widely distributed in nature and posses a serious threat to organism's health. However, little is known about the arsenic-induced inflammatory response in the brain tissues of birds and the relationship and mechanism of the inflammatory response. The purpose of this study was to explore the effects of dietary arsenic on the expression of inflammatory cytokines in the brains of Gallus gallus. Seventy-two 1-day-old male Hy-line chickens were divided into a control group, a low arsenic trioxide (As2O3)-treated (7.5 mg/kg) group, a middle As2O3-treated (15 mg/kg) group, and a high As2O3-treated (30 mg/kg) group. Arsenic exposure caused obvious ultrastructural changes. The mRNA levels of the transcription factor nuclear factor-κB (NF-κB) and of pro-inflammatory cytokines, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E synthase (PTGEs), in chicken brain tissues (cerebrum, cerebellum, thalamus, brainstem and myelencephalon) on days 30, 60 and 90, respectively, were measured by real-time PCR. The protein expression of iNOS was detected by western blot. The results showed that after being treated with As2O3, the levels of inflammatory-related factor NF-κB and pro-inflammatory cytokines in chicken brain tissues increased (P Arsenic exposure in the chickens triggered host defence and induced an inflammatory response by regulating the expression of inflammatory-related genes in the cerebrum, cerebellum, thalamus, brainstem and myelencephalon. These data form a foundation for further research on arsenic-induced neurotoxicity in Gallus gallus.

  12. [Sleep in neurodegenerative disorders].

    Science.gov (United States)

    Happe, S; Mayer, G

    2006-10-01

    Neurodegenerative disorders are a group of heterogeneous, progressive disorders of varying etiology that affect one or more systems. They occur predominantly at older age, during which the structure and amount of sleep undergo changes. Neurodegenerative processes cause structural changes of the sleep/wake generators in the brainstem which result in disorders such as daytime sleepiness, insomnia, sleep-related movement and breathing disturbances, and disorders of the circadian rhythms. Some sleep disorders manifest years before the onset of neurodegenerative disorders and may serve as predictors. Polysomnography shows sleep fragmentation, tonic or phasic movements of the extremities, alteration of respiratory muscles, reduced slow wave sleep, REM sleep absence or without muscle atonia, increased arousal or wake activity, epileptiform EEG activity, and changes in sleep-related breathing. Very frequently, REM sleep behaviour disorder is associated with neurodegenerative disorders. In this overview we present symptoms, pathophysiology, and polysomnographic findings of sleep disorders in prevalent neurodegenerative disorders.

  13. Diffusion MRI at 25: exploring brain tissue structure and function.

    Science.gov (United States)

    Le Bihan, Denis; Johansen-Berg, Heidi

    2012-06-01

    Diffusion MRI (or dMRI) came into existence in the mid-1980s. During the last 25 years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI). Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke. It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity. The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences. The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process. Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Targeting Malignant Brain Tumors with Antibodies

    OpenAIRE

    Rok Razpotnik; Neža Novak; Vladka Čurin Šerbec; Uros Rajcevic

    2017-01-01

    Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood–brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain deli...

  15. BIOLOGICAL EFFECTS OF MICROWAVE RADIATION ON BRAIN TISSUE IN RATS

    Directory of Open Access Journals (Sweden)

    Boris Đinđić

    2003-04-01

    Full Text Available Exposure to microwave radiation induces multiple organ dysfunctions, especially in CNS.The aim of this work was investigation of biological effects of microwave radiation on rats' brain and determination of increased oxidative stress as a possible pathogenetic's mechanism.Wis tar rats 3 months old were divided in experimental (4 female and 4 male animal and control group (5 female and 4 male. This experimental group was constantly exposed to a magnetic field of 5 mG. We simulated using of mobile phones 30 min every day. The source of NIR emitted MF that was similar to mobile phones at 900 MHz. The rats were killed after 2 months. Biological effects were determined by observation of individual and collective behavior and body mass changes. Lipid per oxidation was determined by measuring quantity of malondialdehyde (MDA in brain homogenate.The animals in experimental group exposed to EMF showed les weight gain. The most important observations were changing of basic behavior models and expression of aggressive or panic behavior. The content of MDA in brain tissue is singificantly higher (1.42 times in rats exposed to electromagnetic fields (3,82±0.65 vs. control 2.69±0.42 nmol/mg proteins, p<0.01.Increased oxidative stress and lipid peroxidation after exposition in EM fields induced disorders of function and structure of brain.

  16. The neuropathology and neurobiology of traumatic brain injury

    National Research Council Canada - National Science Library

    Blennow, Kaj; Hardy, John; Zetterberg, Henrik

    2012-01-01

    ... both regenerative and degenerative tissue responses in the brain and in whom repeated concussions may initiate a long-term neurodegenerative process called dementia pugilistica or chronic traumatic encephalopathy (CTE...

  17. Improved segmentation of ultrasound brain tissue incorporating expert evaluation.

    Science.gov (United States)

    Vansteenkiste, Ewout; Pizurica, Aleksandra; Philips, Wilfried

    2005-01-01

    The quantitative analysis of medical ultrasound images for the purpose of diagnosis is a difficult task due to the speckle noise present in the images. Nowadays medical doctors depend strongly on the visual interpretation of the images which is subjective to some account. Trying to reduce this noise should assist the experts in a better understanding of some pathologies. We focus on a brain disease called periventricular leukomalacia, also called white matter damage, which occurs frequently on premature neonates. For the moment the affected brain tissue is segmented semi-automatically using two different techniques that take the speckle noise into little account. Here we propose a framework which includes an efficient preprocessing step and relying on expert-based evaluation we develop an integrated segmentation method, which yields a more accurate and better reproducible segmentation.

  18. Brain Tissue Compartment Density Estimated Using Diffusion-Weighted MRI Yields Tissue Parameters Consistent With Histology

    Science.gov (United States)

    Sepehrband, Farshid; Clark, Kristi A.; Ullmann, Jeremy F.P.; Kurniawan, Nyoman D.; Leanage, Gayeshika; Reutens, David C.; Yang, Zhengyi

    2015-01-01

    We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intra-cellular and intra-neurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin density estimates were compared with the results of electron and light microscopy in ex vivo mouse brain and with published density estimates in a healthy human brain. In ex vivo mouse brain, estimated myelin densities in different sub-regions of the mouse corpus callosum were almost identical to values obtained from electron microscopy (Diffusion MRI: 42±6%, 36±4% and 43±5%; electron microscopy: 41±10%, 36±8% and 44±12% in genu, body and splenium, respectively). In the human brain, good agreement was observed between estimated fiber density measurements and previously reported values based on electron microscopy. Estimated density values were unaffected by crossing fibers. PMID:26096639

  19. Topology-preserving tissue classification of magnetic resonance brain images.

    Science.gov (United States)

    Bazin, Pierre-Louis; Pham, Dzung L

    2007-04-01

    This paper presents a new framework for multiple object segmentation in medical images that respects the topological properties and relationships of structures as given by a template. The technique, known as topology-preserving, anatomy-driven segmentation (TOADS), combines advantages of statistical tissue classification, topology-preserving fast marching methods, and image registration to enforce object-level relationships with little constraint over the geometry. When applied to the problem of brain segmentation, it directly provides a cortical surface with spherical topology while segmenting the main cerebral structures. Validation on simulated and real images characterises the performance of the algorithm with regard to noise, inhomogeneities, and anatomical variations.

  20. Coherent control of an opsin in living brain tissue

    Science.gov (United States)

    Paul, Kush; Sengupta, Parijat; Ark, Eugene D.; Tu, Haohua; Zhao, Youbo; Boppart, Stephen A.

    2017-11-01

    Retinal-based opsins are light-sensitive proteins. The photoisomerization reaction of these proteins has been studied outside cellular environments using ultrashort tailored light pulses. However, how living cell functions can be modulated via opsins by modifying fundamental nonlinear optical properties of light interacting with the retinal chromophore has remained largely unexplored. We report the use of chirped ultrashort near-infrared pulses to modulate light-evoked ionic current from Channelrhodopsin-2 (ChR2) in brain tissue, and consequently the firing pattern of neurons, by manipulating the phase of the spectral components of the light. These results confirm that quantum coherence of the retinal-based protein system, even in a living neuron, can influence its current output, and open up the possibilities of using designer-tailored pulses for controlling molecular dynamics of opsins in living tissue to selectively enhance or suppress neuronal function for adaptive feedback-loop applications in the future.

  1. Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

    Directory of Open Access Journals (Sweden)

    RINI PUSPITANINGRUM

    2010-09-01

    Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxia-tolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

  2. Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

    Directory of Open Access Journals (Sweden)

    RINI PUSPITANINGRUM

    2010-09-01

    Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxiatolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

  3. RBD and Neurodegenerative Diseases.

    Science.gov (United States)

    Jiang, Haiyang; Huang, Jinsha; Shen, Yan; Guo, Shiyi; Wang, Luxi; Han, Chao; Liu, Ling; Ma, Kai; Xia, Yun; Li, Jie; Xu, Xiaoyun; Xiong, Nian; Wang, Tao

    2017-05-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disorder characterized by enacting one's dreams during the REM sleep, with most of the dreams being violent or aggressive, so that patients often come to see the doctor complaining hurting themselves or bed partners during sleep. Prevalence of RBD, based on population, is 0.38-2.01 %, but much higher in patients with neurodegenerative diseases, especially synucleinopathies. RBD may herald the emergence of synucleinopathies by decades, such that it may be used as an effective early marker of neurodegenerative diseases. Pharmaceutical treatment of RBD includes clonazepam, melatonin, pramipexole, and some newly reported medications. In this review, we summarized the clinical and PSG features of RBD, the pathophysiology and the therapy of it, focusing on the correlation between neurodegenerative diseases and RBD, in order to emphasize the significance of RBD as an early marker of neurodegenerative diseases.

  4. State-of-the-Art Methods for Brain Tissue Segmentation: A Review.

    Science.gov (United States)

    Dora, Lingraj; Agrawal, Sanjay; Panda, Rutuparna; Abraham, Ajith

    2017-01-01

    Brain tissue segmentation is one of the most sought after research areas in medical image processing. It provides detailed quantitative brain analysis for accurate disease diagnosis, detection, and classification of abnormalities. It plays an essential role in discriminating healthy tissues from lesion tissues. Therefore, accurate disease diagnosis and treatment planning depend merely on the performance of the segmentation method used. In this review, we have studied the recent advances in brain tissue segmentation methods and their state-of-the-art in neuroscience research. The review also highlights the major challenges faced during tissue segmentation of the brain. An effective comparison is made among state-of-the-art brain tissue segmentation methods. Moreover, a study of some of the validation measures to evaluate different segmentation methods is also discussed. The brain tissue segmentation, content in terms of methodologies, and experiments presented in this review are encouraging enough to attract researchers working in this field.

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

    Science.gov (United States)

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

    2017-10-01

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

  6. Further Controversies About Brain Tissue Oxygenation Pressure-Reactivity After Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Andresen, Morten; Donnelly, Joseph; Aries, Marcel

    2017-01-01

    arterial pressure and intracranial pressure. A new ORx index based on brain tissue oxygenation and cerebral perfusion pressure (CPP) has been proposed that similarly allows for evaluation of cerebrovascular reactivity. Conflicting results exist concerning its clinical utility. METHODS: Retrospective....... Higher mortality related to average CPP regardless of which index was used to calculate CPPopt. CONCLUSION: In the TBI setting, ORx does not appear to correlate with vascular pressure reactivity as assessed with PRx. Its potential use for individualizing CPP thresholds remains unclear....

  7. Metal imaging in neurodegenerative diseases

    Science.gov (United States)

    Bourassa, Megan W.

    2014-01-01

    Metal ions are known to play an important role in many neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and prion diseases. In these diseases, aberrant metal binding or improper regulation of redox active metal ions can induce oxidative stress by producing cytotoxic reactive oxygen species (ROS). Altered metal homeostasis is also frequently seen in the diseased state. As a result, the imaging of metals in intact biological cells and tissues has been very important for understanding the role of metals in neurodegenerative diseases. A wide range of imaging techniques have been utilized, including X-ray fluorescence microscopy (XFM), particle induced X-ray emission (PIXE), energy dispersive X-ray spectroscopy (EDS), laser ablation inductively coupled mass spectrometry (LA-ICP-MS), and secondary ion mass spectrometry (SIMS), all of which allow for the imaging of metals in biological specimens with high spatial resolution and detection sensitivity. These techniques represent unique tools for advancing the understanding of the disease mechanisms and for identifying possible targets for developing treatments. In this review, we will highlight the advances in neurodegenerative disease research facilitated by metal imaging techniques. PMID:22797194

  8. Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology

    Directory of Open Access Journals (Sweden)

    Jose A. Santiago

    2017-05-01

    Full Text Available Neurodegenerative diseases are rarely caused by a mutation in a single gene but rather influenced by a combination of genetic, epigenetic and environmental factors. Emerging high-throughput technologies such as RNA sequencing have been instrumental in deciphering the molecular landscape of neurodegenerative diseases, however, the interpretation of such large amounts of data remains a challenge. Network biology has become a powerful platform to integrate multiple omics data to comprehensively explore the molecular networks in the context of health and disease. In this review article, we highlight recent advances in network biology approaches with an emphasis in brain-networks that have provided insights into the molecular mechanisms leading to the most prevalent neurodegenerative diseases including Alzheimer’s (AD, Parkinson’s (PD and Huntington’s diseases (HD. We discuss how integrative approaches using multi-omics data from different tissues have been valuable for identifying biomarkers and therapeutic targets. In addition, we discuss the challenges the field of network medicine faces toward the translation of network-based findings into clinically actionable tools for personalized medicine applications.

  9. Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology.

    Science.gov (United States)

    Santiago, Jose A; Bottero, Virginie; Potashkin, Judith A

    2017-01-01

    Neurodegenerative diseases are rarely caused by a mutation in a single gene but rather influenced by a combination of genetic, epigenetic and environmental factors. Emerging high-throughput technologies such as RNA sequencing have been instrumental in deciphering the molecular landscape of neurodegenerative diseases, however, the interpretation of such large amounts of data remains a challenge. Network biology has become a powerful platform to integrate multiple omics data to comprehensively explore the molecular networks in the context of health and disease. In this review article, we highlight recent advances in network biology approaches with an emphasis in brain-networks that have provided insights into the molecular mechanisms leading to the most prevalent neurodegenerative diseases including Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases (HD). We discuss how integrative approaches using multi-omics data from different tissues have been valuable for identifying biomarkers and therapeutic targets. In addition, we discuss the challenges the field of network medicine faces toward the translation of network-based findings into clinically actionable tools for personalized medicine applications.

  10. Brain Tissue Oxygen: In Vivo Monitoring with Carbon Paste Electrodes

    Directory of Open Access Journals (Sweden)

    John P. Lowry

    2005-11-01

    Full Text Available In this communication we review selected experiments involving the use ofcarbon paste electrodes (CPEs to monitor and measure brain tissue O2 levels in awakefreely-moving animals. Simultaneous measurements of rCBF were performed using the H2clearance technique. Voltammetric techniques used include both differential pulse (O2 andconstant potential amperometry (rCBF. Mild hypoxia and hyperoxia produced rapidchanges (decrease and increase respectively in the in vivo O2 signal. Neuronal activation(tail pinch and stimulated grooming produced similar increases in both O2 and rCBFindicating that CPE O2 currents provide an index of increases in rCBF when such increasesexceed O2 utilization. Saline injection produced a transient increase in the O2 signal whilechloral hydrate produced slower more long-lasting changes that accompanied the behavioralchanges associated with anaesthesia. Acetazolamide increased O2 levels through an increasein rCBF.

  11. Sleep and neurodegenerative diseases.

    Science.gov (United States)

    Chokroverty, Sudhansu

    2009-09-01

    Sleep disturbances are common in neurodegenerative diseases. Disturbed sleep can result in fatigue, irritability, morning headaches, impaired motor and cognitive skills, depression, and daytime somnolence. The major sleep complaints include insomnia, hypersomnia, parasomnia, excessive nocturnal motor activity, circadian sleep-wake rhythm disturbance, and respiratory dysrhythmia. The pathogenetic mechanisms of sleep disturbances may be secondary to direct structural alteration of the sleep-wake generating neurons or from several other indirect mechanisms. At the biochemical level, neurodegenerative diseases may be largely classified as tauopathies, alpha-synucleinopathies, and other diseases. Overnight polysomnography (PSG), Multiple Sleep Latency Test, Maintenance of Wakefulness Test, and actigraphy are some important diagnostic laboratory tests in the evaluation of sleep disturbances. Management of sleep disturbances is complex and is based primarily on the nature of the sleep disturbance. The clinical profiles, pathogenetic mechanisms, PSG findings, and management issues are discussed here with reference to some common neurodegenerative diseases. Thieme Medical Publishers.

  12. Real-time changes in brain tissue oxygen during endovascular treatment of cerebral vasospasm

    DEFF Research Database (Denmark)

    Rasmussen, Rune; Bache, Søren; Stavngaard, Trine

    2015-01-01

    minute-by-minute changes in brain tissue oxygen during balloon angioplasty and intraarterial administration of vasodilators in three patients.Our results confirm that endovascular intervention is capable of not only resolving angiographic vasospasm, but also of normalizing values of brain tissue oxygen...... pressure (PtiO₂) in target parenchyma. However, during the intervention, dangerously low levels of brain tissue oxygen, leading to cerebral infarction, may occur. Thus, no clinical improvement was seen in two of the patients and a dramatic worsening was observed in the third patient. Because the decrease...... in brain tissue oxygen was seen after administration of vasopressor agents, this may be a contributing factor....

  13. Discriminating healthy from tumor and necrosis tissue in rat brain tissue samples by Raman spectral imaging.

    Science.gov (United States)

    Amharref, Nadia; Beljebbar, Abdelilah; Dukic, Sylvain; Venteo, Lydie; Schneider, Laurence; Pluot, Michel; Manfait, Michel

    2007-10-01

    The purpose of this study was to investigate molecular changes associated with glioma tissues by Raman microspectroscopy in order to develop its use in clinical practice. Spectroscopic markers obtained from C6 glioma tissues were compared to conventional histological and histochemical techniques. Cholesterol and phospholipid contents were highest in corpus callosum and decreased gradually towards the cortex surface as well as in the tumor. Two different necrotic areas have been identified: a fully necrotic zone characterized by the presence of plasma proteins and a peri-necrotic area with a high lipid content. This result was confirmed by Nile Red staining. Additionally, one structure was detected in the periphery of the tumor. Invisible with histopathological hematoxylin and eosin staining, it was revealed by immunohistochemical Ki-67 and MT1-MMP staining used to visualize the proliferative and invasive activities of glioma, respectively. Hierarchical cluster analysis on the only cluster averaged spectra showed a clear distinction between normal, tumoral, necrotic and edematous tissues. Raman microspectroscopy can discriminate between healthy and tumoral brain tissue and yield spectroscopic markers associated with the proliferative and invasive properties of glioblastoma. Development of in vivo Raman spectroscopy could thus accurately define tumor margins, identify tumor remnants, and help in the development of novel therapies for glioblastoma.

  14. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue

    DEFF Research Database (Denmark)

    Hanrieder, Jørg; Wicher, Grzegorz; Bergquist, Jonas

    2011-01-01

    tracers for prediction of oligodendroglial and astroglial localization in brain tissue. The different cell type specific protein distributions in tissue were validated using immunohistochemistry. ICMS of intact neuroglia is a simple and straightforward approach for characterization and discrimination...

  15. Increased brain tissue sodium concentration in Huntington's Disease - a sodium imaging study at 4 T.

    Science.gov (United States)

    Reetz, Kathrin; Romanzetti, Sandro; Dogan, Imis; Saß, Christian; Werner, Cornelius J; Schiefer, Johannes; Schulz, Jörg B; Shah, N Jon

    2012-10-15

    The neuropathological hallmark of the autosomal dominantly inherited, neurodegenerative disorder Huntington's disease is progressive striatal loss starting several years prior to symptom manifestation. Magnetic resonance (MR) imaging has been widely used to detect altered structure in premanifest and early Huntington's disease. Given that neurodegeneration is likely preceded by substantial neuronal dysfunction, we used in vivo sodium MR imaging, which has been shown to be sensitive to cell death and viability, to investigate cellular and metabolic integrity of Huntington's disease brain tissue. We studied a total of thirteen healthy controls and thirteen Huntington's disease gene carriers (11 manifest and 2 premanifest). The manifest Huntington's disease group was subdivided into stages 1 and 2 according to their Total Functional Capacity scores. Clinical total motor and cognitive scores, as well as calibrated sodium and T1-weighted MR images were obtained with a 4 T Siemens MR scanner. Sodium images were acquired by means of a constant time imaging technique with an ultra-short "echo time". T1-weighted MR images were further analysed with voxel-based morphometry. The absolute total sodium concentration and grey matter values were measured in several Huntington's disease-specific and also non-specific areas. Statistical analysis of variance and Pearson correlation were applied. In Huntington's disease subjects, we found an increase of total sodium concentration of the entire brain compared to controls. Increased total sodium concentration values were found in structurally affected, but also in some non-affected, regions. The highest total sodium concentration values were found in the bilateral caudate, which was associated with caudate grey matter atrophy and CAG repeat length. In all Huntington's disease subjects we further found a profound increase of total sodium concentration in the putamen, pallidum, thalamus, hippocampus, insula, precuneus and occipital

  16. Computational cell quantification in the human brain tissues based on hard x-ray phase-contrast tomograms

    Science.gov (United States)

    Hieber, Simone E.; Bikis, Christos; Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Thalmann, Peter; Chicherova, Natalia; Rack, Alexander; Zdora, Marie-Christine; Zanette, Irene; Schweighauser, Gabriel; Hench, Jürgen; Müller, Bert

    2016-10-01

    Cell visualization and counting plays a crucial role in biological and medical research including the study of neurodegenerative diseases. The neuronal cell loss is typically determined to measure the extent of the disease. Its characterization is challenging because the cell density and size already differs by more than three orders of magnitude in a healthy cerebellum. Cell visualization is commonly performed by histology and fluorescence microscopy. These techniques are limited to resolve complex microstructures in the third dimension. Phase- contrast tomography has been proven to provide sufficient contrast in the three-dimensional imaging of soft tissue down to the cell level and, therefore, offers the basis for the three-dimensional segmentation. Within this context, a human cerebellum sample was embedded in paraffin and measured in local phase-contrast mode at the beamline ID19 (ESRF, Grenoble, France) and the Diamond Manchester Imaging Branchline I13-2 (Diamond Light Source, Didcot, UK). After the application of Frangi-based filtering the data showed sufficient contrast to automatically identify the Purkinje cells and to quantify their density to 177 cells per mm3 within the volume of interest. Moreover, brain layers were segmented in a region of interest based on edge detection. Subsequently performed histological analysis validated the presence of the cells, which required a mapping from the two- dimensional histological slices to the three-dimensional tomogram. The methodology can also be applied to further tissue types and shows potential for the computational tissue analysis in health and disease.

  17. Ectopic Brain Tissue in a Child: A Case Report A Case of Ectopic Brain Tissue in the Nasophaynx in Thailand

    Directory of Open Access Journals (Sweden)

    Vannipa Vathanophas

    2017-03-01

    Full Text Available Brain heterotopia is a benign tumor composed of differentiated neural tissue that is located outside the cranial vault. This condition is uncommon and presents as a congenital pharyngeal mass. Here, we report a case of neuroepithelial heterotopia in the nasopharyngeal area of a six-month-old boy who presented with cleft palate and stridor. The tumor demonstrated aggressive growth with oropharyngeal involvement. Radiologic finding revealed a large heterogeneous enhancement on the left side of the nasopharynx, involving the uvula, left lateral pharyngeal wall, and left tonsil. No connection to the brain or spinal cord was apparent on imaging. Histologic features included presence of neuroglial heterotopias, composed predominately of glial cells in a surrounding neurofibrillary matrix. Surgery was the selected intervention, with wide excision performed via cleft palate. Previously published literature relevant to this case were reviewed and discussed. Recurrence is common in incomplete resection, although there was no evidence of recurrence at the two-year follow-up in this patient.

  18. Neurodegenerative Shielding by Curcumin and Its Derivatives on Brain Lesions Induced by 6-OHDA Model of Parkinson's Disease in Albino Wistar Rats

    Directory of Open Access Journals (Sweden)

    Shyam Sunder Agrawal

    2012-01-01

    Full Text Available Study was undertaken to evaluate the neurodegenerative defending potential of curcumin (CUR, demethoxycurcumin (DMC, and bisdemethoxycurcumin (BDMC on 6-hydroxydopamine-(6-OHDA induced Parkinsonism model in rats. Curcuminoids were administered (60 mg/kg, body weight, per oral for three weeks followed by unilateral injection of 6-OHDA on 22nd day (10 μg/2 μL into the right striatum leading to extensive loss of dopaminergic cells. The behavioral observations, biochemical markers, quantification of dopamine (DA, DOPAC, and HVA followed by dopamine (D2 receptor binding assay and tyrosine hydroxylase (TH, using immunohistochemistry were evaluated using HPLC after three weeks of lesion. Pretreated animals showed significant protection against neuronal degeneration compared to lesion animals by normalizing the deranged levels of biomarkers and showed the potency in the order CUR > DMC > BDMC. The same order of effectiveness was observed in D2 receptors binding assay and TH immunohistochemistry study. We conclude that curcuminoids appear to shield progressive neuronal degeneration from increased oxidative attack in 6-OHDA-lesioned rats through its free radical scavenging mechanism, and DA, DOPAC, and HVA enhancing capabilities in the sequence of efficacy CUR > DMC > BDMC. Further, curcuminoids may have potential utility in treatment of many more oxidative stress-induced neurodegenerative disorders.

  19. Tau imaging in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Dani, M.; Edison, P. [Imperial College London, Neurology Imaging Unit, Division of Neuroscience, London (United Kingdom); Brooks, D.J. [Imperial College London, Neurology Imaging Unit, Division of Neuroscience, London (United Kingdom); Aarhus University, Institute of Clinical Medicine, Aarhus (Denmark)

    2016-06-15

    Aggregated tau protein is a major neuropathological substrate central to the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration and chronic traumatic encephalopathy. In AD, it has been shown that the density of hyperphosphorylated tau tangles correlates closely with neuronal dysfunction and cell death, unlike β-amyloid. Until now, diagnostic and pathologic information about tau deposition has only been available from invasive techniques such as brain biopsy or autopsy. The recent development of selective in-vivo tau PET imaging ligands including [{sup 18}F]THK523, [{sup 18}F]THK5117, [{sup 18}F]THK5105 and [{sup 18}F]THK5351, [{sup 18}F]AV1451(T807) and [{sup 11}C]PBB3 has provided information about the role of tau in the early phases of neurodegenerative diseases, and provided support for diagnosis, prognosis, and imaging biomarkers to track disease progression. Moreover, the spatial and longitudinal relationship of tau distribution compared with β - amyloid and other pathologies in these diseases can be mapped. In this review, we discuss the role of aggregated tau in tauopathies, the challenges posed in developing selective tau ligands as biomarkers, the state of development in tau tracers, and the new clinical information that has been uncovered, as well as the opportunities for improving diagnosis and designing clinical trials in the future. (orig.)

  20. Enhancement of Sexual Behavior in Female Rats by Neonatal Transplantation of Brain Tissue from Males

    Science.gov (United States)

    Arendash, Gary W.; Gorski, Roger A.

    1982-09-01

    Transplantation of preoptic tissue from male rat neonates into the preoptic area of female littermates increased masculine and feminine sexual behavior in the recipients during adulthood. This suggests that functional connections develop between the transplanted neural tissue and the host brain. A new intraparenchymal brain transplantation technique was used to achieve these results.

  1. Endocannabinoid system in neurodegenerative disorders.

    Science.gov (United States)

    Basavarajappa, Balapal S; Shivakumar, Madhu; Joshi, Vikram; Subbanna, Shivakumar

    2017-09-01

    Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well-defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may proceed concurrently or successively, and they differ among cell types at different developmental stages in distinct brain regions. The endocannabinoid system, which involves cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), endogenous cannabinoids and the enzymes that catabolize these compounds, has been shown to contribute to the development of NDDs in several animal models and human studies. In this review, we discuss the functions of the endocannabinoid system in NDDs and converse the therapeutic efficacy of targeting the endocannabinoid system to rescue NDDs. © 2017 International Society for Neurochemistry.

  2. Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue

    Directory of Open Access Journals (Sweden)

    Ravid Rivka

    2008-05-01

    Full Text Available Abstract Background Studies of gene expression in post mortem human brain can contribute to understanding of the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD, Parkinson's disease (PD and dementia with Lewy bodies (DLB. Quantitative real-time PCR (RT qPCR is often used to analyse gene expression. The validity of results obtained using RT qPCR is reliant on accurate data normalization. Reference genes are generally used to normalize RT qPCR data. Given that expression of some commonly used reference genes is altered in certain conditions, this study aimed to establish which reference genes were stably expressed in post mortem brain tissue from individuals with AD, PD or DLB. Results The present study investigated the expression stability of 8 candidate reference genes, (ubiquitin C [UBC], tyrosine-3-monooxygenase [YWHAZ], RNA polymerase II polypeptide [RP II], hydroxymethylbilane synthase [HMBS], TATA box binding protein [TBP], β-2-microglobulin [B2M], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], and succinate dehydrogenase complex-subunit A, [SDHA] in cerebellum and medial temporal gyrus of 6 AD, 6 PD, 6 DLB subjects, along with 5 matched controls using RT qPCR (TaqMan® Gene Expression Assays. Gene expression stability was analysed using geNorm to rank the candidate genes in order of decreasing stability in each disease group. The optimal number of genes recommended for accurate data normalization in each disease state was determined by pairwise variation analysis. Conclusion This study identified validated sets of mRNAs which would be appropriate for the normalization of RT qPCR data when studying gene expression in brain tissue of AD, PD, DLB and control subjects.

  3. Inter-laboratory comparison of DNA preservation in archival paraffin-embedded human brain tissue from participating centres on four continents.

    Science.gov (United States)

    Kösel, S; Grasbon-Frodl, E M; Arima, K; Chimelli, L; Hahn, M; Hashizume, Y; Hulette, C; Ikeda, K; Jacobsen, P F; Jones, M; Kobayashi, M; Love, S; Mizutani, T; Rosemberg, S; Sasaki, A; Smith, T W; Takahashi, H; Vortmeyer, A O; Graeber, M B

    2001-07-01

    DNA extracted from formalin-fixed and paraffin-embedded brain tissue is known to contain as yet ill-characterized inhibitors of the PCR process. As part of a project that aims to clarify the role of mitochondrial DNA sequence variation in human neurodegenerative diseases using DNA from various ethnic backgrounds, we have investigated factors that influence the preservation of archival DNA and its suitability for PCR. In this study, neuropathological tissue samples were analysed that had been routinely processed in 18 international centres on four continents. Following DNA extraction, PCR amplification of mitochondrial and nuclear DNA sequences was performed with and without additional purification of the template DNA. In addition, the DNA used for PCR was analysed by HPLC. Phosphate-buffered formalin proved to be a superior fixative compared with unbuffered aldehyde: DNA extraction resulted in greater yields, the molecular weight of the isolated DNA was higher and PCR was more successful. PCR inhibitors were identified as (1) high concentrations of small (analysis did not reveal significant qualitative differences between DNA isolated from fresh-frozen tissue samples and DNA recovered from formalin-fixed, paraffin-embedded brain tissue. The fact that DNA could be amplified from the majority of tissue specimens in this study suggests that rare diseases and diseases where ethnic background plays an important role can be sampled for genetic polymorphism analysis on a global scale using archival neuropathological collections.

  4. Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue

    Science.gov (United States)

    Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw

    2014-01-01

    We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.

  5. Temperature-dependent elastic properties of brain tissues measured with the shear wave elastography method.

    Science.gov (United States)

    Liu, Yan-Lin; Li, Guo-Yang; He, Ping; Mao, Ze-Qi; Cao, Yanping

    2017-01-01

    Determining the mechanical properties of brain tissues is essential in such cases as the surgery planning and surgical training using virtual reality based simulators, trauma research and the diagnosis of some diseases that alter the elastic properties of brain tissues. Here, we suggest a protocol to measure the temperature-dependent elastic properties of brain tissues in physiological saline using the shear wave elastography method. Experiments have been conducted on six porcine brains. Our results show that the shear moduli of brain tissues decrease approximately linearly with a slope of -0.041±0.006kPa/°C when the temperature T increases from room temperature (~23°C) to body temperature (~37°C). A case study has been further conducted which shows that the shear moduli are insensitive to the temperature variation when T is in the range of 37 to 43°C and will increase when T is higher than 43°C. With the present experimental setup, temperature-dependent elastic properties of brain tissues can be measured in a simulated physiological environment and a non-destructive manner. Thus the method suggested here offers a unique tool for the mechanical characterization of brain tissues with potential applications in brain biomechanics research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Compliant intracortical implants reduce strains and strain rates in brain tissue in vivo

    Science.gov (United States)

    Sridharan, Arati; Nguyen, Jessica K.; Capadona, Jeffrey R.; Muthuswamy, Jit

    2015-06-01

    Objective. The objective of this research is to characterize the mechanical interactions of (1) soft, compliant and (2) non-compliant implants with the surrounding brain tissue in a rodent brain. Understanding such interactions will enable the engineering of novel materials that will improve stability and reliability of brain implants. Approach. Acute force measurements were made using a load cell in n = 3 live rats, each with 4 craniotomies. Using an indentation method, brain tissue was tested for changes in force using established protocols. A total of 4 non-compliant, bare silicon microshanks, 3 non-compliant polyvinyl acetate (PVAc)-coated silicon microshanks, and 6 compliant, nanocomposite microshanks were tested. Stress values were calculated by dividing the force by surface area and strain was estimated using a linear stress-strain relationship. Micromotion effects from breathing and vascular pulsatility on tissue stress were estimated from a 5 s interval of steady-state measurements. Viscoelastic properties were estimated using a second-order Prony series expansion of stress-displacement curves for each shank. Main results. The distribution of strain values imposed on brain tissue for both compliant nanocomposite microshanks and PVAc-coated, non-compliant silicon microshanks were significantly lower compared to non-compliant bare silicon shanks. Interestingly, step-indentation experiments also showed that compliant, nanocomposite materials significantly decreased stress relaxation rates in the brain tissue at the interface (p brain tissue. Understanding the material behavior at the site of tissue contact will help to improve neural implant design.

  7. Sleep disturbance in mental health problems and neurodegenerative disease.

    Science.gov (United States)

    Anderson, Kirstie N; Bradley, Andrew J

    2013-01-01

    Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour) processes and is vital for normal brain function. This review will outline the normal sleep-wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed.

  8. The Conductivity of Brain Tissues: Comparison of Results in Vivo and In Vitro Measurements

    Science.gov (United States)

    2001-10-25

    situation in the living piglet . In [7] the estimated resistivity ratio of skull and brain is 14:1. The same ratio calculated from the results of in vivo...brain. Presumably measured from tissue samples at 390C. [19] Foster et al. 1979 2,67 (10 MHz) 3,33 (10 MHz) Tissue samples from dog’s brain at 370C. [22...Biol., vol. 41, pp. 2251-2269, 1996. [13] K. R. Foster , “Dielectric properties of tissues,” In: Bronzino J. D. (ed.). The

  9. Ionic charge transport between blockages: Sodium cation conduction in freshly excised bulk brain tissue

    Directory of Open Access Journals (Sweden)

    David Emin

    2015-08-01

    Full Text Available We analyze the transient-dc and frequency-dependent electrical conductivities between blocking electrodes. We extend this analysis to measurements of ions’ transport in freshly excised bulk samples of human brain tissue whose complex cellular structure produces blockages. The associated ionic charge-carrier density and diffusivity are consistent with local values for sodium cations determined non-invasively in brain tissue by MRI (NMR and diffusion-MRI (spin-echo NMR. The characteristic separation between blockages, about 450 microns, is very much shorter than that found for sodium-doped gel proxies for brain tissue, >1 cm.

  10. Ionic charge transport between blockages: Sodium cation conduction in freshly excised bulk brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Emin, David, E-mail: emin@unm.edu [Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131 (United States); Akhtari, Massoud [Semple Institutes for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States); Ellingson, B. M. [Department of Radiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States); Mathern, G. W. [Department of Neurosurgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States)

    2015-08-15

    We analyze the transient-dc and frequency-dependent electrical conductivities between blocking electrodes. We extend this analysis to measurements of ions’ transport in freshly excised bulk samples of human brain tissue whose complex cellular structure produces blockages. The associated ionic charge-carrier density and diffusivity are consistent with local values for sodium cations determined non-invasively in brain tissue by MRI (NMR) and diffusion-MRI (spin-echo NMR). The characteristic separation between blockages, about 450 microns, is very much shorter than that found for sodium-doped gel proxies for brain tissue, >1 cm.

  11. Selenium, selenoproteins and neurodegenerative diseases.

    Science.gov (United States)

    Cardoso, Bárbara Rita; Roberts, Blaine R; Bush, Ashley I; Hare, Dominic J

    2015-08-01

    It is unsurprising that our understanding of the role of selenium in neurological function is somewhat immature, considering its relatively recent discovery as an essential element to human health. Selenocysteine, the 21st amino acid, is the defining feature of the 25 selenoprotein-encoding genes so far discovered within the human genome. The low abundance of these proteins in the brain belies the integral role they play in normal neurological function, from well-characterised antioxidant activity in the periphery to poorly understood mechanisms that modulate mitochondrial function and response to brain pathology. Selenium has been identified as playing a role in several neurodegenerative disorders, including Alzheimer's and Parkinson's disease, though its function as a 'cause or effect' of disease process remains unclear. This review discusses selenium metabolism in detail, specifically with regard to the role it plays within the central nervous system, and examines the most current literature investigating how selenium may be involved in chronic diseases of the central nervous system.

  12. Proteomic Analyses for the Global S-Nitrosylated Proteins in the Brain Tissues of Different Human Prion Diseases.

    Science.gov (United States)

    Chen, Li-Na; Shi, Qi; Zhang, Bao-Yun; Zhang, Xiao-Mei; Wang, Jing; Xiao, Kang; Lv, Yan; Sun, Jing; Yang, Xiao-Dong; Chen, Cao; Zhou, Wei; Han, Jun; Dong, Xiao-Ping

    2016-10-01

    Human prion diseases are fatal neurodegenerative disorders characterized by neuronal damage in brain. Protein S-nitrosylation, the covalent adduction of a NO to cysteine, plays a role in human brain biology, and brain dysfunction is a prominent feature of prion disease, yet the direct brain targets of S-nitrosylation are largely unknown. We described the first proteomic analysis of global S-nitrosylation in brain tissues of sporadic Creutzfeldt-Jakob disease (sCJD), fatal familial insomnia (FFI), and genetic CJD with a substitution of valine for glycine at codon 114 of the prion protein gene (G114V gCJD) accompanying with normal control with isobaric tags for relative and absolute quantitation (iTRAQ) combined with a nano-HPLC/Q-Exactive mass spectrometry platform. In parallel, we used several approaches to provide quality control for the experimentally defined S-nitrosylated proteins. A total of 1509 S-nitrosylated proteins (SNO-proteins) were identified, and data are available via ProteomeXchange with identifier PXD002813. The cerebellum tissues appeared to contain more commonly differentially expressed SNO-proteins (DESPs) than cortex of sCJD, FFI, and gCJD. Three selected SNO-proteins were verified by Western blots, consistent with proteomics assays. Gene ontology analysis showed that more up-regulated DESPs were involved in metabolism, cell cytoskeleton/structure, and immune system both in the cortex and cerebellum, while more down-regulated ones in both regions were involved in cell cytoskeleton/structure, cell-cell communication, and miscellaneous function protein. Pathway analysis suggested that systemic lupus erythematosus, pathogenic Escherichia coli infection, and extracellular matrix-receptor interaction were the most commonly affected pathways, which were identified from at least two different diseases. Using STRING database, the network of immune system and cell cytoskeleton and structure were commonly identified in the context of the up-regulated and

  13. Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery

    NARCIS (Netherlands)

    Blumcke, Ingmar; Spreafico, Roberto; Haaker, Gerrit; Coras, Roland; Kobow, Katja; Bien, Christian G.; Pfäfflin, Margarete; Elger, Christian; Widman, Guido; Schramm, Johannes; Becker, Albert; Braun, Kees P.; Leijten, Frans; Baayen, Johannes C.; Aronica, Eleonora; Chassoux, Francine; Hamer, Hajo; Stefan, Hermann; Rössler, Karl; Thom, Maria; Walker, Matthew C.; Sisodiya, Sanjay M.; Duncan, John S.; McEvoy, Andrew W.; Pieper, Tom; Holthausen, Hans; Kudernatsch, Manfred; Meencke, H. Joachim; Kahane, Philippe; Schulze-Bonhage, Andreas; Zentner, Josef; Heiland, Dieter H.; Urbach, Horst; Steinhoff, Bernhard J.; Bast, Thomas; Tassi, Laura; Lo Russo, Giorgio; Özkara, Cigdem; Oz, Buge; Krsek, Pavel; Vogelgesang, Silke; Runge, Uwe; Lerche, Holger; Weber, Yvonne; Honavar, Mrinalini; Pimentel, José; Arzimanoglou, Alexis; Ulate-Campos, Adriana; Noachtar, Soheyl; Hartl, Elisabeth; Schijns, Olaf; Guerrini, Renzo; Barba, Carmen; Jacques, Thomas S.; Cross, J. Helen; Feucht, Martha; Mühlebner, Angelika; Grunwald, Thomas; Trinka, Eugen; Winkler, Peter A.; Gil-Nagel, Antonio; Toledano Delgado, Rafael; Mayer, Thomas; Lutz, Martin; Zountsas, Basilios; Garganis, Kyriakos; Rosenow, Felix; Hermsen, Anke; von Oertzen, Tim J.; Diepgen, Thomas L.; Avanzini, Giuliano; Aparicio, Javier; Bento, Conceição; Beckervordersandforth, Jan; Buccoliero, Annamaria; Cabral, Pedro; Chamadoira, Clara; Colon, Albert; Chabardès, Stéphan; Carpenter, Stirling; Czech, Thomas; Dressler, Anastasia; Deleo, Francesco; Dílio, Alves; Dings, Jim; Devaux, Bertrand; de Tisi, Jane; de Bellescize, Julitta; Ebner, Alois; Franke, Kerstin; Groeppel, Gudrun; Giordano, Flavio; Gozzo, Francesca; Garbelli, Rita; Guenot, Marc; García‐Morales, Irene; Gómez‐Angulo, Juan Carlos; Garcia, Gemma; Hainfellner, Johannes A.; Höfler, Julia; Hoogland, Govert; Hendriks, Marc; Hofman, Paul; Harding, Brian; Huppertz, Hans‐Jürgen; Herms, Jochen; Hilkman, Danny M. W.; Hamelin, Sophie; Idema, Sander; Jansen, Floor E.; Jahodova, Alena; Keeley, Angus; Kalss, Gudrun; Kudr, Martin; Kroell, Judith; Kokkinos, Vasileios; Keo Kosal, Pascale; Kalbhenn, Thilo; Leitinger, Markus; Landré, Elisabeth; Melo Pires, Manuel; Matas, Andreia; Mann, Michael W.; Ostrowsky‐Coste, Karine; Prinz, Marco; Puttinger, Gertraud; Peraud, Aurelia; Rangel Pinho, Rui; Romero, Clara; Rego, Ricardo; Rouhl, Rob; Ryvlin, Philippe; Rumia, Jordi; Rampp, Stefan; Scholl, Theresa; Schulz, Reinhard; Stone, Thomas J.; Streichenberger, Nathalie; Tisdall, Martin; Turak, Baris; Taipa, Ricardo; Uzan, Mustafa; van Kranen‐Mastenbroek, Vivianne; Varlet, Pascale; Vlooswijk, Marielle; Wagner, Louis; Weis, Serge

    2017-01-01

    Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures

  14. ALS-causing mutations differentially affect PGC-1α expression and function in the brain vs. peripheral tissues.

    Science.gov (United States)

    Bayer, Hanna; Lang, Kerstin; Buck, Eva; Higelin, Julia; Barteczko, Lara; Pasquarelli, Noemi; Sprissler, Jasmin; Lucas, Tanja; Holzmann, Karlheinz; Demestre, Maria; Lindenberg, Katrin S; Danzer, Karin M; Boeckers, Tobias; Ludolph, Albert C; Dupuis, Luc; Weydt, Patrick; Witting, Anke

    2017-01-01

    Monogenetic forms of amyotrophic lateral sclerosis (ALS) offer an opportunity for unraveling the molecular mechanisms underlying this devastating neurodegenerative disorder. In order to identify a link between ALS-related metabolic changes and neurodegeneration, we investigated whether ALS-causing mutations interfere with the peripheral and brain-specific expression and signaling of the metabolic master regulator PGC (PPAR gamma coactivator)-1α (PGC-1α). We analyzed the expression of PGC-1α isoforms and target genes in two mouse models of familial ALS and validated the stimulated PGC-1α signaling in primary adipocytes and neurons of these animal models and in iPS derived motoneurons of two ALS patients harboring two different frame-shift FUS/TLS mutations. Mutations in SOD1 and FUS/TLS decrease Ppargc1a levels in the CNS whereas in muscle and brown adipose tissue Ppargc1a mRNA levels were increased. Probing the underlying mechanism in neurons, we identified the monocarboxylate lactate as a previously unrecognized potent and selective inducer of the CNS-specific PGC-1α isoforms. Lactate also induced genes like brain-derived neurotrophic factor, transcription factor EB and superoxide dismutase 3 that are down-regulated in PGC-1α deficient neurons. The lactate-induced CNS-specific PGC-1α signaling system is completely silenced in motoneurons derived from induced pluripotent stem cells obtained from two ALS patients harboring two different frame-shift FUS/TLS mutations. ALS mutations increase the canonical PGC-1α system in the periphery while inhibiting the CNS-specific isoforms. We identify lactate as an inducer of the neuronal PGC-1α system directly linking brain metabolism and neuroprotection. Changes in the PGC-1α system might be involved in the ALS accompanied metabolic changes and in neurodegeneration. Copyright © 2016. Published by Elsevier Inc.

  15. Increased TRH and TRH-like peptide release in rat brain and peripheral tissues during proestrus/estrus.

    Science.gov (United States)

    Pekary, A E; Sattin, Albert

    2014-02-01

    Women are at greater risk for major depression, PTSD, and other anxiety disorders. ERβ-selective agonists for the treatment of these disorders are the focus of pharmacologic development and clinical testing. Estradiol and its metabolites contribute to the neuroprotective effects of this steroid class, particularly in men, due to local conversion of testosterone to estiradiol in key brain regions which are predisposed to neurodegenerative diseases. We have used young adult female Sprague-Dawley rats to assess the role of TRH and TRH-like peptides, with the general structure pGlu-X-Pro-NH2 where "X" can be any amino acid residue, as mediators of the neurobiochemical effects of estradiol. The neuroprotective TRH and TRH-like peptides are coreleased with excitotoxic glutamate by glutamatergic neurons which contribute importantly to the regulation of the estrus cycle. The levels of TRH and TRH-like peptides during proestrus and/or estrus in the 12 brain regions analyzed were significantly decreased (due to accelerated release) 106 times but increased only 25 times when compared to the corresponding levels during diestrus days 1 and 2. These changes, listed by brain region in the order of decreasing number of significant decreases (↓) and/or increases (↑), were: striatum (20↓,1↑), medulla oblongata (16↓,2↑), amygdala (14↓,1↑), cerebellum (13↓,1↑), hypothalamus (12↓,1↑), entorhinal cortex (6↓,6↑), posterior cingulate (10↓,1↑), frontal cortex (3↓,5↑), nucleus accumbens (5↓,3↑), hippocampus (5↓,2↑), anterior cingulate (2↓,1↑), and piriform cortex (1↑). In peripheral tissues the corresponding changes were: ovaries (23↓), uterus (16↓,1↑), adrenals (11↓,3↑), and pancreas (1↓,6↑). We conclude that these peptides may be downstream mediators of some of the therapeutic effects of estrogen. Published by Elsevier Inc.

  16. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases.

    Science.gov (United States)

    Vanni, Silvia; Zattoni, Marco; Moda, Fabio; Giaccone, Giorgio; Tagliavini, Fabrizio; Haïk, Stéphane; Deslys, Jean-Philippe; Zanusso, Gianluigi; Ironside, James W; Carmona, Margarita; Ferrer, Isidre; Kovacs, Gabor G; Legname, Giuseppe

    2018-01-01

    Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively) and in different genetic forms of prion diseases (gPrD) in comparison to Alzheimer's disease (AD) subjects and age-matched controls. Methods: Total RNA was obtained from the frontal cortex of vCJD ( n = 20), iCJD ( n = 11), sCJD ( n = 23), gPrD ( n = 30), and AD ( n = 14) patients and age-matched controls ( n = 30). RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis. Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level. Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue)-together with specific molecular and conformational features of the pathological agent of the disease-seem to dictate the peculiar hemoglobin

  17. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

  18. Effect of Cerebrospinal Fluid Drainage on Brain Tissue Oxygenation in Traumatic Brain Injury.

    Science.gov (United States)

    Akbik, Omar S; Krasberg, Mark; Nemoto, Edwin M; Yonas, Howard

    2017-11-15

    The effectiveness of cerebrospinal fluid (CSF) drainage in lowering high intracranial pressure (ICP) is well established in severe traumatic brain injury (TBI). Recently, however, the use of external ventricular drains (EVDs) and ICP monitors in TBI has come under question. The aim of this retrospective study was to investigate the effect of CSF drainage on brain tissue oxygenation (PbtO2). Using a multi-modality monitoring system, we continuously monitored PbtO2 and parenchymal ICP during CSF drainage events via a ventriculostomy in 40 patients with severe TBI. Measurements were time-locked continuous recordings on a Component Neuromonitoring System in a neuroscience intensive care unit. We further selected for therapeutic CSF drainage events initiated at ICP values above 25 mm Hg and analyzed the 4-min periods before and after drainage for the physiologic variables ICP, cerebral perfusion pressure (CPP), and PbtO2. We retrospectively identified 204 CSF drainage events for ICP EVD-opening values greater than 25 mm Hg in 23 patients. During the 4 min of opened EVD, ICP decreased by 5.7 ± 0.6 mm Hg, CPP increased by 4.1 ± 1.2 mm Hg, and PbtO2 increased by 1.15 ± 0.26 mm Hg. ICP, CPP, and PbtO2 all improved with CSF drainage at ICP EVD-opening values above 25 mm Hg. Although the average PbtO2 changes were small, a clinically significant change in PbtO2 of 5 mm Hg or greater occurred in 12% of CSF drainage events, which was correlated with larger decreases in ICP, displaying a complex relationship between ICP and PbtO2 that warrants further studies.

  19. Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    William M. Johnson

    2012-10-01

    Full Text Available Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, and Friedreich’s ataxia. In this review background is provided on the steady-state synthesis, regulation, and transport of glutathione, with primary focus on the brain. A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathione-dependent enzymes. Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation. In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status and/or in the activities of glutathione-dependent enzymes. Mechanisms of dysregulation of glutathione and/or glutathione-dependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease. Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions. The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutathione as a biomarker, are critically evaluated.

  20. Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

    Science.gov (United States)

    Johnson, William M.; Wilson-Delfosse, Amy L.; Mieyal, John. J.

    2012-01-01

    Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, and Friedreich’s ataxia. In this review background is provided on the steady-state synthesis, regulation, and transport of glutathione, with primary focus on the brain. A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathione-dependent enzymes. Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation. In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status and/or in the activities of glutathione-dependent enzymes. Mechanisms of dysregulation of glutathione and/or glutathione-dependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease. Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions. The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutathione as a biomarker, are critically evaluated. PMID:23201762

  1. Evaluation of tissue-equivalent materials to be used as human brain tissue substitute in dosimetry for diagnostic radiology

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, C.C., E-mail: cassio.c.ferreira@gmail.co [Departamento de Fisica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil); Ximenes Filho, R.E.M., E-mail: raimundoximenes@hotmail.co [Departamento de Fisica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil); Vieira, J.W., E-mail: jwvieira@br.inter.ne [Centro Federal de Educacao Tecnologica de Pernambuco (CEFET-PE), Av. Professor Luiz Freire, 500 Curado, CEP 50740-540, Recife (Brazil); Escola Politecnica de Pernambuco, Universidade de Pernambuco (EPP/UPE), Rua Benfica, 455, Madalena, CEP 50720-001, Recife (Brazil); Tomal, A., E-mail: alessandratomal@pg.ffclrp.usp.b [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto-SP 14040-90 (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.b [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto-SP 14040-90 (Brazil); Garcia, C.A.B., E-mail: cgarcia@ufs.b [Departamento de Quimica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil); Maia, A.F., E-mail: afmaia@ufs.b [Departamento de Fisica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil)

    2010-08-15

    Tissue-equivalent materials to be used as substitutes for human brain tissue in dosimetry for diagnostic radiology have been investigated in terms of calculated total mass attenuation coefficient ({mu}/{rho}), calculated mass energy-absorption coefficient ({mu}{sub en}/{rho}) and absorbed dose. Measured linear attenuation coefficients ({mu}) have been used for benchmarking the calculated total mass attenuation coefficient ({mu}/{rho}). The materials examined were bolus, nylon (registered) , orange articulation wax, red articulation wax, PMMA (polymethylmethacrylate), bees wax, paraffin I, paraffin II, pitch and water. The results show that water is the best substitute for brain among the materials investigated. The average percentage differences between the calculated {mu}/{rho} and {mu}{sub en}/{rho} coefficients for water and those for brain were 1.0% and 2.5%, respectively. Absorbed doses determined by Monte Carlo methods confirm water as being the best brain substitute to be used in dosimetry for diagnostic radiology, showing maximum difference of 0.01%. Additionally this study showed that PMMA, a material often used for the manufacturing of head phantoms for computed tomography, cannot be considered to be a suitable substitute for human brain tissue in dosimetry.

  2. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    Science.gov (United States)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  3. Multimodal optical imaging database from tumour brain human tissue: endogenous fluorescence from glioma, metastasis and control tissues

    Science.gov (United States)

    Poulon, Fanny; Ibrahim, Ali; Zanello, Marc; Pallud, Johan; Varlet, Pascale; Malouki, Fatima; Abi Lahoud, Georges; Devaux, Bertrand; Abi Haidar, Darine

    2017-02-01

    Eliminating time-consuming process of conventional biopsy is a practical improvement, as well as increasing the accuracy of tissue diagnoses and patient comfort. We addressed these needs by developing a multimodal nonlinear endomicroscope that allows real-time optical biopsies during surgical procedure. It will provide immediate information for diagnostic use without removal of tissue and will assist the choice of the optimal surgical strategy. This instrument will combine several means of contrast: non-linear fluorescence, second harmonic generation signal, reflectance, fluorescence lifetime and spectral analysis. Multimodality is crucial for reliable and comprehensive analysis of tissue. Parallel to the instrumental development, we currently improve our understanding of the endogeneous fluorescence signal with the different modalities that will be implemented in the stated. This endeavor will allow to create a database on the optical signature of the diseased and control brain tissues. This proceeding will present the preliminary results of this database on three types of tissues: cortex, metastasis and glioblastoma.

  4. Sleep disturbance in mental health problems and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Anderson KN

    2013-05-01

    Full Text Available Kirstie N Anderson1 Andrew J Bradley2,3 1Department of Neurology, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK; 2Eli Lilly and Company Limited, Lilly House, Basingstoke, UK; 3Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK Abstract: Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour processes and is vital for normal brain function. This review will outline the normal sleep–wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed. Keywords: sleep, mental health, neurodegenerative disorders, cognition

  5. B-spline-based stereotactical normalization of brain FDG PET scans in suspected neurodegenerative disease: impact on voxel-based statistical single-subject analysis.

    Science.gov (United States)

    Wenzel, Fabian; Young, Stewart; Wilke, Florian; Apostolova, Ivayla; Arlt, Sönke; Jahn, Holger; Thiele, Frank; Buchert, Ralph

    2010-04-15

    A b-spline-based method 'Lobster', originally designed as a general technique for non-linear image registration, was tailored for stereotactical normalization of brain FDG PET scans. Lobster was compared with the normalization methods of SPM2 and Neurostat with respect to the impact on the accuracy of voxel-based statistical analysis. (i) Computer simulation: Seven representative patterns of cortical hypometabolism served as artificial ground truth. They were inserted into 26 normal control scans with different simulated severity levels. After stereotactical normalization and voxel-based testing, statistical maps were compared voxel-by-voxel with the ground truth. This was done at different levels of statistical significance. There was a highly significant effect of the stereotactical normalization method on the area under the resulting ROC curve. Lobster showed the best average performance and was most stable with respect to variation of the severity level. (ii) Clinical evaluation: Statistical maps were obtained for the normal controls as well as patients with Alzheimer's disease (AD, n=44), Lewy-Body disease (LBD, 9), fronto-temporal dementia (FTD, 13), and cortico-basal dementia (CBD, 4). These maps were classified as normal, AD, LBD, FTD, or CBD by two experienced readers. The stereotactical normalization method had no significant effect on classification by of each of the experts, but it appeared to affect agreement between the experts. In conclusion, Lobster is appropriate for use in single-subject analysis of brain FDG PET scans in suspected dementia, both in early diagnosis (mild hypometabolism) and in differential diagnosis in advanced disease stages (moderate to severe hypometabolism). The computer simulation framework developed in the present study appears appropriate for quantitative evaluation of the impact of the different processing steps and their interaction on the performance of voxel-based single-subject analysis. Copyright 2009 Elsevier Inc

  6. Mesenchymal Stem Cells in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Olcay Ergurhan Kiroglu

    2015-03-01

    Full Text Available Neurodegenerative diseases are almost incurable, debilitating, and they might be fatal, because of limited neurogenesis in nervous system, presence of inhibitory substances and inhibition of recovery due to development of glial scar. Despite many treatment strategies of neurodegenerative diseases no full cure has been achieved. The successful results for mesenchymal stem cells applications on muscles, heart and liver diseases and the application of these cells to the damaged area in particular, hypoxia, inflammation and apoptosis promise hope of using them for neurodegenerative diseases. Mesenchymal stem cells applications constitute a vascular and neuronal phenotype in Parkinsons disease, Huntingtons disease, Amyotrophic lateral sclerosis and Alzheimers disease. Stem cells release bioactive agents that lead to suppression of local immune system, reduction of free radicals, increase in angiogenesis, inhibition of fibrosis, and apoptosis. In addition, tissue stem cells, increase neuronal healing, stimulate proliferation and differentiation. These findings show that stem cells might be a hope of a cure in the treatment of neurodegenerative diseases and intensive work on this issue should continue.

  7. HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

    Science.gov (United States)

    Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

    2010-01-01

    Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

  8. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling

    OpenAIRE

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; Pareto, Deborah; Vilanova, Joan C.; Ramió-Torrentà, LLuís; Sastre-Garriga, Jaume; Montalban, Xavier; Rovira, Àlex; Lladó, Xavier

    2015-01-01

    Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS) lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. Fir...

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

    DEFF Research Database (Denmark)

    Reinstrup, Peter; Nordström, Carl-Henrik

    2011-01-01

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

  10. Probabilistic brain tissue segmentation in neonatal magnetic resonance imaging

    NARCIS (Netherlands)

    Anbeek, Petronella; Vincken, Koen L.; Groenendaal, Floris; Koeman, Annemieke; Van Osch, Matthias J. P.; Van der Grond, Jeroen

    A fully automated method has been developed for segmentation of four different structures in the neonatal brain: white matter (WM), central gray matter (CEGM), cortical gray matter (COGM), and cerebrospinal fluid (CSF). The segmentation algorithm is based on information from T2-weighted (T2-w) and

  11. Automatic Analysis of Brain Tissue and Structural Connectivity in MRI

    NARCIS (Netherlands)

    R. de Boer (Renske)

    2011-01-01

    textabstractStudies of the brain using magnetic resonance imaging (MRI) can provide insights in physiology and pathology that can eventually aid clinical diagnosis and therapy monitoring. MRI data acquired in these studies can be difficult, as well as laborious, to interpret and analyze by

  12. Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research.

    Science.gov (United States)

    Walton, Esther; Hass, Johanna; Liu, Jingyu; Roffman, Joshua L; Bernardoni, Fabio; Roessner, Veit; Kirsch, Matthias; Schackert, Gabriele; Calhoun, Vince; Ehrlich, Stefan

    2016-03-01

    Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Biological fiducial point based registration for multiple brain tissues reconstructed from different imaging modalities

    Science.gov (United States)

    Wu, Huiqun; Zhou, Gangping; Geng, Xingyun; Zhang, Xiaofeng; Jiang, Kui; Tang, Lemin; Zhou, Guomin; Dong, Jiancheng

    2013-10-01

    With the development of computer aided navigation system, more and more tissues shall be reconstructed to provide more useful information for surgical pathway planning. In this study, we aimed to propose a registration framework for different reconstructed tissues from multi-modalities based on some fiducial points on lateral ventricles. A male patient with brain lesion was admitted and his brain scans were performed by different modalities. Then, the different brain tissues were segmented in different modality with relevant suitable algorithms. Marching cubes were calculated for three dimensional reconstructions, and then the rendered tissues were imported to a common coordinate system for registration. Four pairs of fiducial markers were selected to calculate the rotation and translation matrix using least-square measure method. The registration results were satisfied in a glioblastoma surgery planning as it provides the spatial relationship between tumors and surrounding fibers as well as vessels. Hence, our framework is of potential value for clinicians to plan surgery.

  14. Synthetic prions and other human neurodegenerative proteinopathies.

    Science.gov (United States)

    Le, Nhat Tran Thanh; Narkiewicz, Joanna; Aulić, Suzana; Salzano, Giulia; Tran, Hoa Thanh; Scaini, Denis; Moda, Fabio; Giachin, Gabriele; Legname, Giuseppe

    2015-09-02

    Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrP(C)) into a β-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrP(Sc) itself is able to recruit and misfold PrP(C) into the pathological conformation. Recent data have shown that recombinant PrP(C) can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrP(C) into PrP(Sc)in vivo. In this review we describe the state-of-the-art of the body of literature in this field. In addition, we describe a cell-based assay to test synthetic prions in cells, providing further evidence that synthetic amyloids are able to template conversion of PrP into prion inclusions. Studying prions might help to understand the pathological mechanisms governing other neurodegenerative diseases. Aggregation and deposition of misfolded proteins is a common feature of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other disorders. Although the proteins implicated in each of these diseases differ, they share a common prion mechanism. Recombinant proteins are able to aggregate in vitro into β-rich amyloid fibrils, sharing some features of the aggregates found in the brain. Several studies have reported that intracerebral inoculation of synthetic aggregates lead to unique pathology, which spread progressively to distal brain regions and reduced survival time in animals. Here, we review the prion-like features of different proteins involved in neurodegenerative disorders, such as α-synuclein, superoxide dismutase-1, amyloid-β and tau. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. A Hybrid Hierarchical Approach for Brain Tissue Segmentation by Combining Brain Atlas and Least Square Support Vector Machine

    Science.gov (United States)

    Kasiri, Keyvan; Kazemi, Kamran; Dehghani, Mohammad Javad; Helfroush, Mohammad Sadegh

    2013-01-01

    In this paper, we present a new semi-automatic brain tissue segmentation method based on a hybrid hierarchical approach that combines a brain atlas as a priori information and a least-square support vector machine (LS-SVM). The method consists of three steps. In the first two steps, the skull is removed and the cerebrospinal fluid (CSF) is extracted. These two steps are performed using the toolbox FMRIB's automated segmentation tool integrated in the FSL software (FSL-FAST) developed in Oxford Centre for functional MRI of the brain (FMRIB). Then, in the third step, the LS-SVM is used to segment grey matter (GM) and white matter (WM). The training samples for LS-SVM are selected from the registered brain atlas. The voxel intensities and spatial positions are selected as the two feature groups for training and test. SVM as a powerful discriminator is able to handle nonlinear classification problems; however, it cannot provide posterior probability. Thus, we use a sigmoid function to map the SVM output into probabilities. The proposed method is used to segment CSF, GM and WM from the simulated magnetic resonance imaging (MRI) using Brainweb MRI simulator and real data provided by Internet Brain Segmentation Repository. The semi-automatically segmented brain tissues were evaluated by comparing to the corresponding ground truth. The Dice and Jaccard similarity coefficients, sensitivity and specificity were calculated for the quantitative validation of the results. The quantitative results show that the proposed method segments brain tissues accurately with respect to corresponding ground truth. PMID:24696800

  16. Optic disc and retinal nerve fiber layer parameters as indicators of neurodegenerative brain changes in patients with obstructive sleep apnea syndrome.

    Science.gov (United States)

    Huseyinoglu, Nergiz; Ekinci, Metin; Ozben, Serkan; Buyukuysal, Cagatay; Kale, Murat Yildirim; Sanivar, Hilal Safak

    2014-03-01

    Retina is a unique part of the central nervous system (CNS) for visualizing the processes of axonal and neuronal degeneration. Optical coherence tomography (OCT) allows direct visualization and measurement of retinal nerve fiber layer (RNFL) thickness, macular volume, and optic disc (OD) parameters. One of the disorders associated with atrophy in different brain regions is obstructive sleep apnea syndrome (OSAS). In the present study, we aimed to determine OD and RNFL changes measured by OCT for investigating the progress of neurodegeneration development in OSAS, excluding all the other conditions that can directly affect RNFL thickness and optic nerve parameters. Both eyes of 101 patients with OSAS and 20 controls were investigated by OCT. Full-night polysomnography (PSG) and ophthalmologic examination including automated visual field (VF) examination and OCT were performed in all of the patients. According to the OSAS grading, patients were grouped as mild (n=15), moderate (n=27), and severe (n=59). We found significant decrease in RNFL thickness only in the patients with severe OSAS compared with the other groups and decreased macular ganglion cell thickness in the severe OSAS group compared with the control group. VF parameters were significantly worsened in all the OSAS subgroups compared to the control group. We found different data such as normal or increased optic nerve parameters as result of subtle OD edema, which may mask possible peripapillar axonal loss. We think that evaluation of neurodegeneration in OSAS is not always possible by examining OD and RNFL because there are difficulties due to the confounding issues of cerebral atrophy and OD edema.

  17. Brain-Derived Neurotrophic Factor Facilitates Functional Recovery from ALS-Cerebral Spinal Fluid-Induced Neurodegenerative Changes in the NSC-34 Motor Neuron Cell Line.

    Science.gov (United States)

    Shruthi, Shanmukha; Sumitha, R; Varghese, Anu Mary; Ashok, S; Chandrasekhar Sagar, B K; Sathyaprabha, T N; Nalini, A; Kramer, Boris W; Raju, Trichur R; Vijayalakshmi, K; Alladi, Phalguni Anand

    2017-01-01

    The survival of motor neurons is dependent upon neurotrophic factors both during childhood and adolescence and during adult life. In disease conditions, such as in patients with amyotrophic lateral sclerosis (ALS), the mRNA levels of trophic factors like brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and vascular endothelial growth factor are downregulated. This was replicated in our in vivo experimental system following the injection of cerebral spinal fluid (CSF) of sporadic ALS (ALS-CSF) patients. To evaluate the protective role of BDNF in a model of sporadic ALS patients. The expressions of endogenous BDNF, its receptor TrkB, the enzyme choline acetyl transferase (ChAT), and phosphorylated neurofilaments were studied in NSC-34 cells. The calcium-buffering and proapoptotic effects were assessed by calbindin-D28K and caspase-3 expression, respectively. ALS-CSF considerably depleted the endogenous BDNF protein, while its effect on IGF-1 and FGF-2 was inconsequential; this indirectly indicates a key role for BDNF in supporting motor neuronal survival. The exogenous supplementation of BDNF reversed autocrine expression; however, it may not be completely receptor mediated, as the TrkB levels were not restored. BDNF completely revived ChAT expression. It may inhibit apoptosis by restoring Ca2+ homeostasis, since caspase-3 and calbindin-D28K expression was back to normal. The organellar ultrastructural changes were only partially reversed. Our study provides evidence that BDNF supplementation ameliorates most but not all degenerative changes. The incomplete revival at the ultrastructural level signifies the requirement of factors other than BDNF for near-total protection of motor neurons, and, to an extent, it explains why only a partial success is achieved in clinical trials with BDNF in ALS patients. © 2016 S. Karger AG, Basel.

  18. Automatic Analysis of Brain Tissue and Structural Connectivity in MRI

    OpenAIRE

    Boer, Renske

    2011-01-01

    textabstractStudies of the brain using magnetic resonance imaging (MRI) can provide insights in physiology and pathology that can eventually aid clinical diagnosis and therapy monitoring. MRI data acquired in these studies can be difficult, as well as laborious, to interpret and analyze by human observers. Moreover, analysis by human observers can hamper the reproducibility by both inter- and intra-observer variability. These studies do, therefore, require accurate and reproducible quantitati...

  19. Brain tissue modifications induced by cholinergic therapy in Alzheimer's disease.

    Science.gov (United States)

    Bozzali, Marco; Parker, Geoff J M; Spanò, Barbara; Serra, Laura; Giulietti, Giovanni; Perri, Roberta; Magnani, Giuseppe; Marra, Camillo; G Vita, Maria; Caltagirone, Carlo; Cercignani, Mara

    2013-12-01

    A previous preliminary investigation based on a novel MRI approach to map anatomical connectivity revealed areas of increased connectivity in Alzheimer's disease (AD) but not in mild cognitive impairment patients. This prompted the hypothesis tested here, that these areas might reflect phenomena of brain plasticity driven by acetylcholinesterase inhibitors (AChEIs). Thirty-eight patients with probable AD (19 under medication with AChEIs and 19 drug-naïve) were recruited together with 11 healthy controls. All subjects had MRI scanning at 3T, including volumetric and diffusion-weighted scans. Probabilistic tractography was used to initiate streamlines from all parenchymal voxels, and anatomical connectivity maps (ACMs) were obtained by counting, among the total number of streamlines initiated, the fraction passing through each brain voxel. After normalization into standard space, ACMs were used to test for between-group comparisons, and for interactions between the exposure to AChEIs and global level of cognition. Patients with AD had reduced ACM values in the fornix, cingulum, and supramarginal gyri. The ACM value was strongly associated with the AChEI dosage-x-duration product in the anterior limb (non-motor pathway) of the internal capsule. Tractography from this region identified the anterior thalamic radiation as the main white matter (WM) tract passing through it. The reduced connectivity in WM bundles connecting the hippocampi with the rest of the brain (fornix/cingulum) suggests a possible mechanism for the spread of AD pathology. An intriguing explanation for the interaction between AChEIs and ACM is related to the mechanisms of brain plasticity, partially driven by neurotrophic properties of acetylcholine replacement. Copyright © 2012 Wiley Periodicals, Inc.

  20. Extraction of optical properties and prediction of light distribution in rat brain tissue.

    Science.gov (United States)

    Azimipour, Mehdi; Baumgartner, Ryan; Liu, Yuming; Jacques, Steven L; Eliceiri, Kevin; Pashaie, Ramin

    2014-01-01

    Predicting the distribution of light inside any turbid media, such as biological tissue, requires detailed information about the optical properties of the medium, including the absorption and scattering coefficients and the anisotropy factor. Particularly, in biophotonic applications where photons directly interact with the tissue, this information translates to system design optimization, precision in light delivery, and minimization of unintended consequences, such as phototoxicity or photobleaching. In recent years, optogenetics has opened up a new area in deep brain stimulation with light and the method is widely adapted by researchers for the study of the brain circuitries and the dynamics of neurological disorders. A key factor for a successful optogenetic stimulation is delivering an adequate amount of light to the targeted brain objects. The adequate amount of light needed to stimulate each brain object is identified by the tissue optical properties as well as the type of opsin expressed in the tissue, wavelength of the light, and the physical dimensions of the targeted area. Therefore, to implement a precise light delivery system for optogenetics, detailed information about the optical properties of the brain tissue and a mathematical model that incorporates all determining factors is needed to find a good estimation of light distribution in the brain. In general, three measurements are required to obtain the optical properties of any tissue, namely diffuse transmitted light, diffuse reflected light, and transmitted ballistic beam. In this report, these parameters were measured in vitro using intact rat brain slices of 500 μm thickness via a two-integrating spheres optical setup. Then, an inverse adding doubling method was used to extract the optical properties of the tissue from the collected data. These experiments were repeated to cover the whole brain tissue with high spatial resolution for the three different cuts (transverse, sagittal, and coronal

  1. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Manley, N.B.; Fabrikant, J.I.; Alpen, E.L.

    1988-12-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. This study concerns the cell population and cell cycle kinetics of the subependymal layer in the mouse brain, and the effects of charged particle irradiations on this cell population. Quantitative high resolution autoradiography was used to study the kinetic parameters in this cell layer. This study should help in understanding the effects of these high-energy heavy ions on normal mammalian brain tissue. The response of the mammalian brain exposure to charged particle ionizing radiation may be extremely variable. It varies from minimal physiological changes to overt tissue necrosis depending on a number of factors such as: the administered dose, dose-rate, the volume of the irradiated tissue, and the biological end-point being examined.

  2. Long-term changes in the material properties of brain tissue at the implant-tissue interface

    Science.gov (United States)

    Sridharan, Arati; Rajan, Subramaniam D.; Muthuswamy, Jit

    2013-12-01

    Objective. Brain tissue undergoes dramatic molecular and cellular remodeling at the implant-tissue interface that evolves over a period of weeks after implantation. The biomechanical impact of such remodeling on the interface remains unknown. In this study, we aim to assess the changes in the mechanical properties of the brain-electrode interface after chronic implantation of a microelectrode. Approach. Microelectrodes were implanted in the rodent cortex at a depth of 1 mm for different durations—1 day (n = 4), 10-14 days (n = 4), 4 weeks (n = 4) and 6-8 weeks (n = 7). After the initial duration of implantation, the microelectrodes were moved an additional 1 mm downward at a constant speed of 10 µm s-1. Forces experienced by the microelectrode were measured during movement and after termination of movement. The biomechanical properties of the interfacial brain tissue were assessed from measured force-displacement curves using two separate models—a two-parameter Mooney-Rivlin hyperelastic model and a viscoelastic model with a second-order Prony series. Main results. Estimated shear moduli using a second-order viscoelastic model increased from 0.5-2.6 kPa (day 1 of implantation) to 25.7-59.3 kPa (after 4 weeks of implantation) and subsequently decreased to 0.8-7.9 kPa after 6-8 weeks of implantation in 6 of the 7 animals. The estimated elastic modulus increased from 4.1-7.8 kPa on the day of implantation to 24-44.9 kPa after 4 weeks. The elastic modulus was estimated to be 6.8-33.3 kPa in 6 of the 7 animals after 6-8 weeks of implantation. The above estimates suggest that the brain tissue surrounding the microelectrode evolves from a stiff matrix with maximal shear and elastic modulus after 4 weeks of implantation into a composite of two different layers with different mechanical properties—a stiff compact inner layer surrounded by softer brain tissue that is biomechanically similar to brain tissue—during the first week of implantation. Tissue micromotion

  3. The brain modulates insulin sensitivity in multiple tissues

    NARCIS (Netherlands)

    Parlevliet, Edwin T.; Coomans, Claudia P.; Rensen, Patrick C. N.; Romijn, Johannes A.

    2014-01-01

    Insulin sensitivity is determined by direct effects of circulating insulin on metabolically active tissues in combination with indirect effects of circulating insulin, i.e. via the central nervous system. The dose-response effects of insulin differ between the various physiological effects of

  4. Optical clearing and fluorescence deep-tissue imaging for 3D quantitative analysis of the brain tumor microenvironment.

    Science.gov (United States)

    Lagerweij, Tonny; Dusoswa, Sophie A; Negrean, Adrian; Hendrikx, Esther M L; de Vries, Helga E; Kole, Jeroen; Garcia-Vallejo, Juan J; Mansvelder, Huibert D; Vandertop, W Peter; Noske, David P; Tannous, Bakhos A; Musters, René J P; van Kooyk, Yvette; Wesseling, Pieter; Zhao, Xi Wen; Wurdinger, Thomas

    2017-11-01

    Three-dimensional visualization of the brain vasculature and its interactions with surrounding cells may shed light on diseases where aberrant microvascular organization is involved, including glioblastoma (GBM). Intravital confocal imaging allows 3D visualization of microvascular structures and migration of cells in the brain of mice, however, with limited imaging depth. To enable comprehensive analysis of GBM and the brain microenvironment, in-depth 3D imaging methods are needed. Here, we employed methods for optical tissue clearing prior to 3D microscopy to visualize the brain microvasculature and routes of invasion of GBM cells. We present a workflow for ex vivo imaging of optically cleared brain tumor tissues and subsequent computational modeling. This workflow was used for quantification of the microvasculature in relation to nuclear or cellular density in healthy mouse brain tissues and in human orthotopic, infiltrative GBM8 and E98 glioblastoma models. Ex vivo cleared mouse brain tissues had a >10-fold imaging depth as compared to intravital imaging of mouse brain in vivo. Imaging of optically cleared brain tissue allowed quantification of the 3D microvascular characteristics in healthy mouse brains and in tissues with diffuse, infiltrative growing GBM8 brain tumors. Detailed 3D visualization revealed the organization of tumor cells relative to the vasculature, in both gray matter and white matter regions, and patterns of multicellular GBM networks collectively invading the brain parenchyma. Optical tissue clearing opens new avenues for combined quantitative and 3D microscopic analysis of the topographical relationship between GBM cells and their microenvironment.

  5. Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors.

    Science.gov (United States)

    Kangasniemi, Marko; Stafford, R Jason; Price, Roger E; Jackson, Edward F; Hazle, John D

    2003-02-01

    Thermal coagulation of cerebral tumors induces reactive changes within adjacent brain tissue, which appear as Gd-DTPA enhancement in MR images. This makes assessment of therapeutic success difficult to establish radiographically because the reactive changes can mimic residual tumor. Dynamic Gd-DTPA uptake curves in reactive tissue and tumor were investigated to assess the utility of contrast enhanced (CE)-dynamic MRI to distinguish reactive changes from residual tumor in a canine model. Cerebral thermal necrosis was induced using a 980 nm laser in 11 dogs with intracerebral transmissible venereal tumors (TVTs). A fast spin-echo T1-weighted imaging sequence was used for CE-dynamic MRI. Gd-DTPA uptake data were acquired with 10-second temporal resolution and for untreated TVTs for reactive tissue using a sigmoidal-exponential model. Characteristic gadolinium uptake curves were measured and characterized for reactive brain tissue, and untreated and treated TVTs. Both early and delayed dynamic responses were significantly different in reactive brain tissue compared with TVT. Reactive thermal changes in otherwise normal brain tissue can be distinguished from residual tumor after cerebral thermal therapy using CE-dynamic MRI.

  6. Differentiating pediatric epileptic brain tissue from normal brain tissue by using time-dependent diffuse reflectance spectroscopy in vivo: comprehensive data analysis method in the time domain

    Science.gov (United States)

    Oh, Sanghoon; Fernald, Bradley; Bhatia, Sanjiv; Ragheb, John; Sandberg, David; Johnson, Mahlon; Lin, Wei-Chiang

    2009-05-01

    This research investigated the feasibility of using time-dependent diffuse reflectance spectroscopy to differentiate pediatric epileptic brain tissue from normal brain tissue. The optical spectroscopic technique monitored the dynamic optical properties of the cerebral cortex that are associated with its physiological, morphological, and compositional characteristics. Due to the transient irregular epileptic discharge activity within the epileptic brain tissue it was hypothesized that the lesion would express abnormal dynamic optical behavior that would alter normal dynamic behavior. Thirteen pediatric epilepsy patients and seven pediatric brain tumor patients (normal controls) were recruited for this clinical study. Dynamic optical properties were obtained from the cortical surface intraoperatively using a timedependent diffuse reflectance spectroscopy system. This system consisted of a fiber-optic probe, a tungsten-halogen light source, and a spectrophotometer. It acquired diffuse reflectance spectra with a spectral range of 204 nm to 932 nm at a rate of 33 spectra per second for approximately 12 seconds. Biopsy samples were taken from electrophysiologically abnormal cortex and evaluated by a neuropathologist, which served as a gold standard for lesion classification. For data analysis, spectral intensity changes of diffuse reflectance in the time domain at two different wavelengths from each investigated site were compared. Negative correlation segment, defined by the periods where the intensity changes at the two wavelengths were opposite in their slope polarity, were extracted. The total duration of negative correlation, referred to as the "negative correlation time index", was calculated by integrating the negative correlation segments. The negative correlation time indices from all investigated sites were sub-grouped according to the corresponding histological classifications. The difference between the mean indices of two subgroups was evaluated by standard

  7. Gene Expression Profiling during Pregnancy in Rat Brain Tissue

    Directory of Open Access Journals (Sweden)

    Phyllis E. Mann

    2014-03-01

    Full Text Available The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1 whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  8. A longitudinal study of the mechanical properties of injured brain tissue in a mouse model.

    Science.gov (United States)

    Feng, Yuan; Gao, Yuan; Wang, Tao; Tao, Luyang; Qiu, Suhao; Zhao, Xuefeng

    2017-07-01

    Mechanical properties of brain tissue are crucial to understand the mechanism of traumatic brain injury (TBI). Over the past several decades, most of the studies focused on healthy brain tissues, while few of them are about the injured tissues. Therefore, limited knowledge is known about the mechanical properties of the injured brain tissues. In this study, we used an in vivo mouse model with a weight drop device to study injured brain tissues. Around the injury site, mechanical properties of the injured, neighboring, and the corresponding contralateral regions of interest (ROIs) were measured over five temporal points by indentation. Longitudinal and regional comparisons of the mechanical properties revealed that the ROI of the injured tissue had a higher elastic modulus than the contralateral counterpart one-hour post-injury. However, the elastic modulus decreased one-day post-injury and recovered to be close to the contralateral ROI in 7 days. The elastic modulus curves of the injured and the contralateral counterpart ROIs crossed at time points of 12h and 1 day post-injury, where two significant increases of glial fibrillary acidic protein (GFAP) positive cells were observed. Biological staining results indicated that both the astrocytic responses and the morphological structure could affect the mechanical properties of the injured tissue. The observed longitudinal changes of the mechanical properties at the tissue level and the morphological and biological changes at the cellular level provide insights into understanding the mechanism of TBI. Results are also meaningful for applying emerging in vivo diagnostic tools such as magnetic resonance elastography (MRE) in TBI detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues.

    Science.gov (United States)

    Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R; Romer, Micah; Tufik, Sergio; Pack, Allan I

    2013-05-30

    Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed "sleep specific" changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a

  10. Three-dimensional structure of brain tissue at submicrometer resolution

    Energy Technology Data Exchange (ETDEWEB)

    Saiga, Rino; Mizutani, Ryuta, E-mail: ryuta@tokai-u.jp [Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292 (Japan); Inomoto, Chie; Takekoshi, Susumu; Nakamura, Naoya; Tsuboi, Akio; Osawa, Motoki [Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Arai, Makoto; Oshima, Kenichi; Itokawa, Masanari [Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506 (Japan); Uesugi, Kentaro; Takeuchi, Akihisa; Terada, Yasuko; Suzuki, Yoshio [Japan Synchrotron Radiation Research Institute (JASRI/SPring-8), Sayo, Hyogo 679-5198 (Japan)

    2016-01-28

    Biological objects are composed of submicrometer structures such as cells and organelles that are essential for their functions. Here, we report on three-dimensional X-ray visualization of cells and organelles at resolutions up to 100 nm by imaging microtomography (micro-CT) equipped with Fresnel zone plate optics. Human cerebral tissue, fruit fly cephalic ganglia, and Escherichia coli bacteria labeled with high atomic-number elements were embedded in epoxy resin and subjected to X-ray microtomography at the BL37XU and BL47XU beamlines of the SPring-8 synchrotron radiation facility. The obtained results indicated that soft tissue structures can be visualized with the imaging microtomography.

  11. Sleep disorders in neurodegenerative diseases.

    Science.gov (United States)

    Raggi, A; Ferri, R

    2010-11-01

    The aim of this review is to provide data on sleep disturbances in three categories of neurodegenerative disorders: synucleinopathies, tauopathies, and other diseases (this heterogeneous group includes also spinocerebellar degeneration and amyotrophic lateral sclerosis). Analysing and knowing sleep disorders in neurodegenerative diseases may offer important insights into the pathomechanism of some of these diseases and calls attention to the still insufficiently known 'sleep neurology'. The identification of sleep disorders in some neurodegenerative conditions may make their diagnosis easier and earlier; for example, rapid eye movements sleep behaviour disorder may precede any other clinical manifestation of synucleinopathies by more than 10 years. © 2010 The Author(s). Journal compilation © 2010 EFNS.

  12. Investigation on metal elements in the brain tissues from DNTC patients

    Energy Technology Data Exchange (ETDEWEB)

    Ide-Ektessabi, Ari E-mail: h51167@sakura.kudpc.kyoto-u.ac.jp; Kawakami, Takuo; Ishihara, Ryoko; Mizuno, Yutaka; Takeuchi, Tohru

    2004-07-01

    Trace metallic elements in human cells play important roles in various cell functions as metalloprotein, metalloenzyme or metallic ions. Diffuse neurofibrillary tangles with calcification (DNTC) is an atypical dementia and is characterized pathologically by diffuse neurofibrillary tangles without senile plaques. In this study, X-ray fluorescence (XRF) spectroscopy using synchrotron radiation (SR) was applied to determine the distribution and density of the ultra-trace elements in the brain tissues from DTNC patients. This method made it possible to determine trace metallic elements non-destructively. The trace metallic elements (such as Ca, Fe, Zn, and Pb) in the brain tissues were examined. Two-dimension imaging of the elements and relative quantification of the elements in the brains were performed. The lead concentrations were observed in the calcified blood vessel in the brains with DNTC.

  13. Nondestructive recovery and examination of bullet fragments from brain tissue.

    Science.gov (United States)

    Johnson, A C; Kinard, W D; Washington, W D

    1980-04-01

    A technique providing both analytical and toolmark results for lead fragments from bullets is discussed. It permits the nondestructive recovery of bullet fragments from soft cadaver tissue and was used with a plasma asher in an actual homicide case. The lead fragments are examined by neutron activation analysis (but other analytical techniques can be used) for their antimony and arsenic content and by microscopy for matching toolmarks.

  14. Effect of pineapple peel extract on total phospholipids and lipid peroxidation in brain tissues of rats.

    Science.gov (United States)

    Erukainure, O L; Ajiboye, J A; Adejobi, R O; Okafor, O Y; Kosoko, S B; Owolabi, F O

    2011-03-01

    To investigate the ability of the methanolic extract of pineapple peel to attenuate alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Brain tissues were assayed for total phospholipid (TP) content and malondialdehyde (MDA). Administration of alcohol significantly caused a reduction in TP content. Treatment with pineapple peel extract significantly increased the TP content. Significant high levels of MDA was observed in alcohol-fed rats, treatment with pineapple peel extract significantly reduced the MDA levels. Results obtained from this study indicates that pineapple peel extract protects against alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2018-01-09

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

  16. Distribution of lead in the brain tissues from DNTC patients using synchrotron radiation microbeams

    Energy Technology Data Exchange (ETDEWEB)

    Ide-Ektessabi, Ari [International Innovation Center, Kyoto University, Kyoto (Japan); Ota, Yukihide [Department of Precision Engineering, Kyoto University, Yoshida Honnmachi, Sakyo-ku, Kyoto (Japan)]. E-mail: h51167@sakura.kudpc.kyoto-u.ac.jp; Ishihara, Ryoko [Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya (Japan); Mizuno, Yutaka [Obu Dementia Care Research and Training Center, Obu (Japan); Takeuchi, Tohru [Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya (Japan)

    2005-12-15

    Diffuse neurofibrillary tangles with calcification (DNTC) is a form of dementia with certain characteristics. Its pathology is characterized by cerebrum atrophy, calcification on globus pallidus and dentate nucleus and diffuse neurofibrillary tangles without senile plaques. In the present study brain tissues were prepared from patients with patients DNTC, calcified and non-calcified Alzheimer's disease (AD) patients. The brain tissues were examined non-destructively by X-ray fluorescence (XRF) spectroscopy using synchrotron radiation (SR) microbeams for trace metallic elements Ca, Fe, Cu, Zn and Pb. The XRF analysis showed that there were Pb concentrations in the calcified areas in the brain tissues with both DNTC and AD but there was none in those with non-calcified AD.

  17. Analysis of sports related mTBI injuries caused by elastic wave propagation through brain tissue

    Directory of Open Access Journals (Sweden)

    D Case

    2016-10-01

    Full Text Available Repetitive concussions and sub-concussions suffered by athletes have been linked to a series of sequelae ranging from traumatic encephalopathy to dementia pugilistica. A detailed finite element model of the human head was developed based on standard libraries of medical imaging. The model includes realistic material properties for the brain tissue, bone, soft tissue, and CSF, as well as the structure and properties of a protective helmet. Various impact scenarios were studied, with a focus on the strains/stresses and pressure gradients and concentrations created in the brain tissue due to propagation of waves produced by the impact through the complex internal structure of the human head. This approach has the potential to expand our understanding of the mechanism of brain injury, and to better assess the risk of delayed neurological disorders for tens of thousands of young athletes throughout the world.

  18. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been ...... positive correlation between frontal cortex and hippocampal BDNF levels in mice (r2=0.81, p=0.0139). Our data support the view that measures of blood and plasma BDNF levels reflect brain-tissue BDNF levels....

  19. Exosomes in the Pathology of Neurodegenerative Diseases.

    Science.gov (United States)

    Howitt, Jason; Hill, Andrew F

    2016-12-23

    More than 30 years ago, two unexpected findings were discovered that challenged conventional thinking in biology. The first was the identification of a misfolded protein with transmissible properties associated with a group of neurodegenerative diseases known as transmissible spongiform encephalopathies. The second was the discovery of a new pathway used for the extracellular release of biomolecules, including extracellular vesicles called exosomes. Two decades later, the convergence of these pathways was shown when exosomes were found to play a significant role in both the transmission and propagation of protein aggregates in disease. Recent research has now revealed that the majority of proteins involved in neurodegenerative diseases are transported in exosomes, and that external stresses due to age-related impairment of protein quality control mechanisms can promote the transcellular flux of these proteins in exosomes. Significantly, exosomes provide an environment that can induce the conformational conversion of native proteins into aggregates that can be transmitted to otherwise aggregate-free cells in the brain. Here we review the current roles of exosomes in the pathology of neurodegenerative diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Metals and neurodegenerative diseases. A systematic review.

    Science.gov (United States)

    Cicero, Calogero Edoardo; Mostile, Giovanni; Vasta, Rosario; Rapisarda, Venerando; Signorelli, Salvatore Santo; Ferrante, Margherita; Zappia, Mario; Nicoletti, Alessandra

    2017-11-01

    Neurodegenerative processes encompass a large variety of diseases with different pathological patterns and clinical presentation such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer Disease (AD) and Parkinson's disease (PD). Genetic mutations have a known causative role, but the majority of cases are likely to be probably caused by a complex gene-environment interaction. Exposure to metals has been hypothesized to increase oxidative stress in brain cells leading to cell death and neurodegeneration. Neurotoxicity of metals has been demonstrated by several in vitro and in vivo experimental studies and it is likely that each metal could be toxic through specific pathways. The possible pathogenic role of different metals has been supported by some epidemiological evidences coming from occupational and ecological studies. In order to assess the possible association between metals and neurodegenerative disorders, several case-control studies have also been carried out evaluating the metals concentration in different biological specimens such as blood/serum/plasma, cerebrospinal fluid (CSF), nail and hair, often reporting conflicting results. This review provides an overview of our current knowledge on the possible association between metals and ALS, AD and PD as main neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. A low background Raman probe for optical biopsy of brain tissue

    Science.gov (United States)

    Stevens, Oliver A. C.; Hutchings, Joanne; Gray, William; Day, John C.

    2014-03-01

    Removal of intrinsic brain tumours is a delicate process, where a high degree of specificity is required to remove all of the tumour tissue without damaging healthy brain. The accuracy of this process can be greatly enhanced by intraoperative guidance. Optical biopsies using Raman spectroscopy are a minimally invasive and lower cost alternative to current guidance methods. A miniature Raman probe for performing optical biopsies of human brain tissue is presented. The probe allows sampling inside a conventional stereotactic brain biopsy system: a needle of length 200mm and inner diameter of 1.8mm. The probe achieves a very low fluorescent background whilst maintaining good collection of Raman signal by employing a miniature stand-off Raman design. To illustrate this, the probe is compared with a Raman probe that uses a pair of optical fibres for collection. The miniature stand-off Raman probe is shown to collect a comparable number of Raman scattered photons, but the fluorescence caused by silica fibres in a Raman needle probe is reduced by a factor of two for Raman shifts under 500 cm-1, and by 30% at 600-700 cm-1. In addition, this design contains only medically approved materials at the distal end. The probe's suitability for use on tissue is demonstrated by discriminating between different types of porcine brain tissue.

  2. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

    Directory of Open Access Journals (Sweden)

    Guangjun Zhao

    2016-01-01

    Full Text Available Cryosection brain images in Chinese Visible Human (CVH dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel. Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

  3. Neurosurgical sapphire handheld probe for intraoperative optical diagnostics, laser coagulation and aspiration of malignant brain tissue

    Science.gov (United States)

    Shikunova, Irina A.; Zaytsev, Kirill I.; Stryukov, Dmitrii O.; Dubyanskaya, Evgenia N.; Kurlov, Vladimir N.

    2017-07-01

    In this paper, a handheld contact probe based on sapphire shaped crystal was developed for the intraoperative optical diagnosis and aspiration of malignant brain tissue combined with the laser hemostasis. Such a favorable combination of several functions in a single instrument significantly increases its clinical relevance. It makes possible highly-accurate real-time detection and removal of either large-scale malignancies or even separate invasive cancer cells. The proposed neuroprobe was integrated into the clinical neurosurgical workflow for the intraoperative fluorescence identification and removal of malignant tissues of the brain.

  4. Microsensors for in vivo Measurement of Glutamate in Brain Tissue

    Directory of Open Access Journals (Sweden)

    Miranda van der Zeyden

    2008-11-01

    Full Text Available Several immobilized enzyme-based electrochemical biosensors for glutamate detection have been developed over the last decade. In this review, we compare first and second generation sensors. Structures, working mechanisms, interference prevention, in vitro detection characteristics and in vivo performance are summarized here for those sensors that have successfully detected brain glutamate in vivo. In brief, first generation sensors have a simpler structure and are faster in glutamate detection. They also show a better sensitivity to glutamate during calibration in vitro. For second generation sensors, besides their less precise detection, their fabrication is difficult to reproduce, even with a semi-automatic dip-coater. Both generations of sensors can detect glutamate levels in vivo, but the reported basal levels are different. In general, second generation sensors detect higher basal levels of glutamate compared with the results obtained from first generation sensors. However, whether the detected glutamate is indeed from synaptic sources is an issue that needs further attention.

  5. Low-frequency dielectric dispersion of brain tissue due to electrically long neurites

    Science.gov (United States)

    Monai, Hiromu; Inoue, Masashi; Miyakawa, Hiroyoshi; Aonishi, Toru

    2012-12-01

    The dielectric properties of brain tissue are important for understanding how neural activity is related to local field potentials and electroencephalograms. It is known that the permittivity of brain tissue exhibits strong frequency dependence (dispersion) and that the permittivity is very large in the low-frequency region. However, little is known with regard to the cause of the large permittivity in the low-frequency region. Here, we postulate that the dielectric properties of brain tissue can be partially accounted for by assuming that neurites are of sufficient length to be “electrically long.” To test this idea, we consider a model in which a neurite is treated as a long, narrow body, and it is subjected to a stimulus created by electrodes situated in the region external to it. With regard to this electric stimulus, the neurite can be treated as a passive cable. Assuming adequate symmetry so that the tissue packed with multiple cables is equivalent to an isolated system consisting of a single cable and a surrounding extracellular resistive medium, we analytically calculate the extracellular potential of the tissue in response to such an externally created alternating-current electric field using a Green's function that we obtained previously. Our results show that brain tissue modeled by such a cable existing within a purely resistive extracellular medium exhibits a large effective permittivity in the low-frequency region. Moreover, we obtain results suggesting that an extremely large low-frequency permittivity can coexist with weak low-pass filter characteristics in brain tissue.

  6. Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery.

    Science.gov (United States)

    Blumcke, Ingmar; Spreafico, Roberto; Haaker, Gerrit; Coras, Roland; Kobow, Katja; Bien, Christian G; Pfäfflin, Margarete; Elger, Christian; Widman, Guido; Schramm, Johannes; Becker, Albert; Braun, Kees P; Leijten, Frans; Baayen, Johannes C; Aronica, Eleonora; Chassoux, Francine; Hamer, Hajo; Stefan, Hermann; Rössler, Karl; Thom, Maria; Walker, Matthew C; Sisodiya, Sanjay M; Duncan, John S; McEvoy, Andrew W; Pieper, Tom; Holthausen, Hans; Kudernatsch, Manfred; Meencke, H Joachim; Kahane, Philippe; Schulze-Bonhage, Andreas; Zentner, Josef; Heiland, Dieter H; Urbach, Horst; Steinhoff, Bernhard J; Bast, Thomas; Tassi, Laura; Lo Russo, Giorgio; Özkara, Cigdem; Oz, Buge; Krsek, Pavel; Vogelgesang, Silke; Runge, Uwe; Lerche, Holger; Weber, Yvonne; Honavar, Mrinalini; Pimentel, José; Arzimanoglou, Alexis; Ulate-Campos, Adriana; Noachtar, Soheyl; Hartl, Elisabeth; Schijns, Olaf; Guerrini, Renzo; Barba, Carmen; Jacques, Thomas S; Cross, J Helen; Feucht, Martha; Mühlebner, Angelika; Grunwald, Thomas; Trinka, Eugen; Winkler, Peter A; Gil-Nagel, Antonio; Toledano Delgado, Rafael; Mayer, Thomas; Lutz, Martin; Zountsas, Basilios; Garganis, Kyriakos; Rosenow, Felix; Hermsen, Anke; von Oertzen, Tim J; Diepgen, Thomas L; Avanzini, Giuliano

    2017-10-26

    Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients. In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.).

  7. Long-Term Tissue Culture of Adult Brain and Spleen Slices on Nanostructured Scaffolds.

    Science.gov (United States)

    Kallendrusch, Sonja; Merz, Felicitas; Bechmann, Ingo; Mayr, Stefan G; Zink, Mareike

    2017-05-01

    Long-term tissue culture of adult mammalian organs is a highly promising approach to bridge the gap between single cell cultures and animal experiments, and bears the potential to reduce in vivo studies. Novel biomimetic materials open up new possibilities to maintain the complex tissue structure in vitro; however, survival times of adult tissues ex vivo are still limited to a few days with established state-of-the-art techniques. Here, it is demonstrated that TiO2 nanotube scaffolds with specific tissue-tailored characteristics can serve as superior substrates for long-term adult brain and spleen tissue culture. High viability of the explants for at least two weeks is achieved and compared to tissues cultured on standard polytetrafluoroethylene (PTFE) membranes. Histological and immunohistochemical staining and live imaging are used to investigate tissue condition after 5 and 14 d in vitro, while environmental scanning electron microscopy qualifies the interaction with the underlying scaffold. In contrast to tissues cultured on PTFE membranes, enhanced tissue morphology is detected in spleen slices, as well as minor cell death in neuronal tissue, both cultured on nanotube scaffolds. This novel biomimetic tissue model will prove to be useful to address fundamental biological and medical questions from tissue regeneration up to tumor progression and therapeutic approaches. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

    Science.gov (United States)

    Bonar, Nicolle A; Petersen, Christian P

    2017-03-01

    Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema. © 2017. Published by The Company of Biologists Ltd.

  9. The Neuroprotective Effect of Cornus mas on Brain Tissue of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Renata Francik

    2014-01-01

    Full Text Available Cornelian cherry (Cornus mas is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer’s disease or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet. This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma.

  10. Mice Brain Tissue Injury Induced by Diisononyl Phthalate Exposure and the Protective Application of Vitamin E.

    Science.gov (United States)

    Peng, Ling

    2015-07-01

    As a widely used plasticizer in plastic industry, the data of diisononyl phthalate (DINP) toxicity due to exposure are insufficient. This work investigated the brain tissue injury induced by DINP exposure. Through oral exposure to DINP, oxidative stress, inflammatory responses, apoptosis, and hippocampus pathological alterations were found in the mice brain. And through the Morris water maze test, cognitive deficits were tested. Our data also showed that these exacerbations were counteracted by vitamin E. These results above indicated that oral exposure of mice to DINP induced brain damage, and oxidative stress, inflammation, and the consequential apoptosis jointly constituted the potential mechanisms of such induced toxicity. © 2015 Wiley Periodicals, Inc.

  11. Modeling invasion of brain tissue by glioblastoma cells: ECM alignment and motility

    Science.gov (United States)

    Sander, L. M.

    2013-03-01

    A key stage in the development of highly malignant brain tumors (Glioblastoma Multiforme) is invasion of normal brain tissue by motile cells moving through a crowded, complex environment. Evidence from in vitro experiments suggests the cell motion is accompanied by considerable deformation and alignment of the extra-cellular matrix (ECM) of the brain. In the case of breast cancer, alignment effects of this sort have been seen in vivo. We have modeled features of this system including stress confinement in the non-linear elasticity of the ECM and contact guidance of the cell motion.

  12. Effects of tissue fixation on coherent anti-Stokes Raman scattering images of brain

    Science.gov (United States)

    Galli, Roberta; Uckermann, Ortrud; Koch, Edmund; Schackert, Gabriele; Kirsch, Matthias; Steiner, Gerald

    2014-07-01

    Coherent anti-Stokes Raman scattering (CARS) microscopy is an emerging multiphoton technique for the label-free histopathology of the central nervous system, by imaging the lipid content within the tissue. In order to apply the technique on standard histology sections, it is important to know the effects of tissue fixation on the CARS image. Here, we report the effects of two common fixation methods, namely with formalin and methanol-acetone, on mouse brain and human glioblastoma tissue. The variations induced by fixation on the CARS contrast and intensity were compared and interpreted using Raman microspectroscopy. The results show that, whenever unfixed cryosections cannot be used, fixation with formalin constitutes an alternative which does not deteriorate substantially the contrast generated by the different brain structures in the CARS image. Fixation with methanol-acetone strongly modifies the tissue lipid content and is therefore incompatible with the CARS imaging.

  13. Brain Tissue Compartment Density Estimated Using Diffusion-Weighted MRI Yields Tissue Parameters Consistent With Histology

    OpenAIRE

    Sepehrband, Farshid; Clark, Kristi A.; Ullmann, Jeremy F. P.; Kurniawan, Nyoman D; Leanage, Gayeshika; Reutens, David C.; Yang, Zhengyi

    2015-01-01

    We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intra-cellular and intra-neurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin de...

  14. Changes in brain tissue and behavior patterns induced by single short-term fasting in mice.

    Science.gov (United States)

    Hisatomi, Yuko; Asakura, Kyo; Kugino, Kenji; Kurokawa, Mamoru; Asakura, Tomiko; Nakata, Keiko

    2013-01-01

    In humans, emaciation from long-term dietary deficiencies, such as anorexia, reportedly increases physical activity and brain atrophy. However, the effects of single short-term fasting on brain tissue or behavioral activity patterns remain unclear. To clarify the impact of malnutrition on brain function, we conducted a single short-term fasting study as an anorexia model using male adult mice and determined if changes occurred in migratory behavior as an expression of brain function and in brain tissue structure. Sixteen-week-old C57BL/6J male mice were divided into either the fasted group or the control group. Experiments were conducted in a fixed indoor environment. We examined the effects of fasting on the number of nerve cells, structural changes in the myelin and axon density, and brain atrophy. For behavior observation, the amount of food and water consumed, ingestion time, and the pattern of movement were measured using a time-recording system. The fasted mice showed a significant increase in physical activity and their rhythm of movement was disturbed. Since the brain was in an abnormal state after fasting, mice that were normally active during the night became active regardless of day or night and performed strenuous exercise at a high frequency. The brain weight did not change by a fast, and brain atrophy was not observed. Although no textural change was apparent by fasting, the neuronal neogenesis in the subventricular zone and hippocampus was inhibited, causing disorder of the brain function. A clear association between the suppression of encephalic neuropoiesis and overactivity was not established. However, it is interesting that the results of this study suggest that single short-term fasting has an effect on encephalic neuropoiesis.

  15. Analysis of sports related mTBI injuries caused by elastic wave propagation through brain tissue

    OpenAIRE

    Case, D.; Richer, E.

    2016-01-01

    Repetitive concussions and sub-concussions suffered by athletes have been linked to a series of sequelae ranging from traumatic encephalopathy to dementia pugilistica. A detailed finite element model of the human head was developed based on standard libraries of medical imaging. The model includes realistic material properties for the brain tissue, bone, soft tissue, and CSF, as well as the structure and properties of a protective helmet. Various impact scenarios were studied, with a focus on...

  16. Gene expression changes with age in skin, adipose tissue, blood and brain.

    Science.gov (United States)

    Glass, Daniel; Viñuela, Ana; Davies, Matthew N; Ramasamy, Adaikalavan; Parts, Leopold; Knowles, David; Brown, Andrew A; Hedman, Asa K; Small, Kerrin S; Buil, Alfonso; Grundberg, Elin; Nica, Alexandra C; Di Meglio, Paola; Nestle, Frank O; Ryten, Mina; Durbin, Richard; McCarthy, Mark I; Deloukas, Panagiotis; Dermitzakis, Emmanouil T; Weale, Michael E; Bataille, Veronique; Spector, Tim D

    2013-07-26

    Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age. Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues. Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.

  17. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

    1999-01-01

    report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high......-resolution gas chromatography with electron capture detection. Mean concentrations of polychlorinated biphenyls, 2, 2'-bis(4-chlorophenyl)-1,1-dichloroethylene, ss-hexachlorocyclohexane, hexachlorobenzene, mirex, trans-nonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 3-34-fold higher...

  18. Apparatus dependence of normal brain tissue dose in stereotactic radiosurgery for multiple brain metastases.

    Science.gov (United States)

    Ma, Lijun; Petti, Paula; Wang, Brian; Descovich, Martina; Chuang, Cynthia; Barani, Igor J; Kunwar, Sandeep; Shrieve, Dennis C; Sahgal, Arjun; Larson, David A

    2011-06-01

    Technical improvements in commercially available radiosurgery platforms have made it practical to treat a large number of intracranial targets. The goal of this study was to investigate whether the dose to normal brain when planning radiosurgery to multiple targets is apparatus dependent. The authors selected a single case involving a patient with 12 metastatic lesions widely distributed throughout the brain as visualized on contrast-enhanced CT. Target volumes and critical normal structures were delineated with Leksell Gamma Knife Perfexion software. The imaging studies including the delineated contours were digitally exported into the CyberKnife and Novalis multileaf collimator-based planning systems for treatment planning using identical target dose goals and dose-volume constraints. Subsets of target combinations (3, 6, 9, or 12 targets) were planned separately to investigate the relationship of number of targets and radiosurgery platform to the dose to normal brain. Despite similar target dose coverage and dose to normal structures, the dose to normal brain was strongly apparatus dependent. A nonlinear increase in dose to normal brain volumes with increasing number of targets was also noted. The dose delivered to normal brain is strongly dependent on the radiosurgery platform. How general this conclusion is and whether apparatus-dependent differences are related to differences in hardware design or differences in dose-planning algorithms deserve further investigation.

  19. Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders?

    Science.gov (United States)

    Kocot, Joanna; Luchowska-Kocot, Dorota; Kiełczykowska, Małgorzata; Musik, Irena; Kurzepa, Jacek

    2017-06-27

    Vitamin C (Vit C) is considered to be a vital antioxidant molecule in the brain. Intracellular Vit C helps maintain integrity and function of several processes in the central nervous system (CNS), including neuronal maturation and differentiation, myelin formation, synthesis of catecholamine, modulation of neurotransmission and antioxidant protection. The importance of Vit C for CNS function has been proven by the fact that targeted deletion of the sodium-vitamin C co-transporter in mice results in widespread cerebral hemorrhage and death on post-natal day one. Since neurological diseases are characterized by increased free radical generation and the highest concentrations of Vit C in the body are found in the brain and neuroendocrine tissues, it is suggested that Vit C may change the course of neurological diseases and display potential therapeutic roles. The aim of this review is to update the current state of knowledge of the role of vitamin C on neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic sclerosis, as well as psychiatric disorders including depression, anxiety and schizophrenia. The particular attention is attributed to understanding of the mechanisms underlying possible therapeutic properties of ascorbic acid in the presented disorders.

  20. Novel prion protein insert mutation associated with prolonged neurodegenerative illness.

    Science.gov (United States)

    Lewis, V; Collins, S; Hill, A F; Boyd, A; McLean, C A; Smith, M; Masters, C L

    2003-05-27

    Mutations in the prion protein gene (PRNP) are found in approximately 13 to 15% of persons classified as dying from a transmissible spongiform encephalopathy. Point and octapeptide repeat insert and deletion mutations are described in the open reading frame (ORF) of PRNP. The authors present a clinicopathologic study of a patient with a family history of a lengthy and progressive neurodegenerative disorder associated with a novel large octapeptide repeat insert mutation. Neuropathologic examination, including immunohistochemistry for the prion protein, was undertaken. The ORF of PRNP was amplified by PCR, cloned, and sequenced. Homogenate of cerebral tissue underwent Western blot analysis for the prion protein before and after proteinase K treatment. The proband died after a 16-year illness commencing at age 29 years. Confident premortem clinical diagnosis was not achieved despite a brain biopsy. Autopsy examination of the brain confirmed a spongiform encephalopathy. Prion protein immunohistochemistry revealed occasional granular deposits in the cerebellar granular layer. The proband was found to harbor a novel PRNP 168 base pair (bp) insert mutation. The authors have identified a novel 168 bp octapeptide repeat insert mutation. Prion protein immunohistochemistry differs from previous cases harboring seven octapeptide repeat and other long insert mutations. Optimization of PRNP analysis, especially PCR conditions, is essential to avoid overlooking this type of mutation and delay the correct molecular genetic diagnosis.

  1. Study into penetration speed during laser cutting of brain tissues.

    Science.gov (United States)

    Yilbas, Z; Sami, M; Patiroglu, T

    1998-01-01

    The applications of CO2 continuous-wave lasers in neurosurgery have become important in recent years. Theoretical considerations of laser applicability in medicine are subsequently confirmed experimentally. To obtain precision operation in the laser cutting process, further theoretical developments and experimental studies need to be conducted. Consequently, in the present study, the heat transfer mechanism taking place during laser-tissue interaction is introduced using Fourier theory. The results obtained from the theoretical model are compared with the experimental results. In connection with this, an experiment is designed to measure the penetration speed during the laser cutting process. The measurement is carried out using an optical method. It is found that both results for the penetration speed obtained from the theory and experiment are in a good agreement.

  2. Bimodal Spectroscopy of Formalin Fixed Samples to Discriminate Dysplastic and Tumor Brain Tissues

    Directory of Open Access Journals (Sweden)

    Anand S.

    2014-12-01

    Full Text Available Biomedical spectroscopy has gained attention in the past few years for disease diagnosis. Fluorescence and Raman spectroscopies provide finger-print information related to biochemical and morphological alterations when tissues progress from the normal to a malignant stage. Usually, freshly excised tissue specimens are preferred for bio-spectroscopic studies. However, ethical issues, sample availability and distance between the surgery room and the laboratory provide an impelling restriction for in-vitro spectroscopic studies using freshly excised samples. After surgical resection tissues are fixed in 4% formalin for histological studies under a light microscope. The process of fixation prevents degradation of tissues. In this study, we probe the use of formalin fixed sample for differentiating normal and dysplastic brain tissues using fluorescence and Raman spectroscopies. It was found that fluorescence spectral profile changes in the wavelength range from 550-750 nm between dysplastic and tumor samples. Also, significant differences were found in the Raman spectral profiles of such samples. The results indicate a potential diagnostic application of spectroscopy in formalin fixed brain samples for differentiating dysplastic and tumor brain tissues.

  3. Differential expression of the bone and the liver tissue non-specific alkaline phosphatase isoforms in brain tissues.

    Science.gov (United States)

    Brun-Heath, Isabelle; Ermonval, Myriam; Chabrol, Elodie; Xiao, Jinsong; Palkovits, Miklós; Lyck, Ruth; Miller, Florence; Couraud, Pierre-Olivier; Mornet, Etienne; Fonta, Caroline

    2011-03-01

    The enzyme tissue non-specific alkaline phosphatase (TNAP) belongs to the ectophosphatase family. It is present in large amounts in bone in which it plays a role in mineralization but little is known about its function in other tissues. Arguments are accumulating for its involvement in the brain, in particular in view of the neurological symptoms accompanying human TNAP deficiencies. We have previously shown, by histochemistry, alkaline phosphatase (AP) activity in monkey brain vessels and parenchyma in which AP exhibits specific patterns. Here, we clearly attribute this activity to TNAP expression rather than to other APs in primates (human and marmoset) and in rodents (rat and mouse). We have not found any brain-specific transcripts but our data demonstrate that neuronal and endothelial cells exclusively express the bone TNAP transcript in all species tested, except in mouse neurons in which liver TNAP transcripts have also been detected. Moreover, we highlight the developmental regulation of TNAP expression; this also acts during neuronal differentiation. Our study should help to characterize the regulation of the expression of this ectophosphatase in various cell types of the central nervous system.

  4. Is human blood a good surrogate for brain tissue in transcriptional studies?

    Directory of Open Access Journals (Sweden)

    van den Berg Leonard H

    2010-10-01

    Full Text Available Abstract Background Since human brain tissue is often unavailable for transcriptional profiling studies, blood expression data is frequently used as a substitute. The underlying hypothesis in such studies is that genes expressed in brain tissue leave a transcriptional footprint in blood. We tested this hypothesis by relating three human brain expression data sets (from cortex, cerebellum and caudate nucleus to two large human blood expression data sets (comprised of 1463 individuals. Results We found mean expression levels were weakly correlated between the brain and blood data (r range: [0.24,0.32]. Further, we tested whether co-expression relationships were preserved between the three brain regions and blood. Only a handful of brain co-expression modules showed strong evidence of preservation and these modules could be combined into a single large blood module. We also identified highly connected intramodular "hub" genes inside preserved modules. These preserved intramodular hub genes had the following properties: first, their expression levels tended to be significantly more heritable than those from non-preserved intramodular hub genes (p -90; second, they had highly significant positive correlations with the following cluster of differentiation genes: CD58, CD47, CD48, CD53 and CD164; third, a significant number of them were known to be involved in infection mechanisms, post-transcriptional and post-translational modification and other basic processes. Conclusions Overall, we find transcriptome organization is poorly preserved between brain and blood. However, the subset of preserved co-expression relationships characterized here may aid future efforts to identify blood biomarkers for neurological and neuropsychiatric diseases when brain tissue samples are unavailable.

  5. Atlas-based segmentation of developing tissues in the human brain with quantitative validation in young fetuses.

    Science.gov (United States)

    Habas, Piotr A; Kim, Kio; Rousseau, Francois; Glenn, Orit A; Barkovich, A James; Studholme, Colin

    2010-09-01

    Imaging of the human fetus using magnetic resonance (MR) is an essential tool for quantitative studies of normal as well as abnormal brain development in utero. However, because of fundamental differences in tissue types, tissue properties and tissue distribution between the fetal and adult brain, automated tissue segmentation techniques developed for adult brain anatomy are unsuitable for this data. In this paper, we describe methodology for automatic atlas-based segmentation of individual tissue types in motion-corrected 3D volumes reconstructed from clinical MR scans of the fetal brain. To generate anatomically correct automatic segmentations, we create a set of accurate manual delineations and build an in utero 3D statistical atlas of tissue distribution incorporating developing gray and white matter as well as transient tissue types such as the germinal matrix. The probabilistic atlas is associated with an unbiased average shape and intensity template for registration of new subject images to the space of the atlas. Quantitative whole brain 3D validation of tissue labeling performed on a set of 14 fetal MR scans (20.57-22.86 weeks gestational age) demonstrates that this atlas-based EM segmentation approach achieves consistently high DSC performance for the main tissue types in the fetal brain. This work indicates that reliable measures of brain development can be automatically derived from clinical MR imaging and opens up possibility of further 3D volumetric and morphometric studies with multiple fetal subjects. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.

  6. Light-scattering signal may indicate critical time zone to rescue brain tissue after hypoxia

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2011-02-01

    A light-scattering signal, which is sensitive to cellular/subcellular structural integrity, is a potential indicator of brain tissue viability because metabolic energy is used in part to maintain the structure of cells. We previously observed a unique triphasic scattering change (TSC) at a certain time after oxygen/glucose deprivation for blood-free rat brains; TSC almost coincided with the cerebral adenosine triphosphate (ATP) depletion. We examine whether such TSC can be observed in the presence of blood in vivo, for which transcranial diffuse reflectance measurement is performed for rat brains during hypoxia induced by nitrogen gas inhalation. At a certain time after hypoxia, diffuse reflectance intensity in the near-infrared region changes in three phases, which is shown by spectroscopic analysis to be due to scattering change in the tissue. During hypoxia, rats are reoxygenated at various time points. When the oxygen supply is started before TSC, all rats survive, whereas no rats survive when the oxygen supply is started after TSC. Survival is probabilistic when the oxygen supply is started during TSC, indicating that the period of TSC can be regarded as a critical time zone for rescuing the brain. The results demonstrate that light scattering signal can be an indicator of brain tissue reversibility.

  7. Transmission routes of HIV-1 gp120 from brain to lymphoid tissues.

    Science.gov (United States)

    Cashion, M F; Banks, W A; Bost, K L; Kastin, A J

    1999-03-20

    The blood-brain barrier (BBB) restricts the entry of antiviral agents into the CNS thereby facilitating the creation of a reservoir of HIV that could potentially reinfect peripheral tissues. We characterized the efflux from brain of radioactively labeled viral coat HIV-1 gp120 (I-gp120) after intracerebroventricular (i.c.v.) injection. The half-time disappearance rate of I-gp120 from brain was 12.6 min, which was faster than could be explained by the reabsorption of cerebrospinal fluid into blood but could not be explained by a saturable transporter. After i.c.v. injection, I-gp120 appeared in the serum and was sequestered by spleen and the cervical nodes, demonstrating a potential for virus within the CNS to reinfect peripheral tissues. However, the amount of I-gp120 appearing in serum was less than that expected based on the efflux rate, whereas uptake by the cervical nodes was much greater after i. c.v. than after i.v. injection of I-gp120. These findings were explained by drainage from the brain directly to the cervical lymph nodes through the brain's primitive lymphatic system. These lymphatics potentially provide a pathway through which CNS reservoirs of HIV-1 could directly reinfect lymphoid tissue without being exposed to circulating antiviral agents. Copyright 1999 Elsevier Science B.V.

  8. Elderly depression diagnostic of diabetic patients by brain tissue pulsatility imaging

    Science.gov (United States)

    Hachemi, Mélouka Elkateb; Remeniéras, Jean-pierre; Desmidt, Thomas; Camus, Vincent; Tranquart, François

    2010-01-01

    Pulsatile motion of brain parenchyma results from cardiac and breathing cycles and consists in a rapid displacement in systole, with slow diastolic recovery. Based on the vascular depression concept and recent studies where a correlation was found between cerebral haemodynamics and depression in the elderly, we emitted the hypothesis that tissue brain motion due to perfusion is correlated to elderly depression associated with cardiovascular risk factors. Tissue Pulsatlity Imaging (TPI) is a new ultrasound technique developed firstly at the University of Washington to assess the brain tissue motion. We used TPI technique to measure the brain displacement of two groups of elderly patients with diabetes as a vascular risk factor. The first group is composed of 11 depressed diabetic patients. The second group is composed of 12 diabetic patients without depressive symptoms. Transcranial acquisitions were performed with a 1.8 MHz ultrasound phased array probe through the right temporal bone window. The acquisition of six cardiac cycles was realized on each patient with a frame rate of 23 frames/s. Displacements estimation was performed by off-line analysis. A significant decrease in brain pulsatility was observed in the group of depressed patients compared to the group of non depressed patients. Mean displacement magnitude was about 44±7 μm in the first group and 68±13 μm in the second group.

  9. Visualization of damaged brain tissue after ischemic stroke with cobalt-55 positron emission tomography

    NARCIS (Netherlands)

    Jansen, H M; Pruim, J; vd Vliet, A M; Paans, A M; Hew, J M; Franssen, E J; de Jong, B M; Kosterink, J G; Haaxma, R; Korf, J

    UNLABELLED: In animal experiments, the radionuclide 55Co2+ has been shown to accumulate in degenerating cerebral tissue similar to Ca2+. METHODS: The potential role of 55Co2+ for in vivo brain PET imaging was investigated in four patients after ischemic stroke. RESULTS: PET showed uptake of 55Co2+

  10. Mesh electronics: a new paradigm for tissue-like brain probes.

    Science.gov (United States)

    Hong, Guosong; Yang, Xiao; Zhou, Tao; Lieber, Charles M

    2017-12-01

    Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to 'look and behave' like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

    Directory of Open Access Journals (Sweden)

    Caghan Kizil

    Full Text Available Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI, RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

  12. Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages

    NARCIS (Netherlands)

    Huisman, M; Muskiet, FAJ; Van Der Paauw, CG; Essed, CE; Boersma, ER

    We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos.

  13. Three levels of neuroelectronic interfacing: silicon chips with ion channels, nerve cells, and brain tissue.

    Science.gov (United States)

    Fromherz, Peter

    2006-12-01

    We consider the direct electrical interfacing of semiconductor chips with individual nerve cells and brain tissue. At first, the structure of the cell-chip contact is studied. Then we characterize the electrical coupling of ion channels--the electrical elements of nerve cells--with transistors and capacitors in silicon chips. On that basis it is possible to implement signal transmission between microelectronics and the microionics of nerve cells in both directions. Simple hybrid neuroelectronic systems are assembled with neuron pairs and with small neuronal networks. Finally, the interfacing with capacitors and transistors is extended to brain tissue cultured on silicon chips. The application of highly integrated silicon chips allows an imaging of neuronal activity with high spatiotemporal resolution. The goal of the work is an integration of neuronal network dynamics with digital electronics on a microscopic level with respect to experiments in brain research, medical prosthetics, and information technology.

  14. Computational Assessment of Neural Probe and Brain Tissue Interface under Transient Motion

    Directory of Open Access Journals (Sweden)

    Michael Polanco

    2016-06-01

    Full Text Available The functional longevity of a neural probe is dependent upon its ability to minimize injury risk during the insertion and recording period in vivo, which could be related to motion-related strain between the probe and surrounding tissue. A series of finite element analyses was conducted to study the extent of the strain induced within the brain in an area around a neural probe. This study focuses on the transient behavior of neural probe and brain tissue interface with a viscoelastic model. Different stages of the interface from initial insertion of neural probe to full bonding of the probe by astro-glial sheath formation are simulated utilizing analytical tools to investigate the effects of relative motion between the neural probe and the brain while friction coefficients and kinematic frequencies are varied. The analyses can provide an in-depth look at the quantitative benefits behind using soft materials for neural probes.

  15. Use of flow cytometry for high-throughput cell population estimates in brain tissue

    Science.gov (United States)

    Young, Nicole A.; Flaherty, David K.; Airey, David C.; Varlan, Peter; Aworunse, Feyi; Kaas, Jon H.; Collins, Christine E.

    2012-01-01

    The large size of primate brains is an impediment to obtaining high-resolution cell number maps of the cortex in humans and non-human primates. We present a rapid, flow cytometry-based cell counting method that can be used to estimate cell numbers from homogenized brain tissue samples comprising the entire cortical sheet. The new method, called the flow fractionator, is based on the isotropic fractionator (IF) method (Herculano-Houzel and Lent, 2005), but substitutes flow cytometry analysis for manual, microscope analysis using a Neubauer counting chamber. We show that our flow cytometry-based method for total cell estimation in homogenized brain tissue provides comparable data to that obtained using a counting chamber on a microscope. The advantages of the flow fractionator over existing methods are improved precision of cell number estimates and improved speed of analysis. PMID:22798947

  16. PIXE analysis of low concentration aluminum in brain tissues of an Alzheimer's disease patient

    Science.gov (United States)

    Ishihara, R.; Hanaichi, T.; Takeuchi, T.; Ektessabi, A. M.

    1999-06-01

    An excess accumulation and presence of metal ions may significantly alter a brain cell's normal functions. There have been increasing efforts in recent years to measure and quantify the density and distribution of excessive accumulations of constituent elements (such as Fe, Zn, Cu, and Ca) in the brain, as well as the presence and distribution of contaminating elements (such as Al). This is particularly important in cases of neuropathological disorders such as Alzheimer's disease, Parkinson's disease and ALS. The aim of this paper was to measure the Al present in the temporal cortex of the brain of an Alzheimer's disease patient. The specimens were taken from an unfixed autopsy brain which has been preserved for a period of 4 years in the deep freezer at -80 °C. Proton Induced X-ray Emission Spectroscopy was used for the measurement of Al concentration in this brain tissue. A tandem accelerator with 2 MeV of energy was also used. In order to increase the sensitivity of the signals in the low energy region of the spectra, the absorbers were removed. The results show that the peak height depends on the measurement site. However, in certain cases an extremely high concentration of Al was observed in the PIXE spectra, with an intensity higher than those in the other major elements of the brain's matrix element. Samples from tissues affected by the same disease were analyzed using the EDX analyzer. The results are quantitatively in very good agreement with those of the PIXE analysis.

  17. An endogenous inhibitor of cysteine cathepsin B from brain tissues

    Directory of Open Access Journals (Sweden)

    O.L. Lyanna

    2013-11-01

    -nitroanilide N,α-benzoyl-D,L-arginine. Using graphic methods for analysis of enzymatic kinetics we proposed a mechanism of interaction of the endogenous inhibitor with cysteine cathepsin B. This scheme could prove useful for the understanding of biochemical mechanisms occurring in normal and, especially, in pathological human brain processes.

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

    Science.gov (United States)

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

    2013-01-01

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

  19. Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

    Science.gov (United States)

    Rabeneck, Demi B.; Martines, Roosecelis B.; Reagan-Steiner, Sarah; Ermias, Yokabed; Estetter, Lindsey B.C.; Suzuki, Tadaki; Ritter, Jana; Keating, M. Kelly; Hale, Gillian; Gary, Joy; Muehlenbachs, Atis; Lambert, Amy; Lanciotti, Robert; Oduyebo, Titilope; Meaney-Delman, Dana; Bolaños, Fernando; Saad, Edgar Alberto Parra; Shieh, Wun-Ju; Zaki, Sherif R.

    2017-01-01

    Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections. PMID:27959260

  20. A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitro

    Directory of Open Access Journals (Sweden)

    Nathaniel J Killian

    2016-03-01

    Full Text Available Distributed microelectrode array (MEA recordings from consistent, viable, ≥ 500 µm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3 D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step towards the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long brain slice preparations.

  1. Spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging

    Science.gov (United States)

    Singh-Moon, Rajinder P.; Roblyer, Darren M.; Bigio, Irving J.; Joshi, Shailendra

    2014-09-01

    We present an application of spatial frequency-domain imaging (SFDI) to the wide-field imaging of drug delivery to brain tissue. Measurements were compared with values obtained by a previously validated variation of diffuse reflectance spectroscopy, the method of optical pharmacokinetics (OP). We demonstrate a cross-correlation between the two methods for absorption extraction and drug concentration determination in both experimental tissue phantoms and freshly extracted rodent brain tissue. These methods were first used to assess intra-arterial (IA) delivery of cationic liposomes to brain tissue in Sprague Dawley rats under transient cerebral hypoperfusion. Results were found to be in agreement with previously published experimental data and pharmacokinetic models of IA drug delivery. We then applied the same scheme to evaluate IA mitoxantrone delivery to glioma-bearing rats. Good correlation was seen between OP and SFDI determined concentrations taken from normal and tumor averaged sites. This study shows the feasibility of mapping drug/tracer distributions and encourages the use of SFDI for spatial imaging of tissues for drug/tracer-tagged carrier deposition and pharmacokinetic studies.

  2. Limited predictability of postmortem human brain tissue quality by RNA integrity numbers.

    Science.gov (United States)

    Sonntag, Kai-C; Tejada, George; Subburaju, Sivan; Berretta, Sabina; Benes, Francine M; Woo, Tsung-Ung W

    2016-07-01

    The RNA integrity number (RIN) is often considered to be a critical measure of the quality of postmortem human brains. However, it has been suggested that RINs do not necessarily reflect the availability of intact mRNA. Using the Agilent bioanalyzer and qRT-PCR, we explored whether RINs provide a meaningful way of assessing mRNA degradation and integrity in human brain samples by evaluating the expression of 3'-5' mRNA sequences of the cytochrome C-1 (CYC1) gene. Analysis of electropherograms showed that RINs were not consistently correlated with RNA or cDNA profiles and appeared to be poor predictors of overall cDNA quality. Cycle thresholds from qRT-PCR analysis to quantify the amount of CYC1 mRNA revealed positive correlations of RINs with amplification of full-length transcripts, despite the variable degree of linear degradation along the 3'-5' sequence. These data demonstrate that in postmortem human brain tissue the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs. © 2016 International Society for Neurochemistry.

  3. Position sensitive measurement of lithium traces in brain tissue with neutrons.

    Science.gov (United States)

    Lichtinger, Josef; Gernhäuser, Roman; Bauer, Andreas; Bendel, Michael; Canella, Lea; Graw, Matthias; Krücken, Reiner; Kudejova, Petra; Mützel, Elisabeth; Ring, Susanne; Seiler, Dominik; Winkler, Sonja; Zeitelhack, Karl; Schöpfer, Jutta

    2013-02-01

    The application of lithium is well known to have an antimanic-depressive effect, however, the influence it has on the human brain is still insufficiently known. The aim of our work is to develop a method to investigate the lithium concentration in the human brain with a very high sensitivity and a submillimeter resolution. Present methods either do not provide spatial resolution or are not sensitive enough to measure the naturally occurring lithium content in the human brain. Our method provides the opportunity to perform postmortem series measurements and obtain a detailed map of the lithium distribution in the human brain. This way possible correlations of the lithium distribution in the human brain and biological reasons for affective disorder can be clarified. To study the lithium distribution in different regions of the human brain the authors developed a method to measure lithium traces postmortem with a submillimeter spatial resolution using the neutron capture reaction (6)Li(n, α)(3)H. The lithium is measured by coincident detection of the alpha particles and tritons, emitted in opposite directions. The general concept, the preparation of the brain samples, the experimental setup at the measurement station of the Forschungs-Neutronenquelle Heinz Maier-Leibnitz, and a first measurement on human brain tissue are presented. A first measurement on a brain tissue sample nicely showed a spatial distribution of lithium down to a few hundreds of pg∕cm(3) with a maximal resolution of about σ(x) = σ(y) ≈ 200 μm. Also a direct correlation of lithium and optical tissue structure is observable. Typical measurement times of a few minutes allow for series measurements of up to 20 × 20 mm(2) large samples with a thickness of w = 10-20 μm in medical studies. The combination of a very high lithium sensitivity with position resolving measurement makes this method well suited for postmortem studies of the microscopic lithium distribution in the human brain and

  4. Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

    Science.gov (United States)

    Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong

    2016-05-01

    The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.

  5. Neurotrophin Therapy of Neurodegenerative Disorders with Mitochondrial Dysfunction

    Science.gov (United States)

    2007-09-01

    TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Table of Contents 1 Narrative...neurodegenerative disorders including Wernicke -Korsakoff syndrome (reviewed in Martin et al., 2005). 2. Results At E15.5, Ts16 brains are slightly

  6. Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

    Science.gov (United States)

    Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

    2012-02-01

    Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

  7. Methodological issues in protein and lipidic expressions in brain tissue exposed to Co{sup 60} based on DESI/MALDI-MS

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Matheus F.; Campos, Tarcísio P.R.; Augusti, Rodinei, E-mail: matheus.soares@gmail.com, E-mail: tprcampos@pq.cnpq.br, E-mail: augusti.rodinei@gmail.com, E-mail: augusti@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil); Eberlin, Marcos N.; Vendramini, Pedro H., E-mail: eberlin@iqm.unicamp.br, E-mail: ph_vendramini@yahoo.com.br [Universidade de Campinas (UNICAMP), SP (Brazil). Thompson Mass Spectroscopy Laboratory

    2017-07-01

    The present paper attempts to present some issues in the methodology of identifying lipid and protein changes in brain tissue induced by radiation. The goal was to address the analysis of the methodology and to investigate the feasibility of the generation of lipid/protein profiles of irradiated brain tissue, in order to identify radioinduced changes. Lipids and proteins are biomolecules with diverse structures and functionalities that participate in important intracellular processes. Changes in the lipid and the tissue protein profiles may indicate a cellular response to an external stimulus as well as the emergence of neoplasms or neurodegenerative diseases such as Alzheimer's. DESI-MS is a convenient method for identifying lipids and their spatial distribution in tissue beyond analytical quantification. DESI-MS allows the creation of an image of several low lipid m/z classes. MALDI-MS has already been a method used in the study of macromolecules as structural, membrane, hormone, neuromediator and immunological peptides. Through a full-scan matrix scan, with a m/z spectrum between 500-1000 for lipids and with a mass spectrum of 1000-15000 Da for proteins, the molecular profile can be analyzed. Generated pixel shape 2D chemical image. The produced image allows to associate the tissue distribution of the lipids and proteins with their chemical profile identified, allowing the verification of the changes radioinduced. Radiation triggers intense oxidative stress by increasing reactive oxygen species (ROS) and free radicals, causing DNA damage with consequent alterations in proteomics and cellular lipid explaining such changes in the lipid and protein expressions. The cellular morphophysiological changes are responsible for both the clonogenic inhibition and the induction of the apoptotic process. The images's production was directly dependent on the rigorous execution of the methodological procedures. Innumerable interferences could impair the image

  8. The Importance of Brain Banks for Molecular Neuropathological Research: The New South Wales Tissue Resource Centre Experience

    Directory of Open Access Journals (Sweden)

    Antony Harding

    2009-01-01

    Full Text Available New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls. This review highlights changes in TRC operational procedures dictated by modern neuroscience, and provides examples of applications of modern molecular techniques to study the neuropathogenesis of many different brain disorders.

  9. Effects of different concentrations of pollen extract on brain tissues of Oncorhynchus mykiss

    Directory of Open Access Journals (Sweden)

    Mehmet Fuat Gulhan

    2014-03-01

    Full Text Available Objective: To determine the antioxidant capacities of pollen extract applied at different concentrations on biochemical parameters in brain tissues of rainbow trouts. Methods: The effective concentration of pollen was determined with some biochemical parameters in brain tissues of fish treated at various concentrations of the pollen extract (0.5, 2.5, 5, 10, 20 and 30 mg/L for 96 h. The malondialdehyde levels, total antioxidant status, total oxidant status, oxidative stress index and amounts of total free sulfhydryl groups were analyzed in fish brain. Results: The malondialdehyde levels decreased in groups of 0.5, 2.5, 5, 10, 20 and 30 mg/L pollen-treated compared to control group (P<0.05. The highest level of total antioxidant status (P<0.05 and the lowest value (P<0.05 of the total oxidant status was 10 mg/L concentration of pollen. Oxidative stress index and level of sulfhydryl groups showed lowest values (P<0.05 in 10 mg/L pollen treated group compared with control group. Conclusions: To apply the pollen to fish reduces the detrimental effects and modulates oxidative status via activating antioxidant defense systems at brain tissue. As a result, pollen can be added up to 10 mg/L to the medium of rainbow trout to improve health of fish.

  10. Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

    Science.gov (United States)

    2013-01-01

    Background Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. Results In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed “sleep specific” changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Conclusion Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific

  11. Optical histology: a method to visualize microvasculature in thick tissue sections of mouse brain.

    Science.gov (United States)

    Moy, Austin J; Wiersma, Matthew P; Choi, Bernard

    2013-01-01

    The microvasculature is the network of blood vessels involved in delivering nutrients and gases necessary for tissue survival. Study of the microvasculature often involves immunohistological methods. While useful for visualizing microvasculature at the µm scale in specific regions of interest, immunohistology is not well suited to visualize the global microvascular architecture in an organ. Hence, use of immunohistology precludes visualization of the entire microvasculature of an organ, and thus impedes study of global changes in the microvasculature that occur in concert with changes in tissue due to various disease states. Therefore, there is a critical need for a simple, relatively rapid technique that will facilitate visualization of the microvascular network of an entire tissue. The systemic vasculature of a mouse is stained with the fluorescent lipophilic dye DiI using a method called "vessel painting". The brain, or other organ of interest, is harvested and fixed in 4% paraformaldehyde. The organ is then sliced into 1 mm sections and optically cleared, or made transparent, using FocusClear, a proprietary optical clearing agent. After optical clearing, the DiI-labeled tissue microvasculature is imaged using confocal fluorescence microscopy and adjacent image stacks tiled together to produce a depth-encoded map of the microvasculature in the tissue slice. We demonstrated that the use of optical clearing enhances both the tissue imaging depth and the estimate of the vascular density. Using our "optical histology" technique, we visualized microvasculature in the mouse brain to a depth of 850 µm. Presented here are maps of the microvasculature in 1 mm thick slices of mouse brain. Using combined optical clearing and optical imaging techniques, we devised a methodology to enhance the visualization of the microvasculature in thick tissues. We believe this technique could potentially be used to generate a three-dimensional map of the microvasculature in an entire

  12. Quantification of retinoid concentrations in human serum and brain tumor tissues.

    Science.gov (United States)

    Ali, Ramadan; Campos, Benito; Dyckhoff, Gerhard; Haefeli, Walter E; Herold-Mende, Christel; Burhenne, Jürgen

    2012-05-06

    Retinoic acid signaling is essential for central nervous system (CNS) differentiation and appears to be impaired in tumors. Thus far, there are no established methods to quantify relevant retinoids (all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis retinoic acid, and retinol) in human brain tumors. We developed a single step extraction and quantification procedure for polar and apolar retinoids in normal tissue, lipid-rich brain tumor tissues, and serum. This quantification procedure is based on high performance liquid chromatography (HPLC) with diode-array detection (DAD) using all-trans-acitretin as an internal standard and extraction by liquid-liquid partition with ethyl acetate and borate buffer at pH 9. Recovery with this extraction procedure was higher than earlier (two-step) liquid-liquid extraction procedures based on hexane, NaOH, and HCl. The overall quantification procedure was validated according to Food and Drug Administration (FDA) guidelines and fulfilled all criteria of accuracy, precision, selectivity, recovery, and stability. The overall method accuracy varied between -5.6% and +5.4% for serum and -3.8% and +6.2% for tissues, and overall precision ranged from 3.1% to 6.9% for serum and 2.1% to 8.3% for tissues (%CV batch-to-batch). The lower limit of quantification for all compounds in tumor tissue (and serum) was 3.9 ng g(-1) (ng mL(-1)). Using this assay, photodegradation of the retinoids was evaluated and endogenous polar and apolar retinoids were quantified in sera and brain tumor tissues of patients and compared with serum and tonsil tissue concentrations of controls. It may thus serve as a suitable method for the characterization of retinoid uptake and metabolism in the respective compartments. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Optical histology: a method to visualize microvasculature in thick tissue sections of mouse brain.

    Directory of Open Access Journals (Sweden)

    Austin J Moy

    Full Text Available The microvasculature is the network of blood vessels involved in delivering nutrients and gases necessary for tissue survival. Study of the microvasculature often involves immunohistological methods. While useful for visualizing microvasculature at the µm scale in specific regions of interest, immunohistology is not well suited to visualize the global microvascular architecture in an organ. Hence, use of immunohistology precludes visualization of the entire microvasculature of an organ, and thus impedes study of global changes in the microvasculature that occur in concert with changes in tissue due to various disease states. Therefore, there is a critical need for a simple, relatively rapid technique that will facilitate visualization of the microvascular network of an entire tissue.The systemic vasculature of a mouse is stained with the fluorescent lipophilic dye DiI using a method called "vessel painting". The brain, or other organ of interest, is harvested and fixed in 4% paraformaldehyde. The organ is then sliced into 1 mm sections and optically cleared, or made transparent, using FocusClear, a proprietary optical clearing agent. After optical clearing, the DiI-labeled tissue microvasculature is imaged using confocal fluorescence microscopy and adjacent image stacks tiled together to produce a depth-encoded map of the microvasculature in the tissue slice. We demonstrated that the use of optical clearing enhances both the tissue imaging depth and the estimate of the vascular density. Using our "optical histology" technique, we visualized microvasculature in the mouse brain to a depth of 850 µm.Presented here are maps of the microvasculature in 1 mm thick slices of mouse brain. Using combined optical clearing and optical imaging techniques, we devised a methodology to enhance the visualization of the microvasculature in thick tissues. We believe this technique could potentially be used to generate a three-dimensional map of the

  14. Automatic tissue segmentation of neonate brain MR Images with subject-specific atlases

    Science.gov (United States)

    Cherel, Marie; Budin, Francois; Prastawa, Marcel; Gerig, Guido; Lee, Kevin; Buss, Claudia; Lyall, Amanda; Zaldarriaga Consing, Kirsten; Styner, Martin

    2015-03-01

    Automatic tissue segmentation of the neonate brain using Magnetic Resonance Images (MRI) is extremely important to study brain development and perform early diagnostics but is challenging due to high variability and inhomogeneity in contrast throughout the image due to incomplete myelination of the white matter tracts. For these reasons, current methods often totally fail or give unsatisfying results. Furthermore, most of the subcortical midbrain structures are misclassified due to a lack of contrast in these regions. We have developed a novel method that creates a probabilistic subject-specific atlas based on a population atlas currently containing a number of manually segmented cases. The generated subject-specific atlas is sharp and adapted to the subject that is being processed. We then segment brain tissue classes using the newly created atlas with a single-atlas expectation maximization based method. Our proposed method leads to a much lower failure rate in our experiments. The overall segmentation results are considerably improved when compared to using a non-subject-specific, population average atlas. Additionally, we have incorporated diffusion information obtained from Diffusion Tensor Images (DTI) to improve the detection of white matter that is not visible at this early age in structural MRI (sMRI) due to a lack of myelination. Although this necessitates the acquisition of an additional sequence, the diffusion information improves the white matter segmentation throughout the brain, especially for the mid-brain structures such as the corpus callosum and the internal capsule.

  15. Double in situ hybridization for microRNAs and mRNAs in brain tissues

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    Atsushi Kasai

    2016-11-01

    Full Text Available MicroRNAs (miRNAs participate in a variety of functions in the brain. Understanding the in vivo localization of miRNAs is an important step for uncovering their roles in brain function. However, the in situ detection of low-abundance miRNAs in brain tissues remains difficult and requires extensive optimization of in situ hybridization (ISH protocols in individual laboratories. Thus, detailed information regarding experimental conditions would serve as a useful reference for researchers in this field. Here, we investigated and summarized the effects of adjusting a series of critical steps, including tissue fixation, probe accessibility and hybridization stringency, to standardize the currently used miRNA ISH procedures. As a result, we successfully detected several low-abundance miRNAs by ISH using the following experimental conditions: (1 use of fresh brain tissues, (2 digestion of brain samples with proteinase K, (3 LNA-probe hybridization at a temperature 37°C below the melting temperature of the RNA, (4 performance of high-stringency wash steps using 50% formamide in 1× standard saline citrate (SSC buffer. RT-PCR of the punched-out tissues using TaqManTM primers confirmed the ISH results. Finally, double-fluorescence ISH successfully demonstrated the colocalization of miRNAs and mRNAs. Thus, the detailed information regarding the miRNA ISH procedures used in this study may help to resolve the technical hurdles observed in the in vivo localization of miRNAs, and the elucidation of the specific roles of miRNAs.

  16. Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice

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    Kenne Ellinor

    2012-01-01

    Full Text Available Abstract Background Brain edema as a result of secondary injury following traumatic brain injury (TBI is a major clinical concern. Neutrophils are known to cause increased vascular permeability leading to edema formation in peripheral tissue, but their role in the pathology following TBI remains unclear. Methods In this study we used controlled cortical impact (CCI as a model for TBI and investigated the role of neutrophils in the response to injury. The outcome of mice that were depleted of neutrophils using an anti-Gr-1 antibody was compared to that in mice with intact neutrophil count. The effect of neutrophil depletion on blood-brain barrier function was assessed by Evan's blue dye extravasation, and analysis of brain water content was used as a measurement of brain edema formation (24 and 48 hours after CCI. Lesion volume was measured 7 and 14 days after CCI. Immunohistochemistry was used to assess cell death, using a marker for cleaved caspase-3 at 24 hours after injury, and microglial/macrophage activation 7 days after CCI. Data were analyzed using Mann-Whitney test for non-parametric data. Results Neutrophil depletion did not significantly affect Evan's blue extravasation at any time-point after CCI. However, neutrophil-depleted mice exhibited a decreased water content both at 24 and 48 hours after CCI indicating reduced edema formation. Furthermore, brain tissue loss was attenuated in neutropenic mice at 7 and 14 days after injury. Additionally, these mice had a significantly reduced number of activated microglia/macrophages 7 days after CCI, and of cleaved caspase-3 positive cells 24 h after injury. Conclusion Our results suggest that neutrophils are involved in the edema formation, but not the extravasation of large proteins, as well as contributing to cell death and tissue loss following TBI in mice.

  17. Measuring the linear and nonlinear elastic properties of brain tissue with shear waves and inverse analysis.

    Science.gov (United States)

    Jiang, Yi; Li, Guoyang; Qian, Lin-Xue; Liang, Si; Destrade, Michel; Cao, Yanping

    2015-10-01

    We use supersonic shear wave imaging (SSI) technique to measure not only the linear but also the nonlinear elastic properties of brain matter. Here, we tested six porcine brains ex vivo and measured the velocities of the plane shear waves induced by acoustic radiation force at different states of pre-deformation when the ultrasonic probe is pushed into the soft tissue. We relied on an inverse method based on the theory governing the propagation of small-amplitude acoustic waves in deformed solids to interpret the experimental data. We found that, depending on the subjects, the resulting initial shear modulus [Formula: see text] varies from 1.8 to 3.2 kPa, the stiffening parameter [Formula: see text] of the hyperelastic Demiray-Fung model from 0.13 to 0.73, and the third- [Formula: see text] and fourth-order [Formula: see text] constants of weakly nonlinear elasticity from [Formula: see text]1.3 to [Formula: see text]20.6 kPa and from 3.1 to 8.7 kPa, respectively. Paired [Formula: see text] test performed on the experimental results of the left and right lobes of the brain shows no significant difference. These values are in line with those reported in the literature on brain tissue, indicating that the SSI method, combined to the inverse analysis, is an efficient and powerful tool for the mechanical characterization of brain tissue, which is of great importance for computer simulation of traumatic brain injury and virtual neurosurgery.

  18. Brain tissue partial pressure of oxygen predicts the outcome of severe traumatic brain injury under mild hypothermia treatment

    Directory of Open Access Journals (Sweden)

    Sun H

    2016-08-01

    Full Text Available Hongtao Sun,1,* Maohua Zheng,2,* Yanmin Wang,1 Yunfeng Diao,1 Wanyong Zhao,1 Zhengjun Wei1 1Sixth Department of Neurosurgery, Affiliated Hospital of Logistics University of People’s Armed Police Force, Tianjin, 2Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to investigate the clinical significance and changes of brain tissue partial pressure of oxygen (PbtO2 in the course of mild hypothermia treatment (MHT for treating severe traumatic brain injury (sTBI. Methods: There were 68 cases with sTBI undergoing MHT. PbtO2, intracranial pressure (ICP, jugular venous oxygen saturation (SjvO2, and cerebral perfusion pressure (CPP were continuously monitored, and clinical outcomes were evaluated using the Glasgow Outcome Scale score. Results: Of 68 patients with sTBI, PbtO2, SjvO2, and CPP were obviously increased, but decreased ICP level was observed throughout the MHT. PbtO2 and ICP were negatively linearly correlated, while there was a positive linear correlation between PbtO2 and SjvO2. Monitoring CPP and SjvO2 was performed under normal circumstances, and a large proportion of patients were detected with low PbtO2. Decreased PbtO2 was also found after MHT. Conclusion: Continuous PbtO2 monitoring could be introduced to evaluate the condition of regional cerebral oxygen metabolism, thereby guiding the clinical treatment and predicting the outcome. Keywords: severe traumatic brain injury, hypothermia, brain tissue partial pressure of oxygen, therapy

  19. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, John, E-mail: jmweaver@salud.unm.edu [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Yang, Yirong [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Purvis, Rebecca [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Weatherwax, Theodore [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Rosen, Gerald M. [Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD 21201 (United States); Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, MD 21201 (United States); Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Liu, Ke Jian [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    2014-03-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissue pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in

  20. Nanofibrous gelatine scaffolds integrated with nerve growth factor-loaded alginate microspheres for brain tissue engineering.

    Science.gov (United States)

    Büyüköz, Melda; Erdal, Esra; Alsoy Altinkaya, Sacide

    2016-11-12

    Neural regeneration research is designed in part to develop strategies for therapy after nerve damage due to injury or disease. In this study, a new gelatine-based biomimetic scaffold was fabricated for brain tissue engineering applications. A technique combining thermally induced phase separation and porogen leaching was used to create interconnected macropores and nanofibrous structure. To promote tissue regeneration processes, the scaffolds were integrated with nerve growth factor (NGF)-loaded alginate microspheres. The results showed that nanofibrous matrix could only be obtained when gelatine concentration was at least 7.5% (w/v). The scaffold with a modulus value (1.2 kPa) similar to that of brain tissue (0.5-1 kPa) was obtained by optimizing the heat treatment time, macropore size and gelatine concentration. The encapsulation efficiencies of NGF into 0.1% and 1% alginate microspheres were 85% and 100%, respectively. The release rate of NGF from the microspheres was controlled by the alginate concentration and the poly(L-lysine) coating. The immobilization of the microspheres in the scaffold reduced burst release and significantly extended the release period. The nanofibrous architecture and controlled release of NGF from the microspheres induced neurite extension of PC12 cells, demonstrating that the released NGF was in an active form. The results suggest that the scaffolds prepared in this study may have potential applications in brain tissue engineering due to topologic and mechanical properties similar to brain tissue and pore structure suitable for cell growth and differentiation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Risk of hospitalization with neurodegenerative disease after moderate-to-severe traumatic brain injury in the working-age population: A retrospective cohort study using the Finnish national health registries.

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    Rahul Raj

    2017-07-01

    Full Text Available Previous epidemiological studies suggest that working-aged persons with a history of moderate-to-severe traumatic brain injury (TBI may have an increased risk for developing neurodegenerative disease (NDD while persons with a history of mild TBI do not. In this comprehensive nationwide study in Finland, we assessed the risk of NDD and history of moderate-to-severe TBI in the working-age population.We performed a population-based follow-up study using the Finnish Care Register for Health Care to identify all persons between the ages of 18 and 65 years hospitalized during 1987-2014 due to TBI who did not have a baseline NDD diagnosis. We compared the risk of hospitalization with NDD between persons hospitalized due to moderate-to-severe TBI (intracranial lesions and persons hospitalized due to mild TBI (no intracranial lesions. Follow-up NDD diagnoses were recorded from 1 year following the TBI to the end of 2014. NDD diagnoses included dementia, Parkinson disease, and amyotrophic lateral sclerosis. We used a Cox proportional hazards model, adjusting for age, sex, education, and socioeconomic group, to assess the association between TBI and NDD. In total, 19,936 and 20,703 persons with a history of moderate-to-severe TBI and mild TBI, respectively, were included. The overall time at risk was 453,079 person-years (median 10 years per person. In total, 3.5% (N = 696 persons in the moderate-to-severe TBI group developed NDD compared to 1.6% (N = 326 in the mild TBI group. After adjusting for covariates, moderate-to-severe TBI was associated with an increased risk for NDD, with a hazard ratio (HR of 1.8 (95% CI 1.6-2.1 compared to mild TBI. Of the NDD subtypes, only moderate-to-severe TBI was associated with an increased risk for dementia (HR 1.9, 95% CI 1.6-2.2. Yet, this large-scale epidemiological study does not prove that there is a causal relationship between moderate-to-severe TBI and NDD. Further, the Care Register for Health Care includes only

  2. Differential gene expression in brain tissues of aggressive and non-aggressive dogs

    Directory of Open Access Journals (Sweden)

    Tverdal Aage

    2010-06-01

    Full Text Available Abstract Background Canine behavioural problems, in particular aggression, are important reasons for euthanasia of otherwise healthy dogs. Aggressive behaviour in dogs also represents an animal welfare problem and a public threat. Elucidating the genetic background of adverse behaviour can provide valuable information to breeding programs and aid the development of drugs aimed at treating undesirable behaviour. With the intentions of identifying gene-specific expression in particular brain parts and comparing brains of aggressive and non-aggressive dogs, we studied amygdala, frontal cortex, hypothalamus and parietal cortex, as these tissues are reported to be involved in emotional reactions, including aggression. Based on quantitative real-time PCR (qRT-PCR in 20 brains, obtained from 11 dogs euthanised because of aggressive behaviour and nine non-aggressive dogs, we studied expression of nine genes identified in an initial screening by subtraction hybridisation. Results This study describes differential expression of the UBE2V2 and ZNF227 genes in brains of aggressive and non-aggressive dogs. It also reports differential expression for eight of the studied genes across four different brain tissues (amygdala, frontal cortex, hypothalamus, and parietal cortex. Sex differences in transcription levels were detected for five of the nine studied genes. Conclusions The study showed significant differences in gene expression between brain compartments for most of the investigated genes. Increased expression of two genes was associated with the aggression phenotype. Although the UBE2V2 and ZNF227 genes have no known function in regulation of aggressive behaviour, this study contributes to preliminary data of differential gene expression in the canine brain and provides new information to be further explored.

  3. Epileptic rat brain tissue analyzed by 2D correlation Raman spectroscopy

    Science.gov (United States)

    Sacharz, Julia; Wesełucha-Birczyńska, Aleksandra; Zięba-Palus, Janina; Lewandowski, Marian H.; Kowalski, Rafał; Palus, Katarzyna; Chrobok, Łukasz; Moskal, Paulina; Birczyńska, Malwina; Sozańska, Agnieszka

    2018-01-01

    Absence epilepsy is the neurological disorder characterized by the pathological spike-and wave discharges present in the electroencephalogram, accompanying a sudden loss of consciousness. Experiments were performed on brain slices obtained from young male WAG/Rij rats (2-3 weeks old), so that they were sampled before the appearance of brain-damaging seizures symptoms. Two differing brain areas of the rats' brain tissue were studied: the somatosensory cortex (Sc) and the dorsal lateral geniculate nucleus of the thalamus (DLG). The Raman spectra of the fresh brain scraps, kept during measurements in artificial cerebrospinal fluid, were collected using as an excitation source 442 nm, 514.5 nm, 785 nm and 1064 nm laser line. The average spectra were analyzed by 2D correlation method regarding laser line as an external perturbation. In 2D synchronous spectra positive auto-peaks corresponding to the Cdbnd C stretching and amide I band vibrations show maxima at 1660 cm- 1 and 1662 cm- 1 for Sc and DLG, respectively. The prominent auto-peak at 2937 cm- 1, originated from the CH3 mode in DLG brain area, seems to indicate the importance of methylation, considered to be significant in epileptogenesis. Synchronous and asynchronous correlations peaks, glutamic acid and gamma-aminobutyric acid (GABA), appear in Sc and DLG, respectively. In the 1730-1600 cm- 1 range occur cross-peaks which appearance might be triggered by glial fibrillary acidic protein (GFAP) activation.

  4. Hypercoagulation following brain death cannot be reversed by the neutralization of systemic tissue factor.

    Science.gov (United States)

    Hvas, Christine L; Fenger-Eriksen, Christian; Høyer, Søren; Sørensen, Benny; Tønnesen, Else

    2013-08-01

    Cerebral injury and brain death is associated with apparent hypercoagulation and poor organ outcome. This experimental study challenges the hypotheses that i) brain death causes hypercoagulation and microvascular thrombosis and that ii) neutralizing systemic tissue factor (TF) by in vitro addition of a TF inhibitor (recombinant active site-inhibited factor VIIa (ASIS)) can reverse the hypercoagulable profile. Using a validated pig model of intracranial hemorrhage and brain death, 20 pigs were randomized to either control or brain death. The primary endpoints were coagulation parameters measured with whole blood thromboelastometry (ROTEM), thrombin generation and a porcine TF-sensitive plasma clotting time assay. In vitro spiking experiments with ASIS were performed in parallel with the latter two assessments. The kidneys were examined histologically for microvascular thromboses. Brain death induced hypercoagulation, as demonstrated with ROTEM, thrombin generation, and reduced TF-sensitive plasma clotting time. In vitro inhibition of TF with ASIS did not reverse the hypercoagulation. No microvascular thromboses were found in the kidneys. Brain death causes hypercoagulation; however, inhibition of TF does not reverse the coagulopathy. Thus, TF release does not seem to be the primary cause of this hypercoagulation. Minor changes in the levels of protein C suggest that the protein C pathway may be linked to the observed coagulopathy. © 2013.

  5. Nanomedicine and neurodegenerative disorders: so close yet so far.

    Science.gov (United States)

    Tosi, Giovanni; Vandelli, Maria Angela; Forni, Flavio; Ruozi, Barbara

    2015-07-01

    This editorial provides an overview of the main advantages of the use of nanomedicine-based approach for innovation in the treatment of neurodegenerative diseases. Besides these aspects, a critical analysis on the main causes that slow the application of nanomedicine to brain disorders is given along with the identification of possible solutions and possible interventions. Better communication between the main players of research in this field and a detailed understanding of the most critical issues to be addressed should help in defining future directions towards the improvement and, finally, the clinical application of nanomedicine to neurodegenerative diseases.

  6. [Changes of MDA, SOD, TNF-alpha, and IL-1beta in rat brain tissue after concussion].

    Science.gov (United States)

    Gao, Feng; Zhao, Li; Gu, Zhen-Yong; Cong, Bin

    2014-02-01

    To observe the changes of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) in rat brain tissue and to explore the mechanism of secondary cerebral injury after brain concussion. The brain concussion model was established with the pathological changes of rat brain tissue by Weil stain. The expressions of MDA and SOD in brain tissue were examined by photochemical method. The expressions of TNF-alpha and IL-1beta in cerebral cortex and hippocampus were examined by immunochemistry. Nerve myelin sheath showed disorder, disruption, gryposis and swelling by Weil stain. Above changes were more severe at 12h. The quantity of MDA in rat brain tissue after concussion was significantly higher than that in the control group. The activity of SOD was significantly lower than that in the control group. The expressions of TNF-alpha and IL-1beta increased more significantly in cerebral cortex and hippocampus in rat brain tissue after concussion than that in the control group. Oxidative stress and inflammatory injury in the rat brain tissue, which may play an important role in secondary cerebral injury after concussion.

  7. Microinjection of membrane-impermeable molecules into single neural stem cells in brain tissue.

    Science.gov (United States)

    Wong, Fong Kuan; Haffner, Christiane; Huttner, Wieland B; Taverna, Elena

    2014-05-01

    This microinjection protocol allows the manipulation and tracking of neural stem and progenitor cells in tissue at single-cell resolution. We demonstrate how to apply microinjection to organotypic brain slices obtained from mice and ferrets; however, our technique is not limited to mouse and ferret embryos, but provides a means of introducing a wide variety of membrane-impermeable molecules (e.g., nucleic acids, proteins, hydrophilic compounds) into neural stem and progenitor cells of any developing mammalian brain. Microinjection experiments are conducted by using a phase-contrast microscope equipped with epifluorescence, a transjector and a micromanipulator. The procedure normally takes ∼2 h for an experienced researcher, and the entire protocol, including tissue processing, can be performed within 1 week. Thus, microinjection is a unique and versatile method for changing and tracking the fate of a cell in organotypic slice culture.

  8. Identifying signature Zernike modes for efficient light delivery through brain tissue

    CERN Document Server

    Sane, Sharmila; Lee, Woei Ming; Stricker, Christian; Bachor, Hans; Daria, Vincent

    2015-01-01

    Recent progress in neuroscience to image and investigate brain function has been made possible by impressive developments in optogenetic and opto-molecular tools. Such research requires advances in optical techniques for the delivery of light through brain tissue with high spatial resolution. The tissue causes distortions of the wavefront of the incoming light which broadens the focus, thereby reducing the intensity and resolution especially in techniques requiring focal illumination. Adaptive wavefront correction has been demonstrated to compensate for these distortions. However, in many situations iterative derivation of the corrective wavefront introduces time constraints that limit its usefulness when used to probe living cells. Here we demonstrate a direct and fast technique by working with a small set of Zernike modes and demonstrate that corrections derived a priori can lead to significant improvement of the focus. We verify this idea by the electrical response of whole-cell patched neurons following t...

  9. Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

    Science.gov (United States)

    Bhullar, Khushwant S.; Rupasinghe, H. P. Vasantha

    2013-01-01

    Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders. PMID:23840922

  10. Personality and social cognition in neurodegenerative disease.

    Science.gov (United States)

    Shany-Ur, Tal; Rankin, Katherine P

    2011-12-01

    Neurodegenerative diseases often cause focal damage to brain structures mediating social cognition and personality, resulting in altered interpersonal communication and behavior. We review recent research describing this phenomenon in various aspects of social cognition. Corresponding to their pervasive socioemotional deficits, patients with frontotemporal dementia perform poorly on laboratory-based tasks including recognizing emotions, attending to salient information that guides social behavior, representing social knowledge, comprehending others' mental states, and maintaining insight to their own difficulties. Together with poor executive and regulation mechanisms, these social cognition deficits ultimately impact behavior. Patients with logopenic and nonfluent primary progressive aphasia have some deficits recognizing emotional prosody, whereas those with the semantic variant show more widespread deficits in social comprehension. Although Alzheimer's disease patients perform poorly on some social cognition tasks, this typically reflects general cognitive impairment, and their real-life social functioning is less affected than in diseases targeting frontotemporal structures. Studies in motor diseases such as Parkinson's suggest some degradation of emotion recognition and social comprehension, which should be investigated further. We summarize recent findings concerning perception and evaluation of socioemotional information, social knowledge storage and access, advanced information processing mechanisms, and behavioral response selection and regulation across various neurodegenerative diseases.

  11. The role of thiamine in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Irena Bubko

    2015-09-01

    Full Text Available Vitamin B1 (thiamine plays an important role in metabolism. It is indispensable for normal growth and development of the organism. Thiamine has a favourable impact on a number of systems, including the digestive, cardiovascular and nervous systems. It also stimulates the brain and improves the psycho-emotional state. Hence it is often called the vitamin of “reassurance of the spirit”. Thiamine is a water-soluble vitamin. It can be present in the free form as thiamine or as its phosphate esters: mono-, di- or triphosphate. The main source of thiamine as an exogenous vitamin is certain foodstuffs, but trace amounts can be synthesised by microorganisms of the large intestine. The recommended daily intake of thiamine is about 2.0 mg. Since vitamin B1 has no ability to accumulate in the organism, manifestations of its deficiency begin to appear very quickly. The chronic state of thiamine deficiency, to a large extent, because of its function, contributes to the development of neurodegenerative diseases. It was proved that supporting vitamin B1 therapy not only constitutes neuroprotection but can also have a favourable impact on advanced neurodegenerative diseases. This article presents the current state of knowledge as regards the effects of thiamine exerted through this vitamin in a number of diseases such as Parkinson’s disease, Alzheimer’s disease, Wernicke’s encephalopathy or Wernicke-Korsakoff syndrome and Huntington’s disease.

  12. Ghrelin and Neurodegenerative Disorders-a Review.

    Science.gov (United States)

    Shi, Limin; Du, Xixun; Jiang, Hong; Xie, Junxia

    2017-03-01

    Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor 1a (GHS-R1a), is a gut-derived, orexigenic peptide hormone that primarily regulates growth hormone secretion, food intake, and energy homeostasis. With the wide expression of GHS-R1a in extra-hypothalamic regions, the physiological role of ghrelin is more extensive than solely its involvement in metabolic function. Ghrelin has been shown to be involved in numerous higher brain functions, such as memory, reward, mood, and sleep. Some of these functions are disrupted in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). This link between ghrelin and these neurodegenerative diseases is supported by numerous studies. This review aims to provide a comprehensive overview of the most recent evidence of the novel neuromodulatory role of ghrelin in PD, AD, and HD. Moreover, the changes in circulating and/or central ghrelin levels that are associated with disease progression are also postulated to be a biomarker for clinical diagnosis and therapy.

  13. Anomalous frequency-dependent ionic conductivity of lesion-laden human-brain tissue

    Science.gov (United States)

    Emin, David; Akhtari, Massoud; Fallah, Aria; Vinters, Harry V.; Mathern, Gary W.

    2017-10-01

    We study the effect of lesions on our four-electrode measurements of the ionic conductivity of (˜1 cm3) samples of human brain excised from patients undergoing pediatric epilepsy surgery. For most (˜94%) samples, the low-frequency ionic conductivity rises upon increasing the applied frequency. We attributed this behavior to the long-range (˜0.4 mm) diffusion of solvated sodium cations before encountering intrinsic impenetrable blockages such as cell membranes, blood vessels, and cell walls. By contrast, the low-frequency ionic conductivity of some (˜6%) brain-tissue samples falls with increasing applied frequency. We attribute this unusual frequency-dependence to the electric-field induced liberation of sodium cations from traps introduced by the unusually severe pathology observed in samples from these patients. Thus, the anomalous frequency-dependence of the ionic conductivity indicates trap-producing brain lesions.

  14. Characterisation of new monoclonal antibodies reacting with prions from both human and animal brain tissues

    DEFF Research Database (Denmark)

    Cordes, H.; Bergstrom, A.L.; Ohm, J.

    2008-01-01

    Post-mortem diagnosis of transmissible spongiform encephalopathies (prion diseases) is primarily based on the detection of a protease resistant, misfolded disease associated isoform (PrP(Sc)) of the prion protein (PrP(C)) on neuronal cells. These methods depend on antibodies directed against Pr......-type mice and used for western blotting and immunohistochemistry to detect several types of human prion-disease associated PrP(Sc), including sporadic Creutzfeldt-Jakob Disease (CJD) (subtypes MM1 and VV2), familial CJD and Gerstmann-Straussler-Scheinker (GSS) disease PrP(Sc) as well as PrP(Sc) of bovine...... spongiform encephalopathy (bovine brain), scrapie (ovine brain) and experimental scrapie in hamster and in mice. The antibodies were also used for PET-blotting in which PrP(Sc) blotted from brain tissue sections onto a nitrocellulose membrane is visualized with antibodies after protease and denaturant...

  15. On the characterization of the heterogeneous mechanical response of human brain tissue.

    Science.gov (United States)

    Forte, Antonio E; Gentleman, Stephen M; Dini, Daniele

    2017-06-01

    The mechanical characterization of brain tissue is a complex task that scientists have tried to accomplish for over 50 years. The results in the literature often differ by orders of magnitude because of the lack of a standard testing protocol. Different testing conditions (including humidity, temperature, strain rate), the methodology adopted, and the variety of the species analysed are all potential sources of discrepancies in the measurements. In this work, we present a rigorous experimental investigation on the mechanical properties of human brain, covering both grey and white matter. The influence of testing conditions is also shown and thoroughly discussed. The material characterization performed is finally adopted to provide inputs to a mathematical formulation suitable for numerical simulations of brain deformation during surgical procedures.

  16. Regional distribution of opiate alkaloids in experimental animals' brain tissue and blood

    Directory of Open Access Journals (Sweden)

    Đurendić-Brenesel Maja

    2012-01-01

    Full Text Available The aim of this study was to examine the regional distribution of opiate alkaloids from seized heroin in experimental animals' brain regions and blood. Results could be used in the examination of opiate alkaloids' distribution in human biological samples in order to contribute to the solution of the causes of death due to heroin intake. Experimental animals (Wistar rats were treated with seized heroin, and were sacrificed at different time periods: 5, 15, 45 and 120 min after treatment. Opiate alkaloids' (codeine, morphine, acetylcodeine, 6- acetylmorphine and 3,6-diacetylmorphine content was determined in the brain regions (cortex, brainstem, amygdala and basal ganglia and blood of animals using gas chromatography-mass spectrometry (GC-MS method. The highest content of opiate alkaloids in the blood was measured 15 min, and in the brain tissue 45 min after the treatment with heroin. The maximal concentration of opiates was determined in the basal ganglia. The obtained results offer the possibility of selecting this part of the brain tissue as a representative sample for identifying and assessing the content of opiates.

  17. 2D correlation Raman microspectroscopy of chosen parts of rat's brain tissue

    Science.gov (United States)

    Zięba-Palus, J.; Wesełucha-Birczyńska, A.; Sacharz, J.; Lewandowski, M. H.; Palus, K.; Chrobok, Ł.; Kowalski, R.; Moskal, P.; Birczyńska, M.; Sozańska, Agnieszka

    2017-11-01

    Raman spectra of two areas of Wistar rat brain tissue, tissue that are linked functionally to one another -the somatosensory cortex (Sc) and the dorsolateral geniculate nucleus of the thalamus (DLG)- excited with 442 nm, 514.5 nm, 785 nm and 1064 nm laser lines- were studied. No fixation method was used to preserve samples taken from the precisely defined anatomical areas of the brain. The brain slides were kept in artificial cerebrospinal fluid during the measurements. Averaged spectra were analyzed using the 2D correlation method. The varying wavelength/energy of the excitation laser was regarded as an external stimulus. 2D correlation analysis resolved differences between Sc and DLG in the range of 1800-1000 cm-1 and also in the hetero-spectral regions of about 1800-1200 cm-1 and 3100-2500 cm-1. Auto-peaks at 1659 cm-1 and 1666 cm-1 characterize the phase of the constituent lipid clusters with proteins and cholesterol in Sc and cholesterol in DLG, respectively. Appearing cross-peaks indicate the correlations with different phospholipids structures and protein bands and also cholesterol for Sc and DLG, respectively. Asynchronous spectra distinguish between areas of the brain due to the presence of neurotransmitters.

  18. Multigrid Nonlocal Gaussian Mixture Model for Segmentation of Brain Tissues in Magnetic Resonance Images

    Directory of Open Access Journals (Sweden)

    Yunjie Chen

    2016-01-01

    Full Text Available We propose a novel segmentation method based on regional and nonlocal information to overcome the impact of image intensity inhomogeneities and noise in human brain magnetic resonance images. With the consideration of the spatial distribution of different tissues in brain images, our method does not need preestimation or precorrection procedures for intensity inhomogeneities and noise. A nonlocal information based Gaussian mixture model (NGMM is proposed to reduce the effect of noise. To reduce the effect of intensity inhomogeneity, the multigrid nonlocal Gaussian mixture model (MNGMM is proposed to segment brain MR images in each nonoverlapping multigrid generated by using a new multigrid generation method. Therefore the proposed model can simultaneously overcome the impact of noise and intensity inhomogeneity and automatically classify 2D and 3D MR data into tissues of white matter, gray matter, and cerebral spinal fluid. To maintain the statistical reliability and spatial continuity of the segmentation, a fusion strategy is adopted to integrate the clustering results from different grid. The experiments on synthetic and clinical brain MR images demonstrate the superior performance of the proposed model comparing with several state-of-the-art algorithms.

  19. Effect of ginkgolide B on brain metabolism and tissue oxygenation in severe haemorrhagic stroke.

    Science.gov (United States)

    Chi, Chun-Ling; Shen, Dong-Fang; Wang, Peng-Jun; Li, Hu-Lun; Zhang, Li

    2015-01-01

    Ginkgolide B, a diterpene, is an herbal constituent isolated from the leaves of Ginkgo biloba tree. The present study demonstrates the effect of ginkgolide B in osmotherapy on brain metabolism and tissue oxygenation. Multimodality monitoring including intracranial pressure (ICP), cerebral perfusion pressure (CPP), partial pressure of brain tissue oxygen (PbtO2), lactate/pyruvate ratio (LPR) and microdialysis were employed to study the effect of ginkgolide B osmotherapy. The results demonstrated that administration of 15% solution of ginkgolide B to the comatose patients with raised ICP (> 20 mm Hg) and resistant to standard therapy led to a significant decrease in ICP. The cerebral microdialysis was used to compare mean arterial blood pressure (MAP), ICP, CPP, PbtO2, brain lactate, pyruvate and glucose level after hourly intervals starting 3 h before and up to 4 h after hyperosmolar therapy. There was a decrease in ICP in 45 min from 23 ± 14 mm Hg (P therapy. Also the brain glucose remained unaffected.

  20. Super resolution imaging of genetically labelled synapses in Drosophila brain tissue

    Directory of Open Access Journals (Sweden)

    Isabelle Ayumi Spühler

    2016-05-01

    Full Text Available Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labelled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation

  1. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

    2013-01-15

    Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

  2. Alteration of amino acid neurotransmitters in brain tissues of immature rats treated with realgar.

    Science.gov (United States)

    Huo, Taoguang; Chang, Bei; Zhang, Yinghua; Chen, Zaixing; Li, Weikai; Jiang, Hong

    2012-01-05

    Realgar is a traditional Chinese medicine, which has been used for thousands of years and are claimed to have therapeutic effects. The toxicity from realgar or realgar-containing traditional medicines has raised public concern. However, the neurotoxicity induced by realgar is less reported. Amino acid neurotransmitters are closely linked to the vulnerability of the immature brain to neuronal injury. The investigation of amino acid neurotransmitters is important to understand the evolution of developmental brain damage. An improved HPLC-UV method was developed and applied to analyzing amino acid neurotransmitters of aspartate, glutamate, glutamine, homocysteine, serine, glycine, γ-aminobutyric acid and taurine in brain tissues of immature rats after the treatment of realgar. Significant changes of these amino acid neurotransmitters were observed in realgar treated groups. Negative correlations were found between the levels of some amino acids and the contents of arsenic in brain tissues. The result indicates that the neurotoxicity induced by realgar is associated with its effects on amino acid neurotransmitters. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Mechanical Characterization of Brain Tissue in Compression at Dynamic Strain Rates

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.01.022

    2013-01-01

    Traumatic brain injury (TBI) occurs when local mechanical load exceeds certain tolerance levels for brain tissue. Extensive research has been done previously for brain matter experiencing compression at quasistatic loading; however, limited data is available to model TBI under dynamic impact conditions. In this research, an experimental setup was developed to perform unconfined compression tests and stress relaxation tests at strain rates < 90/s. The brain tissue showed a stiffer response with increasing strain rates, showing that hyperelastic models are not adequate. Specifically, the compressive nominal stress at 30% strain was 8.83 +/- 1.94, 12.8 +/- 3.10 and 16.0 +/- 1.41 kPa (mean +/- SD) at strain rates of 30, 60 and 90/s, respectively. Relaxation tests were also conducted at 10%-50% strain with the average rise time of 10 ms, which can be used to derive time dependent parameters. Numerical simulations were performed using one-term Ogden model with initial shear modulus mu_0 = 6.06 +/- 1.44, 9.44 +/-...

  4. Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer's disease brain tissue.

    Science.gov (United States)

    Poole, Sophie; Singhrao, Sim K; Kesavalu, Lakshmyya; Curtis, Michael A; Crean, StJohn

    2013-01-01

    The aim of this study was to establish a link between periodontal disease and Alzheimer's disease (AD) with a view to identifying the major periodontal disease bacteria (Treponema denticola, Tannerella forsythia, and Porphyromonas gingivalis) and/or bacterial components in brain tissue from 12 h postmortem delay. Our request matched 10 AD cases for tissue from Brains for Dementia Research alongside 10 non-AD age-related controls with similar or greater postmortem interval. We exposed SVGp12, an astrocyte cell line, to culture supernatant containing lipopolysaccharide (LPS) from the putative periodontal bacteria P. gingivalis. The challenged SVGp12 cells and cryosections from AD and control brains were immunolabeled and immunoblotted using a battery of antibodies including the anti-P. gingivalis-specific monoclonal antibody. Immunofluorescence labeling demonstrated the SVGp12 cell line was able to adsorb LPS from culture supernatant on its surface membrane; similar labeling was observed in four out of 10 AD cases. Immunoblotting demonstrated bands corresponding to LPS from P. gingivalis in the SVGp12 cell lysate and in the same four AD brain specimens which were positive when screened by immunofluorescence. All controls remained negative throughout while the same four cases were consistently positive for P. gingivalis LPS (p = 0.029). This study confirms that LPS from periodontal bacteria can access the AD brain during life as labeling in the corresponding controls, with equivalent/longer postmortem interval, was absent. Demonstration of a known chronic oral-pathogen-related virulence factor reaching the human brains suggests an inflammatory role in the existing AD pathology.

  5. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    Energy Technology Data Exchange (ETDEWEB)

    Lunsing, Roelineke J.; Strating, Kim [University Medical Centre Groningen, University of Groningen, Department of Child Neurology, Groningen (Netherlands); Koning, Tom J. de [University Medical Centre Groningen, University of Groningen, Department of Pediatric Metabolic Diseases, Groningen (Netherlands); Sijens, Paul E. [University Medical Centre Groningen, University of Groningen, Department of Radiology, Groningen (Netherlands)

    2017-03-15

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  6. Protein analysis through Western blot of cells excised individually from human brain and muscle tissue.

    Science.gov (United States)

    Koob, A O; Bruns, L; Prassler, C; Masliah, E; Klopstock, T; Bender, A

    2012-06-15

    Comparing protein levels from single cells in tissue has not been achieved through Western blot. Laser capture microdissection allows for the ability to excise single cells from sectioned tissue and compile an aggregate of cells in lysis buffer. In this study we analyzed proteins from cells excised individually from brain and muscle tissue through Western blot. After we excised individual neurons from the substantia nigra of the brain, the accumulated surface area of the individual cells was 120,000, 24,000, 360,000, 480,000, 600,000 μm2. We used an optimized Western blot protocol to probe for tyrosine hydroxylase in this cell pool. We also took 360,000 μm2 of astrocytes (1700 cells) and analyzed the specificity of the method. In muscle we were able to analyze the proteins of the five complexes of the electron transport chain through Western blot from 200 human cells. With this method, we demonstrate the ability to compare cell-specific protein levels in the brain and muscle and describe for the first time how to visualize proteins through Western blot from cells captured individually. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. [LINGO-1 expression of brain tissue in experimental autoimmune encephalomyelitis mouse].

    Science.gov (United States)

    Wang, Chunjuan; Guo, Shougang; Qu, Chuanqiang; Zhang, Jie; Fu, Peicai; Tang, Ronghua

    2014-04-22

    To observe the changes of LINGO-1 expression with time after onset in EAE mouse. C57/BL6 mice were completely randomly divided into EAE model group (n = 15) , adjuvant group (n = 15) and control group (n = 15) .LINGO-1 expression of brain tissue was detected on day 1, 7, 14, 21 and 30 after onset by RT-PCR and Western blot.RhoA and p-RhoA expression of brain tissue was analysed by Western blot. The LINGO-1mRNA levels in EAE model group were markedly higher than control group on day 1, 7and 14 after onset (4.63 ± 0.25, 2.72 ± 0.12, 1.98 ± 0.16, P Lingo-1 mRNA was close to control group.Expression levels of Lingo-1 protein on day 1, 7, 14, 21, 30 were higher than control group (2.11 ± 0.15, 3.15 ± 0.09, 2.45 ± 0.12, 1.89 ± 0.17, 1.21 ± 0.05, P LINGO-1 expression of brain tissue of EAE mouse upregulates and changes with time after onset, which may inhibit myelination by RhoA activation.In clinic, the antagonist of LINGO-1 for MS should be applied as soon as possible.

  8. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease.

    Science.gov (United States)

    Wulff, Katharina; Gatti, Silvia; Wettstein, Joseph G; Foster, Russell G

    2010-08-01

    Sleep and circadian rhythm disruption are frequently observed in patients with psychiatric disorders and neurodegenerative disease. The abnormal sleep that is experienced by these patients is largely assumed to be the product of medication or some other influence that is not well defined. However, normal brain function and the generation of sleep are linked by common neurotransmitter systems and regulatory pathways. Disruption of sleep alters sleep-wake timing, destabilizes physiology and promotes a range of pathologies (from cognitive to metabolic defects) that are rarely considered to be associated with abnormal sleep. We propose that brain disorders and abnormal sleep have a common mechanistic origin and that many co-morbid pathologies that are found in brain disease arise from a destabilization of sleep mechanisms. The stabilization of sleep may be a means by which to reduce the symptoms of--and permit early intervention of--psychiatric and neurodegenerative disease.

  9. Outdoor Ambient Air Pollution and Neurodegenerative Diseases: the Neuroinflammation Hypothesis.

    Science.gov (United States)

    Jayaraj, Richard L; Rodriguez, Eric A; Wang, Yi; Block, Michelle L

    2017-06-01

    Accumulating research indicates that ambient outdoor air pollution impacts the brain and may affect neurodegenerative diseases, yet the potential underlying mechanisms are poorly understood. The neuroinflammation hypothesis holds that elevation of cytokines and reactive oxygen species in the brain mediates the deleterious effects of urban air pollution on the central nervous system (CNS). Studies in human and animal research document that neuroinflammation occurs in response to several inhaled pollutants. Microglia are a prominent source of cytokines and reactive oxygen species in the brain, implicated in the progressive neuron damage in diverse neurodegenerative diseases, and activated by inhaled components of urban air pollution through both direct and indirect pathways. The MAC1-NOX2 pathway has been identified as a mechanism through which microglia respond to different forms of air pollution, suggesting a potential common deleterious pathway. Multiple direct and indirect pathways in response to air pollution exposure likely interact in concert to exert CNS effects.

  10. Protein Modification by Dicarbonyl Molecular Species in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Wesley M. Williams

    2011-01-01

    Full Text Available Neurodegeneration results from abnormalities in cerebral metabolism and energy balance within neurons, astrocytes, microglia, or microvascular endothelial cells of the blood-brain barrier. In Alzheimer's disease, -amyloid is considered the primary contributor to neuropathology and neurodegeneration. It now is believed that certain systemic diseases, such as diabetes mellitus, can contribute to neurodegeneration through the effects of chronic hyperglycemia/insulin resistance resulting in protein glycation, oxidative stress and inflammation within susceptible brain regions. Here, we present an overview of research focusing on the role of protein glycation, oxidative stress, and inflammation in the neurodegenerative process. Of special interest in this paper is the effect of methylglyoxal (MGO, a cytotoxic byproduct of glucose metabolism, elevated in neurodegenerative disease, and diabetes mellitus, on cerebral protein function and oxidative stress. How MGO interacts with amino acid residues within -amyloid, and small peptides within the brain, is also discussed in terms of the affect on protein function.

  11. Stem Cells for the Treatment of Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    2010-09-01

    Full Text Available Neurodegenerative diseases are characterized by neurodegenerative changes or apoptosis of neurons involved in networks, leading to permanent paralysis and loss of sensation below the site of the injury. Cell replacement therapy has provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. In recent years, neurons and glial cells have successfully been generated from stem cells, and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. We review here notable previously published experimental and preclinical studies involving stem cell-based cell for neurodegenerative diseases and discuss the future prospects for stem cell therapy of neurological disorders in the clinical setting. Steady and solid progress in stem cell research in both basic and preclinical settings should support the hope for development of stem cell-based cell therapies for neurological diseases.

  12. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Antonio Paoli

    2014-01-01

    Full Text Available An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson’s disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review.

  13. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

    Science.gov (United States)

    Damiani, Ernesto; Bosco, Gerardo

    2014-01-01

    An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson's disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review. PMID:25101284

  14. Sex-specific differences in transcriptome profiles of brain and muscle tissue of the tropical gar.

    Science.gov (United States)

    Cribbin, Kayla M; Quackenbush, Corey R; Taylor, Kyle; Arias-Rodriguez, Lenin; Kelley, Joanna L

    2017-04-07

    The tropical gar (Atractosteus tropicus) is the southernmost species of the seven extant species of gar fishes in the world. In Mexico and Central America, the species is an important food source due to its nutritional quality and low price. Despite its regional importance and increasing concerns about overexploitation and habitat degradation, basic genetic information on the tropical gar is lacking. Determining genetic information on the tropical gar is important for the sustainable management of wild populations, implementation of best practices in aquaculture settings, evolutionary studies of ancient lineages, and an understanding of sex-specific gene expression. In this study, the transcriptome of the tropical gar was sequenced and assembled de novo using tissues from three males and three females using Illumina sequencing technology. Sex-specific and highly differentially expressed transcripts in brain and muscle tissues between adult males and females were subsequently identified. The transcriptome was assembled de novo resulting in 80,611 transcripts with a contig N50 of 3,355 base pairs and over 168 kilobases in total length. Male muscle, brain, and gonad as well as female muscle and brain were included in the assembly. The assembled transcriptome was annotated to identify the putative function of expressed transcripts using Trinotate and SwissProt, a database of well-annotated proteins. The brain and muscle datasets were then aligned to the assembled transcriptome to identify transcripts that were differentially expressed between males and females. The contrast between male and female brain identified 109 transcripts from 106 genes that were significantly differentially expressed. In the muscle comparison, 82 transcripts from 80 genes were identified with evidence for significant differential expression. Almost all genes identified as differentially expressed were sex-specific. The differentially expressed transcripts were enriched for genes involved in

  15. Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Baczko, K.; Liebert, U.G.; Billeter, M.; Cattaneo, R.; Budka, H.; Ter Meulen, V.

    1986-08-01

    The persistence of measles virus in selected areas of the brains of four patients with subacute sclerosing panencephalitis (SSPE) was characterized by immunohistological and biochemical techniques. The five measles virus structural proteins were never simultaneously detectable in any of the bran sections. Nucleocapsid proteins and phosphoproteins were found in every diseased brain area, whereas hemagglutinin protein was detected in two cases, fusion protein was detected in three cases, and matrix protein was detected in only one case. Also, it could be shown that the amounts of measles virus RNA in the brains differed from patient to patient and in the different regions investigated. In all patients, plus-strand RNAs specific for these five viral genes could be detected. However, the amounts of fusion and hemagglutinin mRNAs were low compared with the amounts in lytically infected cells. The presence of particular measles virus RNAs in SSPE-infected brains did not always correlate with mRNA activity. In in vitro translations, the matrix protein was produced in only one case, and the hemagglutinin protein was produced in none. These results indicate that measles virus persistence in SSPE is correlated with different defects of several genes which probably prevent assembly of viral particles in SSPE-infected brain tissue.

  16. A Genotype Resource for Postmortem Brain Samples from the Autism Tissue Program

    Science.gov (United States)

    Wintle, Richard F.; Lionel, Anath C.; Hu, Pingzhao; Ginsberg, Stephen D.; Pinto, Dalila; Thiruvahindrapduram, Bhooma; Wei, John; Marshall, Christian R.; Pickett, Jane; Cook, Edwin H.; Scherer, Stephen W.

    2015-01-01

    The Autism Tissue Program (ATP), a science program of Autism Speaks, provides researchers with access to well-characterized postmortem brain tissues. Researchers access these tissues through a peer-reviewed, project-based approval process, and obtain related clinical information from a secure, online informatics portal. However, few of these samples have DNA banked from other sources (such as a blood sample from the same individual), hindering genotype–phenotype correlation and interpretation of gene expression data derived fromthe banked brain tissue. Here, we describe an initiative to extract DNA from Brodmann Area 19, and genotype these samples using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Human1M-Duo DNA Analysis BeadChip genome-wide microarray technologies. We additionally verify reported gender, and infer ethnic background from the single nucleotide polymorphism data. We have also used a rigorous, multiple algorithm approach to identify genomic copy number variation (CNV) from these array data. Following an initial proof of principle study using two samples, 52 experimental samples, consisting of 27 subjects with confirmed or suspected autism and related disorders, 5 subjects with cytogenetically visible duplications of 15q, 2 with epilepsy and 18 age-matched normal controls were processed, yielding high-quality genotype data in all cases. The genotype and CNV data are provided via the ATP informatics portal as a resource for the autism research community. PMID:21254448

  17. Tissue-specific interferon alpha subtype response to SIV infection in brain, spleen, and lung.

    Science.gov (United States)

    Zaritsky, Luna Alammar; Dery, Alicia; Leong, Wan Yee; Gama, Lucio; Clements, Janice E

    2013-01-01

    Interferon alpha (IFNalpha) is a type I interferon that plays a major role in host defense. There are 13 different IFNalpha genes in humans, but much of the work concerning their role in viral defense has been limited to studying either subtype 2 or pan IFNalpha due to the inability to distinguish between highly similar genetic and amino acid sequences. Because of recent advances in molecular and biochemical techniques, it is possible to study the regulation of individual subtypes. It has been reported that HIV/SIV infection results in impaired IFNalpha responses in certain tissues. Using a pigtailed macaque SIV model, we examined the subtype response during acute infection in 3 tissues that are known to be infected with HIV/SIV, but whose IFNalpha subtype response has not been extensively studied: the brain, spleen, and lung. We found that the expression and regulation of specific subtypes occur in a tissue-specific manner. There was more limited IFNalpha subtype expression in the lung and brain, where predominantly macrophages are infected compared to the spleen, which contains both infected CD4+ lymphocytes and macrophages. Understanding the IFNalpha subtype response in tissues known to be infected with HIV/SIV can help tailor adjunctive treatment regimens to highly active antiretroviral therapy.

  18. Advanced biomaterial strategies to transplant preformed micro-tissue engineered neural networks into the brain

    Science.gov (United States)

    Harris, J. P.; Struzyna, L. A.; Murphy, P. L.; Adewole, D. O.; Kuo, E.; Cullen, D. K.

    2016-02-01

    Objective. Connectome disruption is a hallmark of many neurological diseases and trauma with no current strategies to restore lost long-distance axonal pathways in the brain. We are creating transplantable micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of embedded neurons and long axonal tracts to integrate with the nervous system to physically reconstitute lost axonal pathways. Approach. We advanced micro-tissue engineering techniques to generate micro-TENNs consisting of discrete populations of mature primary cerebral cortical neurons spanned by long axonal fascicles encased in miniature hydrogel micro-columns. Further, we improved the biomaterial encasement scheme by adding a thin layer of low viscosity carboxymethylcellulose (CMC) to enable needle-less insertion and rapid softening for mechanical similarity with brain tissue. Main results. The engineered architecture of cortical micro-TENNs facilitated robust neuronal viability and axonal cytoarchitecture to at least 22 days in vitro. Micro-TENNs displayed discrete neuronal populations spanned by long axonal fasciculation throughout the core, thus mimicking the general systems-level anatomy of gray matter—white matter in the brain. Additionally, micro-columns with thin CMC-coating upon mild dehydration were able to withstand a force of 893 ± 457 mN before buckling, whereas a solid agarose cylinder of similar dimensions was predicted to withstand less than 150 μN of force. This thin CMC coating increased the stiffness by three orders of magnitude, enabling needle-less insertion into brain while significantly reducing the footprint of previous needle-based delivery methods to minimize insertion trauma. Significance. Our novel micro-TENNs are the first strategy designed for minimally invasive implantation to facilitate nervous system repair by simultaneously providing neuronal replacement and physical reconstruction of long-distance axon pathways in the brain

  19. Animal models of neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Fabiola Mara Ribeiro

    2013-01-01

    Full Text Available The prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD and Parkinson's disease (PD, increases with age, and the number of affected patients is expected to increase worldwide in the next decades. Accurately understanding the etiopathogenic mechanisms of these diseases is a crucial step for developing disease-modifying drugs able to preclude their emergence or at least slow their progression. Animal models contribute to increase the knowledge on the pathophysiology of neurodegenerative diseases. These models reproduce different aspects of a given disease, as well as the histopathological lesions and its main symptoms. The purpose of this review is to present the main animal models for AD, PD, and Huntington's disease.

  20. Reward processing in neurodegenerative disease

    Science.gov (United States)

    Perry, David C.; Kramer, Joel H.

    2015-01-01

    Representation of reward value involves a distributed network including cortical and subcortical structures. Because neurodegenerative illnesses target specific anatomic networks that partially overlap with the reward circuit they would be predicted to have distinct impairments in reward processing. This review presents the existing evidence of reward processing changes in neurodegenerative diseases including mild cognitive impairment, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease, as well as in healthy aging. Carefully distinguishing the different aspects of reward processing (primary rewards, secondary rewards, reward-based learning, and reward-based decision-making) and using tasks that differentiate the stages of processing reward will lead to improved understanding of this fundamental process and clarify a contributing cause of behavioral change in these illnesses. PMID:24417286

  1. Molecular diagnostics of neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Megha eAgrawal

    2015-09-01

    Full Text Available Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer’s and Parkinson’s disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

  2. X-ray diffraction from intact tau aggregates in human brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Landahl, Eric C.; Antipova, Olga; Bongaarts, Angela; Barrea, Raul; Berry, Robert; Binder, Lester I.; Irving, Thomas; Orgel, Joseph; Vana, Laurel; Rice, Sarah E. (DePaul); (IIT); (NWU)

    2011-09-15

    We describe an instrument to record X-ray diffraction patterns from diseased regions of human brain tissue by combining an in-line visible light fluorescence microscope with an X-ray diffraction microprobe. We use thiazine red fluorescence to specifically label and detect the filamentous tau protein pathology associated with Pick's disease, as several laboratories have done previously. We demonstrate that thiazine red-enhanced regions within the tissue show periodic structure in X-ray diffraction, which is not observed in healthy tissue. One observed periodicity (4.2 {angstrom}) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein.

  3. X-ray diffraction from intact tau aggregates in human brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Landahl, Eric C. [DePaul University, Department of Physics, 2219 N. Kenmore Ave., IL 60614, Chicago (United States); Antipova, Olga [Illinois Institute of Technology, Department of Biological Chemical and Physical Sciences, 3101 South Dearborn St., IL 60616, Chicago (United States); Bongaarts, Angela [Northwestern University, Department of Cell and Molecular Biology, 303 E. Chicago Ave., IL 60611, Chicago (United States); Barrea, Raul [Illinois Institute of Technology, Department of Biological Chemical and Physical Sciences, 3101 South Dearborn St., IL 60616, Chicago (United States); Berry, Robert; Binder, Lester I. [Northwestern University, Department of Cell and Molecular Biology, 303 E. Chicago Ave., IL 60611, Chicago (United States); Irving, Thomas; Orgel, Joseph [Illinois Institute of Technology, Department of Biological Chemical and Physical Sciences, 3101 South Dearborn St., IL 60616, Chicago (United States); Vana, Laurel [Northwestern University, Department of Cell and Molecular Biology, 303 E. Chicago Ave., IL 60611, Chicago (United States); Rice, Sarah E., E-mail: s-rice@northwestern.edu [Northwestern University, Department of Cell and Molecular Biology, 303 E. Chicago Ave., IL 60611, Chicago (United States)

    2011-09-01

    We describe an instrument to record X-ray diffraction patterns from diseased regions of human brain tissue by combining an in-line visible light fluorescence microscope with an X-ray diffraction microprobe. We use thiazine red fluorescence to specifically label and detect the filamentous tau protein pathology associated with Pick's disease, as several laboratories have done previously. We demonstrate that thiazine red-enhanced regions within the tissue show periodic structure in X-ray diffraction, which is not observed in healthy tissue. One observed periodicity (4.2 A) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein.

  4. Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress.

    Science.gov (United States)

    Akbar, Mohammed; Essa, Musthafa Mohamed; Daradkeh, Ghazi; Abdelmegeed, Mohamed A; Choi, Youngshim; Mahmood, Lubna; Song, Byoung-Joon

    2016-04-15

    Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post-translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities. Published by Elsevier B.V.

  5. Essential Tremor: A Neurodegenerative Disease?

    Directory of Open Access Journals (Sweden)

    Julian Benito-Leon

    2011-08-01

    Full Text Available Background: Essential tremor (ET is one of the most common neurological disorders among adults, and is the most common of the many tremor disorders. It has classically been viewed as a benign monosymptomatic condition, yet over the past decade, a growing body of evidence indicates that ET is a progressive condition that is clinically heterogeneous, as it may be associated with a spectrum of clinical features, with both motor and non‐motor elements. In this review, I will describe the most significant emerging milestones in research which, when taken together, suggest that ET is a neurodegenerative condition.Methods: A PubMed search conducted in June 2014 crossing the terms “essential tremor” (ET and “neurodegenerative” yielded 122 entries, 20 of which included the term “neurodegenerative” in the article title. This was supplemented by articles in the author's files that pertained to this topic.Results/Discussion: There is an open and active dialogue in the medical community as to whether ET is a neurodegenerative disease, with considerable evidence in favor of this. Specifically, ET is a progressive disorder of aging associated with neuronal loss (reduction in Purkinje cells as well as other post‐mortem changes that occur in traditional neurodegenerative disorders. Along with this, advanced neuroimaging techniques are now demonstrating distinct structural changes, several of which are consistent with neuronal loss, in patients with ET. However, further longitudinal clinical and neuroimaging longitudinal studies to assess progression are required.

  6. New aspects of fenestrated vasculature and tissue dynamics in the sensory circumventricular organs of adult brains

    Directory of Open Access Journals (Sweden)

    Seiji eMiyata

    2015-10-01

    Full Text Available The blood–brain barrier (BBB generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs, which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT, subfornical organ (SFO, and area postrema (AP, have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF signaling may be involved in angiogenesis and

  7. Role of Redox Signaling in Neuroinflammation and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Hsi-Lung Hsieh

    2013-01-01

    Full Text Available Reactive oxygen species (ROS, a redox signal, are produced by various enzymatic reactions and chemical processes, which are essential for many physiological functions and act as second messengers. However, accumulating evidence has implicated the pathogenesis of several human diseases including neurodegenerative disorders related to increased oxidative stress. Under pathological conditions, increasing ROS production can regulate the expression of diverse inflammatory mediators during brain injury. Elevated levels of several proinflammatory factors including cytokines, peptides, pathogenic structures, and peroxidants in the central nervous system (CNS have been detected in patients with neurodegenerative diseases such as Alzheimer’s disease (AD. These proinflammatory factors act as potent stimuli in brain inflammation through upregulation of diverse inflammatory genes, including matrix metalloproteinases (MMPs, cytosolic phospholipase A2 (cPLA2, cyclooxygenase-2 (COX-2, and adhesion molecules. To date, the intracellular signaling mechanisms underlying the expression of target proteins regulated by these factors are elusive. In this review, we discuss the mechanisms underlying the intracellular signaling pathways, especially ROS, involved in the expression of several inflammatory proteins induced by proinflammatory factors in brain resident cells. Understanding redox signaling transduction mechanisms involved in the expression of target proteins and genes may provide useful therapeutic strategies for brain injury, inflammation, and neurodegenerative diseases.

  8. Effects of formalin fixation on tissue optical properties of in-vitro brain samples

    Science.gov (United States)

    Anand, Suresh; Cicchi, Riccardo; Martelli, Fabrizio; Giordano, Flavio; Buccoliero, Anna Maria; Guerrini, Renzo; Pavone, Francesco S.

    2015-03-01

    Application of light spectroscopy based techniques for the detection of cancers have emerged as a promising approach for tumor diagnostics. In-vivo or freshly excised samples are normally used for point spectroscopic studies. However, ethical issues related to in-vivo studies, rapid decay of surgically excised tissues and sample availability puts a limitation on in-vivo and in-vitro studies. There has been a few studies reported on the application of formalin fixed samples with good discrimination capability. Usually formalin fixation is performed to prevent degradation of tissues after surgical resection. Fixing tissues in formalin prevents cell death by forming cross-linkages with proteins. Previous investigations have revealed that washing tissues fixed in formalin using phosphate buffered saline is known to reduce the effects of formalin during spectroscopic measurements. But this could not be the case with reflectance measurements. Hemoglobin is a principal absorbing medium in biological tissues in the visible range. Formalin fixation causes hemoglobin to seep out from red blood cells. Also, there could be alterations in the refractive index of tissues when fixed in formalin. In this study, we propose to investigate the changes in tissue optical properties between freshly excised and formalin fixed brain tissues. The results indicate a complete change in the spectral profile in the visible range where hemoglobin has its maximum absorption peaks. The characteristic bands of oxy-hemoglobin at 540, 580 nm and deoxy-hemoglobin at 555 nm disappear in the case of samples fixed in formalin. In addition, an increased spectral intensity was observed for the wavelengths greater than 650 nm where scattering phenomena are presumed to dominate.

  9. DTI and PWI analysis of peri-enhancing tumoral brain tissue in patients treated for glioblastoma.

    Science.gov (United States)

    Stecco, Alessandro; Pisani, Carla; Quarta, Raffaella; Brambilla, Marco; Masini, Laura; Beldì, Debora; Zizzari, Sara; Fossaceca, Rita; Krengli, Marco; Carriero, Alessandro

    2011-04-01

    To analyse the role of MR diffusion-tensor imaging (DTI) and perfusion-weighted imaging (PWI) in characterising tumour boundaries in patients with glioblastoma multiforme. Seventeen patients with surgically treated WHO IV grade gliomas who were candidates for adjuvant chemo-radiotherapy were enrolled. Before (T0) and after radiation treatment (T1), they underwent DTI and PWI, and the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative cerebral blood volume (rCBV) in the enhancing tumour, the hyperintense tissue adjacent to the enhancing tumour, and the normal-appearing white matter (NAWM) adjacent to the hyperintense areas were analysed. The enhancing tissue at T1 was retrospectively divided on the basis of whether or not it was also enhancing at T0. The controls were the corresponding contralateral areas, on which we normalized the rCBV values, calculating the rCBV ratio. In NAWM, we did not find any significant differences in FA, ADC or rCBV. In the hyperintense perilesional regions, FA was significantly lower and ADC significantly higher than in the unaffected contralateral tissue; there were no significant differences in the rCBV maps. The values of FA, ADC and rCBV in enhancing neoplastic tissue were all significantly different from those observed in the contralateral tissue. There was no significant difference in rCBV values between the areas enhancing at T0 and those not enhancing at T0 but enhancing at T1, which may indicate the neoplastic transformation of apparently normal brain tissue. DTI metrics identify ultrastructural changes in hyperintense perilesional areas, but these are not specific for neoplastic tissue. rCBV seemed to reflect an ultrastructural alteration that was not visible at T0, but became visible (as neoplastic progression) on conventional MR images at T1. These findings could help identify tissue at risk of tumour infiltration.

  10. Scattering of Sculpted Light in Intact Brain Tissue, with implications for Optogenetics

    Science.gov (United States)

    Favre-Bulle, Itia A.; Preece, Daryl; Nieminen, Timo A.; Heap, Lucy A.; Scott, Ethan K.; Rubinsztein-Dunlop, Halina

    2015-06-01

    Optogenetics uses light to control and observe the activity of neurons, often using a focused laser beam. As brain tissue is a scattering medium, beams are distorted and spread with propagation through neural tissue, and the beam’s degradation has important implications in optogenetic experiments. To address this, we present an analysis of scattering and loss of intensity of focused laser beams at different depths within the brains of zebrafish larvae. Our experimental set-up uses a 488 nm laser and a spatial light modulator to focus a diffraction-limited spot of light within the brain. We use a combination of experimental measurements of back-scattered light in live larvae and computational modelling of the scattering to determine the spatial distribution of light. Modelling is performed using the Monte Carlo method, supported by generalised Lorenz-Mie theory in the single-scattering approximation. Scattering in areas rich in cell bodies is compared to that of regions of neuropil to identify the distinct and dramatic contributions that cell nuclei make to scattering. We demonstrate the feasibility of illuminating individual neurons, even in nucleus-rich areas, at depths beyond 100 μm using a spatial light modulator in combination with a standard laser and microscope optics.

  11. Elemental composition of `normal` and Alzheimer brain tissue by INA and PIXE analyses

    Energy Technology Data Exchange (ETDEWEB)

    Stedman, J.D.; Spyrou, N.M.

    1997-03-01

    Instrumental methods based on the nuclear and atomic properties of the elements have been used for many years to determine elemental concentrations in a variety of materials for biomedical, industrial and environmental applications. These methods offer high sensitivity for accurate trace element measurements, suffer few interfering or competing effects. Present no blank problems and are convenient for both research and routine analyses. The present article describes the use of two trace element techniques. Firstly the use of activation of stable nuclei irradiated by neutrons in the core of a low power research reactor as a means of detection of elements through the resulting gamma-rays emitted. Secondly, the observations of the interactions of energetic ion beams with the material in order to identify elemental species. Over recent years there has been some interest in determining the elemental composition of `normal` and Alzheimer affected brain tissue, however literature findings are inconsistent. Possible reasons for discrepancies need to be identified for further progress to be made. Here, post-mortem tissue samples, provided by the Alzheimer`s Disease Brain Bank, Institute of Psychiatry, London, were taken from the frontal, occipital, parietal and temporal lobes of both hemispheres of brains from 13 `normal` and 19 Alzheimer subjects. The elemental composition of the samples was determined using the analytical techniques of INAA (instrumental neutron activation analysis), RBS (Rutherford back-scattering) and PIXE (particle induced x-ray emission). The principal findings are summarised here. (author).

  12. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    Directory of Open Access Journals (Sweden)

    Faris Shweikeh

    2014-01-01

    Full Text Available Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing’s sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma, some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma, and a few after 36 months (chondrosarcoma and liposarcoma. Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing’s sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas. Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.

  13. White matter lesion extension to automatic brain tissue segmentation on MRI.

    Science.gov (United States)

    de Boer, Renske; Vrooman, Henri A; van der Lijn, Fedde; Vernooij, Meike W; Ikram, M Arfan; van der Lugt, Aad; Breteler, Monique M B; Niessen, Wiro J

    2009-05-01

    A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.

  14. Role of Soft-Tissue Heterogeneity in Computational Models of Deep Brain Stimulation.

    Science.gov (United States)

    Howell, Bryan; McIntyre, Cameron C

    Bioelectric field models of deep brain stimulation (DBS) are commonly utilized in research and industrial applications. However, the wide range of different representations used for the human head in these models may be responsible for substantial variance in the stimulation predictions. Determine the relative error of ignoring cerebral vasculature and soft-tissue heterogeneity outside of the brain in computational models of DBS. We used a detailed atlas of the human head, coupled to magnetic resonance imaging data, to construct a range of subthalamic DBS volume conductor models. We incrementally simplified the most detailed base model and quantified changes in the stimulation thresholds for direct activation of corticofugal axons. Ignoring cerebral vasculature altered predictions of stimulation thresholds by brain altered predictions between -44 % and 174%. Heterogeneity in the soft tissues of the head, if unaccounted for, introduces a degree of uncertainty in predicting electrical stimulation of neural elements that is not negligible and thereby warrants consideration in future modeling studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Unified model of brain tissue microstructure dynamically binds diffusion and osmosis with extracellular space geometry

    Science.gov (United States)

    Yousefnezhad, Mohsen; Fotouhi, Morteza; Vejdani, Kaveh; Kamali-Zare, Padideh

    2016-09-01

    We present a universal model of brain tissue microstructure that dynamically links osmosis and diffusion with geometrical parameters of brain extracellular space (ECS). Our model robustly describes and predicts the nonlinear time dependency of tortuosity (λ =√{D /D* } ) changes with very high precision in various media with uniform and nonuniform osmolarity distribution, as demonstrated by previously published experimental data (D = free diffusion coefficient, D* = effective diffusion coefficient). To construct this model, we first developed a multiscale technique for computationally effective modeling of osmolarity in the brain tissue. Osmolarity differences across cell membranes lead to changes in the ECS dynamics. The evolution of the underlying dynamics is then captured by a level set method. Subsequently, using a homogenization technique, we derived a coarse-grained model with parameters that are explicitly related to the geometry of cells and their associated ECS. Our modeling results in very accurate analytical approximation of tortuosity based on time, space, osmolarity differences across cell membranes, and water permeability of cell membranes. Our model provides a unique platform for studying ECS dynamics not only in physiologic conditions such as sleep-wake cycles and aging but also in pathologic conditions such as stroke, seizure, and neoplasia, as well as in predictive pharmacokinetic modeling such as predicting medication biodistribution and efficacy and novel biomolecule development and testing.

  16. Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats

    DEFF Research Database (Denmark)

    Lof, A.; Lam, Henrik Rye; Gullstrand, E.

    1999-01-01

    spirit was 1.5 and 5.6 mg/kg in blood; 7.1 and 17.1 mg/kg in brain; 432 and 1452 mg/kg in fat tissue at the exposure levels of 400 and 800 p.p.m., respectively. The concentrations of n-nonane, n-decane, n-undecane, and total white spirit in blood and brain were not affected by the duration of exposure......Petroleum products with low content of aromatics have been increasingly used during the past years. This study investigates tissue disposition of dearomatised white spirit. In addition, brain neurotransmitter concentrations were measured. Male rats were exposed by inhalation to 0, 400 (2.29 mg....../l), or 800 p.p.m. (4.58 mg/l) of dearomatised white spirit, 6 hr/day, 5 days/week up to 3 weeks. Five rats from each group were sacrificed immediately after the exposure for 1, 2, or 3 weeks and 2, 4, 6, or 24 hr after the end of 3 weeks' exposure. After 3 weeks of exposure the concentration of total white...

  17. Development and Validation of a Method for Alcohol Analysis in Brain Tissue by Headspace Gas Chromatography with Flame Ionization Detector

    OpenAIRE

    Chun, Hao-Jung; Poklis, Justin L.; Poklis, Alphonse; Wolf, Carl E.

    2016-01-01

    Ethanol is the most widely used and abused drug. While blood is the preferred specimen for analysis, tissue specimens such as brain serve as alternative specimens for alcohol analysis in post-mortem cases where blood is unavailable or contaminated. A method was developed using headspace gas chromatography with flame ionization detection (HS-GC-FID) for the detection and quantification of ethanol, acetone, isopropanol, methanol and n-propanol in brain tissue specimens. Unfixed volatile-free br...

  18. Relationship between concentrations of lutein and StARD3 among pediatric and geriatric human brain tissue

    Science.gov (United States)

    Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and c...

  19. A white matter lesion-filling approach to improve brain tissue volume measurements

    Directory of Open Access Journals (Sweden)

    Sergi Valverde

    2014-01-01

    Full Text Available Multiple sclerosis white matter (WM lesions can affect brain tissue volume measurements of voxel-wise segmentation methods if these lesions are included in the segmentation process. Several authors have presented different techniques to improve brain tissue volume estimations by filling WM lesions before segmentation with intensities similar to those of WM. Here, we propose a new method to refill WM lesions, where contrary to similar approaches, lesion voxel intensities are replaced by random values of a normal distribution generated from the mean WM signal intensity of each two-dimensional slice. We test the performance of our method by estimating the deviation in tissue volume between a set of 30 T1-w 1.5 T and 30 T1-w 3 T images of healthy subjects and the same images where: WM lesions have been previously registered and afterwards replaced their voxel intensities to those between gray matter (GM and WM tissue. Tissue volume is computed independently using FAST and SPM8. When compared with the state-of-the-art methods, on 1.5 T data our method yields the lowest deviation in WM between original and filled images, independently of the segmentation method used. It also performs the lowest differences in GM when FAST is used and equals to the best method when SPM8 is employed. On 3 T data, our method also outperforms the state-of-the-art methods when FAST is used while performs similar to the best method when SPM8 is used. The proposed technique is currently available to researchers as a stand-alone program and as an SPM extension.

  20. A white matter lesion-filling approach to improve brain tissue volume measurements.

    Science.gov (United States)

    Valverde, Sergi; Oliver, Arnau; Lladó, Xavier

    2014-01-01

    Multiple sclerosis white matter (WM) lesions can affect brain tissue volume measurements of voxel-wise segmentation methods if these lesions are included in the segmentation process. Several authors have presented different techniques to improve brain tissue volume estimations by filling WM lesions before segmentation with intensities similar to those of WM. Here, we propose a new method to refill WM lesions, where contrary to similar approaches, lesion voxel intensities are replaced by random values of a normal distribution generated from the mean WM signal intensity of each two-dimensional slice. We test the performance of our method by estimating the deviation in tissue volume between a set of 30 T1-w 1.5 T and 30 T1-w 3 T images of healthy subjects and the same images where: WM lesions have been previously registered and afterwards replaced their voxel intensities to those between gray matter (GM) and WM tissue. Tissue volume is computed independently using FAST and SPM8. When compared with the state-of-the-art methods, on 1.5 T data our method yields the lowest deviation in WM between original and filled images, independently of the segmentation method used. It also performs the lowest differences in GM when FAST is used and equals to the best method when SPM8 is employed. On 3 T data, our method also outperforms the state-of-the-art methods when FAST is used while performs similar to the best method when SPM8 is used. The proposed technique is currently available to researchers as a stand-alone program and as an SPM extension.

  1. Behcet brain tissue identified with increased levels of Si and Al

    Science.gov (United States)

    Aranyosiova, Monika; Kopani, Martin; Rychly, Boris; Jakubovsky, Jan; Velic, Dusan

    2008-12-01

    Behcet disease is a multi-system disorder with still uncertain chemical causality. Chemical composition of molecules and elements in a human brain tissue of Behcet diseased patient is of interest. Time-of-flight secondary ion mass spectrometry is used to provide complex composition in Behcet disease and control tissues. Determined organic compounds are represented by fragments of carbohydrates, phospholipids, amino acids, and peptides in both samples without any qualitative differences. Trace heavy elements as Fe, Zn, and Cu are identified in Behcet disease tissue with increased intensities by only an averaged factor of 2.2 in comparison to the control. The significant differences between the control and Behcet disease tissues are in the presence of Si and Al. These two elements have significantly higher intensities by an averaged factor of 10.0 in Behcet disease tissue. The origin of Al and Si occurrence and the chronology of their accumulation are not clear, moreover this observation supports a significance of chemical characterization in an early stage of disease.

  2. Monoaminergic uptake in synaptosomes prepared from frozen brain tissue samples of normal and narcoleptic canines.

    Science.gov (United States)

    Valtier, D; Dement, W C; Mignot, E

    1992-08-14

    Canine narcolepsy, a model of the human disorder, is associated with altered catecholamine but not serotonin (5-HT) metabolism in some brain areas, particularly the amygdala. A possible explanation for these global changes could be the existence of specific defects in monoamine uptake processes. We have studied the uptake of [3H]norepinephrine (NE), [3H]dopamine (DA) and [3H]5-HT in synaptosomes prepared from cortex and amygdala of narcoleptic and control Doberman pinscher brains. Since narcoleptic canines are relatively few in number, we have used a specific brain freezing procedure that has been reported to allow restoration of metabolically functional tissue upon thawing. Preliminary studies comparing monoamine uptake in fresh and frozen brain samples of both groups of dogs were carried out and demonstrated that this procedure significantly altered serotoninergic but not noradrenergic and dopaminergic uptake. All further investigations were then done on synaptosomes prepared from frozen samples. Our results demonstrate that synaptosomal uptake of [3H]NE, [3H]DA and [3H]5-HT in cortex and amygdala are not altered in narcolepsy.

  3. Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder

    Energy Technology Data Exchange (ETDEWEB)

    Streitberger, Kaspar-Josche [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Fehlner, Andreas; Sack, Ingolf [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Pache, Florence [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Lacheta, Anna; Papazoglou, Sebastian; Brandt, Alexander [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Bellmann-Strobl, Judith [Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Ruprecht, Klemens [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Braun, Juergen [Charite - Universitaetsmedizin Berlin, Institute of Medical Informatics, Berlin (Germany); Paul, Friedemann [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Wuerfel, Jens [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Medical Image Analysis Center (MIAC AG), Basel (Switzerland)

    2017-05-15

    Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC). 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude G* and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz. In NMOSD patients, a significant reduction of G* was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044). MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration. (orig.)

  4. Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Milsted, A.; Barna, B.P.; Ransohoff, R.M.; Brosnihan, K.B.; Ferrario, C.M. (Cleveland Clinic Foundation, OH (USA))

    1990-08-01

    The authors have identified human cultured cell lines that are useful for studying angiotensinogen gene expression and its regulation in the central nervous system. A model cell system of human central nervous system origin expressing angiotensinogen has not previously been available. Expression of angiotensinogen mRNA appears to be a basal property of noninduced human astrocytes, since astrocytic cell lines derived from human glioblastomas or nonneoplastic human brain tissue invariably produced angiotensinogen mRNA. In situ hybridization histochemistry revealed that angiotensinogen mRNA production was not limited to a subpopulation of astrocytes because >99% of cells in these cultures contained angiotensinogen mRNA. These cell lines will be useful in studies of the molecular mechanisms controlling angiotensin synthesis and the role of biologically active angiotensin in the human brain by allowing the authors to examine regulation of expression of the renin-angiotensin system in human astrocyte cultures.

  5. Proposals for best-quality immunohistochemical staining of paraffin-embedded brain tissue slides in forensics.

    Science.gov (United States)

    Trautz, Florian; Dreßler, Jan; Stassart, Ruth; Müller, Wolf; Ondruschka, Benjamin

    2018-01-03

    Immunohistochemistry (IHC) has become an integral part in forensic histopathology over the last decades. However, the underlying methods for IHC vary greatly depending on the institution, creating a lack of comparability. The aim of this study was to assess the optimal approach for different technical aspects of IHC, in order to improve and standardize this procedure. Therefore, qualitative results from manual and automatic IHC staining of brain samples were compared, as well as potential differences in suitability of common IHC glass slides. Further, possibilities of image digitalization and connected issues were investigated. In our study, automatic staining showed more consistent staining results, compared to manual staining procedures. Digitalization and digital post-processing facilitated direct analysis and analysis for reproducibility considerably. No differences were found for different commercially available microscopic glass slides regarding suitability of IHC brain researches, but a certain rate of tissue loss should be expected during the staining process.

  6. IMPROVED HYBRID SEGMENTATION OF BRAIN MRI TISSUE AND TUMOR USING STATISTICAL FEATURES

    Directory of Open Access Journals (Sweden)

    S. Allin Christe

    2010-08-01

    Full Text Available Medical image segmentation is the most essential and crucial process in order to facilitate the characterization and visualization of the structure of interest in medical images. Relevant application in neuroradiology is the segmentation of MRI data sets of the human brain into the structure classes gray matter, white matter and cerebrospinal fluid (CSF and tumor. In this paper, brain image segmentation algorithms such as Fuzzy C means (FCM segmentation and Kohonen means(K means segmentation were implemented. In addition to this, new hybrid segmentation technique, namely, Fuzzy Kohonen means of image segmentation based on statistical feature clustering is proposed and implemented along with standard pixel value clustering method. The clustered segmented tissue images are compared with the Ground truth and its performance metric is also found. It is found that the feature based hybrid segmentation gives improved performance metric and improved classification accuracy rather than pixel based segmentation.

  7. Automated tissue segmentation of MR brain images in the presence of white matter lesions.

    Science.gov (United States)

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; González-Villà, Sandra; Pareto, Deborah; Vilanova, Joan C; Ramió-Torrentà, Lluís; Rovira, Àlex; Lladó, Xavier

    2017-01-01

    Over the last few years, the increasing interest in brain tissue volume measurements on clinical settings has led to the development of a wide number of automated tissue segmentation methods. However, white matter lesions are known to reduce the performance of automated tissue segmentation methods, which requires manual annotation of the lesions and refilling them before segmentation, which is tedious and time-consuming. Here, we propose a new, fully automated T1-w/FLAIR tissue segmentation approach designed to deal with images in the presence of WM lesions. This approach integrates a robust partial volume tissue segmentation with WM outlier rejection and filling, combining intensity and probabilistic and morphological prior maps. We evaluate the performance of this method on the MRBrainS13 tissue segmentation challenge database, which contains images with vascular WM lesions, and also on a set of Multiple Sclerosis (MS) patient images. On both databases, we validate the performance of our method with other state-of-the-art techniques. On the MRBrainS13 data, the presented approach was at the time of submission the best ranked unsupervised intensity model method of the challenge (7th position) and clearly outperformed the other unsupervised pipelines such as FAST and SPM12. On MS data, the differences in tissue segmentation between the images segmented with our method and the same images where manual expert annotations were used to refill lesions on T1-w images before segmentation were lower or similar to the best state-of-the-art pipeline incorporating automated lesion segmentation and filling. Our results show that the proposed pipeline achieved very competitive results on both vascular and MS lesions. A public version of this approach is available to download for the neuro-imaging community. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Growth trajectories of the human fetal brain tissues estimated from 3D reconstructed in utero MRI.

    Science.gov (United States)

    Scott, Julia A; Habas, Piotr A; Kim, Kio; Rajagopalan, Vidya; Hamzelou, Kia S; Corbett-Detig, James M; Barkovich, A James; Glenn, Orit A; Studholme, Colin

    2011-08-01

    In the latter half of gestation (20-40 gestational weeks), human brain growth accelerates in conjunction with cortical folding and the deceleration of ventricular zone progenitor cell proliferation. These processes are reflected in changes in the volume of respective fetal tissue zones. Thus far, growth trajectories of the fetal tissue zones have been extracted primarily from 2D measurements on histological sections and magnetic resonance imaging (MRI). In this study, the volumes of major fetal zones-cortical plate (CP), subplate and intermediate zone (SP+IZ), germinal matrix (GMAT), deep gray nuclei (DG), and ventricles (VENT)--are calculated from automatic segmentation of motion-corrected, 3D reconstructed MRI. We analyzed 48 T2-weighted MRI scans from 39 normally developing fetuses in utero between 20.57 and 31.14 gestational weeks (GW). The supratentorial volume (STV) increased linearly at a rate of 15.22% per week. The SP+IZ (14.75% per week) and DG (15.56% per week) volumes increased at similar rates. The CP increased at a greater relative rate (18.00% per week), while the VENT (9.18% per week) changed more slowly. Therefore, CP increased as a fraction of STV and the VENT fraction declined. The total GMAT volume slightly increased then decreased after 25 GW. We did not detect volumetric sexual dimorphisms or total hemispheric volume asymmetries, which may emerge later in gestation. Further application of the automated fetal brain segmentation to later gestational ages will bridge the gap between volumetric studies of premature brain development and normal brain development in utero. Published by Elsevier Ltd.

  9. Controlled single bubble cavitation collapse results in jet-induced injury in brain tissue.

    Science.gov (United States)

    Canchi, Saranya; Kelly, Karen; Hong, Yu; King, Michael A; Subhash, Ghatu; Sarntinoranont, Malisa

    2017-10-01

    Multiscale damage due to cavitation is considered as a potential mechanism of traumatic brain injury (TBI) associated with explosion. In this study, we employed a TBI relevant hippocampal ex vivo slice model to induce bubble cavitation. Placement of single reproducible seed bubbles allowed control of size, number, and tissue location to visualize and measure deformation parameters. Maximum strain value was measured at 45 µs after bubble collapse, presented with a distinct contour and coincided temporally and spatially with the liquid jet. Composite injury maps combined this maximum strain value with maximum measured bubble size and location along with histological injury patterns. This facilitated the correlation of bubble location and subsequent jet direction to the corresponding regions of high strain which overlapped with regions of observed injury. A dynamic threshold strain range for tearing of cerebral cortex was estimated to be between 0.5 and 0.6. For a seed bubble placed underneath the hippocampus, cavitation induced damage was observed in hippocampus (local), proximal cerebral cortex (marginal) and the midbrain/forebrain (remote) upon histological evaluation. Within this test model, zone of cavitation injury was greater than the maximum radius of the bubble. Separation of apposed structures, tissue tearing, and disruption of cellular layers defined early injury patterns that were not detected in the blast-exposed half of the brain slice. Ultrastructural pathology of the neurons exposed to cavitation was characterized by disintegration of plasma membrane along with loss of cellular content. The developed test system provided a controlled experimental platform to study cavitation induced high strain deformations on brain tissue slice. The goal of the future studies will be to lower underpressure magnitude and cavitation bubble size for more sensitive evaluation of injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Lysosomal dysfunction in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Klaudia Tomala

    2017-05-01

    Full Text Available Recent data advocate for the implication of lysosomes in the development of programmed cell death. Lysosomal dysfunction decreased the efficiency of autophagosome/lysosome fusion that leads to vacuolation of cells. Autophagic vacuoles containing damaged organelles and altered proteins are hallmarks in most neurodegenerative disorders. These aggregates consequently disrupt cellular homeostasis causing neuronal cell death due apoptosis or necrosis. Moreover calpain mediated or mutation inducted lysosomal rupture result in release of lysosomal cathepsins into the cytoplasm and inducing neuronal cell death. In this review we emphasize the pathophysiological mechanism connecting disrupting autophagy – lysosomal pathway and lysosomal dysfunction in neuronal cell death called lysosomal cell death.

  11. Experimental study on the toxicity of povidone-iodine solution in brain tissues of rabbits

    OpenAIRE

    Li, Shu-Hua; Wang, Yu; Gao, Hai-Bin; Zhao, Kun; Hou, Yu-Chen; Sun, Wei

    2015-01-01

    Objective: To determine whether Povidone-iodine was toxic to brain tissues by rinsing the cerebral cortex of New Zealand rabbits with Povidone-iodine Solution of different concentrations. Methods: 12 New Zealand rabbits were randomly divided into 4 groups (Group A, B, C and D, 3 rabbits each group). In each group, the left cerebral cortex of rabbits was rinsed with physiological saline after the craniotomy; in Group A and B, the right cerebral cortex of rabbits was also locally rinsed with Po...

  12. Pediatric brain tumors of neuroepithelial tissue; Hirntumoren des neuroepithelialen Gewebes im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Papanagiotou, P.; Politi, M. [Klinikum Bremen-Mitte/Bremen-Ost, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Bremen (Germany); Bergmann, M. [Klinikum Bremen-Mitte, Institut fuer Klinische Neuropathologie, Bremen (Germany); Pekrun, A. [Klinikum Bremen-Mitte, Klinik fuer Kinder- und Jugendmedizin, paed. Haematologie/Onkologie, Neonatologie, Bremen (Germany); Juergens, K.U. [Klinikum Bremen-Mitte, ZEMODI-Zentrum fuer moderne Diagnostik, MRT, Nuklearmedizin und PET-CT, Bremen (Germany)

    2014-08-15

    Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [German] Tumoren des neuroepithelialen Gewebes stellen die mit Abstand groesste Gruppe der paediatrischen Hirntumoren dar und werden je nach deren Ursprung in diversen Subtypen unterteilt. Das Neuropil beinhaltet diverse Subtypen von Gliazellen: Astrozyten, Oligodendrozyten, ependymale Zellen und modifizierte ependymale Zellen, die den Plexus choroideus formen. In diesem Review werden die bildgebenden Aspekte mittels CT und MRT der haeufigsten Tumoren des neuroepithelialen Gewebes diskutiert. (orig.)

  13. The Hsp70/Hsp90 Chaperone Machinery in Neurodegenerative Diseases

    OpenAIRE

    Rachel E. Lackie; Rachel E. Lackie; Andrzej Maciejewski; Andrzej Maciejewski; Valeriy G. Ostapchenko; Jose Marques-Lopes; Wing-Yiu Choy; Martin L. Duennwald; Vania F. Prado; Vania F. Prado; Vania F. Prado; Vania F. Prado; Marco A. M. Prado; Marco A. M. Prado; Marco A. M. Prado

    2017-01-01

    The accumulation of misfolded proteins in the human brain is one of the critical features of many neurodegenerative diseases, including Alzheimer's disease (AD). Assembles of beta-amyloid (Aβ) peptide—either soluble (oligomers) or insoluble (plaques) and of tau protein, which form neurofibrillary tangles, are the major hallmarks of AD. Chaperones and co-chaperones regulate protein folding and client maturation, but they also target misfolded or aggregated proteins for refolding or for degrada...

  14. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Klin, Yael [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel); Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram [The Division of Anesthesiology, Soroka Medical Center and Ben Gurion University of the Negev, Beer-Sheva (Israel); Teichberg, Vivian I., E-mail: Vivian.teichberg@weizmann.ac.il [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel)

    2010-09-03

    Research highlights: {yields} Blood glutamate has a half-life time of 2-3 min. {yields} Blood glutamate is submitted to rapid decarboxylation. {yields} Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. {yields} The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1-{sup 14}C] Glutamic acid (L-[1-{sup 14}C] Glu), L-[G-{sup 3}H] Glutamic acid (L-[G-{sup 3}H] Glu) or D-[2,3-{sup 3}H] Aspartic acid (D-[2,3-{sup 3}H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1-{sup 14}C] Glu and L-[G-{sup 3}H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3-{sup 3}H] Asp. L-[1-{sup 14}C] Glu was subjected in blood to a rapid decarboxylation with the loss of {sup 14}CO{sub 2}. The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U-{sup 14}C] Glu or D-[2,3-{sup 3}H] Asp radioactivity capture. L-[U-{sup 14}C] Glu and D-[2,3-{sup 3}H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues

  15. Transgenic nonhuman primates for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Chan Anthony WS

    2004-06-01

    Full Text Available Abstract Animal models that represent human diseases constitute an important tool in understanding the pathogenesis of the diseases, and in developing effective therapies. Neurodegenerative diseases are complex disorders involving neuropathologic and psychiatric alterations. Although transgenic and knock-in mouse models of Alzheimer's disease, (AD, Parkinson's disease (PD and Huntington's disease (HD have been created, limited representation in clinical aspects has been recognized and the rodent models lack true neurodegeneration. Chemical induction of HD and PD in nonhuman primates (NHP has been reported, however, the role of intrinsic genetic factors in the development of the diseases is indeterminable. Nonhuman primates closely parallel humans with regard to genetic, neuroanatomic, and cognitive/behavioral characteristics. Accordingly, the development of NHP models for neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Therefore, a transgenic NHP carrying a mutant gene similar to that of patients will help to clarify our understanding of disease onset and progression. Additionally, monitoring disease onset and development in the transgenic NHP by high resolution brain imaging technology such as MRI, and behavioral and cognitive testing can all be carried out simultaneously in the NHP but not in other animal models. Moreover, because of the similarity in motor repertoire between NHPs and humans, it will also be possible to compare the neurologic syndrome observed in the NHP model to that in patients. Understanding the correlation between genetic defects and physiologic changes (e.g. oxidative damage will lead to a better understanding of disease progression and the development of patient treatments, medications and preventive approaches for high risk individuals. The impact of the transgenic NHP model in understanding the role which

  16. Use of flow cytometry for high-throughput cell population estimates in fixed brain tissue

    Directory of Open Access Journals (Sweden)

    Nicole A Young

    2012-07-01

    Full Text Available The numbers and types of cells in an area of cortex define its function. Therefore it is essential to characterize the numbers and distributions of total cells in areas of the cortex, as well as to identify numbers of subclasses of neurons and glial cells. To date, the large size of the primate brain and the lack of innovation in cell counting methods have been a roadblock to obtaining high-resolution maps of cell and neuron density across the cortex in humans and non-human primates. Stereological counting methods and the isotropic fractionator are valuable tools for estimating cell numbers, but are better suited to smaller, well-defined brain structures or to cortex as a whole. In the present study, we have extended our flow-cytometry based counting method, the flow fractionator (Collins et al., 2010a, to include high-throughput total cell population estimates in homogenized cortical samples. We demonstrate that our method produces consistent, accurate and repeatable cell estimates quickly. The estimates we report are in excellent agreement with estimates for the same samples obtained using a Neubauer chamber and a fluorescence microscope. We show that our flow cytometry-based method for total cell estimation in homogenized brain tissue is more efficient and more precise than manual counting methods. The addition of automated nuclei counting to our flow fractionator method allows for a fully automated, rapid characterization of total cells and neuronal and non-neuronal populations in human and non-human primate brains, providing valuable data to further our understanding of the functional organization of normal, aging and diseased brains.

  17. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling

    Directory of Open Access Journals (Sweden)

    Sergi Valverde

    2015-01-01

    Full Text Available Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. First of all, images were processed using the LST and SLS toolkits with different pipeline combinations that differed in either automated or manual lesion segmentation, and lesion filling or masking out lesions. Then, images processed following each of the pipelines were segmented into gray matter (GM and white matter (WM using SPM8, and compared with the same images where expert lesion annotations were filled before segmentation. Our results showed that fully automated lesion segmentation and filling pipelines reduced significantly the % of error in GM and WM volume on images of MS patients, and performed similarly to the images where expert lesion annotations were masked before segmentation. In all the pipelines, the amount of misclassified lesion voxels was the main cause in the observed error in GM and WM volume. However, the % of error was significantly lower when automatically estimated lesions were filled and not masked before segmentation. These results are relevant and suggest that LST and SLS toolboxes allow the performance of accurate brain tissue volume measurements without any kind of manual intervention, which can be convenient not only in terms of time and economic costs, but also to avoid the inherent intra/inter variability between manual annotations.

  18. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling.

    Science.gov (United States)

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; Pareto, Deborah; Vilanova, Joan C; Ramió-Torrentà, Lluís; Sastre-Garriga, Jaume; Montalban, Xavier; Rovira, Àlex; Lladó, Xavier

    2015-01-01

    Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS) lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. First of all, images were processed using the LST and SLS toolkits with different pipeline combinations that differed in either automated or manual lesion segmentation, and lesion filling or masking out lesions. Then, images processed following each of the pipelines were segmented into gray matter (GM) and white matter (WM) using SPM8, and compared with the same images where expert lesion annotations were filled before segmentation. Our results showed that fully automated lesion segmentation and filling pipelines reduced significantly the % of error in GM and WM volume on images of MS patients, and performed similarly to the images where expert lesion annotations were masked before segmentation. In all the pipelines, the amount of misclassified lesion voxels was the main cause in the observed error in GM and WM volume. However, the % of error was significantly lower when automatically estimated lesions were filled and not masked before segmentation. These results are relevant and suggest that LST and SLS toolboxes allow the performance of accurate brain tissue volume measurements without any kind of manual intervention, which can be convenient not only in terms of time and economic costs, but also to avoid the inherent intra/inter variability between manual annotations.

  19. Chameleon sequences in neurodegenerative diseases.

    Science.gov (United States)

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Salari, Ali

    2016-03-25

    Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to "helix to strand (HE)", "helix to coil (HC)" and "strand to coil (CE)" alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Chameleon sequences in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Bahramali, Golnaz [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Goliaei, Bahram, E-mail: goliaei@ut.ac.ir [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Minuchehr, Zarrin, E-mail: minuchehr@nigeb.ac.ir [Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology, (NIGEB), Tehran (Iran, Islamic Republic of); Salari, Ali [Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology, (NIGEB), Tehran (Iran, Islamic Republic of)

    2016-03-25

    Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to “helix to strand (HE)”, “helix to coil (HC)” and “strand to coil (CE)” alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

  1. Dynamic, mating-induced gene expression changes in female head and brain tissues of Drosophila melanogaster

    Science.gov (United States)

    2010-01-01

    Background Drosophila melanogaster females show changes in behavior and physiology after mating that are thought to maximize the number of progeny resulting from the most recent copulation. Sperm and seminal fluid proteins induce post-mating changes in females, however, very little is known about the resulting gene expression changes in female head and central nervous system tissues that contribute to the post-mating response. Results We determined the temporal gene expression changes in female head tissues 0-2, 24, 48 and 72 hours after mating. Females from each time point had a unique post-mating gene expression response, with 72 hours post-mating having the largest number of genes with significant changes in expression. At most time points, genes expressed in the head fat body that encode products involved in metabolism showed a marked change in expression. Additional analysis of gene expression changes in dissected brain tissues 24 hours post-mating revealed changes in transcript abundance of many genes, notably, the reduced transcript abundance of genes that encode ion channels. Conclusions Substantial changes occur in the regulation of many genes in female head tissues after mating, which might underlie aspects of the female post-mating response. These results provide new insights into the physiological and metabolic changes that accompany changes in female behaviors. PMID:20925960

  2. Dynamic, mating-induced gene expression changes in female head and brain tissues of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Stirling Emma J

    2010-10-01

    Full Text Available Abstract Background Drosophila melanogaster females show changes in behavior and physiology after mating that are thought to maximize the number of progeny resulting from the most recent copulation. Sperm and seminal fluid proteins induce post-mating changes in females, however, very little is known about the resulting gene expression changes in female head and central nervous system tissues that contribute to the post-mating response. Results We determined the temporal gene expression changes in female head tissues 0-2, 24, 48 and 72 hours after mating. Females from each time point had a unique post-mating gene expression response, with 72 hours post-mating having the largest number of genes with significant changes in expression. At most time points, genes expressed in the head fat body that encode products involved in metabolism showed a marked change in expression. Additional analysis of gene expression changes in dissected brain tissues 24 hours post-mating revealed changes in transcript abundance of many genes, notably, the reduced transcript abundance of genes that encode ion channels. Conclusions Substantial changes occur in the regulation of many genes in female head tissues after mating, which might underlie aspects of the female post-mating response. These results provide new insights into the physiological and metabolic changes that accompany changes in female behaviors.

  3. Terahertz spectroscopy and detection of brain tumor in rat fresh-tissue samples

    Science.gov (United States)

    Yamaguchi, S.; Fukushi, Y.; Kubota, O.; Itsuji, T.; Yamamoto, S.; Ouchi, T.

    2015-03-01

    Terahertz (THz) spectroscopy and imaging of biomedical samples is expected to be an important application of THz analysis techniques. Identification and localization of tumor tissue, imaging of biological samples, and analysis of DNA by THz spectroscopy have been reported. THz time-domain spectroscopy (TDS) is useful for obtaining the refractive index over a broad frequency range. However, THz-TDS spectra of fresh tissue samples are sensitive to procedures such as sample preparation, and a standardized measurement protocol is required. Therefore, in this work, we establish a protocol for measurements of THz spectra of fresh tissue and demonstrate reliable detection of rat brain tumor tissue. We use a reflection THz-TDS system to measure the refractive index spectra of the samples mounted on a quartz plate. The tissue samples were measured immediately after sectioning to avoid sample denaturalization during storage. Special care was taken in THz data processing to eliminate parasitic reflections and reduce noise. The error level in our refractive index measurements was as low as 0.02 in the frequency range 0.8-1.5 THz. With increasing frequency, the refractive index in the tumor and normal regions monotonically decreased, similarly to water, and it was 0.02 higher in the tumor regions. The spectral data suggest that the tumor regions have higher water content. Hematoxylin-eosin stained images showed that increased cell density was also responsible for the observed spectral features. A set of samples from 10 rats showed consistent results. Our results suggest that reliable tumor detection in fresh tissue without pretreatment is possible with THz spectroscopy measurements. THz spectroscopy has the potential to become a real-time in vivo diagnostic method.

  4. Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain?liver axis

    OpenAIRE

    Yang, B; Ren, Q; Zhang, J-c; Chen, Q-X; Hashimoto, K

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF...

  5. Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke.

    Science.gov (United States)

    Cook, Douglas J; Nguyen, Cynthia; Chun, Hyun N; L Llorente, Irene; Chiu, Abraham S; Machnicki, Michal; Zarembinski, Thomas I; Carmichael, S Thomas

    2017-03-01

    Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood-brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel + BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate ( Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel + BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2 cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.

  6. Hierarchical brain tissue segmentation and its application in multiple sclerosis and Alzheimer's disease

    Science.gov (United States)

    Lei, Tianhu; Udupa, Jayaram K.; Moonis, Gul; Schwartz, Eric; Balcer, Laura

    2005-04-01

    Based on Fuzzy Connectedness (FC) object delineation principles and algorithms, a hierarchical brain tissue segmentation technique has been developed for MR images. After MR image background intensity inhomogeneity correction and intensity standardization, three FC objects for cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) are generated via FC object delineation, and an intracranial (IC) mask is created via morphological operations. Then, the IC mask is decomposed into parenchymal (BP) and CSF masks, while the BP mask is separated into WM and GM masks. WM mask is further divided into pure and dirty white matter masks (PWM and DWM). In Multiple Sclerosis studies, a severe white matter lesion (LS) mask is defined from DWM mask. Based on the segmented brain tissue images, a histogram-based method has been developed to find disease-specific, image-based quantitative markers for characterizing the macromolecular manifestation of the two diseases. These same procedures have been applied to 65 MS (46 patients and 19 normal subjects) and 25 AD (15 patients and 10 normal subjects) data sets, each of which consists of FSE PD- and T2-weighted MR images. Histograms representing standardized PD and T2 intensity distributions and their numerical parameters provide an effective means for characterizing the two diseases. The procedures are systematic, nearly automated, robust, and the results are reproducible.

  7. Characterisation of carbon paste electrodes for real-time amperometric monitoring of brain tissue oxygen.

    Science.gov (United States)

    Bolger, Fiachra B; McHugh, Stephen B; Bennett, Rachel; Li, Jennifer; Ishiwari, Keita; Francois, Jennifer; Conway, Michael W; Gilmour, Gary; Bannerman, David M; Fillenz, Marianne; Tricklebank, Mark; Lowry, John P

    2011-02-15

    Tissue O₂ can be monitored using a variety of electrochemical techniques and electrodes. In vitro and in vivo characterisation studies for O₂ reduction at carbon paste electrodes (CPEs) using constant potential amperometry (CPA) are presented. Cyclic voltammetry indicated that an applied potential of -650 mV is required for O₂ reduction at CPEs. High sensitivity (-1.49 ± 0.01 nA/μM), low detection limit (ca. 0.1 μM) and good linear response characteristics (R² > 0.99) were observed in calibration experiments performed at this potential. There was also no effect of pH, temperature, and ion changes, and no dependence upon flow/fluid convection (stirring). Several compounds (e.g. dopamine and its metabolites) present in brain extracellular fluid were tested at physiological concentrations and shown not to interfere with the CPA O₂ signal. In vivo experiments confirmed a sub-second response time observed in vitro and demonstrated long-term stability extending over twelve weeks, with minimal O₂ consumption (ca. 1 nmol/h). These results indicate that CPEs operating amperometrically at a constant potential of -650 mV (vs. SCE) can be used reliably to continuously monitor brain extracellular tissue O₂. © 2010 Elsevier B.V. All rights reserved.

  8. Study on Material Parameters Identification of Brain Tissue Considering Uncertainty of Friction Coefficient

    Science.gov (United States)

    Guan, Fengjiao; Zhang, Guanjun; Liu, Jie; Wang, Shujing; Luo, Xu; Zhu, Feng

    2017-10-01

    Accurate material parameters are critical to construct the high biofidelity finite element (FE) models. However, it is hard to obtain the brain tissue parameters accurately because of the effects of irregular geometry and uncertain boundary conditions. Considering the complexity of material test and the uncertainty of friction coefficient, a computational inverse method for viscoelastic material parameters identification of brain tissue is presented based on the interval analysis method. Firstly, the intervals are used to quantify the friction coefficient in the boundary condition. And then the inverse problem of material parameters identification under uncertain friction coefficient is transformed into two types of deterministic inverse problem. Finally the intelligent optimization algorithm is used to solve the two types of deterministic inverse problems quickly and accurately, and the range of material parameters can be easily acquired with no need of a variety of samples. The efficiency and convergence of this method are demonstrated by the material parameters identification of thalamus. The proposed method provides a potential effective tool for building high biofidelity human finite element model in the study of traffic accident injury.

  9. Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders.

    Directory of Open Access Journals (Sweden)

    Alejandra Borjabad

    2011-09-01

    Full Text Available Antiretroviral therapy (ART has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing

  10. Detection of Neospora caninum-DNA in brain tissues from pigeons in Changchun, Jilin (China).

    Science.gov (United States)

    Du, Ling; Yang, Dongsheng; Zhai, Tao; Gong, Pengtao; Zhang, Xichen; Li, Jianhua

    2015-11-30

    Neospora caninum is an intracellular protozoan infecting many domestic and wild animals. The domestic chicken (Gallus domesticus) and the sparrow (Passer domesticus) are known as natural intermediate hosts of N. caninum, whereas the role of other birds such as pigeons is still unclear. In the present study, pigeon brain tissues collected in Jilin of China were screened by N. caninum specific-nested PCR to determine whether pigeons functioned as the natural intermediate hosts of N. caninum. The prevalences of N. caninum DNA and Toxoplasma gondii DNA among the brain samples were 30% (63/210) and 13.33% (28/210), respectively. One brain sample was co-infected with N. caninum and T. gondii in naturally infected pigeon. Of the 63 positive samples 42 could be assigned to the NC-PR genotype, 10 to the NC-1 genotypes and 5, 3 and 3 respectively to the each of the three new genotypes identified, indicating genetic polymorphism of N. caninum in pigeons in Jilin of China. The present study expanded the list of intermediate hosts of N. caninum to include pigeons which suggests that pigeons are involved in the transmission of the N. caninum. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue.

    Science.gov (United States)

    Hughes, Michael E; Hong, Hee-Kyung; Chong, Jason L; Indacochea, Alejandra A; Lee, Samuel S; Han, Michael; Takahashi, Joseph S; Hogenesch, John B

    2012-01-01

    The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN) orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock(Δ19) mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian "harmonics") are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude that 12-hour rhythms

  12. Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue.

    Directory of Open Access Journals (Sweden)

    Michael E Hughes

    Full Text Available The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock(Δ19 mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian "harmonics" are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude

  13. Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.

    Science.gov (United States)

    Rogalska, Anna; Kuter, Katarzyna; Żelazko, Aleksandra; Głogowska-Gruszka, Anna; Świętochowska, Elżbieta; Nowak, Przemysław

    2017-04-01

    The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

  14. Circadian clocks and neurodegenerative diseases: time to aggregate?

    Science.gov (United States)

    Hastings, Michael H; Goedert, Michel

    2013-10-01

    The major neurodegenerative diseases are characterised by a disabling loss of the daily pattern of sleep and wakefulness, which may be reflective of a compromise to the underlying circadian clock that times the sleep cycle. At a molecular level, the canonical property of neurodegenerative diseases is aberrant aggregation of otherwise soluble neuronal proteins. They can thus be viewed as disturbances of proteostasis, raising the question whether the two features - altered daily rhythms and molecular aggregation - are related. Recent discoveries have highlighted the fundamental contribution of circadian clocks to the correct ordering of daily cellular metabolic cycles, imposing on peripheral organs such as the liver a strict programme that alternates between anabolic and catabolic states. The discovery that circadian mechanisms are active in local brain regions suggests that they may impinge upon physiological and pathological elements that influence pro-neurodegenerative aggregation. This review explores how introducing the dimension of circadian time and the circadian clock might refine the analysis of aberrant aggregation, thus expanding our perspective on the cell biology common to neurodegenerative diseases. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Pharmacological Modulation of Functional Phenotypes of Microglia in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Gyun Jee Song

    2017-05-01

    Full Text Available Microglia are the resident innate immune cells of the central nervous system that mediate brain homeostasis maintenance. Microglia-mediated neuroinflammation is a hallmark shared by various neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Numerous studies have shown microglial activation phenotypes to be heterogeneous; however, these microglial phenotypes can largely be categorized as being either M1 or M2 type. Although the specific classification of M1 and M2 functionally polarized microglia remains a topic for debate, the use of functional modulators of microglial phenotypes as potential therapeutic approaches for the treatment of neurodegenerative diseases has garnered considerable attention. This review discusses M1 and M2 microglial phenotypes and their relevance in neurodegenerative disease models, as described in recent literature. The modulation of microglial polarization toward the M2 phenotype may lead to development of future therapeutic and preventive strategies for neuroinflammatory and neurodegenerative diseases. Thus, we focus on recent studies of microglial polarization modulators, with a particular emphasis on the small-molecule compounds and their intracellular target proteins.

  16. Molecular Chaperone Dysfunction in Neurodegenerative Diseases and Effects of Curcumin

    Directory of Open Access Journals (Sweden)

    Panchanan Maiti

    2014-01-01

    Full Text Available The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thought to play a major role in disease severity and progression. The principal machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal autophagy systems, where heat shock proteins play a crucial role. Many protein aggregates are degraded by the lysosomes, depending on aggregate size, peptide sequence, and degree of misfolding, while others are selectively tagged for removal by heat shock proteins and degraded by either the proteasome or phagosomes. These systems are compromised in different neurodegenerative diseases. Therefore, developing novel targets and classes of therapeutic drugs, which can reduce aggregates and maintain proteostasis in the brains of neurodegenerative models, is vital. Natural products that can modulate heat shock proteins/proteosomal pathway are considered promising for treating neurodegenerative diseases. Here we discuss the current knowledge on the role of HSPs in protein misfolding diseases and knowledge gained from animal models of Alzheimer’s disease, tauopathies, and Huntington’s diseases. Further, we discuss the emerging treatment regimens for these diseases using natural products, like curcumin, which can augment expression or function of heat shock proteins in the cell.

  17. Two-stage multishape segmentation of brain structures using image intensity, tissue type, and location information.

    Science.gov (United States)

    Akhondi-Asl, Alireza; Soltanian-Zadeh, Hamid

    2010-08-01

    The authors propose a fast, robust, nonparametric, entropy-based, coupled, multishape approach to segment subcortical brain structures from magnetic resonance images (MRIs). The proposed method uses three types of information: Image intensity, tissue types, and locations of structures. The image intensity information is captured by estimating the probability density function (pdf) of the image intensities in each structure. The tissue type information is captured by applying an unsupervised tissue segmentation method to the image and estimating a probability mass function (pmf) for the tissue type of each structure. The location information is captured by estimating pdf of the location of each structure from the training datasets. The resulting pmf's and pdf's are used to define an entropy function whose minimum corresponds to a desirable segmentation of the structures. The authors propose a three-step optimization strategy for the segmentation method. In the first step, a powerful automatic initialization method is developed based on tissue type and location information of the structures. In the second step, a quasi-Newton method is used to optimize the parameters of the energy function. To speed up the iterations, derivatives of the energy function with respect to its parameters are analytically derived and used in the optimization process. In the last step, the limitations related to the prior shape model are removed and a level-set method is applied for the fine tuning of the segmentation results. The proposed method is applied to two different datasets and the results are compared to those of previous methods in literature. Experimental results are presented for lateral ventricles, caudate, thalamus, putamen, pallidum, hippocampus, and amygdala. The results illustrate superior performance of the proposed segmentation method compared to other methods in literature. The execution time of the algorithm is a few minutes, suitable for a variety of applications.

  18. Fixation-dependent vimentin immunoreactivity of mono- and polyclonal antibodies in brain tissue of cattle, rabbits, rats and mice.

    Science.gov (United States)

    Urban, K; Hewicker-Trautwein, M

    1994-12-01

    The immunohistochemical staining of vimentin in paraffin-embedded sections from adult cattle, rabbit, rat and mouse brain fixed in different fixatives (formaldehyde, methacarn, ethanol) was examined using two monoclonal antibodies and a polyclonal antiserum. In non-trypsinized formaldehyde-fixed tissue sections both monoclonal antibodies and the polyclonal antibodies failed to stain vimentin. Following trypsinization of formaldehyde-fixed sections of the four species the meninges, endothelial cells of blood vessels, ependymal cells and the stroma of the choroid plexus were labelled by the monoclonal and polyclonal antibodies used. Astrocytes and Bergmann glial fibers in pretrypsinized formaldehyde-fixed sections from cattle, rabbit and rat brain, however, showed only weak staining. Fixation of cattle and rat brain in methacarn markedly improved the vimentin immunoreactivity of astrocytes and Bergmann glial fibers. The best fixative for the preservation of immunoreactive determinants of vimentin in astrocytes and Bergmann glial fibers in cattle, rabbit and rat brain was ethanol. In brain tissue from mice both monoclonal antibodies labelled only mesoderm-derived tissue components, but did not recognize vimentin in astrocytes and Bergmann glial fibers. Pre-heating formaldehyde-fixed sections from cattle, rabbit and rat brain in a microwave oven prior to the immunohistochemical reaction resulted in an enormous enhancement of vimentin staining of mesoderm-derived tissues, of astrocytes and bergmann cell fibers.

  19. Correlative analysis of head kinematics and brain's tissue response: a computational approach toward understanding the mechanisms of blast TBI

    Science.gov (United States)

    Sarvghad-Moghaddam, H.; Rezaei, A.; Ziejewski, M.; Karami, G.

    2017-11-01

    Upon impingement of blast waves on the head, stress waves generated at the interface of the skull are transferred into the cranium and the brain tissue and may cause mild to severe blast traumatic brain injury. The intensity of the shock front, defined by the blast overpressure (BoP), that is, the blast-induced peak static overpressure, significantly affects head kinematics as well as the tissue responses of the brain. While evaluation of global linear and rotational accelerations may be feasible, an experimental determination of dynamic responses of the brain in terms of intracranial pressure (ICP), maximum shear stress (MSS), and maximum principal strain (MPS) is almost impossible. The main objective of this study is to investigate possible correlations between head accelerations and the brain's ICP, MSS, and MPS. To this end, three different blasts were simulated by modeling the detonation of 70, 200, and 500 g of TNT at a fixed distance from the head, corresponding to peak BoPs of 0.52, 1.2, and 2 MPa, respectively. A nonlinear multi-material finite element algorithm was implemented in the LS-DYNA explicit solver. Fluid-solid interaction between the blast waves and head was modeled using a penalty-based method. Strong correlations were found between the brain's dynamic responses and both global linear and rotational accelerations at different blast intensities (R^{2 }≥98%), implying that global kinematic parameters of the head might be strong predictors of brain tissue biomechanical parameters.

  20. Correlative analysis of head kinematics and brain's tissue response: a computational approach toward understanding the mechanisms of blast TBI

    Science.gov (United States)

    Sarvghad-Moghaddam, H.; Rezaei, A.; Ziejewski, M.; Karami, G.

    2017-09-01

    Upon impingement of blast waves on the head, stress waves generated at the interface of the skull are transferred into the cranium and the brain tissue and may cause mild to severe blast traumatic brain injury. The intensity of the shock front, defined by the blast overpressure (BoP), that is, the blast-induced peak static overpressure, significantly affects head kinematics as well as the tissue responses of the brain. While evaluation of global linear and rotational accelerations may be feasible, an experimental determination of dynamic responses of the brain in terms of intracranial pressure (ICP), maximum shear stress (MSS), and maximum principal strain (MPS) is almost impossible. The main objective of this study is to investigate possible correlations between head accelerations and the brain's ICP, MSS, and MPS. To this end, three different blasts were simulated by modeling the detonation of 70, 200, and 500 g of TNT at a fixed distance from the head, corresponding to peak BoPs of 0.52, 1.2, and 2 MPa, respectively. A nonlinear multi-material finite element algorithm was implemented in the LS-DYNA explicit solver. Fluid-solid interaction between the blast waves and head was modeled using a penalty-based method. Strong correlations were found between the brain's dynamic responses and both global linear and rotational accelerations at different blast intensities (R^{2 }≥ 98%), implying that global kinematic parameters of the head might be strong predictors of brain tissue biomechanical parameters.

  1. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  2. Some growth factors in neoplastic tissues of brain tumors of different histological structure

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

  3. Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

    Science.gov (United States)

    Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

    2017-07-01

    Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic

  4. Accumulation of natural killer cells in ischemic brain tissues and the chemotactic effect of IP-10.

    Science.gov (United States)

    Zhang, Yao; Gao, Zhongming; Wang, Dandan; Zhang, Tongshuai; Sun, Bo; Mu, Lili; Wang, Jinghua; Liu, Yumei; Kong, Qingfei; Liu, Xijun; Zhang, Yue; Zhang, Haoqiang; He, Jiqing; Li, Hulun; Wang, Guangyou

    2014-04-17

    Stroke is accompanied by a distinguished inflammatory reaction that is initiated by the infiltration of immunocytes, expression of cytokines, and other inflammatory mediators. As natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the innate immune system, we investigated the mechanism of NK cells-induced brain injuries after cerebral ischemia and the chemotactic effect of IP-10 simultaneously. NK cells infiltration, interferon-gamma (IFN-γ) and IP-10 expression were detected by immunohistochemistry, immunofluorescence, PCR and flow cytometry in human and C57/BL6 wild type mouse ischemic brain tissues. The ischemia area was detected via 2,3,5-triphenyltetrazolium chloride staining. CXCR3 mean fluorescence intensity of isolated NK cells was measured by flow cytometry. The neuronal injury made by NK cells was examined via apoptosis experiment. The chemotactic of IP-10 was detected by migration and permeability assays. In human ischemic brain tissue, infiltrations of NK cells were observed and reached a peak at 2 to 5 days. In a permanent middle cerebral artery occlusion (pMCAO) model, infiltration of NK cells into the ischemic infarct region reached their highest levels 12 hours after ischemia. IFN-γ-positive NK cells and levels of the chemokine IP-10 were also detected within the ischemic region, from 6 hours up to 4 days after pMCAO was performed, and IFN-γ levels decreased after NK cells depletion in vivo. Co-culture experiments of neural cells with NK cells also showed that neural necrosis was induced via IFN-γ. In parallel experiments with IP-10, the presence of CXCR3 indicates that NK cells were affected by IP-10 via CXCR3, and the effect was dose-dependent. After IP-10 depletion in vivo, NK cells decreased. In migration assays and permeability experiments, disintegration of the blood-brain barrier (BBB) was observed following the addition of NK cells. Moreover, in the presence of IP-10 this injury was aggravated. All findings

  5. Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.

    Science.gov (United States)

    Zawaski, Janice A; Sabek, Omaima M; Voicu, Horatiu; Eastwood Leung, Hon-Chiu; Gaber, M Waleed

    2017-11-15

    Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. (1)H magnetic resonance spectroscopy ((1)H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. Eighty-four genes had a false discovery rate tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. (1)H-MRS showed significant reduction in taurine levels (Ptumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. Our data indicate that tumor presence during radiation significantly affects long-term functional transcriptomics landscape and neurotransmitter levels at the tumor implantation site

  6. Drosophila as an In Vivo Model for Human Neurodegenerative Disease

    Science.gov (United States)

    McGurk, Leeanne; Berson, Amit; Bonini, Nancy M.

    2015-01-01

    With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research. PMID:26447127

  7. Myeloid dendritic cells are potential players in human neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Paola eBossù

    2015-12-01

    Full Text Available Alzheimer’s (AD and Parkinson’s (PD diseases are devastating neurodegenerative disturbances wherein neuroinflammation is a chronic pathogenic process with high therapeutic potential. Major mediators of AD/PD neuroimmune processes are resident immune cells, but immune cells derived from periphery may also participate and to some extent modify neuroinflammation. Specifically, blood borne myeloid cells emerge as crucial components of AD/PD progression and susceptibility. Among these, dendritic cells (DCs are key immune orchestrators and players of brain immune surveillance: we candidate them as potential mediators of both AD and PD and as relevant cell model for unraveling myeloid cell role in neurodegeneration. Hence, we recapitulate and discuss emerging data suggesting that blood-derived DCs play a role in experimental and human neurodegenerative diseases. In humans, in particular, DCs are modified by in vitro culture with neurodegeneration-associated pathogenic factors and dysregulated in AD patients, while the levels of DC precursors are decreased in AD and PD patients’ blood, possibly as an index of their recruitment to the brain. Overall, we emphasize the need to explore the impact of DCs on neurodegeneration to uncover peripheral immune mechanisms of pathogenic importance, recognize potential biomarkers and improve therapeutic approaches for neurodegenerative diseases.

  8. X-ray micro-tomography for investigations of brain tissues on cellular level

    Science.gov (United States)

    Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Thalmann, Peter; Zanette, Irene; Zdora, Marie-Christine; Bikis, Christos; Hipp, Alexander; Hieber, Simone E.; Schweighauser, Gabriel; Hench, Jürgen; Müller, Bert

    2016-10-01

    X-ray imaging in absorption contrast mode is well established for hard tissue visualization. However, performance for lower density materials is limited due to a reduced contrast. Our aim is three-dimensional (3D) characterization of micro-morphology of human brain tissues down to (sub-)cellular resolution within a laboratory environment. Using the laboratory-based microtomography (μCT) system nanotom m (GE Sensing and Inspection Technologies GmbH, Wunstorf, Germany) and synchrotron radiation at the Diamond-Manchester Imaging Branchline I13-2 (Diamond Light Source, Didcot, UK), we have acquired 3D data with a resolution down to 0.45 μm for visualization of a human cerebellum specimen down to cellular level. We have shown that all selected modalities, namely laboratory-based absorption contrast micro-tomography (LBμCT), synchrotron radiation based in-line single distance phase contrast tomography (SDPR) and synchrotron radiation based single-grating interferometry (GI), can reach cellular resolution for tissue samples with a size in the mm-range. The results are discussed qualitatively in comparison to optical microscopy of haematoxylin and eosin (HE) stained sections. As phase contrast yields to a better data quality for soft tissues and in order to overcome restrictions of limited beamline access for phase contrast measurements, we have equipped the μCT system nanotom m with a double-grating phase contrast set-up. Preliminary experimental results of a knee sample consisting of a bony part and a cartilage demonstrate that phase contrast data exhibits better quality compared to absorption contrast. Currently, the set-up is under adjustment. It is expected that cellular resolution would also be achieved. The questions arise (1) what would be the quality gain of laboratory-based phase contrast in comparison to laboratory-based absorption contrast tomography and (2) could laboratory-based phase contrast data provide comparable results to synchrotron radiation based

  9. A comparison of mitochondrial DNA isolation methods in frozen post-mortem human brain tissue--applications for studies of mitochondrial genetics in brain disorders.

    Science.gov (United States)

    Devall, Matthew; Burrage, Joe; Caswell, Richard; Johnson, Matthew; Troakes, Claire; Al-Sarraj, Safa; Jeffries, Aaron R; Mill, Jonathan; Lunnon, Katie

    2015-10-01

    Given that many brain disorders are characterized by mitochondrial dysfunction, there is a growing interest in investigating genetic and epigenetic variation in mitochondrial DNA (mtDNA). One major caveat for such studies is the presence of nuclear-mitochondrial pseudogenes (NUMTs), which are regions of the mitochondrial genome that have been inserted into the nuclear genome over evolution and, if not accounted for, can confound genetic studies of mtDNA. Here we provide the first systematic comparison of methods for isolating mtDNA from frozen post-mortem human brain tissue. Our data show that a commercial method from Miltenyi Biotec, which magnetically isolates mitochondria using antibodies raised against the mitochondrial import receptor subunit TOM22, gives significant mtDNA enrichment and should be considered the method of choice for mtDNA studies in frozen brain tissue.

  10. Development and Validation of a Method for Alcohol Analysis in Brain Tissue by Headspace Gas Chromatography with Flame Ionization Detector.

    Science.gov (United States)

    Chun, Hao-Jung; Poklis, Justin L; Poklis, Alphonse; Wolf, Carl E

    2016-10-01

    Ethanol is the most widely used and abused drug. While blood is the preferred specimen for analysis, tissue specimens such as brain serve as alternative specimens for alcohol analysis in post-mortem cases where blood is unavailable or contaminated. A method was developed using headspace gas chromatography with flame ionization detection (HS-GC-FID) for the detection and quantification of ethanol, acetone, isopropanol, methanol and n-propanol in brain tissue specimens. Unfixed volatile-free brain tissue specimens were obtained from the Department of Pathology at Virginia Commonwealth University. Calibrators and controls were prepared from 4-fold diluted homogenates of these brain tissue specimens, and were analyzed using t-butanol as the internal standard. The chromatographic separation was performed with a Restek BAC2 column. A linear calibration was generated for all analytes (mean r(2) > 0.9992) with the limits of detection and quantification of 100-110 mg/kg. Matrix effect from the brain tissue was determined by comparing the slopes of matrix prepared calibration curves with those of aqueous calibration curves; no significant differences were observed for ethanol, acetone, isopropanol, methanol and n-propanol. The bias and the CVs for all volatile controls were ≤10%. The method was also evaluated for carryover, selectivity, interferences, bench-top stability and freeze-thaw stability. The HS-GC-FID method was determined to be reliable and robust for the analysis of ethanol, acetone, isopropanol, methanol and n-propanol concentrations in brain tissue, effectively expanding the specimen options for post-mortem alcohol analysis. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Novel Discrete Compactness-Based Training for Vector Quantization Networks: Enhancing Automatic Brain Tissue Classification

    Directory of Open Access Journals (Sweden)

    Ricardo Pérez-Aguila

    2013-01-01

    Full Text Available An approach for nonsupervised segmentation of Computed Tomography (CT brain slices which is based on the use of Vector Quantization Networks (VQNs is described. Images are segmented via a VQN in such way that tissue is characterized according to its geometrical and topological neighborhood. The main contribution rises from the proposal of a similarity metric which is based on the application of Discrete Compactness (DC which is a factor that provides information about the shape of an object. One of its main strengths lies in the sense of its low sensitivity to variations, due to noise or capture defects, in the shape of an object. We will present, compare, and discuss some examples of segmentation networks trained under Kohonen’s original algorithm and also under our similarity metric. Some experiments are established in order to measure the effectiveness and robustness, under our application of interest, of the proposed networks and similarity metric.

  12. Multiscale vision model highlights spontaneous glial calcium waves recorded by 2-photon imaging in brain tissue.

    Science.gov (United States)

    Brazhe, Alexey; Mathiesen, Claus; Lauritzen, Martin

    2013-03-01

    Intercellular glial calcium waves (GCW) constitute a signaling pathway which can be visualized by fluorescence imaging of cytosolic Ca(2+) changes. Reliable detection of calcium waves in multiphoton imaging data is challenging because of low signal-to-noise ratio. We modified the multiscale vision model (MVM), originally employed to detect faint objects in astronomy data to process stacks of fluorescent images. We demonstrate that the MVM identified and characterized GCWs with much higher sensitivity and detail than pixel thresholding. Origins of GCWs were often associated with prolonged secondary Ca(2+) elevations. The GCWs had variable shapes, and secondary GCWs were observed to bud from the primary, larger GCW. GCWs evaded areas shortly before occupied by a preceding GCW instead circulating around the refractory area. Blood vessels uniquely reshaped GCWs and were associated with secondary GCW events. We conclude that the MVM provides unique possibilities to study spatiotemporally correlated Ca(2+) signaling in brain tissue. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Imaging MALDI MS of Dosed Brain Tissues Utilizing an Alternative Analyte Pre-extraction Approach

    Science.gov (United States)

    Quiason, Cristine M.; Shahidi-Latham, Sheerin K.

    2015-06-01

    Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry has been adopted in the pharmaceutical industry as a useful tool to detect xenobiotic distribution within tissues. A unique sample preparation approach for MALDI imaging has been described here for the extraction and detection of cobimetinib and clozapine, which were previously undetectable in mouse and rat brain using a single matrix application step. Employing a combination of a buffer wash and a cyclohexane pre-extraction step prior to standard matrix application, the xenobiotics were successfully extracted and detected with an 8 to 20-fold gain in sensitivity. This alternative approach for sample preparation could serve as an advantageous option when encountering difficult to detect analytes.

  14. Regional muscle tissue saturation is an indicator of global inadequate circulation during cardiopulmonary bypass: a randomized porcine study using muscle, intestinal and brain tissue metabolomics.

    Science.gov (United States)

    Thomassen, Sisse Anette; Kjærgaard, Benedict; Sørensen, Preben; Andreasen, Jan Jesper; Larsson, Anders; Rasmussen, Bodil Steen

    2017-04-01

    Muscle tissue saturation (StO2) measured with near-infrared spectroscopy has generally been considered a measurement of the tissue microcirculatory condition. However, we hypothesized that StO2 could be more regarded as a fast and reliable measure of global than of regional circulatory adequacy and tested this with muscle, intestinal and brain metabolomics at normal and two levels of low cardiopulmonary bypass blood flow rates in a porcine model. Twelve 80 kg pigs were connected to normothermic cardiopulmonary bypass with a blood flow of 60 mL/kg/min for one hour, reduced randomly to 47.5 mL/kg/min (Group I) or 35 mL/kg/min (Group II) for one hour followed by one hour of 60 mL/kg/min in both groups. Regional StO2 was measured continuously above the musculus gracilis (non-cannulated leg). Metabolomics were obtained by brain tissue oxygen monitoring system (Licox) measurements of the brain and microdialysis perfusate from the muscle, intestinal mucosa and brain. A non-parametric statistical method was used. The systemic parameters showed profound systemic ischaemia during low CPB blood flow. StO2 did not change markedly in Group I, but in Group II, StO2 decreased immediately when blood flow was reduced and, furthermore, was not restored despite blood flow being normalized. Changes in the metabolomics from the muscle, colon and brain followed the changes in StO2. We found, in this experimental cardiopulmonary bypass model, that StO2 reacted rapidly when the systemic circulation became inadequate and, furthermore, reliably indicate insufficient global tissue perfusion even when the systemic circulation was restored after a period of systemic hypoperfusion.

  15. Astrocytes in neurodegenerative diseases (I): function and molecular description.

    Science.gov (United States)

    Guillamón-Vivancos, T; Gómez-Pinedo, U; Matías-Guiu, J

    2015-03-01

    Astrocytes have been considered mere supporting cells in the CNS. However, we now know that astrocytes are actively involved in many of the functions of the CNS and may play an important role in neurodegenerative diseases. This article reviews the roles astrocytes play in CNS development and plasticity; control of synaptic transmission; regulation of blood flow, energy, and metabolism; formation of the blood-brain barrier; regulation of the circadian rhythms, lipid metabolism and secretion of lipoproteins; and in neurogenesis. Astrocyte markers and the functions of astrogliosis are also described. Astrocytes play an active role in the CNS. A good knowledge of astrocytes is essential to understanding the mechanisms of neurodegenerative diseases. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  16. Searching for MIND: MicroRNAs in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Christian Barbato

    2009-01-01

    Full Text Available In few years our understanding of microRNA (miRNA biogenesis, molecular mechanisms by which miRNAs regulate gene expression, and the functional roles of miRNAs has been expanded. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system, suggesting that their posttrascriptional regulation may be particularly relevant in neural development and function. MiRNA studies in neurobiology showed their involvement in synaptic plasticity and brain diseases. In this review ,correlations between miRNA-mediated gene silencing and Alzheimer's, Parkinson's, and other neurodegenerative diseases will be discussed. Molecular and cellular neurobiological studies of the miRNAs in neurodegeneration represent the exploration of a new Frontier of miRNAs biology and the potential development of new diagnostic tests and genetic therapies for neurodegenerative diseases.

  17. High dose Erythropoietin increases Brain Tissue Oxygen Tension in Severe Vasospasm after Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Helbok Raimund

    2012-06-01

    Full Text Available Abstract Background Vasospasm-related delayed cerebral ischemia (DCI significantly impacts on outcome after aneurysmal subarachnoid hemorrhage (SAH. Erythropoietin (EPO may reduce the severity of cerebral vasospasm and improve outcome, however, underlying mechanisms are incompletely understood. In this study, the authors aimed to investigate the effect of EPO on cerebral metabolism and brain tissue oxygen tension (PbtO2. Methods Seven consecutive poor grade SAH patients with multimodal neuromonitoring (MM received systemic EPO therapy (30.000 IU per day for 3 consecutive days for severe cerebral vasospasm. Cerebral perfusion pressure (CPP, mean arterial blood pressure (MAP, intracranial pressure (ICP, PbtO2 and brain metabolic changes were analyzed during the next 24 hours after each dose given. Statistical analysis was performed with a mixed effects model. Results A total of 22 interventions were analyzed. Median age was 47 years (32–68 and 86 % were female. Three patients (38 % developed DCI. MAP decreased 2 hours after intervention (P btO2 significantly increased over time (P  Conclusions EPO increases PbtO2 in poor grade SAH patients with severe cerebral vasospasm. The effect on outcome needs further investigation.

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

    DEFF Research Database (Denmark)

    Aradi, Mihaly; Koszegi, Edit; Orsi, Gergely

    2013-01-01

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

  19. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis.

    Science.gov (United States)

    Sato, Ryo; Nakano, Teppei; Hosonaga, Mari; Sampetrean, Oltea; Harigai, Ritsuko; Sasaki, Takashi; Koya, Ikuko; Okano, Hideyuki; Kudoh, Jun; Saya, Hideyuki; Arima, Yoshimi

    2017-01-01

    Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non-small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  20. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Ryo Sato

    2017-01-01

    Full Text Available Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  1. A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells.

    Science.gov (United States)

    Volovitz, Ilan; Shapira, Netanel; Ezer, Haim; Gafni, Aviv; Lustgarten, Merav; Alter, Tal; Ben-Horin, Idan; Barzilai, Ori; Shahar, Tal; Kanner, Andrew; Fried, Itzhak; Veshchev, Igor; Grossman, Rachel; Ram, Zvi

    2016-06-01

    Conducting research on the molecular biology, immunology, and physiology of brain tumors (BTs) and primary brain tissues requires the use of viably dissociated single cells. Inadequate methods for tissue dissociation generate considerable loss in the quantity of single cells produced and in the produced cells' viability. Improper dissociation may also demote the quality of data attained in functional and molecular assays due to the presence of large quantities cellular debris containing immune-activatory danger associated molecular patterns, and due to the increased quantities of degraded proteins and RNA. Over 40 resected BTs and non-tumorous brain tissue samples were dissociated into single cells by mechanical dissociation or by mechanical and enzymatic dissociation. The quality of dissociation was compared for all frequently used dissociation enzymes (collagenase, DNase, hyaluronidase, papain, dispase) and for neutral protease (NP) from Clostridium histolyticum. Single-cell-dissociated cell mixtures were evaluated for cellular viability and for the cell-mixture dissociation quality. Dissociation quality was graded by the quantity of subcellular debris, non-dissociated cell clumps, and DNA released from dead cells. Of all enzymes or enzyme combinations examined, NP (an enzyme previously not evaluated on brain tissues) produced dissociated cell mixtures with the highest mean cellular viability: 93 % in gliomas, 85 % in brain metastases, and 89 % in non-tumorous brain tissue. NP also produced cell mixtures with significantly less cellular debris than other enzymes tested. Dissociation using NP was non-aggressive over time-no changes in cell viability or dissociation quality were found when comparing 2-h dissociation at 37 °C to overnight dissociation at ambient temperature. The use of NP allows for the most effective dissociation of viable single cells from human BTs or brain tissue. Its non-aggressive dissociative capacity may enable ambient

  2. Escitalopram regulates expression of TRH and TRH-like peptides in rat brain and peripheral tissues.

    Science.gov (United States)

    Sattin, Albert; Pekary, Albert E; Blood, James

    2008-01-01

    Escitalopram (eCIT) is a highly selective serotonin reuptake inhibitor (SSRI) that can be an effective treatment for a number of neuropsychiatric disorders including major depression. We, and others, have previously reported that thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) and TRH-like peptides with the general structure pGlu-X-Pro-NH(2), where 'X' can be any amino acid residue, have neuroprotective, antidepressant, analeptic, arousal, and anti-epileptic effects that could mediate the neuropsychiatric and therapeutic effects of a variety of neurotropic agents. The present work explores the possible mediation of the therapeutic effects of eCIT by TRH and TRH-like peptides. In order to extend our understanding of the range of neurotransmitter systems that are modulated by and, in turn, influence the expression of TRH and TRH-like peptides, 16 male Sprague-Dawley rats were injected i.p. with eCIT (24 mg/kg BW) and the brain levels of TRH and TRH-like peptides in various brain regions involved in mood regulation and peripheral tissues with serotonergic innervation were measured 0, 2, 4, and 6 h later by combined HPLC and RIA. Remarkable 3- to 25-fold increases in TRH and TRH-like peptide levels were observed 2 h after i.p. eCIT in the epididymis. This reproductive tissue has the highest level of serotonin found in most mammals. The acute (2 h) effect of eCIT in brain regions involved in mood regulation, particularly the nucleus accumbens and medulla oblongata, cerebellum, and striatum was to increase the levels of TRH-like peptides, most consistently Phe-TRH. An important exception was a decrease in the level of TRH in the nucleus accumbens. These responses, in general, were the opposite of those we have previously observed after acute restraint stress in this same rat strain. We conclude that some of the therapeutic effects of inhibition of serotonin reuptake are mediated by altered release of TRH and TRH-like peptides. (c) 2008 S. Karger AG, Basel.

  3. Sources of Technical Variability in Quantitative LC-MS Proteomics: Human Brain Tissue Sample Analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Piehowski, Paul D.; Petyuk, Vladislav A.; Orton, Daniel J.; Xie, Fang; Moore, Ronald J.; Ramirez Restrepo, Manuel; Engel, Anzhelika; Lieberman, Andrew P.; Albin, Roger L.; Camp, David G.; Smith, Richard D.; Myers, Amanda J.

    2013-05-03

    To design a robust quantitative proteomics study, an understanding of both the inherent heterogeneity of the biological samples being studied as well as the technical variability of the proteomics methods and platform is needed. Additionally, accurately identifying the technical steps associated with the largest variability would provide valuable information for the improvement and design of future processing pipelines. We present an experimental strategy that allows for a detailed examination of the variability of the quantitative LC-MS proteomics measurements. By replicating analyses at different stages of processing, various technical components can be estimated and their individual contribution to technical variability can be dissected. This design can be easily adapted to other quantitative proteomics pipelines. Herein, we applied this methodology to our label-free workflow for the processing of human brain tissue. For this application, the pipeline was divided into four critical components: Tissue dissection and homogenization (extraction), protein denaturation followed by trypsin digestion and SPE clean-up (digestion), short-term run-to-run instrumental response fluctuation (instrumental variance), and long-term drift of the quantitative response of the LC-MS/MS platform over the 2 week period of continuous analysis (instrumental stability). From this analysis, we found the following contributions to variability: extraction (72%) >> instrumental variance (16%) > instrumental stability (8.4%) > digestion (3.1%). Furthermore, the stability of the platform and its’ suitability for discovery proteomics studies is demonstrated.

  4. A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation.

    Science.gov (United States)

    Fujiu, Katsuhito; Shibata, Munehiko; Nakayama, Yukiteru; Ogata, Fusa; Matsumoto, Sahohime; Noshita, Koji; Iwami, Shingo; Nakae, Susumu; Komuro, Issei; Nagai, Ryozo; Manabe, Ichiro

    2017-05-01

    Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. In addition to abnormalities intrinsic to the heart, dysfunction of other organs and dysregulation of systemic factors greatly affect the development and consequences of heart failure. Here we show that the heart and kidneys function cooperatively in generating an adaptive response to cardiac pressure overload. In mice subjected to pressure overload in the heart, sympathetic nerve activation led to activation of renal collecting-duct (CD) epithelial cells. Cell-cell interactions among activated CD cells, tissue macrophages and endothelial cells within the kidney led to secretion of the cytokine CSF2, which in turn stimulated cardiac-resident Ly6Clo macrophages, which are essential for the myocardial adaptive response to pressure overload. The renal response to cardiac pressure overload was disrupted by renal sympathetic denervation, adrenergic β2-receptor blockade or CD-cell-specific deficiency of the transcription factor KLF5. Moreover, we identified amphiregulin as an essential cardioprotective mediator produced by cardiac Ly6Clo macrophages. Our results demonstrate a dynamic interplay between the heart, brain and kidneys that is necessary for adaptation to cardiac stress, and they highlight the homeostatic functions of tissue macrophages and the sympathetic nervous system.

  5. Multiscale biomechanics of brain tumours favours cancer invasion by cell softening and tissue stiffening

    Science.gov (United States)

    Kas, Josef; Fritsch, Anatol; Grosser, Steffen; Friebe, Sabrina; Reiss-Zimmermann, Martin; Müller, Wolf; Hoffmann, Karl-Titus; Sack, Ingolf

    Cancer progression needs two contradictory mechanical prerequisites. For metastasis individual cancer cells or small clusters have to flow through the microenvironment by overcoming the yield stress exerted by the surrounding. On the other hand a tumour has to behave as a solid to permit cell proliferation and spreading of the tumour mass against its surrounding. We determine that the high mechanical adaptability of cancer cells and the scale controlled viscoelastic properties of tissues reconcile both conflicting properties, fluid and solid, simultaneously in brain tumours. We resolve why different techniques that assess cell and tissue mechanics have produced apparently conflicting results by our finding that tumours generate different viscoelastic behaviours on different length scales, which are in concert optimal for tumour spreading and metastasis. Single cancer cells become very soft in their elastic behavior which promotes cell unjamming. On the level of direct cell-to-cell interactions cells feel their micro-environment as rigid elastic substrate that stimulates cancer on the molecular level. All over a tumour has predominately a stiff elastic character in terms of viscoelastic behaviour caused by a solid backbone. Simultaneously, the tumour mass is characterized by a large local variability in the storage and loss modulus that is caused by areas of a more fluid nature.

  6. Liquid crystal elastomer foams with elastic properties specifically engineered as biodegradable brain tissue scaffolds.

    Science.gov (United States)

    Prévôt, M E; Andro, H; Alexander, S L M; Ustunel, S; Zhu, C; Nikolov, Z; Rafferty, S T; Brannum, M T; Kinsel, B; Korley, L T J; Freeman, E J; McDonough, J A; Clements, R J; Hegmann, E

    2017-12-13

    Tissue regeneration requires 3-dimensional (3D) smart materials as scaffolds to promote transport of nutrients. To mimic mechanical properties of extracellular matrices, biocompatible polymers have been widely studied and a diverse range of 3D scaffolds have been produced. We propose the use of responsive polymeric materials to create dynamic substrates for cell culture, which goes beyond designing only a physical static 3D scaffold. Here, we demonstrated that lactone- and lactide-based star block-copolymers (SBCs), where a liquid crystal (LC) moiety has been attached as a side-group, can be crosslinked to obtain Liquid Crystal Elastomers (LCEs) with a porous architecture using a salt-leaching method to promote cell infiltration. The obtained SmA LCE-based fully interconnected-porous foams exhibit a Young modulus of 0.23 ± 0.07 MPa and a biodegradability rate of around 20% after 15 weeks both of which are optimized to mimic native environments. We present cell culture results showing growth and proliferation of neurons on the scaffold after four weeks. This research provides a new platform to analyse LCE scaffold-cell interactions where the presence of liquid crystal moieties promotes cell alignment paving the way for a stimulated brain-like tissue.

  7. Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles

    Science.gov (United States)

    Muller, Ludovic; Baldwin, Kathrine; Barbacci, Damon C.; Jackson, Shelley N.; Roux, Aurélie; Balaban, Carey D.; Brinson, Bruce E.; McCully, Michael I.; Lewis, Ernest K.; Schultz, J. Albert; Woods, Amina S.

    2017-08-01

    Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within <10% tolerance by selecting argentated instead of alkali cationized ions. The imaging of brain tissues spotted with pure standards was used to demonstrate that Ag cationized ceramide and diacylglycerol ions are from intact, endogenous species. In contrast, almost all Ag cationized fatty acid ions are a result of fragmentations of numerous lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue.

  8. Tissue Probability-Based Attenuation Correction for Brain PET/MR by Using SPM8

    Science.gov (United States)

    Teuho, J.; Linden, J.; Johansson, J.; Tuisku, J.; Tuokkola, T.; Teräs, M.

    2016-10-01

    Bone attenuation remains a methodological challenge in hybrid PET/MR, as bone is hard to visualize via magnetic resonance imaging (MRI). Therefore, novel methods for taking into account bone attenuation in MR-based attenuation correction (MRAC) are needed. In this study, we propose a tissue-probability based attenuation correction (TPB-AC), which employs the commonly available neurological toolbox SPM8, to derive a subject-specific μ-map by segmentation of T1-weighted MR images. The procedures to derive a μ-map representing soft tissue, air and bone from the New Segment function in SPM8 and MATLAB are described. Visual and quantitative comparisons against CT-based attenuation correction (CTAC) data were performed using two μ-values ( 0.135 cm-1 and 0.145 cm-1) for bone. Results show improvement of visual quality and quantitative accuracy of positron emission tomography (PET) images when TPB-AC μ-map is used in PET/MR image reconstruction. Underestimation in PET images was decreased by an average of 5 ±2 percent in the whole brain across all patients. In addition, the method performed well when compared to CTAC, with maximum differences (mean ± standard deviation) of - 3 ±2 percent and 2 ±4 percent in two regions out of 28. Finally, the method is simple and computationally efficient, offering a promising platform for further development. Therefore, a subject-specific MR-based μ-map can be derived only from the tissue probability maps from the New Segment function of SPM8.

  9. Sound Naming in Neurodegenerative Disease

    Science.gov (United States)

    Chow, Maggie L.; Brambati, Simona M.; Gorno-Tempini, Maria Luisa; Miller, Bruce L.; Johnson, Julene K.

    2010-01-01

    Modern cognitive neuroscientific theories and empirical evidence suggest that brain structures involved in movement may be related to action-related semantic knowledge. To test this hypothesis, we examined the naming of environmental sounds in patients with corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), two…

  10. Evaluating the effects of white matter multiple sclerosis lesions on the volume estimation of 6 brain tissue segmentation methods.

    Science.gov (United States)

    Valverde, S; Oliver, A; Díez, Y; Cabezas, M; Vilanova, J C; Ramió-Torrentà, L; Rovira, À; Lladó, X

    2015-06-01

    The accuracy of automatic tissue segmentation methods can be affected by the presence of hypointense white matter lesions during the tissue segmentation process. Our aim was to evaluate the impact of MS white matter lesions on the brain tissue measurements of 6 well-known segmentation techniques. These include straightforward techniques such as Artificial Neural Network and fuzzy C-means as well as more advanced techniques such as the Fuzzy And Noise Tolerant Adaptive Segmentation Method, fMRI of the Brain Automated Segmentation Tool, SPM5, and SPM8. Thirty T1-weighted images from patients with MS from 3 different scanners were segmented twice, first including white matter lesions and then masking the lesions before segmentation and relabeling as WM afterward. The differences in total tissue volume and tissue volume outside the lesion regions were computed between the images by using the 2 methodologies. Total gray matter volume was overestimated by all methods when lesion volume increased. The tissue volume outside the lesion regions was also affected by white matter lesions with differences up to 20 cm(3) on images with a high lesion load (≈50 cm(3)). SPM8 and Fuzzy And Noise Tolerant Adaptive Segmentation Method were the methods less influenced by white matter lesions, whereas the effect of white matter lesions was more prominent on fuzzy C-means and the fMRI of the Brain Automated Segmentation Tool. Although lesions were removed after segmentation to avoid their impact on tissue segmentation, the methods still overestimated GM tissue in most cases. This finding is especially relevant because on images with high lesion load, this bias will most likely distort actual tissue atrophy measurements. © 2015 by American Journal of Neuroradiology.

  11. The post-synaptic density of human postmortem brain tissues: an experimental study paradigm for neuropsychiatric illnesses.

    Directory of Open Access Journals (Sweden)

    Chang-Gyu Hahn

    Full Text Available Recent molecular genetics studies have suggested various trans-synaptic processes for pathophysiologic mechanisms of neuropsychiatric illnesses. Examination of pre- and post-synaptic scaffolds in the brains of patients would greatly aid further investigation, yet such an approach in human postmortem tissue has yet to be tested. We have examined three methods using density gradient based purification of synaptosomes followed by detergent extraction (Method 1 and the pH based differential extraction of synaptic membranes (Methods 2 and 3. All three methods separated fractions from human postmortem brains that were highly enriched in typical PSD proteins, almost to the exclusion of pre-synaptic proteins. We examined these fractions using electron microscopy (EM and verified the integrity of the synaptic membrane and PSD fractions derived from human postmortem brain tissues. We analyzed protein composition of the PSD fractions using two dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS and observed known PSD proteins by mass spectrometry. Immunoprecipitation and immunoblot studies revealed that expected protein-protein interactions and certain posttranscriptional modulations were maintained in PSD fractions. Our results demonstrate that PSD fractions can be isolated from human postmortem brain tissues with a reasonable degree of integrity. This approach may foster novel postmortem brain research paradigms in which the stoichiometry and protein composition of specific microdomains are examined.

  12. Weak mitochondrial targeting sequence determines tissue-specific subcellular localization of glutamine synthetase in liver and brain cells.

    NARCIS (Netherlands)

    Matthews, G.D.; Gur, N.; Koopman, W.J.H.; Pines, O.; Vardimon, L.

    2010-01-01

    Evolution of the uricotelic system for ammonia detoxification required a mechanism for tissue-specific subcellular localization of glutamine synthetase (GS). In uricotelic vertebrates, GS is mitochondrial in liver cells and cytoplasmic in brain. Because these species contain a single copy of the GS

  13. In-vivo measurements of human brain tissue conductivity using focal electrical current injection through intracerebral multicontact electrodes.

    Science.gov (United States)

    Koessler, Laurent; Colnat-Coulbois, Sophie; Cecchin, Thierry; Hofmanis, Janis; Dmochowski, Jacek P; Norcia, Anthony M; Maillard, Louis G

    2017-02-01

    In-vivo measurements of human brain tissue conductivity at body temperature were conducted using focal electrical currents injected through intracerebral multicontact electrodes. A total of 1,421 measurements in 15 epileptic patients (age: 28 ± 10) using a radiofrequency generator (50 kHz current injection) were analyzed. Each contact pair was classified as being from healthy (gray matter, n = 696; white matter, n = 530) or pathological (epileptogenic zone, n = 195) tissue using neuroimaging analysis of the local tissue environment and intracerebral EEG recordings. Brain tissue conductivities were obtained using numerical simulations based on conductivity estimates that accounted for the current flow in the local brain volume around the contact pairs (a cube with a side length of 13 mm). Conductivity values were 0.26 S/m for gray matter and 0.17 S/m for white matter. Healthy gray and white matter had statistically different median impedances (P Brain Mapp 38:974-986, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Automated tissue segmentation and blind recovery of (1)H MRS imaging spectral patterns of normal and diseased human brain.

    Science.gov (United States)

    Du, Shuyan; Mao, Xiangling; Sajda, Paul; Shungu, Dikoma C

    2008-01-01

    Constrained non-negative matrix factorization (cNMF) with iterative data selection is described and demonstrated as a data analysis method for fast and automatic recovery of biochemically meaningful and diagnostically specific spectral patterns of the human brain from (1)H MRS imaging ((1)H MRSI) data. To achieve this goal, cNMF decomposes in vivo multidimensional (1)H MRSI data into two non-negative matrices representing (a) the underlying tissue-specific spectral patterns and (b) the spatial distribution of the corresponding metabolite concentrations. Central to the proposed approach is automatic iterative data selection which uses prior knowledge about the spatial distribution of the spectra to remove voxels that are due to artifacts and undesired metabolites/tissues such as the strong lipid and water components. The automatic recovery of diagnostic spectral patterns is demonstrated for long-TE (1)H MRSI data on normal human brain, multiple sclerosis, and serial brain tumor. The results show the ability of cNMF with iterative data selection to automatically and simultaneously recover tissue-specific spectral patterns and achieve segmentation of normal and diseased human brain tissue, concomitant with simplification of information content. These features of cNMF, which permit rapid recovery, reduction and interpretation of the complex diagnostic information content of large multi-dimensional spectroscopic imaging data sets, have the potential to enhance the clinical utility of in vivo(1)H MRSI.

  15. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke

    DEFF Research Database (Denmark)

    Olsen, T S; Larsen, B; Herning, M

    1983-01-01

    In a group of 48 patients with completed stroke, 8 patients had viable collaterally perfused brain tissue which was accessible for rCBF recordings with a two dimensional technique. All 8 had deep subcortical infarcts on CT-scan, and angiographic occlusion of the arteries normally supplying...

  16. Presence of Tissue Transglutaminase in Granular Endoplasmic Reticulum is Characteristic of Melanized Neurons in Parkinson's Disease Brain

    NARCIS (Netherlands)

    Wilhelmus, M.M.; Verhaar, R.; Andringa, G.; Bol, J.G.J.M.; Cras, P.; Shan, L.; Hoozemans, J.J.; Drukarch, B.

    2011-01-01

    Parkinson's disease (PD) is characterized by the accumulation of α-synuclein aggregates and degeneration of melanized neurons. The tissue transglutaminase (tTG) enzyme catalyzes molecular protein cross-linking. In PD brain, tTG-induced cross-links have been identified in α-synuclein monomers,

  17. CX(3)CL1 and CX(3)CR1 expression in human brain tissue : Noninflammatory control versus multiple sclerosis

    NARCIS (Netherlands)

    Van Haastert, ES; Kuipers, HF; Van Den Elsen, PJ; De Groot, CJ; Van Der Valk, P; Ravid, R; Biber, K

    An important role for CX(3)CL1 in neuroinflammation and neurodegeneration has been suggested in recent publications. In this study, we compared the expression of CX(3)CL1 and its receptor CX(3)CR1 in human brain tissue derived from control patients without neurological complications and in multiple

  18. On the consequences of non linear constitutive modelling of brain tissue for injury prediction with numerical head models

    NARCIS (Netherlands)

    Hrapko, M.; Dommelen, J.A.W. van; Peters, G.W.M.; Wismans, J.S.H.M.

    2009-01-01

    The objective of this work was to investigate the influences of constitutive non linearities of brain tissue in numerical head model simulations by comparing the performance of a recently developed non linear constitutive model [10, 11] with a simplified version, based on neo-Hookean elastic

  19. Characterisation of new monoclonal antibodies reacting with prions from both human and animal brain tissues.

    Science.gov (United States)

    Cordes, Henriette; Bergström, Ann-Louise; Ohm, Jakob; Laursen, Henning; Heegaard, Peter M H

    2008-09-15

    Post-mortem diagnosis of transmissible spongiform encephalopathies (prion diseases) is primarily based on the detection of a protease resistant, misfolded disease associated isoform (PrP(Sc)) of the prion protein (PrP(C)) on neuronal cells. These methods depend on antibodies directed against PrP(C) and capable of reacting with PrP(Sc)in situ (immunohistochemistry on nervous tissue sections) or with the unfolded form of the protein (western and paraffin embedded tissue (PET) blotting). Here, high-affinity monoclonal antibodies (mAbs 1.5D7, 1.6F4) were produced against synthetic PrP peptides in wild-type mice and used for western blotting and immunohistochemistry to detect several types of human prion-disease associated PrP(Sc), including sporadic Creutzfeldt-Jakob Disease (CJD) (subtypes MM1 and VV2), familial CJD and Gerstmann-Sträussler-Scheinker (GSS) disease PrP(Sc) as well as PrP(Sc) of bovine spongiform encephalopathy (bovine brain), scrapie (ovine brain) and experimental scrapie in hamster and in mice. The antibodies were also used for PET-blotting in which PrP(Sc) blotted from brain tissue sections onto a nitrocellulose membrane is visualized with antibodies after protease and denaturant treatment allowing the detection of protease resistant PrP forms (PrP(RES)) in situ. Monoclonal antibodies 1.5D7 and 1.6F4 were raised against the reported epitope (PrP153-165) of the commercial antibody 6H4. While 1.5D7 and 1.6F4 were completely inhibitable by PrP153-165, 6H4 was not, indicating that the specificity of 6H4 is not defined completely by PrP153-165. The two antibodies performed similarly to 6H4 in western blotting with human samples, but showed less reactivity and enhanced background staining with animal samples in this method. In immunohistochemistry 1.5D7 and 1.6F4 performed better than 6H4 suggesting that the binding affinity of 1.5D7 and 1.6F4 with native (aggregated) PrP(Sc)in situ was higher than that of 6H4. On the other hand in PET-blotting, 6H4

  20. Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells.

    Science.gov (United States)

    Choi, Seung Ah; Lee, Ji Yeoun; Kwon, Sung Eun; Wang, Kyu-Chang; Phi, Ji Hoon; Choi, Jung Won; Jin, Xiong; Lim, Ja Yun; Kim, Hyunggee; Kim, Seung-Ki

    2015-01-01

    In neuro-oncology, the biology of neural stem cells (NSCs) has been pursued in two ways: as tumor-initiating cells (TICs) and as a potential cell-based vehicle for gene therapy. NSCs as well as mesenchymal stem cells (MSCs) have been reported to possess tumor tropism capacities. However, there is little data on the migratory capacity of MSCs toward brain tumor-initiating cells (BTICs). This study focuses on the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their crosstalk in the microenvironment. BTICs were isolated from three different types of brain tumors. The migration capacities of hAT-MSCs toward BTICs were examined using an in vitro migration assay and in vivo bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cyto-chemokine receptors by RT-qPCR and the protein level of their ligands in co-cultured medium. The candidate cyto-chemokine receptors were selectively inhibited using siRNAs. Both in vitro and in vivo experiments showed that hAT-MSCs possess migratory abilities to target BTICs isolated from medulloblastoma, atypical teratoid/rhabdoid tumors (AT/RT) and glioblastoma. Different types of cyto-chemokines are involved in the crosstalk between hAT-MSCs and BTICs (medulloblastoma and AT/RT: CXCR4/SDF-1, CCR5/RANTES, IL6R/IL-6 and IL8R/IL8; glioblastoma: CXCR4/SDF-1, IL6R/IL-6, IL8R/IL-8 and IGF1R/IGF-1). Our findings demonstrated the migratory ability of hAT-MSCs for BTICs, implying the potential use of MSCs as a delivery vehicle for gene therapy. This study also confirmed the expression of hAT-MSCs cytokine receptors and the BTIC ligands that play roles in their crosstalk.

  1. Resected Brain Tissue, Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control.

    Science.gov (United States)

    Rummel, Christian; Abela, Eugenio; Andrzejak, Ralph G; Hauf, Martinus; Pollo, Claudio; Müller, Markus; Weisstanner, Christian; Wiest, Roland; Schindler, Kaspar

    2015-01-01

    Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure. Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels. In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied. We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent with growing evidence that spatially

  2. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes

    Science.gov (United States)

    Nitzsche, Björn; Frey, Stephen; Collins, Louis D.; Seeger, Johannes; Lobsien, Donald; Dreyer, Antje; Kirsten, Holger; Stoffel, Michael H.; Fonov, Vladimir S.; Boltze, Johannes

    2015-01-01

    Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs, and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM) that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams) were acquired on a 1.5 T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight (BW), age, and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM) and white (WM) matter as well as cerebrospinal fluid (CSF) classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM). Overall, a positive correlation of GM volume and BW explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species. PMID:26089780

  3. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes

    Directory of Open Access Journals (Sweden)

    Björn eNitzsche

    2015-06-01

    Full Text Available Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams were acquired on a 1.5T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight, age and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM and white (WM matter as well as cerebrospinal fluid (CSF classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM. Overall, a positive correlation of GM volume and body weight explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species.

  4. Neural network-based brain tissue segmentation in MR images using extracted features from intraframe coding in H.264

    Science.gov (United States)

    Jafari, Mehdi; Kasaei, Shohreh

    2012-01-01

    Automatic brain tissue segmentation is a crucial task in diagnosis and treatment of medical images. This paper presents a new algorithm to segment different brain tissues, such as white matter (WM), gray matter (GM), cerebral spinal fluid (CSF), background (BKG), and tumor tissues. The proposed technique uses the modified intraframe coding yielded from H.264/(AVC), for feature extraction. Extracted features are then imposed to an artificial back propagation neural network (BPN) classifier to assign each block to its appropriate class. Since the newest coding standard, H.264/AVC, has the highest compression ratio, it decreases the dimension of extracted features and thus yields to a more accurate classifier with low computational complexity. The performance of the BPN classifier is evaluated using the classification accuracy and computational complexity terms. The results show that the proposed technique is more robust and effective with low computational complexity compared to other recent works.

  5. Gestational age dependent changes of the fetal brain, liver and adipose tissue fatty acid compositions in a population with high fish intakes

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Offringa, Pieter J.; Boersma, E. Rudy; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    2012-01-01

    Introduction: There are no data on the intrauterine fatty acid (FA) compositions of brain, liver and adipose tissue of infants born to women with high fish intakes. Subjects and methods: We analyzed the brain (n = 18), liver (n = 14) and adipose tissue (n = 11) FA compositions of 20 stillborn

  6. Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome.

    Science.gov (United States)

    Lin, Peijie; Nicholls, Laura; Assareh, Hassan; Fang, Zhiming; Amos, Timothy G; Edwards, Richard J; Assareh, Amelia A; Voineagu, Irina

    2016-06-06

    MECP2, the gene mutated in the majority of Rett syndrome cases, is a transcriptional regulator that can activate or repress transcription. Although the transcription regulatory function of MECP2 has been known for over a decade, it remains unclear how transcriptional dysregulation leads to the neurodevelopmental disorder. Notably, little convergence was previously observed between the genes abnormally expressed in the brain of Rett syndrome mouse models and those identified in human studies. Here we carried out a comprehensive transcriptome analysis of human brain tissue from Rett syndrome brain using both RNA-seq and microarrays. We identified over two hundred differentially expressed genes, and identified the complement C1Q complex genes (C1QA, C1QB and C1QC) as a point of convergence between gene expression changes in human and mouse Rett syndrome brain. The results of our study support a role for alterations in the expression level of C1Q complex genes in RTT pathogenesis.

  7. Mitochondrial Iron-Sulfur Cluster Dysfunction In Neurodegenerative Disease

    Directory of Open Access Journals (Sweden)

    Grazia eIsaya

    2014-03-01

    Full Text Available Growing evidence supports a role for mitochondrial iron metabolism in the pathophysiology of neurodegenerative disorders such as Friedreich ataxia and Parkinson disease as well as in the motor and cognitive decline associated with the aging process. Iron-sulfur enzyme deficits and regional iron accumulation have been observed in each of these conditions. In spite of significant etiological, clinical and pathological differences that exist between Friedreich ataxia and Parkinson disease, it is possible that defects in mitochondrial iron-sulfur clusters biogenesis represent a common underlying mechanism leading to abnormal intracellular iron distribution with mitochondrial iron accumulation, OXPHOS deficits and oxidative stress in susceptible cells and specific regions of the nervous system. Moreover, a similar mechanism may contribute to the age-dependent iron accumulation that occurs in certain brain regions such as the globus pallidus and the substantia nigra. Targeting chelatable iron and reactive oxygen species appear as possible therapeutic options for Friedreich ataxia and Parkinson disease, and possibly other age-related neurodegenerative conditions. However, new technology to interrogate iron-sulfur cluster synthesis in humans is needed to (i assess how defects in this pathway contribute to the natural history of neurodegenerative disorders and (ii develop treatments to correct those defects early in the disease process, before they cause irreversible neuronal cell damage.

  8. The association between brain natriuretic peptide and tissue Doppler parameters in children with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Taliha Öner

    2016-01-01

    Full Text Available In this study, we investigated the association between brain natriuretic peptide (BNP levels and tissue Doppler imaging measurements and also screening for deadly mutations in patients with hypertrophic cardiomyopathy (HCM. We enrolled 20 patients diagnosed with HCM (age:10.7±5 years (1-17, 85% male, weight:42.25±23.10 kg, height:141.80±32.45 cm and 20 age, gender and body weight-matched control subjects. We performed electrocardiography, transthoracic echocardiography, and tissue Doppler echocardiography in each group, as well as genetic tests (for Arg403Gln, Arg453Cys, Arg719Trp and Arg719Gln mutations in MYH7 Exons 13, 14, 19 and BNP in the patients. The patients were divided into two groups according to the presence (Group 1 or absence (Group 2 of left ventricular (LV outflow tract obstruction. QTc dispersion and the LV ejection fraction and left atrial (LA volume index were increased in Group 1. The LA volume index and the mitral and septal E/Ea ratio and septum Z-score were increased while the mitral lateral annulus and septal annulus Ea wave velocities and the mitral and tricuspid E/A ratio were decreased in patients with high levels of BNP compared to those with normal BNP levels. There were no mutations that are associated with increased risk of sudden death found in patients included in this study. In the light of our data, we conclude that such parameters BNP levels above the 98 pg/mL, septal thickness Z-score ˃6, and higher mitral and septal E/Ea ratios can be used for management of patients with HCM according to life-threatening conditions.

  9. The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment.

    Directory of Open Access Journals (Sweden)

    Benjamin B Gelman

    Full Text Available The National NeuroAIDS Tissue Consortium (NNTC performed a brain gene expression array to elucidate pathophysiologies of Human Immunodeficiency Virus type 1 (HIV-1-associated neurocognitive disorders.Twenty-four human subjects in four groups were examined A Uninfected controls; B HIV-1 infected subjects with no substantial neurocognitive impairment (NCI; C Infected with substantial NCI without HIV encephalitis (HIVE; D Infected with substantial NCI and HIVE. RNA from neocortex, white matter, and neostriatum was processed with the Affymetrix® array platform.With HIVE the HIV-1 RNA load in brain tissue was three log(10 units higher than other groups and over 1,900 gene probes were regulated. Interferon response genes (IFRGs, antigen presentation, complement components and CD163 antigen were strongly upregulated. In frontal neocortex downregulated neuronal pathways strongly dominated in HIVE, including GABA receptors, glutamate signaling, synaptic potentiation, axon guidance, clathrin-mediated endocytosis and 14-3-3 protein. Expression was completely different in neuropsychologically impaired subjects without HIVE. They had low brain HIV-1 loads, weak brain immune responses, lacked neuronally expressed changes in neocortex and exhibited upregulation of endothelial cell type transcripts. HIV-1-infected subjects with normal neuropsychological test results had upregulation of neuronal transcripts involved in synaptic transmission of neostriatal circuits.Two patterns of brain gene expression suggest that more than one pathophysiological process occurs in HIV-1-associated neurocognitive impairment. Expression in HIVE suggests that lowering brain HIV-1 replication might improve NCI, whereas NCI without HIVE may not respond in kind; array results suggest that modulation of transvascular signaling is a potentially promising approach. Striking brain regional differences highlighted the likely importance of circuit level disturbances in HIV/AIDS. In

  10. Brain tissue oxygen tension and its response to physiological manipulations: influence of distance from injury site in a swine model of traumatic brain injury.

    Science.gov (United States)

    Hawryluk, Gregory W J; Phan, Nicolas; Ferguson, Adam R; Morabito, Diane; Derugin, Nikita; Stewart, Campbell L; Knudson, M Margaret; Manley, Geoffrey; Rosenthal, Guy

    2016-11-01

    OBJECTIVE The optimal site for placement of tissue oxygen probes following traumatic brain injury (TBI) remains unresolved. The authors used a previously described swine model of focal TBI and studied brain tissue oxygen tension (PbtO2) at the sites of contusion, proximal and distal to contusion, and in the contralateral hemisphere to determine the effect of probe location on PbtO2 and to assess the effects of physiological interventions on PbtO2 at these different sites. METHODS A controlled cortical impact device was used to generate a focal lesion in the right frontal lobe in 12 anesthetized swine. PbtO2 was measured using Licox brain tissue oxygen probes placed at the site of contusion, in pericontusional tissue (proximal probe), in the right parietal region (distal probe), and in the contralateral hemisphere. PbtO2 was measured during normoxia, hyperoxia, hypoventilation, and hyperventilation. RESULTS Physiological interventions led to expected changes, including a large increase in partial pressure of oxygen in arterial blood with hyperoxia, increased intracranial pressure (ICP) with hypoventilation, and decreased ICP with hyperventilation. Importantly, PbtO2 decreased substantially with proximity to the focal injury (contusion and proximal probes), and this difference was maintained at different levels of fraction of inspired oxygen and partial pressure of carbon dioxide in arterial blood. In the distal and contralateral probes, hypoventilation and hyperventilation were associated with expected increased and decreased PbtO2 values, respectively. However, in the contusion and proximal probes, these effects were diminished, consistent with loss of cerebrovascular CO2 reactivity at and near the injury site. Similarly, hyperoxia led to the expected rise in PbtO2 only in the distal and contralateral probes, with little or no effect in the proximal and contusion probes, respectively. CONCLUSIONS PbtO2 measurements are strongly influenced by the distance from the

  11. Sleep in Neurodevelopmental and Neurodegenerative Disorders.

    Science.gov (United States)

    Kotagal, Suresh

    2015-06-01

    There is a close relationship between sleep and childhood neurodevelopmental/neurodegenerative disorders. Understanding the sleep issues may provide greater insight into pathophysiology and treatment of these disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf.

    Science.gov (United States)

    Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; Nguyen, Thien An; Alfano, Robert R

    2014-06-01

    Two-photon (2P) excitation of the second singlet (S₂) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S₂ state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S₂ state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

  13. Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf

    Science.gov (United States)

    Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; An Nguyen, Thien; Alfano, Robert R.

    2014-06-01

    Two-photon (2P) excitation of the second singlet (S) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S2 state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

  14. Magnetization transfer studies of the fast and slow tissue water diffusion components in the human brain.

    Science.gov (United States)

    Mulkern, Robert V; Vajapeyam, Sridhar; Haker, Steven J; Maier, Stephan E

    2005-05-01

    Magnetization transfer (MT) properties of the fast and slow diffusion components recently observed in the human brain were assessed experimentally. One set of experiments, performed at 1.5 T in healthy volunteers, was designed to determine whether the amplitudes of fast and slow diffusion components, differentiated on the basis of biexponential fits to signal decays over a wide range of b-factors, demonstrated a different or similar magnetization transfer ratio (MTR). Another set of experiments, performed at 3 T in healthy volunteers, was designed to determine whether MTRs differed when measured from high signal-to-noise images acquired with b-factor weightings of 350 vs 3500 s/mm2. The 3 T studies included measurements of MTR as a function of off-resonance frequency for the MT pulse at both low and high b-factors. The primary conclusion drawn from all the studies is that there appears to be no significant difference between the magnetization transfer properties of the fast and slow tissue water diffusion components. The conclusions do not lend support to a direct interpretation of the 'components' of the biexponential diffusion decay in terms of the 'compartments' associated with intra- and extracellular water. Copyright 2004 John Wiley & Sons, Ltd.

  15. Visual Spatial Cognition in Neurodegenerative Disease

    OpenAIRE

    Possin, Katherine L.

    2010-01-01

    Visual spatial impairment is often an early symptom of neurodegenerative disease; however, this multi-faceted domain of cognition is not well-assessed by most typical dementia evaluations. Neurodegenerative diseases cause circumscribed atrophy in distinct neural networks, and accordingly, they impact visual spatial cognition in different and characteristic ways. Anatomically-focused visual spatial assessment can assist the clinician in making an early and accurate diagnosis. This article will...

  16. Multimodal Raman-fluorescence spectroscopy of formalin fixed samples is able to discriminate brain tumors from dysplastic tissue

    Science.gov (United States)

    Anand, Suresh; Cicchi, Riccardo; Giordano, Flavio; Buccoliero, Anna Maria; Pavone, Francesco Saverio

    2014-05-01

    In the recent years, there has been a considerable surge in the application of spectroscopy for disease diagnosis. Raman and fluorescence spectra provide characteristic spectral profile related to biochemical and morphological changes when tissues progress from normal state towards malignancy. Spectroscopic techniques offer the advantage of being minimally invasive compared to traditional histopathology, real time and quantitative. In biomedical optical diagnostics, freshly excised specimens are preferred for making ex-vivo spectroscopic measurements. With regard to fresh tissues, if the lab is located far away from the clinic it could pose a problem as spectral measurements have to be performed immediately after dissection. Tissue samples are usually placed in a fixative agent such as 4% formaldehyde to preserve the samples before processing them for routine histopathological studies. Fixation prevents the tissues from decomposition by arresting autolysis. In the present study, we intend to investigate the possibility of using formalin fixed samples for discrimination of brain tumours from dysplastic tissue using Raman and fluorescence spectroscopy. Formalin fixed samples were washed with phosphate buffered saline for about 5 minutes in order to remove the effects of formalin during spectroscopic measurements. In case of fluorescence spectroscopy, changes in spectral profile have been observed in the region between 550-670 nm between dysplastic and tumor samples. For Raman measurements, we found significant differences in the spectral profiles between dysplasia and tumor. In conclusion, formalin fixed samples can be potentially used for the spectroscopic discrimination of tumor against dysplastic tissue in brain samples.

  17. White matter segmentation by estimating tissue optical attenuation from volumetric OCT massive histology of whole rodent brains

    Science.gov (United States)

    Lefebvre, Joël.; Castonguay, Alexandre; Lesage, Frédéric

    2017-02-01

    A whole rodent brain was imaged using an automated massive histology setup and an Optical Coherence Tomography (OCT) microscope. Thousands of OCT volumetric tiles were acquired, each covering a size of about 2.5x2.5x0.8 mm3 with a sampling resolution of 4.9x4.9x6.5 microns. This paper shows the techniques for reconstruction, attenuation compensation and segmentation of the sliced brains. The tile positions within the mosaic were evaluated using a displacement model of the motorized stage and pairwise coregistration. Volume blending was then performed by solving the 3D Laplace equation, and consecutive slices were assembled using the cross-correlation of their 2D image gradient. This reconstruction algorithm resulted in a 3D map of optical reflectivity for the whole brain at micrometric resolution. OCT tissue slices were then used to estimate the local attenuation coefficient based on a single scattering photon model. The attenuation map obtained exhibits a high contrast for all white matter fibres, regardless of their orientation. The tissue optical attenuation from the intrinsic OCT reflectivity contributes to better white matter tissue segmentation. The combined 3D maps of reflectivity and attenuation is a step toward the study of white matter at a microscopic scale for the whole brain in small animals.

  18. Neurobiology of sleep disturbances in neurodegenerative disorders.

    Science.gov (United States)

    Gagnon, J-F; Petit, D; Latreille, V; Montplaisir, J

    2008-01-01

    This review presents sleep disturbances and their underlying pathophysiology in three categories of neurodegenerative disorders namely tauopathies, synucleinopathies, and Huntington's disease (HD) and prion-related diseases. Sleep abnormalities are a major and early feature of neurodegenerative disorders, especially for synucleinopathies, HD and prion-related diseases, in which the sleep-related brainstem regions are severely altered and impaired sooner than in most of the tauopathies. In synucleinopathies, HD and prion-related diseases, specific sleep disturbances, different from those observed in tauopathies, are considered as core manifestations of the disease and in some cases, as preclinical signs. For this reason, the evaluation of sleep components in these neurodegenerative disorders may be useful to make a diagnosis and to assess the efficacy of pharmacotherapy. Since sleep disruption may occur early in the course of neurodegeneration, sleep disturbance may serve as groundwork to study the efficacy of neuroprotective agents to prevent or delay the development of a full-blown neurodegenerative disorder. The cause of sleep disturbances in neurodegenerative disorders may be attributed to several factors, including age-related modifications, symptoms of the disease, comorbid conditions and the neurodegenerative process itself.

  19. Coenzyme Q10 effects in neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Meredith Spindler

    2009-11-01

    Full Text Available Meredith Spindler1, M Flint Beal1,2, Claire Henchcliffe1,21Department of Neurology, 2Department of Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Coenzyme Q10 (CoQ10 is an essential cofactor in the mitochondrial respiratory chain, and as a dietary supplement it has recently gained attention for its potential role in the treatment of neurodegenerative disease. Evidence for mitochondrial dysfunction in neurodegenerative disorders derives from animal models, studies of mitochondria from patients, identification of genetic defects in patients with neurodegenerative disease, and measurements of markers of oxidative stress. Studies of in vitro models of neuronal toxicity and animal models of neurodegenerative disorders have demonstrated potential neuroprotective effects of CoQ10. With this data in mind, several clinical trials of CoQ10 have been performed in Parkinson’s disease and atypical Parkinson’s syndromes, Huntington’s disease, Alzheimer disease, Friedreich’s ataxia, and amyotrophic lateral sclerosis, with equivocal findings. CoQ10 is widely available in multiple formulations and is very well tolerated with minimal adverse effects, making it an attractive potential therapy. Phase III trials of high-dose CoQ10 in large sample sizes are needed to further ascertain the effects of CoQ10 in neurodegenerative diseases.Keywords: coenzyme Q10, neurodegenerative disease, Parkinson’s disease, Huntington’s disease, mitochondrial dysfunction

  20. A Hybrid DE-RGSO-ELM for Brain Tumor Tissue Categorization in 3D Magnetic Resonance Images

    Directory of Open Access Journals (Sweden)

    K. Kothavari

    2014-01-01

    Full Text Available Medical diagnostics, a technique used for visualizing the internal structures and functions of human body, serves as a scientific tool to assist physicians and involves direct use of digital imaging system analysis. In this scenario, identification of brain tumors is complex in the diagnostic process. Magnetic resonance imaging (MRI technique is noted to best assist tissue contrast for anatomical details and also carries out mechanisms for investigating the brain by functional imaging in tumor predictions. Considering 3D MRI model, analyzing the anatomy features and tissue characteristics of brain tumor is complex in nature. Henceforth, in this work, feature extraction is carried out by computing 3D gray-level cooccurence matrix (3D GLCM and run-length matrix (RLM and feature subselection for dimensionality reduction is performed with basic differential evolution (DE algorithm. Classification is performed using proposed extreme learning machine (ELM, with refined group search optimizer (RGSO technique, to select the best parameters for better simplification and training of the classifier for brain tissue and tumor characterization as white matter (WM, gray matter (GM, cerebrospinal fluid (CSF, and tumor. Extreme learning machine outperforms the standard binary linear SVM and BPN for medical image classifier and proves better in classifying healthy and tumor tissues. The comparison between the algorithms proves that the mean and standard deviation produced by volumetric feature extraction analysis are higher than the other approaches. The proposed work is designed for pathological brain tumor classification and for 3D MRI tumor image segmentation. The proposed approaches are applied for real time datasets and benchmark datasets taken from dataset repositories.

  1. The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues.

    Science.gov (United States)

    Al-Mahdawi, Sahar; Pinto, Ricardo Mouro; Ismail, Ozama; Varshney, Dhaval; Lymperi, Stefania; Sandi, Chiranjeevi; Trabzuni, Daniah; Pook, Mark

    2008-03-01

    Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, leading to reduced expression of frataxin protein. Evidence suggests that the mutation may induce epigenetic changes and heterochromatin formation, thereby impeding gene transcription. In particular, studies using FRDA patient blood and lymphoblastoid cell lines have detected increased DNA methylation of specific CpG sites upstream of the GAA repeat and histone modifications in regions flanking the GAA repeat. In this report we show that such epigenetic changes are also present in FRDA patient brain, cerebellum and heart tissues, the primary affected systems of the disorder. Bisulfite sequence analysis of the FXN flanking GAA regions reveals a shift in the FRDA DNA methylation profile, with upstream CpG sites becoming consistently hypermethylated and downstream CpG sites becoming consistently hypomethylated. We also identify differential DNA methylation at three specific CpG sites within the FXN promoter and one CpG site within exon 1. Furthermore, we show by chromatin immunoprecipitation analysis that there is overall decreased histone H3K9 acetylation together with increased H3K9 methylation of FRDA brain tissue. Further studies of brain, cerebellum and heart tissues from our GAA repeat expansion-containing FRDA YAC transgenic mice reveal comparable epigenetic changes to those detected in FRDA patient tissue. We have thus developed a mouse model that will be a valuable resource for future therapeutic studies targeting epigenetic modifications of the FXN gene to increase frataxin expression.

  2. Dietary krill oil enhances neurocognitive functions and modulates proteomic changes in brain tissues of d-galactose induced aging mice.

    Science.gov (United States)

    Cheong, Ling-Zhi; Sun, Tingting; Li, Yanyan; Zhou, Jun; Lu, Chenyang; Li, Ye; Huang, Zhongbai; Su, Xiurong

    2017-05-24

    The effects of dietary krill oil on neurocognitive functions and proteomic changes in brain tissues of d-galactose-induced aging mice were evaluated. Dietary krill oil enhanced the neurocognitive functions of aging mice with a significant (P aging mice administered with krill oil showed significant (P changes in the serum malondialdehyde (MDA) level. In terms of proteomic changes, krill oil resulted in upregulation of the Celsr3 and Ppp1r1b gene expression, which contribute to brain development, learning and memory behavior processes. In particular, the Ppp1r1b gene is associated with the inhibition of dopamine releases, which decreases the motivation for learning.

  3. Protective Effects of Beta Glucan and Gliclazide on Brain Tissue and Sciatic Nerve of Diabetic Rats Induced by Streptozosin

    Directory of Open Access Journals (Sweden)

    Harun Alp

    2012-01-01

    Full Text Available There have not been yet enough studies about effects of beta glucan and gliclazide on oxidative stress created by streptozotocin in the brain and sciatic nerve of diabetic rats. The aim of this paper was to investigate the antioxidant effects of gliclazide and beta glucan on oxidative stress and lipid peroxidation created by streptozotosin in brain and sciatic nerve. Total of 42 rats were divided into 6 groups including control, diabetic untreated (DM (only STZ, diabetic, STZ (DM + beta glucan, STZ (DM + gliclazide, only beta glucan treated (no diabetic, and only gliclazide treated (no diabetic. The brain and sciatic nerve tissue samples were analyzed for malondialdehyde (MDA, total oxidant status (TOS, total antioxidant status (TAS, oxidative stress index (OSI, and paraoxonase (PON-1 levels. We found a significant increase in MDA, TOS, and OSI along with a reduction in TAS level, catalase, and PON-1 activities in brain and sciatic nerve of streptozotocin-induced diabetic rats. Also, this study shows that in terms of these parameters both gliclazide and beta glucan have a neuroprotective effect on the brain and sciatic nerve of the streptozotocin-induced diabetic rat. Our conclusion was that gliclazide and beta glucan have antioxidant effects on the brain and sciatic nerve of the streptozotocin-induced diabetic rat.

  4. Understanding the Neurophysiology and Quantification of Brain Perfusion.

    Science.gov (United States)

    Tong, Elizabeth; Sugrue, Leo; Wintermark, Max

    2017-04-01

    Newer neuroimaging technology has moved beyond pure anatomical imaging and ventured into functional and physiological imaging. Perfusion magnetic resonance imaging (PWI), which depicts hemodynamic conditions of the brain at the microvascular level, has an increasingly important role in clinical central nervous system applications. This review provides an overview of the established role of PWI in brain tumor and cerebrovascular imaging, as well as some emerging applications in neuroimaging. PWI allows better characterization of brain tumors, grading, and monitoring. In acute stroke imaging, PWI is utilized to distinguish penumbra from infarcted tissue. PWI is a promising tool in the assessment of neurodegenerative and neuropsychiatric diseases, although its clinical role is not yet defined.

  5. Stem cell treatment for age-related neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Nurković J.

    2015-01-01

    Full Text Available The belief in the inability of neurogenesis, that is the inability to create new neurons after embryonic and early postnatal development of the central nervous system, was rejected in the mid-nineties, when the existence of neurogenesis in restricted areas of CNS adult mammals, including humans, was discovered.Transplantation of stem cells or their derivatives into respective tissues or organs is considered as one of the most promising remedies for many incurable diseases.In this review, we summarized current knowledge and present and future perspectives andchallenges regarding stem cells treatment for Parkinson's and Alzheimer's disease, as the most common age-related neurodegenerative diseases.

  6. Perspective Insights of Exosomes in Neurodegenerative Diseases: A Critical Appraisal

    Directory of Open Access Journals (Sweden)

    Arif Tasleem Jan

    2017-09-01

    Full Text Available Exosomes are small membranous entities of endocytic origin. Their production by a wide variety of cells in eukaryotes implicates their roles in the execution of essential processes, especially cellular communication. Exosomes are secreted under both physiological and pathophysiological conditions, and their actions on neighboring and distant cells lead to the modulations of cellular behaviors. They also assist in the delivery of disease causing entities, such as prions, α-syn, and tau, and thus, facilitate spread to non-effected regions and accelerate the progressions of neurodegenerative diseases. The characterization of exosomes, provides information on aberrant processes, and thus, exosome analysis has many clinical applications. Because they are associated with the transport of different cellular entities across the blood-brain barrier (BBB, exosomes might be useful for delivering drugs and other therapeutic molecules to brain. Herein, we review roles played by exosomes in different neurodegenerative diseases, and the possibilities of using them as diagnostic biomarkers of disease progression, drug delivery vehicles and in gene therapy.

  7. Perspective Insights of Exosomes in Neurodegenerative Diseases: A Critical Appraisal

    Science.gov (United States)

    Jan, Arif Tasleem; Malik, Mudasir A.; Rahman, Safikur; Yeo, Hye R.; Lee, Eun J.; Abdullah, Tasduq S.; Choi, Inho

    2017-01-01

    Exosomes are small membranous entities of endocytic origin. Their production by a wide variety of cells in eukaryotes implicates their roles in the execution of essential processes, especially cellular communication. Exosomes are secreted under both physiological and pathophysiological conditions, and their actions on neighboring and distant cells lead to the modulations of cellular behaviors. They also assist in the delivery of disease causing entities, such as prions, α-syn, and tau, and thus, facilitate spread to non-effected regions and accelerate the progressions of neurodegenerative diseases. The characterization of exosomes, provides information on aberrant processes, and thus, exosome analysis has many clinical applications. Because they are associated with the transport of different cellular entities across the blood-brain barrier (BBB), exosomes might be useful for delivering drugs and other therapeutic molecules to brain. Herein, we review roles played by exosomes in different neurodegenerative diseases, and the possibilities of using them as diagnostic biomarkers of disease progression, drug delivery vehicles and in gene therapy. PMID:29033828

  8. Understanding the cellular and molecular alterations in PTSD brains : The necessity of post-mortem brain tissue

    NARCIS (Netherlands)

    De Lange, G.

    2017-01-01

    The personal, social and economic burden of post-traumatic stress disorder (PTSD) is high and therapeutic approaches are only partially effective. Therefore, there is an urgent need to understand the cellular and molecular alterations in PTSD brains in order to design more effective treatment

  9. Nanoparticles and Colloids as Contributing Factors in Neurodegenerative Disease

    Science.gov (United States)

    Bondy, Stephen C.

    2011-01-01

    This review explores the processes underlying the deleterious effects of the presence of insoluble or colloidal depositions within the central nervous system. These materials are chemically unreactive and can have a prolonged residence in the brain. They can be composed of mineral or proteinaceous materials of intrinsic or exogenous origin. Such nanoparticulates and colloids are associated with a range of slow-progressing neurodegenerative states. The potential common basis of toxicity of these materials is discussed. A shared feature of these disorders involves the appearance of deleterious inflammatory changes in the CNS. This may be due to extended and ineffective immune responses. Another aspect is the presence of excess levels of reactive oxygen species within the brain. In addition with their induction by inflammatory events, these may be further heightened by the presence of redox active transition metals to the large surface area afforded by nanoparticles and amphipathic micelles. PMID:21776226

  10. Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by prazosin.

    Science.gov (United States)

    Sattin, Albert; Pekary, Albert Eugene; Blood, James

    2011-08-01

    Hyperresponsiveness to norepinephrine contributes to post-traumatic stress disorder (PTSD). Prazosin, a brain-active blocker of α(1)-adrenoceptors, originally used for the treatment of hypertension, has been reported to alleviate trauma nightmares, sleep disturbance and improve global clinical status in war veterans with PTSD. Thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) may play a role in the pathophysiology and treatment of neuropsychiatric disorders such as major depression, and PTSD (an anxiety disorder). To investigate whether TRH or TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) participate in the therapeutic effects of prazosin, male rats were injected with prazosin and these peptides then measured in brain and endocrine tissues. Prazosin stimulated TRH and TRH-like peptide release in those tissues with high α(1)-adrenoceptor levels suggesting that these peptides may play a role in the therapeutic effects of prazosin. Published by Elsevier Inc.

  11. Differences in supratentorial white matter diffusion after radiotherapy - New biomarker of normal brain tissue damage?

    Energy Technology Data Exchange (ETDEWEB)

    Ravn, Soeren; Jens Broendum Froekaer, Jens [Dept. of Radiology, Aalborg Univ. Hospital, Aalborg (Denmark)], e-mail: sorl@rn.dk; Holmberg, Mats [Dept. of Oncology, Aalborg Univ. Hospital, Aalborg (Denmark); Soerensen, Preben [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark); Carl, Jesper [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark)

    2013-10-15

    Introduction: Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. Material and methods: DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35-71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0-7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on iso curves from Eclipse. Data was analysed by t-test. Estimates are given with 95 % CI. Results: A mean ADC difference of 4.6(0.3;8.9) X 10{sup -5} mm{sup 2}/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60) X 10{sup -5} mm{sup 2}/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(-1.76;5.58) X 10{sup -5} mm{sup 2}/s, p = 0.29; 15 Gy; 5.81(1.53;10.11) X 10{sup -5} mm{sup 2}/s, p = 0.01; 25 Gy; 5.80(2.43;9.18) X 10{sup -5} mm{sup 2}/s, p = 0.002; 35 Gy; 5.93(2.89;8.97) X 10

  12. Recombinant tissue plasminogen activator enhances microparticle release from mouse brain-derived endothelial cells through plasmin.

    Science.gov (United States)

    Garraud, Marie; Khacef, Kahina; Vion, Anne-Clémence; Leconte, Claire; Yin, Min; Renard, Jean-Marie; Marchand-Leroux, Catherine; Boulanger, Chantal M; Margaill, Isabelle; Beray-Berthat, Virginie

    2016-11-15

    Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is currently the only approved pharmacological strategy for acute ischemic stroke. However, rt-PA exhibits vascular toxicity mainly due to endothelial damage. To investigate the mechanisms underlying rt-PA-induced endothelial alterations, we assessed the role of rt-PA in the generation of endothelial microparticles (EMPs), emerging biological markers and effectors of endothelial dysfunction. The mouse brain-derived endothelial cell line bEnd.3 was used. Cells were treated with rt-PA at 20, 40 or 80μg/ml for 15 or 24h, and EMPs were quantified in the culture media using Annexin-V staining coupled with flow cytometry. Rt-PA enhanced EMP release from bEnd.3 cells with a maximal increase at the 40μg/ml dose for 24h (+78% compared to controls). Using tranexamic acid and aprotinin we demonstrated that plasmin is responsible for rt-PA-induced EMP release. The p38 MAPK inhibitor SB203580 and the poly(ADP-ribose)polymerase (PARP) inhibitor PJ34 also reduced rt-PA-induced EMP production, suggesting that p38 MAPK and PARP are downstream intracellular effectors of rt-PA/plasmin. Rt-PA also altered through plasmin the morphology and the confluence of bEnd.3 cells. By contrast, these changes did not implicate p38 MAPK and PARP. This study demonstrates that rt-PA induces the production of microparticles by cerebral endothelial cells, through plasmin, p38 MAPK and PARP pathways. Determining the phenotype of these EMPs to clarify their role on the endothelium in ischemic conditions could thus be of particular interest. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Tissue Response to Deep Brain Stimulation and Microlesion: A Comparative Study.

    Science.gov (United States)

    Vedam-Mai, Vinata; Baradaran-Shoraka, Massoud; Reynolds, Brent A; Okun, Michael S

    2016-07-01

    Deep brain stimulation (DBS) is used for a variety of movement disorders, including Parkinson's disease. There are several theories regarding the biology and mechanisms of action of DBS. Previously, we observed an up-regulation of neural progenitor cell proliferation in post-mortem tissue suggesting that DBS can influence cellular plasticity in regions beyond the site of stimulation. We wanted to support these observations and investigate the relationship if any, between DBS, neural progenitor cells, and microglia. We used naïve rats in this study for DBS electrode implantation, stimulation, and microlesions. We used immunohistochemistry techniques for labeling microglial and progenitor cells, and fluorescence microscopy for viewing and quantification of labeled cells. We present data that demonstrates a reciprocal relationship of microglia and neural precursor cells in the presence of acute high frequency stimulation. In our hands, stimulated animals demonstrate significantly lower numbers of activated microglia (p = 0.026) when compared to microlesion and sham animals. The subthalamic region surrounding the DBS stimulating electrode reveals a significant increase in the number of neural precursor cells expressing cell cycle markers, plasticity and precursor cell markers (Ki67; p = 0.0013, MCM2; p = 0.0002). We conclude that in this animal model, acute DBS results in modest local progenitor cell proliferation and influenced the total number of activated microglia. This could be of clinical significance in patients with PD, as it is thought to progress via neuroinflammatory processes involving microglia, cytokines, and the complement system. Further studies are required to comprehend the behavior of microglia in different activation states and their ability to regulate adult neurogenesis under physiologic and pathologic conditions. © 2016 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of

  14. THE RAPID PRODUCTION OF ACUTE DISSEMINATED ENCEPHALOMYELITIS IN RHESUS MONKEYS BY INJECTION OF HETEROLOGOUS AND HOMOLOGOUS BRAIN TISSUE WITH ADJUVANTS

    Science.gov (United States)

    Kabat, Elvin A.; Wolf, Abner; Bezer, Ada E.

    1947-01-01

    1. A picture resembling acute disseminated encephalomyelitis in the human being has been regularly and rapidly produced in rhesus monkeys by injection of emulsions of adult rabbit and monkey brain administered with adjuvants. 2. No lesions of the central nervous system resulted from injection of similar emulsions of fetal rabbit brain or adult rabbit lung. 3. A description of the gross and histological findings in the central nervous system is given and compared with features of human demyelinating disease. 4. The experimental findings are in accord with the hypothesis that antibody to the injected brain emulsion reacts with the tissues of the nervous system of the animal to produce the pathological changes. PMID:19871595

  15. Effect of zibushenjing fang on skeletal development and brain tissue antioxidation in mice with kidney essence insufficiency: a mechanistic study.

    Science.gov (United States)

    He, Yuezhen; Yao, Junxiao; Shen, Shilin; Su, Xiaojun; Wang, Yuping; Li, Li; Wang, Wenhui; Shi, Jiping

    2013-06-01

    To investigate the effects of Zibushenjing Fang (formula for tonifying the kidney essence) on skeletal development and brain tissue antioxidation in mice with kidney essence insufficiency. Fifty male Kunming mice were randomly divided into five groups: normal group, model group, Jinkuishenqi Wan group, Zibushenjing Fang high dose group, and Zibushenjing Fang low dose group, with 10 mice in each group. The model of kidney essence insufficiency syndrome was established in all the mice except the normal group by using a cat to threaten the mice and by swimming until exhaustion daily which lasted about 21 days. Mice in the model group were administered 20 mL/ kg(-1) x d(-1) of normal saline intragastrically. The Jinkuishenqi Wan group was given 2.7 g/kg(-1) x d(-1) of a solution of Jinkuishenqi Wan. The Zibushenjing Fang high dose group was given 20 g/kg(-1) x d(-1) and the Zibushenjing Fang low dose group was given 10 g/kg(-1) x d(-1) of a solution of Zibushenjing Fang. The general condition of all the groups was observed, including the quantity of food and water intake, swimming time, length of femur, and weight of the femur and musculus quadriceps femoris. The total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and methane dicarboxylic aldehyde (MDA) activities in the brain tissues were detected. Zibushenjing Fang could improve the manifestation of kidney essence insufficiency, increase the quantity of food and water intake, swimming time, femur length, and femur and musculus quadriceps femoris weight. It could also regulate the activities of T-SOD, GSH-Px, and MDA in brain tissue. Zibushenjing Fang may play an important role in treating kidney essence insufficiency syndrome by promoting body development and improving brain tissue antioxidation.

  16. Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy

    Science.gov (United States)

    Berndt, Bianca; Landry, Guillaume; Schwarz, Florian; Tessonnier, Thomas; Kamp, Florian; Dedes, George; Thieke, Christian; Würl, Matthias; Kurz, Christopher; Ganswindt, Ute; Verhaegen, Frank; Debus, Jürgen; Belka, Claus; Sommer, Wieland; Reiser, Maximilian; Bauer, Julia; Parodi, Katia

    2017-03-01

    The purpose of this work was to evaluate the ability of single and dual energy computed tomography (SECT, DECT) to estimate tissue composition and density for usage in Monte Carlo (MC) simulations of irradiation induced β + activity distributions. This was done to assess the impact on positron emission tomography (PET) range verification in proton therapy. A DECT-based brain tissue segmentation method was developed for white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). The elemental composition of reference tissues was assigned to closest CT numbers in DECT space (DECTdist). The method was also applied to SECT data (SECTdist). In a validation experiment, the proton irradiation induced PET activity of three brain equivalent solutions (BES) was compared to simulations based on different tissue segmentations. Five patients scanned with a dual source DECT scanner were analyzed to compare the different segmentation methods. A single magnetic resonance (MR) scan was used for comparison with an established segmentation toolkit. Additionally, one patient with SECT and post-treatment PET scans was investigated. For BES, DECTdist and SECTdist reduced differences to the reference simulation by up to 62% when compared to the conventional stoichiometric segmentation (SECTSchneider). In comparison to MR brain segmentation, Dice similarity coefficients for WM, GM and CSF were 0.61, 0.67 and 0.66 for DECTdist and 0.54, 0.41 and 0.66 for SECTdist. MC simulations of PET treatment verification in patients showed important differences between DECTdist/SECTdist and SECTSchneider for patients with large CSF areas within the treatment field but not in WM and GM. Differences could be misinterpreted as PET derived range shifts of up to 4 mm. DECTdist and SECTdist yielded comparable activity distributions, and comparison of SECTdist to a measured patient PET scan showed improved agreement when compared to SECTSchneider. The agreement between predicted and measured PET

  17. Genetically modified pig models for neurodegenerative disorders.

    Science.gov (United States)

    Holm, Ida E; Alstrup, Aage Kristian Olsen; Luo, Yonglun

    2016-01-01

    Increasing incidence of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease has become one of the most challenging health issues in ageing humans. One approach to combat this is to generate genetically modified animal models of neurodegenerative disorders for studying pathogenesis, prognosis, diagnosis, treatment, and prevention. Owing to the genetic, anatomic, physiologic, pathologic, and neurologic similarities between pigs and humans, genetically modified pig models of neurodegenerative disorders have been attractive large animal models to bridge the gap of preclinical investigations between rodents and humans. In this review, we provide a neuroanatomical overview in pigs and summarize and discuss the generation of genetically modified pig models of neurodegenerative disorders including Alzheimer's diseases, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and ataxia-telangiectasia. We also highlight how non-invasive bioimaging technologies such as positron emission tomography (PET), computer tomography (CT), and magnetic resonance imaging (MRI), and behavioural testing have been applied to characterize neurodegenerative pig models. We further propose a multiplex genome editing and preterm recloning (MAP) approach by using the rapid growth of the ground-breaking precision genome editing technology CRISPR/Cas9 and somatic cell nuclear transfer (SCNT). With t